Janssen Pharmaceuticals, Inc.

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Janssen Pharmaceuticals, Inc. Drugs

Invega Trinza

Invega Trinza

2.1 Administration Instructions

INVEGA TRINZA™ should be administered once every 3 months.

Each injection must be administered only by a health care professional.

Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration. It is important to shake the syringe vigorously for at least 15 seconds to ensure a homogeneous suspension. Inject INVEGA TRINZA™ within 5 minutes of shaking vigorously [see Dosage and Administration (2.8)].

INVEGA TRINZA™ is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. Administer the dose in a single injection; do not administer the dose in divided injections. Inject slowly, deep into the deltoid or gluteal muscle.

INVEGA TRINZA™ must be administered using only the thin wall needles that are provided in the INVEGA TRINZA™ pack. Do not use needles from the 1-month paliperidone palmitate extended-release injectable suspension pack or other commercially-available needles to reduce the risk of blockage.

Deltoid Injection

The recommended needle size for administration of INVEGA TRINZA™ into the deltoid muscle is determined by the patient's weight:
For patients weighing less than 90 kg, the 1-inch, 22 gauge thin wall needle is recommended. For patients weighing 90 kg or more, the 1½-inch, 22 gauge thin wall needle is recommended.
Administer into the center of the deltoid muscle. Deltoid injections should be alternated between the two deltoid muscles.

Gluteal Injection

Regardless of patient weight, the recommended needle size for administration of INVEGA TRINZA™ into the gluteal muscle is the 1½-inch, 22 gauge thin wall needle. Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.

Incomplete Administration

To avoid an incomplete administration of INVEGA TRINZA™, ensure that the prefilled syringe is shaken vigorously for at least 15 seconds within 5 minutes prior to administration to ensure a homogeneous suspension and ensure the needle does not get clogged during injection [see Dosage and Administration (2.8)].

However, in the event of an incompletely administered dose, do not re-inject the dose remaining in the syringe and do not administer another dose of INVEGA TRINZA™. Closely monitor and treat the patient with oral supplementation as clinically appropriate until the next scheduled 3-month injection of INVEGA TRINZA™.

2.2 Schizophrenia

Adults

INVEGA TRINZA™ is to be used only after INVEGA SUSTENNA® (1-month paliperidone palmitate extended-release injectable suspension) has been established as adequate treatment for at least four months. In order to establish a consistent maintenance dose, it is recommended that the last two doses of INVEGA SUSTENNA® be the same dosage strength before starting INVEGA TRINZA™.

Initiate INVEGA TRINZA™ when the next 1-month paliperidone palmitate dose is scheduled with an INVEGA TRINZA™ dose based on the previous 1-month injection dose, using the equivalent 3.5-fold higher dose as shown in Table 1. INVEGA TRINZA™ may be administered up to 7 days before or after the monthly time point of the next scheduled paliperidone palmitate 1-month dose.
Table 1. INVEGA TRINZA™ Doses for Adult Patients Adequately Treated with INVEGA SUSTENNA® If the Last Dose of INVEGA SUSTENNA® is: Initiate INVEGA TRINZA™ at the Following Dose: Conversion from the INVEGA SUSTENNA® 39 mg dose was not studied. 78 mg 273 mg 117 mg 410 mg 156 mg 546 mg 234 mg 819 mg
Following the initial INVEGA TRINZA™ dose, INVEGA TRINZA™ should be administered every 3 months. If needed, dose adjustment can be made every 3 months in increments within the range of 273 mg to 819 mg based on individual patient tolerability and/or efficacy. Due to the long-acting nature of INVEGA TRINZA™, the patient's response to an adjusted dose may not be apparent for several months [see Clinical Pharmacology (12.3)].

2.3 Missed Doses

Dosing Window

Missing doses of INVEGA TRINZA™ should be avoided. If necessary, patients may be given the injection up to 2 weeks before or after the 3-month time point.

Missed Dose 3½ Months to 4 Months Since Last Injection

If more than 3½ months (up to but less than 4 months) have elapsed since the last injection of INVEGA TRINZA™, the previously administered INVEGA TRINZA™ dose should be administered as soon as possible, then continue with the 3-month injections following this dose.

Missed Dose 4 Months to 9 Months Since Last Injection

If 4 months up to and including 9 months have elapsed since the last injection of INVEGA TRINZA™, do NOT administer the next dose of INVEGA TRINZA™. Instead, use the re-initiation regimen shown in Table 2.
Table 2. Re-initiation Regimen After Missing 4 Months to 9 Months of INVEGA TRINZA™ If the Last Dose of INVEGA TRINZA™ was: Administer INVEGA SUSTENNA®, two doses one week apart (into deltoid muscle) Then administer INVEGA TRINZA™ (into deltoid* or gluteal muscle) Day 1 Day 8 1 month after Day 8 * See Instructions for Use for deltoid injection needle selection based on body weight. 273 mg 78 mg 78 mg 273 mg 410 mg 117 mg 117 mg 410 mg 546 mg 156 mg 156 mg 546 mg 819 mg 156 mg 156 mg 819 mg
Missed Dose Longer than 9 Months Since Last Injection

If more than 9 months have elapsed since the last injection of INVEGA TRINZA™, re-initiate treatment with the 1-month paliperidone palmitate extended-release injectable suspension as described in the prescribing information for that product. INVEGA TRINZA™ can then be resumed after the patient has been adequately treated with the 1-month paliperidone palmitate extended-release injectable suspension for at least 4 months.

2.4 Use with Risperidone or with Oral Paliperidone

Since paliperidone is the major active metabolite of risperidone, caution should be exercised when INVEGA TRINZA™ is coadministered with risperidone or oral paliperidone for extended periods of time. Safety data involving concomitant use of INVEGA TRINZA™ with other antipsychotics is limited.

2.5 Dosage Adjustment in Renal Impairment

INVEGA TRINZA™ has not been systematically studied in patients with renal impairment [see Clinical Pharmacology (12.3)]. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min [Cockcroft-Gault Formula], adjust dosage and stabilize the patient using the 1-month paliperidone palmitate extended-release injectable suspension, then transition to INVEGA TRINZA™ [see Table 1, Dosage and Administration (2.2)]. [See also Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)]

INVEGA TRINZA™ is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.6 Switching from INVEGA TRINZA™ to the 1-Month Paliperidone Palmitate Extended-Release Injectable Suspension

For switching from INVEGA TRINZA™ to INVEGA SUSTENNA® (1-month paliperidone palmitate extended-release injectable suspension), the 1-month paliperidone palmitate extended-release injectable suspension should be started 3 months after the last INVEGA TRINZA™ dose, using the equivalent 3.5-fold lower dose as shown in Table 3. The 1-month paliperidone palmitate extended-release injectable suspension should then continue, dosed at monthly intervals.
Table 3. Conversion From INVEGA TRINZA™ to INVEGA SUSTENNA® If the Last Dose of INVEGA TRINZA™ is: Initiate* INVEGA SUSTENNA® 3 Months Later at the Following Dose: * The initiation dosing as described in the prescribing information for INVEGA SUSTENNA ® is not required. 273 mg 78 mg 410 mg 117 mg 546 mg 156 mg 819 mg 234 mg
2.7 Switching from INVEGA TRINZA™ to Oral Paliperidone Extended-Release Tablets

For switching from INVEGA TRINZA™ to oral paliperidone extended-release tablets, the daily dosing of the paliperidone extended-release tablets should be started 3 months after the last INVEGA TRINZA™ dose and transitioned over the next several months following the last INVEGA TRINZA™ dose as described in Table 4. Table 4 provides dose conversion regimens to allow patients previously stabilized on different doses of INVEGA TRINZA™ to attain similar paliperidone exposure with once daily paliperidone extended-release tablets.
Table 4. INVEGA TRINZA™ Doses and Once-Daily Paliperidone Extended-Release Conversion Regimens Needed to Attain Similar Paliperidone Exposures Weeks Since Last INVEGA TRINZA™ Dose 3 months to 18 weeks Longer than 18 weeks to 24 weeks Longer than 24 weeks Last INVEGA TRINZA™ Dose Doses of oral paliperidone extended-release tablets 273 mg 3 mg 3 mg 3 mg 410 mg 3 mg 3 mg 6 mg 546 mg 3 mg 6 mg 9 mg 819 mg 6 mg 9 mg 12 mg
2.8 Instructions for Use
Administer every 3 months Shake syringe vigorously for at least 15 seconds
For intramuscular injection only. Do not administer by any other route.

Important

INVEGA TRINZA™ should be administered by a healthcare professional as a single injection. DO NOT divide dose into multiple injections.

INVEGA TRINZA™ is intended for intramuscular use only. Inject slowly, deep into the muscle taking care to avoid injection into a blood vessel.

Read complete instructions prior to use.

Dosing

This medication should be administered once every 3 months.

Preparation

Peel off tab label from the syringe and place in patient record.

INVEGA TRINZA™ requires longer and more vigorous shaking than INVEGA SUSTENNA® (1-month paliperidone palmitate extended-release injectable suspension). Shake the syringe vigorously, with the syringe tip pointing up, for at least 15 seconds within 5 minutes prior to administration (see Step 2).

Thin Wall Safety Needle Selection

Thin wall safety needles are designed to be used with INVEGA TRINZA™. Therefore, it is important to only use the needles provided in the INVEGA TRINZA™ kit.

Dose pack contents
Prefilled Syringe Thin Wall Safety Needles
1 Select needle

Needle selection is determined by injection area and patient weight.
If administering a Deltoid injectionIf patient weighs:Less than 90 kg pink hub If administering a Gluteal injectionIf patient weighs:Less than 90 kg yellow hub 90 kg or more yellow hub 90 kg or more yellow hub
2 Prepare for injection

Check suspension

After shaking the syringe for at least 15 seconds, check the liquid in the viewing window.

The suspension should appear uniform and milky white in color.

It is also normal to see small air bubbles.

Open needle pouch and remove cap

First, open needle pouch by peeling the cover back half way. Place on a clean surface.

Then, holding the syringe upright, twist and pull the rubber cap to remove.

Grasp needle pouch

Fold back needle cover and plastic tray. Then, firmly grasp the needle sheath through the pouch, as shown.

Attach needle

With your other hand, hold the syringe by the luer connection and attach it to the safety needle with a gentle clockwise twisting motion.

Do not remove the pouch until the syringe and needle are securely attached.

Remove needle sheath

Pull the needle sheath away from the needle in a straight motion.

Do not twist the sheath, as this may loosen the needle from the syringe.

Remove air bubbles

Hold the syringe upright and tap gently to make any air bubbles rise to the top.

Remove air by pressing the plunger rod upward carefully until a drop of liquid comes out of the needle tip.

3 Inject

Inject dose

Slowly inject the entire contents of the syringe intramuscularly, deep into the selected deltoid or gluteal muscle.

Do not administer by any other route.

4 After injection

Secure needle

After the injection is complete, use your thumb or a flat surface to secure the needle in the safety device. The needle is secure when a "click" sound is heard.

Dispose properly

Dispose of the syringe and unused needle in an approved sharps container.
Parafon Forte Dsc

Parafon Forte Dsc

Usual Adult Dosage

One caplet three or four times daily. If adequate response is not obtained with this dose, it may be increased to 1 ½ caplets (750 mg) three or four times daily. As improvement occurs dosage can usually be reduced.
Elmiron

Elmiron

The recommended dose of ELMIRON® is 300 mg/day taken as one 100 mg capsule orally three times daily. The capsules should be taken with water at least 1 hour before meals or 2 hours after meals.

Patients receiving ELMIRON® should be reassessed after 3 months. If improvement has not occurred and if limiting adverse events are not present, ELMIRON® may be continued for another 3 months.

The clinical value and risks of continued treatment in patients whose pain has not improved by 6 months is not known.
Eucerin Q10 Anti-wrinkl...

Eucerin Q10 Anti-wrinkle Sensitive Skin

2.1 Recommended Dosage
Individualize the starting dose of INVOKAMET (canagliflozin and metformin hydrochloride) based on the patient's current regimen: – In patients on metformin, switch to INVOKAMET containing canagliflozin 50 mg with a similar total daily dose of metformin; – In patients on canagliflozin, switch to INVOKAMET containing metformin 500 mg with a similar total daily dose of canagliflozin; – In patients already treated with canagliflozin and metformin, switch to INVOKAMET containing the same total daily doses of each component. Take INVOKAMET twice daily with meals, with gradual dose escalation to reduce the gastrointestinal side effects due to metformin [see Dosage Forms and Strengths (3)]. In patients with volume depletion not previously treated with canagliflozin, correct this condition before initiating INVOKAMET [see Warnings and Precautions (5.2), Use in Specific Populations (8.5), (8.6), and Patient Counseling Information (17)]. Adjust dosing based on effectiveness and tolerability while not exceeding the maximum recommended daily dose of metformin 2000 mg and canagliflozin 300 mg in patients with an eGFR of 60 mL/min/1.73 m2 or greater [see Dosage and Administration (2.2)].
2.2 Recommended Dosage for Patients with Renal Impairment
Assess renal function before initiating INVOKAMET and periodically thereafter. Do not initiate or continue INVOKAMET in patients with serum creatinine levels greater than or equal to 1.5 mg/dL for males or 1.4 mg/dL for females. In patients who meet these serum creatinine levels, do not initiate or continue INVOKAMET if eGFR is persistently less than 45 mL/min/1.73 m2 [see Contraindications (4) and Warnings and Precautions (5.3)]. No dose adjustment of INVOKAMET is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater). Limit the dose of INVOKAMET to canagliflozin 50 mg twice daily in patients with moderate renal impairment with an eGFR of 45 to less than 60 mL/min/1.73 m2.
2.3 Concomitant Use with UDP-Glucuronosyl Transferase (UGT) Enzyme Inducers

If an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKAMET, consider increasing the dose to canagliflozin 150 mg twice daily in patients currently tolerating 50 mg twice daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control [see Drug Interactions (7.2)].

Consider another antihyperglycemic agent in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 receiving concurrent therapy with a UGT inducer.
Meloxicam

Meloxicam

To achieve maximum contraceptive effectiveness, ORTHO-NOVUM® Tablets and MODICON® Tablets must be taken exactly as directed and at intervals not exceeding 24 hours. ORTHO-NOVUM® Tablets and MODICON® Tablets are available with the DIALPAK® Tablet Dispenser which is preset for a Sunday Start. Day 1 Start is also available.

Sunday Start

When taking ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON®, the first "active" tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first "active" tablet should be taken that day. Take one active tablet daily for 21 days followed by one green "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception such as a condom or spermicide should be used until after the first 7 consecutive days of administration.

If the patient misses one (1) "active" tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) "active" tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) "active" tablets in the third week or misses three (3) or more "active" tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

Day 1 Start

The dosage of ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON®, for the initial cycle of therapy, is one "active" tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1" followed by one green "reminder" tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day.

If the patient misses one (1) "active" tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) "active" tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) "active" tablets in the third week or misses three (3) or more "active" tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section).

The use of ORTHO-NOVUM® 7/7/7, ORTHO-NOVUM® 1/35, and MODICON® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) The possibility of ovulation and conception prior to initiation of medication should be considered.

(See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.)
Doribax

Doribax

2.1 Recommended Dosage

The recommended dosage of DORIBAX® is 500 mg administered every 8 hours by intravenous infusion over one hour in patients ≥18 years of age. The recommended dosage and administration by infection is described in Table 1:
Table 1: Dosage of DORIBAX® by Infection Infection Dosage Frequency Infusion Time(hours) Duration * Duration includes a possible switch to an appropriate oral therapy, after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated. † Duration can be extended up to 14 days for patients with concurrent bacteremia. Complicated intra-abdominal infection 500 mg every 8 hours 1 5–14 days* Complicated UTI, including pyelonephritis 500 mg every 8 hours 1 10 days*†
2.2 Patients with Renal Impairment
Table 2: Dosage of DORIBAX® in Patients with Renal Impairment Estimated CrCl (mL/min) Recommended Dosage Regimen of DORIBAX® * [see Preparation of 250 mg DORIBAX ® dose using the 250 mg vial and Preparation of 250 mg DORIBAX ® dose using the 500 mg vial ( 2.3)] > 50 No dosage adjustment necessary ≥ 30 to ≤ 50 250 mg* administered intravenously (over 1 hour) every 8 hours > 10 to < 30 250 mg* administered intravenously (over 1 hour) every 12 hours
The following formula may be used to estimate CrCl. The serum creatinine used in the formula should represent a steady state of renal function.
Males: Creatinine clearance (mL/min) = weight (kg) × (140 - age in years) 72 × serum creatinine (mg/dL) Females: Creatinine clearance (mL/min) = 0.85 × value calculated for males
DORIBAX® is hemodialyzable; however, there is insufficient information to make dose adjustment recommendations in patients on hemodialysis.

2.3 Preparation of Solutions

DORIBAX® does not contain a bacteriostatic preservative. Aseptic technique must be followed in preparation of the infusion solution.

To prepare DORIBAX infusions in Baxter Minibag Plus™ infusion bags consult the infusion bag manufacturer's instructions.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to use whenever solution and container permit. DORIBAX infusions range from clear, colorless solutions to solutions that are clear and slightly yellow. Variations in color within this range do not affect the potency of the product.

Preparation of 500 mg DORIBAX® dose using the 500 mg vial
Constitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 50 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION. Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing 100 mL of normal saline or 5% dextrose; gently shake until clear. The final infusion solution concentration is approximately 4.5 mg/mL.
Preparation of 250 mg DORIBAX® dose using the 250 mg vial
Constitute the 250 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 25 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION. Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing either 50 or 100 mL of normal saline or 5% dextrose; gently shake until clear. The final infusion solution concentration is approximately 4.2 mg/mL (50 mL infusion bag) or approximately 2.3 mg/mL (100 mL infusion bag).
Preparation of 250 mg DORIBAX® dose using the 500 mg vial
Constitute the 500 mg vial with 10 mL of sterile water for injection or 0.9% sodium chloride injection (normal saline) and gently shake to form a suspension. The resultant concentration is approximately 50 mg/mL. CAUTION: THE CONSTITUTED SUSPENSION IS NOT FOR DIRECT INJECTION. Withdraw the suspension using a syringe with a 21 gauge needle and add it to an infusion bag containing 100 mL of normal saline or 5% dextrose; gently shake until clear. Remove 55 mL of this solution from the bag and discard. Infuse the remaining solution, which contains 250 mg (approximately 4.5 mg/mL).
2.4 Compatibility

The compatibility of DORIBAX® with other drugs has not been established. DORIBAX® should not be mixed with or physically added to solutions containing other drugs.

2.5 Storage of Constituted Solutions

Upon constitution with sterile water for injection or 0.9% sodium chloride (normal saline) injection, DORIBAX suspension in the vial may be held for 1-hour prior to transfer and dilution in the infusion bag.

Following dilution of the suspension with normal saline or 5% dextrose, DORIBAX infusions stored at room temperature or under refrigeration should be completed according to the times in Table 3.
Table 3: Storage and Stability Times of Infusion Solutions Prepared in Normal Saline or 5% Dextrose Infusion prepared in Stability Time at Room Temp. (includes room temperature storage and infusion time) Stability time at 2–8°C (Refrigeration) (includes refrigerator storage and infusion time) Normal saline 12 hours 72 hours 5% Dextrose 4 hours 24 hours
Constituted DORIBAX suspension or DORIBAX infusion should not be frozen. This storage information applies also to DORIBAX® diluted in Baxter Minibag Plus™.
Ditropan Xl

Ditropan Xl

DITROPAN XL® must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed.

DITROPAN XL® may be administered with or without food.

2.1 Adults

The recommended starting dose of DITROPAN XL® is 5 or 10 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 30 mg/day). In general, dosage adjustment may proceed at approximately weekly intervals.

2.2 Pediatric Patients Aged 6 Years of Age and Older

The recommended starting dose of DITROPAN XL® is 5 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 20 mg/day).
Firmagon

Firmagon

2.1 How to Start ORTHO-CYCLEN or ORTHO TRI-CYCLEN

ORTHO-CYCLEN and ORTHO TRI-CYCLEN are dispensed in either a DIALPAK Tablet dispenser or a VERIDATE Tablet Dispenser [see How Supplied/Storage and Handling (16)]. ORTHO-CYCLEN and ORTHO TRI-CYCLEN may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

2.2 How to Take ORTHO-CYCLEN or ORTHO TRI-CYCLEN
Table 1: Instructions for Administration of ORTHO-CYCLEN or ORTHO TRI-CYCLEN Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling.
Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start)

Important: Consider the possibility of ovulation and conception prior to initiation of this product.
Tablet Color: ORTHO-CYCLEN active tablets are blue (Day 1 to Day 21). ORTHO TRI-CYCLEN active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 15) and blue (Day 16 to Day 21). ORTHO-CYCLEN and ORTHO TRI-CYCLEN both have dark green inactive tablets (Day 22 to Day 28). Day 1 Start: Take first active tablet without regard to meals on the first day of menses. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet) Sunday Start: Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of ORTHO-CYCLEN or ORTHO TRI-CYCLEN. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to ORTHO-CYCLEN or ORTHO TRI-CYCLEN from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to ORTHO-CYCLEN or ORTHO TRI-CYCLEN Start ORTHO-CYCLEN or ORTHO TRI-CYCLEN: Transdermal patch On the day when next application would have been scheduled Vaginal ring On the day when next insertion would have been scheduled Injection On the day when next injection would have been scheduled Intrauterine contraceptive On the day of removal If the IUD is not removed on first day of the patient's menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. Implant On the day of removal
Starting ORTHO-CYCLEN or ORTHO TRI-CYCLEN after Abortion or Miscarriage

First-trimester
After a first-trimester abortion or miscarriage, ORTHO-CYCLEN or ORTHO TRI-CYCLEN may be started immediately. An additional method of contraception is not needed if ORTHO-CYCLEN or ORTHO TRI-CYCLEN is started immediately. If ORTHO-CYCLEN or ORTHO TRI-CYCLEN is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of ORTHO-CYCLEN or ORTHO TRI-CYCLEN.
Second-trimester
Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start ORTHO-CYCLEN or ORTHO TRI-CYCLEN, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of ORTHO-CYCLEN or ORTHO TRI-CYCLEN. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]
Starting ORTHO-CYCLEN or ORTHO TRI-CYCLEN after Childbirth
Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with ORTHO-CYCLEN or ORTHO TRI-CYCLEN following the instructions in Table 1 for women not currently using hormonal contraception. ORTHO-CYCLEN or ORTHO TRI-CYCLEN are not recommended for use in lactating women [see Use in Specific Populations (8.3)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of ORTHO-CYCLEN or ORTHO TRI-CYCLEN. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].
DIALPAK® Tablet Dispenser:
SET THE DAY: □ Day 1 Start: turn the dial on the empty DIALPAK until the arrow points to the first day of the patient's period. □ Sunday Start: the arrow on the empty DIALPAK should point to SU (Sunday). Insert the new refill by lining up the "V" shape on the refill with the "V" shape at the top of the DIALPAK. Snap the refill in place. Pill "1" is ready to be taken. Always begin the pill cycle with pill "1," as shown on the inner part of the refill ring. Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the DIALPAK. The patient should wait 24 hours to take the next pill. To take pill "2," turn the dial on the DIALPAK in a clockwise direction to the next day. Continue to take one pill each day until all the pills have been taken. Turn the dial to the pill "1" position to remove the empty refill and insert a new refill. The first pill in every refill will always be taken on the same day of the week, no matter when the patient's next period starts.
VERIDATE® Tablet Dispenser
Place the refill in the VERIDATE Tablet Dispenser so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under all the nibs (see illustration below). If the patient starts pill-taking on Sunday, the first active pill should be taken on the first Sunday after the patient's menstrual period begins. Remove the first active pill at the top of the dispenser (Sunday) by pressing the pill through the hole in the bottom of the dispenser.
ORTHO-CYCLEN:
If the patient will start pill-taking on "Day 1," choose a blue pill that corresponds with the day of the week the patient will take the first pill. Remove that blue pill by pressing the pill through the hole in the bottom of the dispenser.
ORTHO TRI-CYCLEN:
If the patient will start pill-taking on a day other than Sunday, a calendar label has been provided and should be placed over the calendar in the center of the VERIDATE. To place the label correctly, identify the correct starting day, locate that day printed in blue on the label, and line that day up with the first white pill directly under the V notch at the top of the dispenser. Remove the label from the backing. Press the center of the label down onto the center of the printed calendar. Remove that white pill by pressing the pill through the hole in the bottom of the dispenser. After all the dark green pills have been taken, insert a new refill into the VERIDATE. The patient should take the first pill on the next day, even if the patient's period is not over yet.
To Insert New Refill (ORTHO-CYCLEN or ORTHO TRI-CYCLEN):
Lift the empty refill out of the VERIDATE Tablet Dispenser. Insert the new refill so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under the nibs.
2.3 Missed Tablets
Table 2: Instructions for Missed ORTHO-CYCLEN or ORTHO TRI-CYCLEN Tablets If one active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the pack and start a new pack that same day.Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.
2.4 Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].

2.5 ORTHO-TRICYCLEN Use for Acne

The timing of initiation of dosing with ORTHO TRI-CYCLEN for acne should follow the guidelines for use of ORTHO TRI-CYCLEN as an oral contraceptive. Consult the DOSAGE AND ADMINISTRATION section (2.1) for instructions.
Ortho Cept

Ortho Cept

To achieve maximum contraceptive effectiveness, ORTHO-CEPT® must be taken exactly as directed and at intervals not exceeding 24 hours. ORTHO-CEPT® is available in a blister card with a tablet dispenser which is preset for a Sunday Start. Day 1 Start is also provided.

Day 1 Start

The dosage of ORTHO-CEPT® for the initial cycle of therapy is one light orange "active" tablet administered daily from the 1st day through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1". Tablets are taken without interruption as follows: One light orange "active" tablet daily for 21 days, then one green "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a light orange "active" tablet is taken the next day.

The use of ORTHO-CEPT® for contraception may be initiated 4 weeks postpartum in women who elect not to breastfeed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) If the patient starts on ORTHO-CEPT® postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a light orange "active" tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) light orange "active" tablet in Weeks 1, 2, or 3, the light orange "active" tablet should be taken as soon as she remembers. If the patient misses two (2) light orange "active" tablets in Week 1 or Week 2, the patient should take two (2) light orange "active" tablets the day she remembers and two (2) light orange "active" tablets the next day; and then continue taking one (1) light orange "active" tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) light orange "active" tablets in the third week or misses three (3) or more light orange "active" tablets in a row, the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

Sunday Start

When taking ORTHO-CEPT®, the first light orange "active" tablet should be taken on the first Sunday after menstruation begins. If the period begins on Sunday, the first light orange "active" tablet is taken on that day. If switching directly from another oral contraceptive, the first light orange "active" tablet should be taken on the first Sunday after the last ACTIVE tablet of the previous product. Tablets are taken without interruption as follows: One light orange "active" tablet daily for 21 days, then one green "reminder" tablet daily for 7 days. After 28 tablets have been taken, a new course is started and a light orange "active" tablet is taken the next day (Sunday). When initiating a Sunday start regimen, another method of contraception should be used until after the first 7 consecutive days of administration.

The use of ORTHO-CEPT® for contraception may be initiated 4 weeks postpartum. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS: Nursing Mothers.) If the patient starts on ORTHO-CEPT® postpartum, and has not yet had a period, she should be instructed to use another method of contraception until a light orange "active" tablet has been taken daily for 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. If the patient misses one (1) light orange active tablet in Weeks 1, 2, or 3, the light orange "active" tablet should be taken as soon as she remembers. If the patient misses two (2) light orange "active" tablets in Week 1 or Week 2, the patient should take two (2) light orange "active" tablets the day she remembers and two (2) light orange "active" tablets the next day; and then continue taking one (1) light orange "active" tablet a day until she finishes the pack. The patient should be instructed to use a back-up method of birth control such as a condom or spermicide if she has sex in the seven (7) days after missing pills. If the patient misses two (2) light orange "active" tablets in the third week or misses three (3) or more light orange "active" tablets in a row, the patient should continue taking one light orange "active" tablet every day until Sunday. On Sunday the patient should throw out the rest of the pack and start a new pack that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills.

ADDITIONAL INSTRUCTIONS FOR ALL DOSING REGIMENS

Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease.

Use of oral contraceptives in the event of a missed menstrual period:
If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued if pregnancy is confirmed. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out.
Nizoral

Nizoral

Apply the shampoo to the damp skin of the affected area and a wide margin surrounding this area. Lather, leave in place for 5 minutes, and then rinse off with water.

One application of the shampoo should be sufficient.
Pancreaze

Pancreaze

2.1 Dosage

PANCREAZE is not interchangeable with other pancrelipase products.

PANCREAZE is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of PANCREAZE should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see Limitations on Dosing below).

Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences.1,2,3 PANCREAZE should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.

Infants (up to 12 months)

Infants may be given 2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Do not mix PANCREAZE capsule contents directly into formula or breast milk prior to administration [see Dosage and Administration (2.2)].

Children Older than 12 Months and Younger than 4 Years

Enzyme dosing should begin with 1,000 lipase units/kg of body weight per meal for children less than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Children 4 Years and Older and Adults

Enzyme dosing should begin with 500 lipase units/kg of body weight per meal for those older than age 4 years to a maximum of 2,500 lipase units/kg of body weight per meal (or less than or equal to 10,000 lipase units/kg of body weight per day), or less than 4,000 lipase units/g fat ingested per day.

Usually, half of the prescribed PANCREAZE dose for an individualized full meal should be given with each snack. The total daily dose should reflect approximately three meals plus two or three snacks per day.

Enzyme doses expressed as lipase units/kg of body weight per meal should be decreased in older patients because they weigh more but tend to ingest less fat per kilogram of body weight.

Limitations on Dosing

Dosing should not exceed the recommended maximum dosage set forth by the Cystic Fibrosis Foundation Consensus Conferences Guidelines.1, 2, 3

If symptoms and signs of steatorrhea persist, the dosage may be increased by a healthcare professional. Patients should be instructed not to increase the dosage on their own. There is great inter-individual variation in response to enzymes; thus, a range of doses is recommended. Changes in dosage may require an adjustment period of several days. If doses are to exceed 2,500 lipase units/kg of body weight per meal, further investigation is warranted.

Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorption. Doses greater than 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures, indicative of fibrosing colonopathy, in children with cystic fibrosis less than 12 years of age [see Warnings and Precautions (5.1)]. Patients currently receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.

2.2 Administration

PANCREAZE should always be taken as prescribed by a healthcare professional.

Infants (up to 12 months)

PANCREAZE should be administered to infants immediately prior to each feeding, using a dosage of 2,000 to 4,000 lipase units per 120 mL of formula or per breast-feeding. Contents of the capsule may be sprinkled on small amounts of acidic soft food with a pH of 4.5 or less (e.g., applesauce) and given to the infant within 15 minutes. Contents of the capsule may also be administered directly to the mouth. Administration should be followed by breast milk or formula. Contents of the capsule should not be mixed directly into formula or breast milk as this may diminish efficacy. Care should be taken to ensure that PANCREAZE is not crushed or chewed or retained in the mouth, to avoid irritation of the oral mucosa.

Children and Adults

PANCREAZE should be taken during meals or snacks, with sufficient fluid. PANCREAZE capsules and capsule contents should not be crushed or chewed. Capsules should be swallowed whole.

For patients who are unable to swallow intact capsules, the capsules may be carefully opened and the contents sprinkled on small amounts of acidic soft food with a pH of 4.5 or less (e.g., applesauce). The PANCREAZE-soft food mixture should be swallowed immediately without crushing or chewing, and followed with water or juice to ensure complete ingestion. Care should be taken to ensure that no drug is retained in the mouth.
Haldol Decanoate

Haldol Decanoate

HALDOL Decanoate 50 and HALDOL Decanoate 100 should be administered by deep intramuscular injection. A 21 gauge needle is recommended. The maximum volume per injection site should not exceed 3 mL. DO NOT ADMINISTER INTRAVENOUSLY.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

HALDOL Decanoate 50 and HALDOL Decanoate 100 are intended for use in schizophrenic patients who require prolonged parenteral antipsychotic therapy. These patients should be previously stabilized on antipsychotic medication before considering a conversion to haloperidol decanoate. Furthermore, it is recommended that patients being considered for haloperidol decanoate therapy have been treated with, and tolerate well, short-acting HALDOL (haloperidol) in order to reduce the possibility of an unexpected adverse sensitivity to haloperidol. Close clinical supervision is required during the initial period of dose adjustment in order to minimize the risk of overdosage or reappearance of psychotic symptoms before the next injection. During dose adjustment or episodes of exacerbation of symptoms of schizophrenia, haloperidol decanoate therapy can be supplemented with short-acting forms of haloperidol.

The dose of HALDOL Decanoate 50 or HALDOL Decanoate 100 should be expressed in terms of its haloperidol content. The starting dose of haloperidol decanoate should be based on the patient's age, clinical history, physical condition, and response to previous antipsychotic therapy. The preferred approach to determining the minimum effective dose is to begin with lower initial doses and to adjust the dose upward as needed. For patients previously maintained on low doses of antipsychotics (e.g. up to the equivalent of 10 mg/day oral haloperidol), it is recommended that the initial dose of haloperidol decanoate be 10–15 times the previous daily dose in oral haloperidol equivalents; limited clinical experience suggests that lower initial doses may be adequate.

Initial Therapy

Conversion from oral haloperidol to haloperidol decanoate can be achieved by using an initial dose of haloperidol decanoate that is 10 to 20 times the previous daily dose in oral haloperidol equivalents.

In patients who are elderly, debilitated, or stable on low doses of oral haloperidol (e.g. up to the equivalent of 10 mg/day oral haloperidol), a range of 10 to 15 times the previous daily dose in oral haloperidol equivalents is appropriate for initial conversion.

In patients previously maintained on higher doses of antipsychotics for whom a low dose approach risks recurrence of psychiatric decompensation and in patients whose long-term use of haloperidol has resulted in a tolerance to the drug, 20 times the previous daily dose in oral haloperidol equivalents should be considered for initial conversion, with downward titration on succeeding injections.

The initial dose of haloperidol decanoate should not exceed 100 mg regardless of previous antipsychotic dose requirements. If, therefore, conversion requires more than 100 mg of haloperidol decanoate as an initial dose, that dose should be administered in two injections, i.e. a maximum of 100 mg initially followed by the balance in 3 to 7 days.

Maintenance Therapy

The maintenance dosage of haloperidol decanoate must be individualized with titration upward or downward based on therapeutic response. The usual maintenance range is 10 to 15 times the previous daily dose in oral haloperidol equivalents dependent on the clinical response of the patient.
HALDOL DECANOATE DOSING RECOMMENDATIONS Patients Monthly1st Month Maintenance Stabilized on low daily oral doses(up to 10 mg/day) Elderly or Debilitated 10–15 × Daily Oral Dose 10–15 × Previous Daily Oral Dose High doseRisk of relapse 20 × Daily Oral Dose 10–15 × Previous Daily Oral Dose Tolerant to oral haloperidol
Close clinical supervision is required during initiation and stabilization of haloperidol decanoate therapy. Haloperidol decanoate is usually administered monthly or every 4 weeks. However, variation in patient response may dictate a need for adjustment of the dosing interval as well as the dose (See CLINICAL PHARMACOLOGY).

Clinical experience with haloperidol decanoate at doses greater than 450 mg per month has been limited.

Instructions for Opening Ampule
1. Medication often rests in the top part of the ampule. Before breaking the ampule, lightly tap the top of the ampule with your finger until all fluid moves to the bottom portion of the ampule. The ampule has a colored ring(s) and colored point which aids in the placement of fingers while breaking the ampule. Step 1

2. Hold the ampule between thumb and index finger with the colored point facing you. Step 2

3. Position the index finger of the other hand to support the neck of the ampule. Position the thumb so that it covers the colored point and is parallel to the colored ring(s). Step 3

4. Keeping the thumb on the colored point and with the index fingers close together, apply firm pressure on the colored point in the direction of the arrow to snap the ampule open. Step 4
Asacol

Asacol

There is considerable variation from patient to patient in the amount of medication required for treatment. As with all drugs used to treat schizophrenia, dosage should be individualized according to the needs and response of each patient. Dosage adjustments, either upward or downward, should be carried out as rapidly as practicable to achieve optimum therapeutic control.

To determine the initial dosage, consideration should be given to the patient's age, severity of illness, previous response to other antipsychotic drugs, and any concomitant medication or disease state. Debilitated or geriatric patients, as well as those with a history of adverse reactions to antipsychotic drugs, may require less HALDOL (haloperidol). The optimal response in such patients is usually obtained with more gradual dosage adjustments and at lower dosage levels.

Parenteral medication, administered intramuscularly in doses of 2 to 5 mg, is utilized for prompt control of the acutely agitated schizophrenic patient with moderately severe to very severe symptoms. Depending on the response of the patient, subsequent doses may be given, administered as often as every hour, although 4 to 8 hour intervals may be satisfactory. The maximum dose is 20 mg/day.

Controlled trials to establish the safety and effectiveness of intramuscular administration in children have not been conducted.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Switchover Procedure

An oral form should supplant the injectable as soon as practicable. In the absence of bioavailability studies establishing bioequivalence between these two dosage forms the following guidelines for dosage are suggested. For an initial approximation of the total daily dose required, the parenteral dose administered in the preceding 24 hours may be used. Since this dose is only an initial estimate, it is recommended that careful monitoring of clinical signs and symptoms, including clinical efficacy, sedation, and adverse effects, be carried out periodically for the first several days following the initiation of switchover. In this way, dosage adjustments, either upward or downward, can be quickly accomplished. Depending on the patient's clinical status, the first oral dose should be given within 12–24 hours following the last parenteral dose.

INSTRUCTIONS FOR OPENING AMPULE
1. Medication often rests in the top part of the ampule. Before breaking the ampule, lightly tap the top of the ampule with your finger until all fluid moves to the bottom portion of the ampule. The ampule has a colored ring(s) and colored point which aids in the placement of fingers while breaking the ampule. Step 1

2. Hold the ampule between thumb and index finger with the colored point facing you. Step 2

3. Position the index finger of the other hand to support the neck of the ampule. Position the thumb so that it covers the colored point and is parallel to the colored ring(s). Step 3

4. Keeping the thumb on the colored point and with the index fingers close together, apply firm pressure on the colored point in the direction of the arrow to snap the ampule open. Step 4
Nizoral

Nizoral

There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. The usual duration of therapy for systemic infection is 6 months. Treatment should be continued until active fungal infection has subsided.

Adults

The recommended starting dose of NIZORAL® (ketoconazole) Tablets is a single daily administration of 200 mg (one tablet). If clinical responsiveness is insufficient within the expected time, the dose of NIZORAL® Tablets may be increased to 400 mg (two tablets) once daily.

Children

In small numbers of children over 2 years of age, a single daily dose of 3.3 to 6.6 mg/kg has been used. NIZORAL® Tablets have not been studied in children under 2 years of age.
Nucynta

Nucynta

2.1 Individualization of Dosage

As with any opioid drug product, adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. In the selection of the initial dose of tapentadol, give attention to the following:
the total daily dose, potency and specific characteristics of the opioid the patient has been taking previously; the reliability of the relative potency estimate used to calculate the equivalent morphine sulfate dose needed; the patient's degree of opioid tolerance; the general condition and medical status of the patient; concurrent medications; the type and severity of the patient's pain; risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.
The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient.

Continual re-evaluation of the patient receiving tapentadol is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy.

During chronic therapy, especially for non-cancer-related pain, periodically re-assess the continued need for the use of opioid analgesics.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family. Monitor the patient for signs of respiratory or central nervous system depression.

2.2 Initiation of Therapy

The dose is 50 mg, 75 mg, or 100 mg every 4 to 6 hours depending upon pain intensity.

On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 50 mg, 75 mg, or 100 mg every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

NUCYNTA® may be given with or without food [see Clinical Pharmacology (12.3)].

2.3 Renal Impairment

Use of NUCYNTA® in patients with severe renal impairment is not recommended [see Warnings and Precautions (5.16) and Clinical Pharmacology (12.3)].

No dosage adjustment is recommended in patients with mild or moderate renal impairment.

2.4 Hepatic Impairment

The safety and efficacy of NUCYNTA® has not been studied in patients with severe hepatic impairment (Child-Pugh Score 10–15) and use in this population is not recommended [see Warnings and Precautions (5.15)].

Initiate treatment of patients with moderate hepatic impairment (Child-Pugh Score 7 to 9) with 50 mg no more frequently than once every 8 hours (maximum of three doses in 24 hours). Further treatment should reflect maintenance of analgesia with acceptable tolerability, to be achieved by either shortening or lengthening the dosing interval [see Clinical Pharmacology (12.3)].

No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6) [see Clinical Pharmacology (12.3)].

2.5 Elderly Patients

In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses.

2.6 Cessation of Therapy

When the patient no longer requires therapy with tapentadol, gradually taper the dose to prevent signs and symptoms of withdrawal in the physically dependent patient [see Warnings and Precautions (5.13)].
Nucynta Er

Nucynta Er

2.1 Initial Dosing

NUCYNTA® ER should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy with NUCYNTA® ER [see Warnings and Precautions (5.2)].

NUCYNTA® ER tablets must be taken whole. Crushing, chewing, or dissolving NUCYNTA® ER tablets will result in uncontrolled delivery of tapentadol and can lead to overdose or death [see Warnings and Precautions (5.2)].

NUCYNTA® ER is administered at a frequency of twice daily (every 12 hours).

Discontinue all other tapentadol and tramadol products when beginning and while taking NUCYNTA® ER [see Warnings and Precautions (5.10)]. Although the maximum approved total daily dose of NUCYNTA® immediate-release formulation is 600 mg per day, the maximum total daily dose of NUCYNTA® ER is 500 mg. Do not exceed a total daily dose of NUCYNTA® ER of 500 mg.

Use of NUCYNTA® ER as the First Opioid Analgesic

Initiate treatment with NUCYNTA® ER with the 50 mg tablet orally twice daily (approximately every 12 hours).

Use of NUCYNTA® ER in Patients who are not Opioid Tolerant

The starting dose for patients who are not opioid tolerant is NUCYNTA® ER 50 mg orally twice daily (approximately every 12 hours). Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression. Patients who are opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day or an equianalgesic dose of another opioid.

Conversion from NUCYNTA® to NUCYNTA® ER

Patients can be converted from NUCYNTA® to NUCYNTA® ER using the equivalent total daily dose of NUCYNTA® and dividing it into two equal doses of NUCYNTA® ER separated by approximately 12-hour intervals. As an example, a patient receiving 50 mg of NUCYNTA® four times per day (200 mg/day) may be converted to 100 mg NUCYNTA® ER twice a day.

Conversion from Other Opioids to NUCYNTA® ER

There are no established conversion ratios for conversion from other opioid to NUCYNTA® ER defined by clinical trials. Discontinue all other around-the-clock opioid drugs when NUCYNTA® ER therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is safer to underestimate a patient's 24-hour oral tapentadol requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral tapentadol requirements which could result in adverse reactions.

In general, as with other opioid analgesics, begin with half of the estimated daily tapentadol requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release rescue medication.

Conversion from Methadone to NUCYNTA® ER

Close monitoring is of particular importance when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma.

2.2 Titration and Maintenance of Therapy

Individually titrate NUCYNTA® ER to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving NUCYNTA® ER to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.

Titrate patients to adequate analgesia with dose increases of 50 mg no more than twice daily every three days. In clinical studies, efficacy with NUCYNTA® ER was demonstrated relative to placebo in the dosage range of 100 mg to 250 mg twice daily [see Clinical Studies (14)].

Patients who experience breakthrough pain may require a dose increase of NUCYNTA® ER, or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the NUCYNTA® ER dose.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

2.3 Discontinuation of NUCYNTA® ER

When the patient no longer requires therapy with NUCYNTA® ER tablets, use a gradual downward titration of the dose to prevent signs and symptoms of withdrawal in the physically-dependent patient.

2.4 Patients with Hepatic Impairment

The use of NUCYNTA® ER in patients with severe hepatic impairment (Child-Pugh Score 10–15) is not recommended.

In patients with moderate hepatic impairment (Child-Pugh Score 7 to 9), initiate treatment using 50 mg NUCYNTA® ER and administer no more frequently than once every 24 hours. The maximum recommended dose for patients with moderate hepatic impairment is 100 mg of NUCYNTA® ER per day [see Clinical Pharmacology (12.3)].

No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6) [see Warnings and Precautions (5.14) and Clinical Pharmacology (12.3)].

2.5 Patients with Renal Impairment

No dosage adjustment is recommended in patients with mild or moderate renal impairment. Use of NUCYNTA® ER in patients with severe renal impairment is not recommended [see Warnings and Precautions (5.15) and Clinical Pharmacology (12.3)].

2.6 Elderly Patients

In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses [see Clinical Pharmacology (12.3)].

2.7 Administration of NUCYNTA® ER

Instruct patients to swallow NUCYNTA® ER tablets whole. The tablets are not to be cut, crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of tapentadol [see Warnings and Precautions (5.1, 5.2)].

Instruct patients to take NUCYNTA® ER one tablet at a time and with enough water to ensure complete swallowing immediately after placing in the mouth [see Warnings and Precautions (5.2), and Patient Counseling Information (17)].
Topamax

Topamax

2.1 Epilepsy

It is not necessary to monitor topiramate plasma concentrations to optimize TOPAMAX® (topiramate) therapy.

On occasion, the addition of TOPAMAX® to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and/or carbamazepine during adjunctive therapy with TOPAMAX® may require adjustment of the dose of TOPAMAX®.

Because of the bitter taste, tablets should not be broken.

TOPAMAX® can be taken without regard to meals.

Monotherapy Use

Adults and Pediatric Patients 10 Years and Older

The recommended dose for TOPAMAX® monotherapy in adults and pediatric patients 10 years of age and older is 400 mg/day in two divided doses. Approximately 58% of patients randomized to 400 mg/day achieved this maximal dose in the monotherapy controlled trial; the mean dose achieved in the trial was 275 mg/day. The dose should be achieved by titration according to the following schedule (Table 1):
Table 1: Monotherapy Titration Schedule for Adults and Pediatric Patients 10 years and older Morning Dose Evening Dose Week 1 25 mg 25 mg Week 2 50 mg 50 mg Week 3 75 mg 75 mg Week 4 100 mg 100 mg Week 5 150 mg 150 mg Week 6 200 mg 200 mg
Children Ages 2 to <10 Years

Dosing of topiramate as initial monotherapy in children 2 to < 10 years of age with partial onset or primary generalized tonic-clonic seizures was based on a pharmacometric bridging approach [see Clinical Studies (14.1)].

Dosing in patients 2 to <10 years is based on weight. During the titration period, the initial dose of TOPAMAX® should be 25 mg/day administered nightly for the first week. Based upon tolerability, the dosage can be increased to 50 mg/day (25 mg twice daily) in the second week. Dosage can be increased by 25–50 mg/day each subsequent week as tolerated. Titration to the minimum maintenance dose should be attempted over 5–7 weeks of the total titration period. Based upon tolerability and clinical response, additional titration to a higher dose (up to the maximum maintenance dose) can be attempted at 25–50 mg/day weekly increments. The total daily dose should not exceed the maximum maintenance dose for each range of body weight (Table 2).
Table 2: Monotherapy Target Total Daily Maintenance Dosing for Patients 2 to <10 Years Weight (kg) Total Daily Dose (mg/day)* Minimum Maintenance Dose Total Daily Dose (mg/day)* Maximum Maintenance Dose * Administered in two equally divided doses Up to 11 150 250 12 – 22 200 300 23 – 31 200 350 32 – 38 250 350 Greater than 38 250 400
Adjunctive Therapy Use

Adults 17 Years of Age and Over - Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of TOPAMAX® as adjunctive therapy in adults with partial onset seizures is 200 to 400 mg/day in two divided doses, and 400 mg/day in two divided doses as adjunctive treatment in adults with primary generalized tonic-clonic seizures. It is recommended that therapy be initiated at 25 to 50 mg/day followed by titration to an effective dose in increments of 25 to 50 mg/day every week. Titrating in increments of 25 mg/day every week may delay the time to reach an effective dose. Doses above 400 mg/day (600, 800 or 1,000 mg/day) have not been shown to improve responses in dose-response studies in adults with partial onset seizures. Daily doses above 1,600 mg have not been studied.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose was reached at the end of 8 weeks [see Clinical Studies (14.1)].

Pediatric Patients Ages 2 – 16 Years – Partial Onset Seizures, Primary Generalized Tonic-Clonic Seizures, or Lennox-Gastaut Syndrome

The recommended total daily dose of TOPAMAX® as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 to 9 mg/kg/day in two divided doses. Titration should begin at 25 mg/day (or less, based on a range of 1 to 3 mg/kg/day) nightly for the first week. The dosage should then be increased at 1- or 2-week intervals by increments of 1 to 3 mg/kg/day (administered in two divided doses), to achieve optimal clinical response. Dose titration should be guided by clinical outcome.

In the study of primary generalized tonic-clonic seizures, the initial titration rate was slower than in previous studies; the assigned dose of 6 mg/kg/day was reached at the end of 8 weeks [see Clinical Studies (14.1)].

2.2 Migraine

The recommended total daily dose of TOPAMAX® as treatment for adults and adolescents 12 years of age and older for prophylaxis of migraine headache is 100 mg/day administered in two divided doses (Table 3). The recommended titration rate for topiramate for migraine prophylaxis to 100 mg/day is:
Table 3: Migraine Prophylaxis Titration Schedule for Adults and Adolescents Patients 12 Years and Older Morning Dose Evening Dose Week 1 None 25 mg Week 2 25 mg 25 mg Week 3 25 mg 50 mg Week 4 50 mg 50 mg
Dose and titration rate should be guided by clinical outcome. If required, longer intervals between dose adjustments can be used.

TOPAMAX® can be taken without regard to meals.

2.3 Administration of TOPAMAX® Sprinkle Capsules

TOPAMAX® (topiramate capsules) Sprinkle Capsules may be swallowed whole or may be administered by carefully opening the capsule and sprinkling the entire contents on a small amount (teaspoon) of soft food. This drug/food mixture should be swallowed immediately and not chewed. It should not be stored for future use.

2.4 Patients with Renal Impairment

In renally impaired subjects (creatinine clearance less than 70 mL/min/1.73 m2), one-half of the usual adult dose is recommended. Such patients will require a longer time to reach steady-state at each dose.

2.5 Geriatric Patients (Ages 65 Years and Over)

Dosage adjustment may be indicated in the elderly patient when impaired renal function (creatinine clearance rate <70 mL/min/1.73 m2) is evident [see Clinical Pharmacology (12.3)].

2.6 Patients Undergoing Hemodialysis

Topiramate is cleared by hemodialysis at a rate that is 4 to 6 times greater than a normal individual. Accordingly, a prolonged period of dialysis may cause topiramate concentration to fall below that required to maintain an anti-seizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed.

2.7 Patients with Hepatic Disease

In hepatically impaired patients, topiramate plasma concentrations may be increased. The mechanism is not well understood.
Invega

Invega

2.1 Schizophrenia

Adults

The recommended dose of INVEGA® (paliperidone) Extended-Release Tablets for the treatment of schizophrenia in adults is 6 mg administered once daily. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.

In a longer-term study, INVEGA® has been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on INVEGA® for 6 weeks [see Clinical Studies (14)]. INVEGA® should be prescribed at the lowest effective dose for maintaining clinical stability and the physician should periodically reevaluate the long-term usefulness of the drug in individual patients.

Adolescents (12–17 years of age)

The recommended starting dose of INVEGA® (paliperidone) Extended-Release Tablets for the treatment of schizophrenia in adolescents 12–17 years of age is 3 mg administered once daily. Initial dose titration is not required. Dose increases, if considered necessary, should be made only after clinical reassessment and should occur at increments of 3 mg/day at intervals of more than 5 days. Prescribers should be mindful that, in the adolescent schizophrenia study, there was no clear enhancement to efficacy at the higher doses, i.e., 6 mg for subjects weighing less than 51 kg and 12 mg for subjects weighing 51 kg or greater, while adverse events were dose-related.

2.2 Schizoaffective Disorder

The recommended dose of INVEGA® (paliperidone) Extended-Release Tablets for the treatment of schizoaffective disorder in adults is 6 mg administered once daily. Initial dose titration is not required. Some patients may benefit from lower or higher doses within the recommended dose range of 3 to 12 mg once daily. A general trend for greater effects was seen with higher doses. This trend must be weighed against dose-related increase in adverse reactions. Dosage adjustment, if indicated, should occur only after clinical reassessment. Dose increases, if indicated, generally should occur at intervals of more than 4 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.

2.3 Administration Instructions

INVEGA® can be taken with or without food.

INVEGA® must be swallowed whole with the aid of liquids. Tablets should not be chewed, divided, or crushed. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.

2.4 Use with Risperidone

Concomitant use of INVEGA® with risperidone has not been studied. Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is coadministered with INVEGA®.

2.5 Dosage in Special Populations

Renal Impairment

Dosing must be individualized according to the patient's renal function status. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min), the recommended initial dose of INVEGA® is 3 mg once daily. The dose may then be increased to a maximum of 6 mg once daily based on clinical response and tolerability. For patients with moderate to severe renal impairment (creatinine clearance ≥ 10 mL/min to < 50 mL/min), the recommended initial dose of INVEGA® is 1.5 mg once daily, which may be increased to a maximum of 3 mg once daily after clinical reassessment. As INVEGA® has not been studied in patients with creatinine clearance below 10 mL/min, use is not recommended in such patients. [See Clinical Pharmacology (12.3)]

Hepatic Impairment

For patients with mild to moderate hepatic impairment, (Child-Pugh Classification A and B), no dose adjustment is recommended [see Clinical Pharmacology (12.3)]. INVEGA® has not been studied in patients with severe hepatic impairment.

Elderly

Because elderly patients may have diminished renal function, dose adjustments may be required according to their renal function status. In general, recommended dosing for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. For patients with moderate to severe renal impairment (creatinine clearance 10 mL/min to < 50 mL/min), the maximum recommended dose of INVEGA® is 3 mg once daily [see Renal Impairment above].
Invega Sustenna

Invega Sustenna

2.1 Administration Instructions

Each injection must be administered only by a health care professional.

Parenteral drug products should be inspected visually for foreign matter and discoloration prior to administration, whenever product and container permit.

INVEGA SUSTENNA® is intended for intramuscular use only. Do not administer by any other route. Avoid inadvertent injection into a blood vessel. Administer the dose in a single injection; do not administer the dose in divided injections. Inject slowly, deep into the muscle.

The recommended needle size for administration of INVEGA SUSTENNA® into the deltoid muscle is determined by the patient's weight:
For patients weighing less than 90 kg, the 1-inch, 23 gauge needle is recommended. For patients weighing 90 kg or more, the 1½-inch, 22 gauge needle is recommended.
Deltoid injections should be alternated between the two deltoid muscles.

The recommended needle size for administration of INVEGA SUSTENNA® into the gluteal muscle is the 1½-inch, 22 gauge needle regardless of patient weight.

Administer into the upper-outer quadrant of the gluteal muscle. Gluteal injections should be alternated between the two gluteal muscles.

2.2 Schizophrenia and Schizoaffective Disorder

For patients who have never taken oral paliperidone or oral or injectable risperidone, it is recommended to establish tolerability with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA®.

The recommended dosing of INVEGA SUSTENNA® for each approved indication is displayed in Table 1. The recommended initiation of INVEGA SUSTENNA® is with a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle. Following the second initiation dose, monthly maintenance doses can be administered in either the deltoid or gluteal muscle.
Table 1. Recommended Dosing of INVEGA SUSTENNA® for Adults with Schizophrenia or Schizoaffective Disorder Indication Initiation Dosing(deltoid) Monthly Maintenance Dose* (deltoid or gluteal) Maximum Monthly Dose Day 1 Day 8 * Administered 5 weeks after the first injection. † The recommended maintenance dose for treatment of schizophrenia is 117 mg. Some patients may benefit from lower or higher maintenance doses within the additional available strengths (39 mg, 78 mg, 156 mg, and 234 mg). ‡ Adjust dose based on tolerability and/or efficacy using available strengths. The 39 mg strength was not studied in the long-term schizoaffective disorder study. Schizophrenia 234 mg 156 mg 39–234 mg† 234 mg Schizoaffective disorder 234 mg 156 mg 78–234 mg‡ 234 mg
Adjustment of the maintenance dose may be made monthly. When making dose adjustments, the prolonged-release characteristics of INVEGA SUSTENNA® should be considered [see Clinical Pharmacology (12.3)], as the full effect of the dose adjustment may not be evident for several months.

2.3 Missed Doses

Avoiding Missed Doses

It is recommended that the second initiation dose of INVEGA SUSTENNA® be given one week after the first dose. To avoid a missed dose, patients may be given the second dose 4 days before or after the one-week time point. Similarly, the third and subsequent injections after the initiation regimen are recommended to be given monthly. To avoid a missed monthly dose, patients may be given the injection up to 7 days before or after the monthly time point.

Management of a Missed Second Initiation Dose

If the target date for the second INVEGA SUSTENNA® injection (one week ± 4 days) is missed, the recommended reinitiation depends on the length of time which has elapsed since the patient's first injection. In case of a missed second initiation dose follow the dosing instructions provided in Table 2.
Table 2. Management of a Missed Second Initiation Dose TIMING OF MISSED SECOND INITIATION DOSE DOSING Less than 4 weeks since first injection Administer the second initiation dose of 156 mg in the deltoid muscle as soon as possible. It is recommended to administer a third injection of 117 mg in either the deltoid or gluteal muscle 5 weeks after the first injection (regardless of the timing of the second injection). Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle. 4 to 7 weeks since first injection Resume dosing with two injections of 156 mg in the following manner: Administer a deltoid injection as soon as possible. Administer a second deltoid injection 1 week later. Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle. More than 7 weeks since first injection Restart dosing with recommended initiation (see Section 2.2, Table 1): Administer a 234 mg deltoid injection on Day 1. Administer a 156 mg deltoid injection 1 week later. Thereafter, resume regular monthly dosing in either the deltoid or gluteal muscle.
Management of a Missed Maintenance Dose

In case of a missed maintenance dose follow the dosing instructions provided in Table 3.
Table 3. Management of a Missed Maintenance Dose TIMING OF MISSED MAINTENANCE DOSE DOSING 4 to 6 weeks since last injection Resume regular monthly dosing as soon as possible at the patient's previously stabilized dose, followed by injections at monthly intervals. More than 6 weeks to 6 months since last injection Resume the same dose the patient was previously stabilized on (unless the patient was stabilized on a dose of 234 mg, then the first 2 injections should each be 156 mg) in the following manner: Administer a deltoid injection as soon as possible. Administer a second deltoid injection 1 week later at the same dose. Thereafter, resume administering the previously stabilized dose in the deltoid or gluteal muscle 1 month after the second injection. More than 6 months since last injection Restart dosing with recommended initiation (see Section 2.2, Table 1): Administer a 234 mg deltoid injection on Day 1. Administer a 156 mg deltoid injection 1 week later. Thereafter, resume administering the previously stabilized dose in the deltoid or gluteal muscle 1 month after the second injection.
2.4 Use with Risperidone or with Oral Paliperidone

Since paliperidone is the major active metabolite of risperidone, caution should be exercised when INVEGA SUSTENNA® is coadministered with risperidone or with oral paliperidone for extended periods of time. Safety data involving concomitant use of INVEGA SUSTENNA® with other antipsychotics is limited.

2.5 Dosage Adjustments

Renal Impairment

INVEGA SUSTENNA® has not been systematically studied in patients with renal impairment [see Clinical Pharmacology (12.3)]. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min [Cockcroft-Gault Formula]), initiate INVEGA SUSTENNA® with a dose of 156 mg on treatment day 1 and 117 mg one week later. Administer both doses in the deltoid muscle. Thereafter, follow with monthly injections of 78 mg in either the deltoid or gluteal muscle [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

INVEGA SUSTENNA® is not recommended in patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Coadministration with Strong CYP3A4/P-glycoprotein (P-gp) Inducers

It may be necessary to increase the dose of INVEGA SUSTENNA® when a strong inducer of both CYP3A4 and P-gp (e.g., carbamazepine, rifampin, St John's wort) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of INVEGA SUSTENNA® [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

2.6 Switching from Other Antipsychotics

There are no systematically collected data to specifically address switching patients with schizophrenia or schizoaffective disorder from other antipsychotics to INVEGA SUSTENNA®, or concerning concomitant administration with other antipsychotics.

2.6.1 Switching from Oral Antipsychotics

For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA®.

Previous oral antipsychotics can be gradually discontinued at the time of initiation of treatment with INVEGA SUSTENNA®. Recommended initiation of INVEGA SUSTENNA® is with a dose of 234 mg on treatment day 1 and 156 mg one week later, both administered in the deltoid muscle [see Dosage and Administration (2.2)]. Patients previously stabilized on different doses of INVEGA® Extended-Release tablets can attain similar paliperidone steady-state exposure during maintenance treatment with INVEGA SUSTENNA® monthly doses as depicted in Table 4.
Table 4. Doses of INVEGA® and INVEGA SUSTENNA® needed to attain similar steady-state paliperidone exposure during maintenance treatment Formulation INVEGA® Extended-Release Tablet INVEGA SUSTENNA® Injection Dosing Frequency Once Daily Once every 4 weeks Dose (mg) 1263 23411739–78
2.6.2 Switching from Long-Acting Injectable Antipsychotics

For patients who have never taken oral paliperidone or oral or injectable risperidone, tolerability should be established with oral paliperidone or oral risperidone prior to initiating treatment with INVEGA SUSTENNA®.

When switching patients currently at steady-state on a long-acting injectable antipsychotic, initiate INVEGA SUSTENNA® therapy in place of the next scheduled injection. INVEGA SUSTENNA® should then be continued at monthly intervals. The one-week initiation dosing regimen as described in Section 2.2 is not required. See Table 1 above for recommended monthly maintenance dosing. Based on previous clinical history of tolerability and/or efficacy, some patients may benefit from lower or higher maintenance doses within the available strengths (39 mg, 78 mg, 117 mg, 156 mg, and 234 mg). The 39 mg strength was not studied in the long-term schizoaffective disorder study. Monthly maintenance doses can be administered in either the deltoid or gluteal muscle [see Dosage and Administration (2.2)].

If INVEGA SUSTENNA® is discontinued, its prolonged-release characteristics must be considered. As recommended with other antipsychotic medications, the need for continuing existing extrapyramidal symptoms (EPS) medication should be re-evaluated periodically.

2.7 Instructions for Use

Each injection must be administered only by a health care professional.

The kit contains a prefilled syringe and 2 safety needles (a 1 ½-inch 22 gauge needle and a 1-inch 23 gauge needle) for intramuscular injection.

INVEGA SUSTENNA® is for single use only.
a. Shake the syringe vigorously for a minimum of 10 seconds to ensure a homogeneous suspension. b. Select the appropriate needle.
For DELTOID injection:
If the patient weighs less than 90 kg, use the 1-inch 23 gauge needle (needle with blue colored hub). If the patient weighs 90 kg or more, use the 1 ½-inch 22 gauge needle (needle with gray colored hub).
For GLUTEAL injection:

Use the 1 ½-inch 22 gauge needle (needle with gray colored hub) regardless of patient's weight.
c. While holding the syringe upright, remove the rubber tip cap with an easy clockwise twisting motion. d. Peel the safety needle pouch half way open. Grasp the needle sheath using the plastic peel pouch. Attach the safety needle to the luer connection of the syringe with an easy clockwise twisting motion. e. Pull the needle sheath away from the needle with a straight pull. Do not twist the sheath as the needle may be loosened from the syringe. f. Bring the syringe with the attached needle in upright position to de-aerate. De-aerate the syringe by moving the plunger rod carefully forward. g. Inject the entire contents intramuscularly slowly, deep into the selected deltoid or gluteal muscle of the patient. Do not administer by any other route. h. After the injection is complete, use either thumb or finger of one hand (h1, h2) or a flat surface (h3) to activate the needle protection system. The needle protection system is fully activated when a 'click' is heard. Discard the syringe with needle appropriately. h1 h2 h3
Risperdal

Risperdal

Table 1. Recommended Daily Dosage by Indication Initial Dose Titration (Increments) Target Dose Effective Dose Range Schizophrenia: adults (2.1) 2 mg 1 to 2 mg 4 to 8 mg 4 to 16 mg Schizophrenia: adolescents (2.2) 0.5 mg 0.5 to 1 mg 3 mg 1 to 6 mg Bipolar mania: adults (2.2) 2 to 3 mg 1 mg 1 to 6 mg 1 to 6 mg Bipolar mania: children andadolescents (2.2) 0.5 mg 0.5 to 1 mg 1 to 2.5 mg 1 to 6 mg Irritability in autistic disorder (2.3) 0.25 mgCan increase to0.5 mg by Day 4:(body weight less than 20 kg)0.5 mgCan increase to1 mg by Day 4:(body weight greater than or equal to 20 kg) After Day 4, at intervals of > 2 weeks:0.25 mg(body weight less than 20 kg)0.5 mg(body weight greater than or equal to 20 kg) 0.5 mg:(body weight less than 20 kg)1 mg:(body weight greater than or equal to 20 kg) 0.5 to 3 mg
Severe Renal and Hepatic Impairment in Adults: use a lower starting dose of 0.5 mg twice daily. May increase to dosages above 1.5 mg twice daily at intervals of one week or longer.

2.1 Schizophrenia

Adults

Usual Initial Dose

RISPERDAL® can be administered once or twice daily. Initial dosing is 2 mg per day. May increase the dose at intervals of 24 hours or greater, in increments of 1 to 2 mg per day, as tolerated, to a recommended dose of 4 to 8 mg per day. In some patients, slower titration may be appropriate. Efficacy has been demonstrated in a range of 4 mg to 16 mg per day. However, doses above 6 mg per day for twice daily dosing were not demonstrated to be more efficacious than lower doses, were associated with more extrapyramidal symptoms and other adverse effects, and are generally not recommended. In a single study supporting once-daily dosing, the efficacy results were generally stronger for 8 mg than for 4 mg. The safety of doses above 16 mg per day has not been evaluated in clinical trials [see Clinical Studies (14.1)].

Adolescents

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to a recommended dose of 3 mg per day. Although efficacy has been demonstrated in studies of adolescent patients with schizophrenia at doses between 1 mg to 6 mg per day, no additional benefit was observed above 3 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.

Maintenance Therapy

While it is unknown how long a patient with schizophrenia should remain on RISPERDAL®, the effectiveness of RISPERDAL® 2 mg per day to 8 mg per day at delaying relapse was demonstrated in a controlled trial in adult patients who had been clinically stable for at least 4 weeks and were then followed for a period of 1 to 2 years [see Clinical Studies (14.1)]. Both adult and adolescent patients who respond acutely should generally be maintained on their effective dose beyond the acute episode. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued

Although there are no data to specifically address reinitiation of treatment, it is recommended that after an interval off RISPERDAL®, the initial titration schedule should be followed.

Switching From Other Antipsychotics

There are no systematically collected data to specifically address switching schizophrenic patients from other antipsychotics to RISPERDAL®, or treating patients with concomitant antipsychotics.

2.2 Bipolar Mania

Usual Dose

Adults

The initial dose range is 2 mg to 3 mg per day. The dose may be adjusted at intervals of 24 hours or greater, in increments of 1 mg per day. The effective dose range is 1 mg to 6 mg per day, as studied in the short-term, placebo-controlled trials. In these trials, short-term (3 week) anti-manic efficacy was demonstrated in a flexible dosage range of 1 mg to 6 mg per day [see Clinical Studies (14.2, 14.3)]. RISPERDAL® doses higher than 6 mg per day were not studied.

Pediatrics

The initial dose is 0.5 mg once daily, administered as a single-daily dose in the morning or evening. The dose may be adjusted at intervals of 24 hours or greater, in increments of 0.5 mg or 1 mg per day, as tolerated, to the recommended target dose of 1 mg to 2.5 mg per day. Although efficacy has been demonstrated in studies of pediatric patients with bipolar mania at doses between 0.5 mg and 6 mg per day, no additional benefit was observed above 2.5 mg per day, and higher doses were associated with more adverse events. Doses higher than 6 mg per day have not been studied.

Patients experiencing persistent somnolence may benefit from administering half the daily dose twice daily.

Maintenance Therapy

There is no body of evidence available from controlled trials to guide a clinician in the longer-term management of a patient who improves during treatment of an acute manic episode with RISPERDAL®. While it is generally agreed that pharmacological treatment beyond an acute response in mania is desirable, both for maintenance of the initial response and for prevention of new manic episodes, there are no systematically obtained data to support the use of RISPERDAL® in such longer-term treatment (i.e., beyond 3 weeks). The physician who elects to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 Irritability Associated with Autistic Disorder – Pediatrics (Children and Adolescents)

The dosage of RISPERDAL® should be individualized according to the response and tolerability of the patient. The total daily dose of RISPERDAL® can be administered once daily, or half the total daily dose can be administered twice daily.

For patients with body weight less than 20 kg, initiate dosing at 0.25 mg per day. For patients with body weight greater than or equal to 20 kg, initiate dosing at 0.5 mg per day. After a minimum of four days, the dose may be increased to the recommended dose of 0.5 mg per day for patients less than 20 kg and 1.0 mg per day for patients greater than or equal to 20 kg. Maintain this dose for a minimum of 14 days. In patients not achieving sufficient clinical response, the dose may be increased at intervals of 2 weeks or greater, in increments of 0.25 mg per day for patients less than 20 kg, or increments of 0.5 mg per day for patients greater than or equal to 20 kg. The effective dose range is 0.5 mg to 3 mg per day. No dosing data are available for children who weigh less than 15 kg.

Once sufficient clinical response has been achieved and maintained, consider gradually lowering the dose to achieve the optimal balance of efficacy and safety. The physician who elects to use RISPERDAL® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

Patients experiencing persistent somnolence may benefit from a once-daily dose administered at bedtime or administering half the daily dose twice daily, or a reduction of the dose.

2.4 Dosing in Patients with Severe Renal or Hepatic Impairment

For patients with severe renal impairment (CLcr < 30 mL/min) or hepatic impairment (10–15 points on Child Pugh System), the initial starting dose is 0.5 mg twice daily. The dose may be increased in increments of 0.5 mg or less, administered twice daily. For doses above 1.5 mg twice daily, increase in intervals of one week or greater [see Use in Specific Populations (8.6 and 8.7)].

2.5 Dose Adjustments for Specific Drug Interactions

When RISPERDAL® is co-administered with enzyme inducers (e.g., carbamazepine), the dose of RISPERDAL® should be increased up to double the patient's usual dose. It may be necessary to decrease the RISPERDAL® dose when enzyme inducers such as carbamazepine are discontinued [see Drug Interactions (7.1)]. Similar effect may be expected with co-administration of RISPERDAL® with other enzyme inducers (e.g., phenytoin, rifampin, and phenobarbital).

When fluoxetine or paroxetine is co-administered with RISPERDAL®, the dose of RISPERDAL® should be reduced. The RISPERDAL® dose should not exceed 8 mg per day in adults when co-administered with these drugs. When initiating therapy, RISPERDAL® should be titrated slowly. It may be necessary to increase the RISPERDAL® dose when enzyme inhibitors such as fluoxetine or paroxetine are discontinued [see Drug Interactions (7.1)].

2.6 Administration of RISPERDAL® Oral Solution

RISPERDAL® Oral Solution can be administered directly from the calibrated pipette, or can be mixed with a beverage prior to administration. RISPERDAL® Oral Solution is compatible in the following beverages: water, coffee, orange juice, and low-fat milk; it is NOT compatible with either cola or tea.

2.7 Directions for Use of RISPERDAL® M-TAB® Orally Disintegrating Tablets

Tablet Accessing

RISPERDAL® M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg

RISPERDAL® M-TAB® Orally Disintegrating Tablets 0.5 mg, 1 mg, and 2 mg are supplied in blister packs of 4 tablets each.

Do not open the blister until ready to administer. For single tablet removal, separate one of the four blister units by tearing apart at the perforations. Bend the corner where indicated. Peel back foil to expose the tablet. DO NOT push the tablet through the foil because this could damage the tablet.

RISPERDAL® M-TAB® Orally Disintegrating Tablets 3 mg and 4 mg

RISPERDAL® M-TAB® Orally Disintegrating Tablets 3 mg and 4 mg are supplied in a child-resistant pouch containing a blister with 1 tablet each.

The child-resistant pouch should be torn open at the notch to access the blister. Do not open the blister until ready to administer. Peel back foil from the side to expose the tablet. DO NOT push the tablet through the foil, because this could damage the tablet.

Tablet Administration

Using dry hands, remove the tablet from the blister unit and immediately place the entire RISPERDAL® M-TAB® Orally Disintegrating Tablet on the tongue. The RISPERDAL® M-TAB® Orally Disintegrating Tablet should be consumed immediately, as the tablet cannot be stored once removed from the blister unit. RISPERDAL® M-TAB® Orally Disintegrating Tablets disintegrate in the mouth within seconds and can be swallowed subsequently with or without liquid. Patients should not attempt to split or to chew the tablet.
Risperdal Consta

Risperdal Consta

For patients who have never taken oral RISPERDAL®, it is recommended to establish tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®.

RISPERDAL CONSTA® should be administered every 2 weeks by deep intramuscular (IM) deltoid or gluteal injection. Each injection should be administered by a health care professional using the appropriate enclosed safety needle [see Dosage and Administration (2.8)]. For deltoid administration, use the 1-inch needle alternating injections between the two arms. For gluteal administration, use the 2-inch needle alternating injections between the two buttocks. Do not administer intravenously.

2.1 Schizophrenia

The recommended dose for the treatment of schizophrenia is 25 mg IM every 2 weeks. Although dose response for effectiveness has not been established for RISPERDAL CONSTA®, some patients not responding to 25 mg may benefit from a higher dose of 37.5 mg or 50 mg. The maximum dose should not exceed 50 mg RISPERDAL CONSTA® every 2 weeks. No additional benefit was observed with dosages greater than 50 mg RISPERDAL CONSTA®; however, a higher incidence of adverse effects was observed.

The efficacy of RISPERDAL CONSTA® in the treatment of schizophrenia has not been evaluated in controlled clinical trials for longer than 12 weeks. Although controlled studies have not been conducted to answer the question of how long patients with schizophrenia should be treated with RISPERDAL CONSTA®, oral risperidone has been shown to be effective in delaying time to relapse in longer-term use. It is recommended that responding patients be continued on treatment with RISPERDAL CONSTA® at the lowest dose needed. The physician who elects to use RISPERDAL CONSTA® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.2 Bipolar Disorder

The recommended dose for monotherapy or adjunctive therapy to lithium or valproate for the maintenance treatment of Bipolar I Disorder is 25 mg IM every 2 weeks. Some patients may benefit from a higher dose of 37.5 mg or 50 mg. Dosages above 50 mg have not been studied in this population. The physician who elects to use RISPERDAL CONSTA® for extended periods should periodically re-evaluate the long-term risks and benefits of the drug for the individual patient.

2.3 General Dosing Information

A lower initial dose of 12.5 mg may be appropriate when clinical factors warrant dose adjustment, such as in patients with hepatic or renal impairment, for certain drug interactions that increase risperidone plasma concentrations [see Drug Interactions (7.11)] or in patients who have a history of poor tolerability to psychotropic medications. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Oral RISPERDAL® (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA® and continued for 3 weeks (and then discontinued) to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site [see Clinical Pharmacology (12.3)].

Upward dose adjustment should not be made more frequently than every 4 weeks. The clinical effects of this dose adjustment should not be anticipated earlier than 3 weeks after the first injection with the higher dose.

In patients with clinical factors such as hepatic or renal impairment or certain drug interactions that increase risperidone plasma concentrations [see Drug Interactions (7.11)], dose reduction as low as 12.5 mg may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Do not combine two different dose strengths of RISPERDAL CONSTA® in a single administration.

2.4 Dosage in Special Populations

Elderly

For elderly patients treated with RISPERDAL CONSTA®, the recommended dosage is 25 mg IM every 2 weeks. Oral RISPERDAL® (or another antipsychotic medication) should be given with the first injection of RISPERDAL CONSTA® and should be continued for 3 weeks to ensure that adequate therapeutic plasma concentrations are maintained prior to the main release phase of risperidone from the injection site [see Clinical Pharmacology (12.3)].

Renal or Hepatic Impairment

Patients with renal or hepatic impairment should be treated with titrated doses of oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®. The recommended starting dose is 0.5 mg oral RISPERDAL® twice daily during the first week, which can be increased to 1 mg twice daily or 2 mg once daily during the second week. If a total daily dose of at least 2 mg oral RISPERDAL® is well tolerated, an injection of 25 mg RISPERDAL CONSTA® can be administered every 2 weeks. Oral supplementation should be continued for 3 weeks after the first injection until the main release of risperidone from the injection site has begun. In some patients, slower titration may be medically appropriate. Alternatively, a starting dose of RISPERDAL CONSTA® of 12.5 mg may be appropriate. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Patients with renal impairment may have less ability to eliminate risperidone than normal adults. Patients with impaired hepatic function may have an increase in the free fraction of the risperidone, possibly resulting in an enhanced effect [see Clinical Pharmacology (12.3)]. Elderly patients and patients with a predisposition to hypotensive reactions or for whom such reactions would pose a particular risk should be instructed in nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position). These patients should avoid sodium depletion or dehydration, and circumstances that accentuate hypotension (alcohol intake, high ambient temperature, etc.). Monitoring of orthostatic vital signs should be considered [see Warnings and Precautions (5.7)].

2.5 Reinitiation of Treatment in Patients Previously Discontinued

There are no data to specifically address reinitiation of treatment. When restarting patients who have had an interval off treatment with RISPERDAL CONSTA®, supplementation with oral RISPERDAL® (or another antipsychotic medication) should be administered.

2.6 Switching from Other Antipsychotics

There are no systematically collected data to specifically address switching patients from other antipsychotics to RISPERDAL CONSTA®, or concerning concomitant administration with other antipsychotics. Previous antipsychotics should be continued for 3 weeks after the first injection of RISPERDAL CONSTA® to ensure that therapeutic concentrations are maintained until the main release phase of risperidone from the injection site has begun [see Clinical Pharmacology (12.3)]. For patients who have never taken oral RISPERDAL®, it is recommended to establish tolerability with oral RISPERDAL® prior to initiating treatment with RISPERDAL CONSTA®. As recommended with other antipsychotic medications, the need for continuing existing EPS medication should be re-evaluated periodically.

2.7 Co-Administration of RISPERDAL CONSTA® with Certain Other Medications

Co-administration of carbamazepine and other CYP 3A4 enzyme inducers (e.g., phenytoin, rifampin, phenobarbital) with risperidone would be expected to cause decreases in the plasma concentrations of the sum of risperidone and 9-hydroxyrisperidone combined, which could lead to decreased efficacy of RISPERDAL CONSTA® treatment. The dose of risperidone needs to be titrated accordingly for patients receiving these enzyme inducers, especially during initiation or discontinuation of therapy with these inducers [see Drug Interactions (7.11)]. At the initiation of therapy with carbamazepine or other known CYP 3A4 hepatic enzyme inducers, patients should be closely monitored during the first 4–8 weeks, since the dose of RISPERDAL CONSTA® may need to be adjusted. A dose increase, or additional oral RISPERDAL®, may need to be considered. On discontinuation of carbamazepine or other CYP 3A4 hepatic enzyme inducers, the dosage of RISPERDAL CONSTA® should be re-evaluated and, if necessary, decreased. Patients may be placed on a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before the planned discontinuation of carbamazepine or other CYP 3A4 inducers to adjust for the expected increase in plasma concentrations of risperidone plus 9-hydroxyrisperidone. For patients treated with the recommended dose of 25 mg RISPERDAL CONSTA® and discontinuing from carbamazepine or other CYP3A4 enzyme inducers, it is recommended to continue treatment with the 25-mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA® dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA® treatment. The efficacy of the 12.5 mg dose has not been investigated in clinical trials.

Fluoxetine and paroxetine, CYP 2D6 inhibitors, have been shown to increase the plasma concentration of risperidone 2.5–2.8 fold and 3–9 fold respectively. Fluoxetine did not affect the plasma concentration of 9-hydroxyrisperidone. Paroxetine lowered the concentration of 9-hydroxyrisperidone by about 10%. The dose of risperidone needs to be titrated accordingly when fluoxetine or paroxetine is co-administered. When either concomitant fluoxetine or paroxetine is initiated or discontinued, the physician should re-evaluate the dose of RISPERDAL CONSTA®. When initiation of fluoxetine or paroxetine is considered, patients may be placed on a lower dose of RISPERDAL CONSTA® between 2 to 4 weeks before the planned start of fluoxetine or paroxetine therapy to adjust for the expected increase in plasma concentrations of risperidone. When fluoxetine or paroxetine is initiated in patients receiving the recommended dose of 25 mg RISPERDAL CONSTA®, it is recommended to continue treatment with the 25 mg dose unless clinical judgment necessitates lowering the RISPERDAL CONSTA® dose to 12.5 mg or necessitates interruption of RISPERDAL CONSTA® treatment. When RISPERDAL CONSTA® is initiated in patients already receiving fluoxetine or paroxetine, a starting dose of 12.5 mg can be considered. The efficacy of the 12.5 mg dose has not been investigated in clinical trials. The effects of discontinuation of concomitant fluoxetine or paroxetine therapy on the pharmacokinetics of risperidone and 9-hydroxyrisperidone have not been studied. [see Drug Interactions (7.11)]

2.8 Instructions for Use

Important information

RISPERDAL CONSTA® requires close attention to these step-by-step Instructions for Use to help ensure successful administration.

Use components provided

The components in this dose pack are specifically designed for use with RISPERDAL CONSTA®. RISPERDAL CONSTA® must be reconstituted only in the diluent supplied in the dose pack.

Do not substitute ANY components of the dose pack.

Do not store suspension after reconstitution

Administer dose as soon as possible after reconstitution to avoid settling.

Proper dosing

The entire contents of the vial must be administered to ensure intended dose of RISPERDAL CONSTA® is delivered.

SINGLE-USE DEVICE

Do not reuse. Medical devices require specific material characteristics to perform as intended. These characteristics have been verified for single use only. Any attempt to re-process the device for subsequent re-use may adversely affect the integrity of the device or lead to deterioration in performance.

Dose pack contents

Step 1         Assemble components Take out dose pack         Connect vial adapter to vial

Wait 30 minutes Remove dose pack from the refrigerator and allow to sit at room temperature for at least 30 minutes before reconstituting.Do not warm any other way. Remove cap from vial Flip off colored cap from vial.Wipe top of the grey stopper with an alcohol swab. Allow to air dry.Do not remove grey rubber stopper. Prepare vial adapter Hold sterile blister as shown. Peel back and remove paper backing.Do not remove vial adapter from blister.Do not touch spike tip at any time. This will result in contamination. Connect vial adapter to vial Place vial on a hard surface and hold by the base. Center vial adapter over the grey rubber stopper. Push vial adapter straight down onto vial top until it snaps securely into place.Do not place vial adapter on at an angle or diluent may leak upon transfer to the vial.

Connect prefilled syringe to vial adapter

Remove sterile blister

Keep vial vertical to prevent leakage. Hold base of vial and pull up on the sterile blister to remove.Do not shake.Do not touch exposed luer opening on vial adapter.This will result in contamination. Use proper grip Hold by white collar at the tip of the syringe.Do not hold syringe by the glass barrel during assembly.

Remove cap Holding the white collar, snap off the white cap.Do not twist or cut off the white cap.Do not touch syringe tip. This will result in contamination.

The broken-off cap can be discarded. Connect syringe to vial adapter Hold vial adapter by skirt to keep stationary.Hold syringe by white collar then insert tip into the luer opening of the vial adapter.Do not hold the glass syringe barrel. This may cause the white collar to loosen or detach.Attach the syringe to the vial adapter with a firm clockwise twisting motion until it feels snug.Do not over-tighten. Over-tightening may cause the syringe tip to break. Step 2         Reconstitute microspheres

Inject diluent Inject entire amount of diluent from syringe into the vial.

Suspend microspheres in diluent Continuing to hold down the plunger rod, shake vigorously for at least 10 seconds, as shown.Check the suspension. When properly mixed, the suspension appears uniform, thick and milky in color. Microspheres will be visible in the liquid.Immediately proceed to the next step so suspension does not settle. Transfer suspension to syringe Invert vial completely. Slowly pull plunger rod down to withdraw entire contents from the vial into the syringe. Remove vial adapter Hold white collar on the syringe and unscrew from vial adapter.Tear section of the vial label at the perforation. Apply detached label to the syringe for identification purposes.Discard both vial and vial adapter appropriately. Step 3         Attach needle

Select appropriate needle Choose needle based on injection location (gluteal or deltoid). Attach needle Peel blister pouch open part way and use to grasp the base of the needle, as shown.Holding the white collar on the syringe, attach syringe to needle luer connection with a firm clockwise twisting motion until snug.Do not touch needle luer opening. This will result in contamination. Resuspend microspheres Fully remove the blister pouch.Just before injection, shake syringe vigorously again, as some settling will have occurred. Step 4         Inject dose

Remove transparent needle protector Move the needle safety device back towards the syringe, as shown. Then hold white collar on syringe and carefully pull the transparent needle protector straight off.Do not twist transparent needle protector, as the luer connection may loosen. Remove air bubbles Hold needle upright and tap gently to make any air bubbles rise to the top.Slowly and carefully press plunger rod upward to remove air. Inject Immediately inject entire contents of syringe intramuscularly (IM) into the gluteal or deltoid muscle of the patient.Gluteal injection should be made into the upper-outer quadrant of the gluteal area.Do not administer intravenously. Secure needle in safety device Using one hand, place needle safety device at a 45 degree angle on a hard, flat surface. Press down with a firm, quick motion until needle is fully engaged in safety device.Avoid needle stick injury: Do not use two hands.Do not intentionally disengage or mishandle the needle safety device.Do not attempt to straighten the needle or engage the safety device if the needle is bent or damaged. Properly dispose of needles Check to confirm needle safety device is fully engaged.Discard in an approved sharps container.Also discard the unused needle provided in the dose pack.
Ortho Tri Cyclen Lo

Ortho Tri Cyclen Lo

2.1 How to Start ORTHO TRI-CYCLEN Lo

ORTHO TRI-CYCLEN Lo is dispensed in either a DIALPAK Tablet dispenser or a VERIDATE Tablet Dispenser [see How Supplied/Storage and Handling (16)]. ORTHO TRI-CYCLEN Lo may be started using either a Day 1 start or a Sunday start (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration.

2.2 How to Take ORTHO TRI-CYCLEN Lo
Table 1: Instructions for Administration of ORTHO TRI-CYCLEN Lo Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-Approved Patient Labeling. Starting COCs in women not currently using hormonal contraception (Day 1 Start or Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product.Tablet Color: ORTHO TRI-CYCLEN Lo active tablets are white (Day 1 to Day 7), light blue (Day 8 to Day 15) and dark blue (Day 16 to Day 21). ORTHO TRI‑CYCLEN Lo inactive tablets are dark green (Day 22 to Day 28). Day 1 Start: Take first active tablet without regard to meals on the first day of menses. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the day after taking the last inactive tablet) Sunday Start: Take first active tablet without regard to meals on the first Sunday after the onset of menses. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of ORTHO TRI-CYCLEN Lo. Take subsequent active tablets once daily at the same time each day for a total of 21 days. Take one dark green inactive tablet daily for the following 7 days and at the same time of day that active tablets were taken. Begin each subsequent pack on the same day of the week as the first cycle pack (i.e., on the Sunday after taking the last inactive tablet) and additional non-hormonal contraceptive is not needed. Switching to ORTHO TRI-CYCLEN Lo from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to ORTHO TRI-CYCLEN Lo Start ORTHO TRI-CYCLEN Lo: Transdermal patch On the day when next application would have been scheduled Vaginal ring On the day when next insertion would have been scheduled Injection On the day when next injection would have been scheduled Intrauterine contraceptive On the day of removal If the IUD is not removed on first day of the patient's menstrual cycle, additional non-hormonal contraceptive (such as condoms and spermicide) is needed for the first seven days of the first cycle pack. Implant On the day of removal
Starting ORTHO TRI-CYCLEN Lo after Abortion or Miscarriage

First-trimester
After a first-trimester abortion or miscarriage, ORTHO TRI-CYCLEN Lo may be started immediately. An additional method of contraception is not needed if ORTHO TRI-CYCLEN Lo is started immediately. If ORTHO TRI-CYCLEN Lo is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of her first cycle pack of ORTHO TRI-CYCLEN Lo.
Second-trimester
Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start ORTHO TRI-CYCLEN Lo, following the instructions in Table 1 for Day 1 or Sunday start, as desired. If using Sunday start, use additional non-hormonal contraception (such as condoms and spermicide) for the first seven days of the patient's first cycle pack of ORTHO TRI-CYCLEN Lo. [See Contraindications (4), Warnings and Precautions (5.1), and FDA-Approved Patient Labeling.]
Starting ORTHO TRI-CYCLEN Lo after Childbirth
Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with ORTHO TRI-CYCLEN Lo following the instructions in Table 1 for women not currently using hormonal contraception. ORTHO TRI-CYCLEN Lo is not recommended for use in lactating women [see Use in Specific Populations (8.3)]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of ORTHO TRI-CYCLEN Lo. [See Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1 and 8.3), and FDA-Approved Patient Labeling].
DIALPAK® Tablet Dispenser:

SET THE DAY: □ Day 1 Start: turn the dial on the empty DIALPAK until the arrow points to the first day of the patient's period. □ Sunday Start: the arrow on the empty DIALPAK should point to SU (Sunday).

Insert the new refill by lining up the "V" shape on the refill with the "V" shape at the top of the DIALPAK. Snap the refill in place. Pill "1" is ready to be taken. Always begin the pill cycle with pill "1," as shown on the inner part of the refill ring.

Remove pill "1" by pushing down on the pill. The pill will come out through a hole in the back of the DIALPAK.

The patient should wait 24 hours to take the next pill. To take pill "2," turn the dial on the DIALPAK in a clockwise direction to the next day. Continue to take one pill each day until all the pills have been taken.

Turn the dial to the pill "1" position to remove the empty refill and insert a new refill. The first pill in every refill will always be taken on the same day of the week, no matter when the patient's next period starts.
VERIDATE® Tablet Dispenser
Place the refill in the VERIDATE Tablet Dispenser so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under all the nibs (see illustration below). If the patient starts pill-taking on Sunday, the first active pill should be taken on the first Sunday after the patient's menstrual period begins. Remove the first active pill at the top of the dispenser (Sunday) by pressing the pill through the hole in the bottom of the dispenser. If the patient will start pill-taking on a day other than Sunday, a calendar label has been provided and should be placed over the calendar in the center of the VERIDATE. To place the label correctly, identify the correct starting day, locate that day printed in blue on the label, and line that day up with the first white pill directly under the V notch at the top of the dispenser. Remove the label from the backing. Press the center of the label down onto the center of the printed calendar. Remove that white pill by pressing the pill through the hole in the bottom of the dispenser. After all the dark green pills have been taken, insert a new refill into the VERIDATE. The patient should take the first pill on the next day, even if the patient's period is not over yet.
To Insert New Refill:
Lift the empty refill out of the VERIDATE Tablet Dispenser. Insert the new refill so that the V notch in the refill is at the top of the dispenser. Press the refill down so that it fits firmly under the nibs.
2.3 Missed Tablets
Table 2: Instructions for Missed ORTHO TRI-CYCLEN Lo Tablets If one active tablet is missed in Weeks 1, 2, or 3 Take the tablet as soon as possible. Continue taking one tablet a day until the pack is finished. If two active tablets are missed in Week 1 or Week 2 Take the two missed tablets as soon as possible and the next two active tablets the next day. Continue taking one tablet a day until the pack is finished. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets. If two active tablets are missed in the third week or three or more active tablets are missed in a row in Weeks 1, 2, or 3 Day 1 start: Throw out the rest of the pack and start a new pack that same day.Sunday start: Continue taking one tablet a day until Sunday, then throw out the rest of the pack and start a new pack that same day. Additional non-hormonal contraception (such as condoms and spermicide) should be used as back-up if the patient has sex within 7 days after missing tablets.
2.4 Advice in Case of Gastrointestinal Disturbances

In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3 to 4 hours after taking an active tablet, handle this as a missed tablet [see FDA-Approved Patient Labeling].
Equate Hair Regrowth Tr...

Equate Hair Regrowth Treatment For Women

NUCYNTA® oral solution is available in one concentration: 20 mg/mL.

Take care when prescribing and administering NUCYNTA® oral solution to avoid dosing errors, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed. Include the dose in milliliters (mL) and milligrams (mg) when writing prescriptions. Always use the enclosed calibrated oral syringe when administering NUCYNTA® oral solution to ensure the dose is measured and administered accurately.

2.1 Individualization of Dosage

As with any opioid drug product, adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. In the selection of the initial dose of tapentadol, give attention to the following:
the total daily dose, potency and specific characteristics of the opioid the patient has been taking previously; the reliability of the relative potency estimate used to calculate the equivalent morphine sulfate dose needed; the patient's degree of opioid tolerance; the general condition and medical status of the patient; concurrent medications; the type and severity of the patient's pain; risk factors for abuse, addiction or diversion, including a prior history of abuse, addiction or diversion.
The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of each individual patient. Continual re-evaluation of the patient receiving tapentadol is important, with special attention to the maintenance of pain control and the relative incidence of side effects associated with therapy. During chronic therapy, especially for non-cancer-related pain, periodically re-assess the continued need for the use of opioid analgesics.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family. Monitor the patient for signs of respiratory or central nervous system depression.

2.2 Initiation of Therapy

The dose is 2.5 mL (equivalent to 50 mg), 3.75 mL (equivalent to 75 mg), or 5 mL (equivalent to 100 mg) every 4 to 6 hours depending upon pain intensity.

On the first day of dosing, the second dose may be administered as soon as one hour after the first dose, if adequate pain relief is not attained with the first dose. Subsequent dosing is 2.5 mL (equivalent to 50 mg), 3.75 mL (equivalent to 75 mg), or 5 mL (equivalent to 100 mg) every 4 to 6 hours and should be adjusted to maintain adequate analgesia with acceptable tolerability.

Daily doses greater than 700 mg on the first day of therapy and 600 mg on subsequent days have not been studied and are not recommended.

NUCYNTA® may be given with or without food [see Clinical Pharmacology (12.3)].

2.3 Renal Impairment

Use of NUCYNTA® in patients with severe renal impairment is not recommended [see Warnings and Precautions (5.16) and Clinical Pharmacology (12.3)].

No dosage adjustment is recommended in patients with mild or moderate renal impairment.

2.4 Hepatic Impairment

The safety and efficacy of NUCYNTA® has not been studied in patients with severe hepatic impairment (Child-Pugh Score 10–15) and use in this population is not recommended [see Warnings and Precautions (5.15)].

Initiate treatment of patients with moderate hepatic impairment (Child-Pugh Score 7 to 9) with 50 mg no more frequently than once every 8 hours (maximum of three doses in 24 hours). Further treatment should reflect maintenance of analgesia with acceptable tolerability, to be achieved by either shortening or lengthening the dosing interval [see Clinical Pharmacology (12.3)].

No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Score 5 to 6) [see Clinical Pharmacology (12.3)].

2.5 Elderly Patients

In general, recommended dosing for elderly patients with normal renal and hepatic function is the same as for younger adult patients with normal renal and hepatic function. Because elderly patients are more likely to have decreased renal and hepatic function, consideration should be given to starting elderly patients with the lower range of recommended doses.

2.6 Cessation of Therapy

When the patient no longer requires therapy with tapentadol, gradually taper the dose to prevent signs and symptoms of withdrawal in the physically dependent patient [see Warnings and Precautions (5.13)].

2.7 Instructions for Use

Concentration and Dispensing: The oral solution contains 20 mg tapentadol per milliliter (mL) and prescriptions should be written in milliliters (mL) and milligrams (mg). An oral syringe is supplied with dose marks corresponding directly to 2.5 mL (equals 50 mg) oral solution, 3.75 mL (equals 75 mg) oral solution, and 5 mL (equals 100 mg) oral solution.

Inform patients of the availability of FDA-approved patient labeling, Instructions for Use, for step-by-step instructions for patients on how to use the medicine bottle and the oral syringe.
Vida Mia Hand Sanitizer...

Vida Mia Hand Sanitizer

2.1 Recommended Dosage

The recommended starting dose of INVOKANA (canagliflozin) is 100 mg once daily, taken before the first meal of the day. In patients tolerating INVOKANA 100 mg once daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control, the dose can be increased to 300 mg once daily [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2), and Patient Counseling Information (17)].

In patients with volume depletion, correcting this condition prior to initiation of INVOKANA is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5 and 8.6), and Patient Counseling Information (17)].

2.2 Patients with Renal Impairment

No dose adjustment is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater).

The dose of INVOKANA is limited to 100 mg once daily in patients with moderate renal impairment with an eGFR of 45 to less than 60 mL/min/1.73 m2.

INVOKANA should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2.

Assessment of renal function is recommended prior to initiation of INVOKANA therapy and periodically thereafter. INVOKANA should be discontinued when eGFR is persistently less than 45 mL/min/1.73 m2 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

2.3 Concomitant Use with UDP-Glucuronosyl Transferase (UGT) Enzyme Inducers

If an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKANA, consider increasing the dosage to 300 mg once daily in patients currently tolerating INVOKANA 100 mg once daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control [see Drug Interactions (7.1)].

Consider another antihyperglycemic agent in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 receiving concurrent therapy with a UGT inducer.
Sporanox

Sporanox

Treatment of Oropharyngeal and Esophageal Candidiasis

The solution should be vigorously swished in the mouth (10 mL at a time) for several seconds and swallowed.

The recommended dosage of SPORANOX® (itraconazole) Oral Solution for oropharyngeal candidiasis is 200 mg (20 mL) daily for 1 to 2 weeks. Clinical signs and symptoms of oropharyngeal candidiasis generally resolve within several days.

For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose is 100 mg (10 mL) b.i.d. For patients responding to therapy, clinical response will be seen in 2 to 4 weeks. Patients may be expected to relapse shortly after discontinuing therapy. Limited data on the safety of long-term use (>6 months) of SPORANOX® Oral Solution are available at this time.

The recommended dosage of SPORANOX® Oral Solution for esophageal candidiasis is 100 mg (10 mL) daily for a minimum treatment of three weeks. Treatment should continue for 2 weeks following resolution of symptoms. Doses up to 200 mg (20 mL) per day may be used based on medical judgment of the patient's response to therapy.

SPORANOX® Oral Solution and SPORANOX® Capsules should not be used interchangeably. Patients should be instructed to take SPORANOX® Oral Solution without food, if possible. Only SPORANOX® Oral Solution has been demonstrated effective for oral and/or esophageal candidiasis.

Use in Patients with Renal Impairment

Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS.)

Use in Patients with Hepatic Impairment

Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations, WARNINGS, and PRECAUTIONS.)
Sporanox

Sporanox

SPORANOX® (itraconazole) Capsules should be taken with a full meal to ensure maximal absorption. SPORANOX® (itraconazole) Capsules must be swallowed whole.

SPORANOX® Capsules is a different preparation than SPORANOX® Oral Solution and should not be used interchangeably.

Treatment of Blastomycosis and Histoplasmosis

The recommended dose is 200 mg once daily (2 capsules). If there is no obvious improvement, or there is evidence of progressive fungal disease, the dose should be increased in 100-mg increments to a maximum of 400 mg daily. Doses above 200 mg/day should be given in two divided doses.

Treatment of Aspergillosis

A daily dose of 200 to 400 mg is recommended.

Treatment in Life-Threatening Situations

In life-threatening situations, a loading dose should be used.

Although clinical studies did not provide for a loading dose, it is recommended, based on pharmacokinetic data, that a loading dose of 200 mg (2 capsules) three times daily (600 mg/day) be given for the first 3 days of treatment.

Treatment should be continued for a minimum of three months and until clinical parameters and laboratory tests indicate that the active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection.

SPORANOX® Capsules and SPORANOX® Oral Solution should not be used interchangeably. Only the oral solution has been demonstrated effective for oral and/or esophageal candidiasis.

Treatment of Onychomycosis

Toenails with or without fingernail involvement: The recommended dose is 200 mg (2 capsules) once daily for 12 consecutive weeks.

Treatment of Onychomycosis

Fingernails only: The recommended dosing regimen is 2 treatment pulses, each consisting of 200 mg (2 capsules) b.i.d. (400 mg/day) for 1 week. The pulses are separated by a 3-week period without SPORANOX®.

Use in Patients with Renal Impairment:

Limited data are available on the use of oral itraconazole in patients with renal impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations and PRECAUTIONS.)

Use in Patients with Hepatic Impairment

Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when this drug is administered in this patient population. (See CLINICAL PHARMACOLOGY: Special Populations, WARNINGS, and PRECAUTIONS.)
Claravis

Claravis

2.1 Recommended Dosage

The recommended starting dose of INVOKANA (canagliflozin) is 100 mg once daily, taken before the first meal of the day. In patients tolerating INVOKANA 100 mg once daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control, the dose can be increased to 300 mg once daily [see Warnings and Precautions (5.2), Clinical Pharmacology (12.2), and Patient Counseling Information (17)].

In patients with volume depletion, correcting this condition prior to initiation of INVOKANA is recommended [see Warnings and Precautions (5.1), Use in Specific Populations (8.5 and 8.6), and Patient Counseling Information (17)].

2.2 Patients with Renal Impairment

No dose adjustment is needed in patients with mild renal impairment (eGFR of 60 mL/min/1.73 m2 or greater).

The dose of INVOKANA is limited to 100 mg once daily in patients with moderate renal impairment with an eGFR of 45 to less than 60 mL/min/1.73 m2.

INVOKANA should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2.

Assessment of renal function is recommended prior to initiation of INVOKANA therapy and periodically thereafter. INVOKANA should be discontinued when eGFR is persistently less than 45 mL/min/1.73 m2 [see Warnings and Precautions (5.2) and Use in Specific Populations (8.6)].

2.3 Concomitant Use with UDP-Glucuronosyl Transferase (UGT) Enzyme Inducers

If an inducer of UGTs (e.g., rifampin, phenytoin, phenobarbital, ritonavir) is co-administered with INVOKANA, consider increasing the dosage to 300 mg once daily in patients currently tolerating INVOKANA 100 mg once daily who have an eGFR of 60 mL/min/1.73 m2 or greater and require additional glycemic control [see Drug Interactions (7.1)].

Consider another antihyperglycemic agent in patients with an eGFR of 45 to less than 60 mL/min/1.73 m2 receiving concurrent therapy with a UGT inducer.
Levaquin

Levaquin

2.1 Dosage in Adult Patients with Normal Renal Function

The usual dose of LEVAQUIN® Tablets or Oral Solution is 250 mg, 500 mg, or 750 mg administered orally every 24 hours, as indicated by infection and described in Table 1. The usual dose of LEVAQUIN® Injection is 250 mg or 500 mg administered by slow infusion over 60 minutes every 24 hours or 750 mg administered by slow infusion over 90 minutes every 24 hours, as indicated by infection and described in Table 1.

These recommendations apply to patients with creatinine clearance ≥ 50 mL/min. For patients with creatinine clearance <50 mL/min, adjustments to the dosing regimen are required [see Dosage and Administration (2.3)].
Table 1: Dosage in Adult Patients with Normal Renal Function (creatinine clearance ≥ 50 mL/min) Type of Infection* Dosed Every 24 hours Duration (days)† * Due to the designated pathogens [see Indications and Usage (1)]. † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ Due to methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae (including multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydophila pneumoniae, Legionella pneumophila, or Mycoplasma pneumoniae [see Indications and Usage (1.2)]. § Due to Streptococcus pneumoniae (excluding multi-drug-resistant isolates [MDRSP]), Haemophilus influenzae, Haemophilus parainfluenzae, Mycoplasma pneumoniae, or Chlamydophila pneumoniae [see Indications and Usage (1.3)]. ¶ This regimen is indicated for cUTI due to Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and AP due to E. coli, including cases with concurrent bacteremia. # This regimen is indicated for cUTI due to Enterococcus faecalis, Enterococcus cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa; and for AP due to E. coli. Þ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)]. ß The safety of LEVAQUIN ® in adults for durations of therapy beyond 28 days or in pediatric patients for durations beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged LEVAQUIN ® therapy should only be used when the benefit outweighs the risk. à Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Higher doses of LEVAQUIN ® typically used for treatment of pneumonia can be used for treatment of plague, if clinically indicated. Nosocomial Pneumonia 750 mg 7–14 Community Acquired Pneumonia‡ 500 mg 7–14 Community Acquired Pneumonia§ 750 mg 5 Acute Bacterial Sinusitis 750 mg 5 500 mg 10–14 Acute Bacterial Exacerbation of Chronic Bronchitis 500 mg 7 Complicated Skin and Skin Structure Infections (SSSI) 750 mg 7–14 Uncomplicated SSSI 500 mg 7–10 Chronic Bacterial Prostatitis 500 mg 28 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)¶ 750 mg 5 Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP)# 250 mg 10 Uncomplicated Urinary Tract Infection 250 mg 3 Inhalational Anthrax (Post-Exposure), adult and pediatric patients > 50 kg Þ,ß 500 mg 60ß Pediatric patients < 50 kg and ≥ 6 months of ageÞ,ß see Table 2 below (2.2) 60ß Plague, adult and pediatric patients > 50 kg à 500 mg 10 to 14 Pediatric patients < 50 kg and ≥ 6 months of age see Table 2 below (2.2) 10 to 14
2.2 Dosage in Pediatric Patients

The dosage in pediatric patients ≥ 6 months of age is described below in Table 2.
Table 2: Dosage in Pediatric Patients ≥ 6 months of age Type of Infection* Dose Freq. Once every Duration† * Due to Bacillus anthracis [see Indications and Usage (1.13)] and Yersinia pestis [see Indications and Usage (1.14)]. † Sequential therapy (intravenous to oral) may be instituted at the discretion of the physician. ‡ Drug administration should begin as soon as possible after suspected or confirmed exposure to aerosolized B. anthracis. This indication is based on a surrogate endpoint. Levofloxacin plasma concentrations achieved in humans are reasonably likely to predict clinical benefit [see Clinical Studies (14.9)] § The safety of LEVAQUIN ® in pediatric patients for durations of therapy beyond 14 days has not been studied. An increased incidence of musculoskeletal adverse events compared to controls has been observed in pediatric patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.4), and Clinical Studies (14.9)]. Prolonged LEVAQUIN ® therapy should only be used when the benefit outweighs the risk. ¶ Drug administration should begin as soon as possible after suspected or confirmed exposure to Yersinia pestis. Inhalational Anthrax (post-exposure)‡,§ Pediatric patients > 50 kg 500 mg 24 hr 60 days§ Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg(not to exceed 250 mg per dose) 12 hr 60 days§ Plague¶ Pediatric patients > 50 kg 500 mg 24 hr 10 to 14 days Pediatric patients < 50 kg and ≥ 6 months of age 8 mg/kg(not to exceed 250 mg per dose) 12 hr 10 to 14 days
2.3 Dosage Adjustment in Adults with Renal Impairment

Administer LEVAQUIN® with caution in the presence of renal insufficiency. Careful clinical observation and appropriate laboratory studies should be performed prior to and during therapy since elimination of levofloxacin may be reduced.

No adjustment is necessary for patients with a creatinine clearance ≥ 50 mL/min.

In patients with impaired renal function (creatinine clearance < 50 mL/min), adjustment of the dosage regimen is necessary to avoid the accumulation of levofloxacin due to decreased clearance [see Use in Specific Populations (8.6)].

Table 3 shows how to adjust dose based on creatinine clearance.
Table 3: Dosage Adjustment in Adult Patients with Renal Impairment (creatinine clearance < 50 mL/min) Dosage in Normal Renal Function Every 24 hours Creatinine Clearance20 to 49 mL/min Creatinine Clearance10 to 19 mL/min Hemodialysis or Chronic Ambulatory Peritoneal Dialysis (CAPD) 750 mg 750 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 750 mg initial dose, then 500 mg every 48 hours 500 mg 500 mg initial dose, then 250 mg every 24 hours 500 mg initial dose, then 250 mg every 48 hours 500 mg initial dose, then 250 mg every 48 hours 250 mg No dosage adjustment required 250 mg every 48 hours. If treating uncomplicated UTI, then no dosage adjustment is required No information on dosing adjustment is available
2.4 Drug Interaction With Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins

LEVAQUIN® Tablets and Oral Solution

LEVAQUIN® Tablets and Oral Solution should be administered at least two hours before or two hours after antacids containing magnesium, aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc or didanosine chewable/buffered tablets or the pediatric powder for oral solution [see Drug Interactions (7.1) and Patient Counseling Information (17.2)].

LEVAQUIN® Injection

LEVAQUIN® Injection should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration (2.6)].

2.5 Administration Instructions

Food and LEVAQUIN® Tablets and Oral Solution

LEVAQUIN® Tablets can be administered without regard to food. It is recommended that LEVAQUIN® Oral Solution be taken 1 hour before or 2 hours after eating.

LEVAQUIN® Injection

Caution: Rapid or bolus intravenous infusion of LEVAQUIN® has been associated with hypotension and must be avoided. LEVAQUIN® Injection should be infused intravenously slowly over a period of not less than 60 or 90 minutes, depending on the dosage. LEVAQUIN® Injection should be administered only by intravenous infusion. It is not for intramuscular, intrathecal, intraperitoneal, or subcutaneous administration.

Hydration for Patients Receiving LEVAQUIN® Tablets, Oral Solution, and Injection

Adequate hydration of patients receiving oral or intravenous LEVAQUIN® should be maintained to prevent the formation of highly concentrated urine. Crystalluria and cylindruria have been reported with quinolones [see Adverse Reactions (6.1) and Patient Counseling Information (17.2)].

2.6 Preparation of Intravenous Product

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Because only limited data are available on the compatibility of LEVAQUIN® Injection with other intravenous substances, additives or other medications should not be added to LEVAQUIN® Injection Premix in Single-Use Flexible Containers, or infused simultaneously through the same intravenous line. If the same intravenous line is used for sequential infusion of several different drugs, the line should be flushed before and after infusion of LEVAQUIN® Injection with an infusion solution compatible with LEVAQUIN® Injection and with any other drug(s) administered via this common line.

LEVAQUIN® Injection Premix in Single-Use Flexible Containers (5 mg/mL)

LEVAQUIN® Injection is supplied in flexible containers within a foil overwrap. These contain a premixed, ready to use levofloxacin solution in 5% dextrose (D5W) for single-use. The 100 mL premixed flexible containers contain either 250 mg/50 mL or 500 mg/100 mL of levofloxacin solution. The 150 mL flexible container contains 750 mg/150 mL of levofloxacin solution. The concentration of each container is 5 mg/mL. No further dilution of these preparations is necessary. Because the premix flexible containers are for single-use only, any unused portion should be discarded.

Instructions for the Use of LEVAQUIN® Injection Premix in Flexible Containers:
Tear outer wrap at the notch and remove solution container. Check the container for minute leaks by squeezing the inner bag firmly. If leaks are found, or if the seal is not intact, discard the solution, as the sterility may be compromised. Do not use if the solution is cloudy or a precipitate is present. Use sterile equipment. WARNING: Do not use flexible containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
Preparation for Administration:
Close flow control clamp of administration set. Remove cover from port at bottom of container. Insert piercing pin of administration set into port with a twisting motion until the pin is firmly seated. NOTE: See full directions on administration set carton. Suspend container from hanger. Squeeze and release drip chamber to establish proper fluid level in chamber during infusion of LEVAQUIN® Injection Premix in Flexible Containers. Open flow control clamp to expel air from set. Close clamp. Regulate rate of administration with flow control clamp.
Terazol 7

Terazol 7

TERAZOL® 7 (terconazole) Vaginal Cream 0.4%

One full applicator (5 g) of TERAZOL® 7 Vaginal Cream (20 mg terconazole) should be administered intravaginally once daily at bedtime for seven consecutive days.

TERAZOL® 3 (terconazole) Vaginal Cream 0.8%

One full applicator (5 g) of TERAZOL® 3 Vaginal Cream (40 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days.

TERAZOL® 3 (terconazole) Vaginal Suppositories 80 mg

One TERAZOL® 3 Vaginal Suppository (80 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days.

Before prescribing another course of therapy, the diagnosis should be reconfirmed by smears and/or cultures and other pathogens commonly associated with vulvovaginitis ruled out. The therapeutic effect of these products is not affected by menstruation.
Ultracet

Ultracet

For the short-term (five days or less) management of acute pain, the recommended dose of ULTRACET® is 2 tablets every 4 to 6 hours as needed for pain relief, up to a maximum of 8 tablets per day.

Individualization of Dose

In patients with creatinine clearances of less than 30 mL/min, it is recommended that the dosing interval of ULTRACET® be increased not to exceed 2 tablets every 12 hours. Dose selection for an elderly patient should be cautious, in view of the potential for greater sensitivity to adverse events.
Ultram

Ultram

Adults (17 years of age and over)

For patients with moderate to moderately severe chronic pain not requiring rapid onset of analgesic effect, the tolerability of ULTRAM® can be improved by initiating therapy with the following titration regimen: ULTRAM® should be started at 25 mg/day qAM and titrated in 25 mg increments as separate doses every 3 days to reach 100 mg/day (25 mg q.i.d.). Thereafter the total daily dose may be increased by 50 mg as tolerated every 3 days to reach 200 mg/day (50 mg q.i.d.). After titration, ULTRAM® 50 to 100 mg can be administered as needed for pain relief every 4 to 6 hours not to exceed 400 mg/day.

For the subset of patients for whom rapid onset of analgesic effect is required and for whom the benefits outweigh the risk of discontinuation due to adverse events associated with higher initial doses, ULTRAM® 50 mg to 100 mg can be administered as needed for pain relief every four to six hours, not to exceed 400 mg per day.

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Studies with tramadol in adults have shown that starting at the lowest possible dose and titrating upward will result in fewer discontinuations and increased tolerability.
In all patients with creatinine clearance less than 30 mL/min, it is recommended that the dosing interval of ULTRAM® be increased to 12 hours, with a maximum daily dose of 200 mg. Since only 7% of an administered dose is removed by hemodialysis, dialysis patients can receive their regular dose on the day of dialysis. The recommended dose for adult patients with cirrhosis is 50 mg every 12 hours. In general, dose selection for an elderly patient over 65 years old should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. For elderly patients over 75 years old, total dose should not exceed 300 mg/day.
Ultram Er

Ultram Er

ULTRAM ER should not be used in patients with:
• creatinine clearance less than 30 mL/min, • severe hepatic impairment (Child-Pugh Class C)
(See PRECAUTIONS, Use in Renal and Hepatic Disease).

ULTRAM ER must be swallowed whole and must not be chewed, crushed, or split (see WARNINGS, Misuse, Abuse and Diversion of Opioids and DRUG ABUSE AND ADDICTION).

Adults (18 years of age and over)

Patients Not Currently on Tramadol Immediate-Release Products

For patients not currently treated with tramadol immediate-release (IR) products, ULTRAM ER should be initiated at a dose of 100 mg once daily and titrated up as necessary by 100-mg increments every five days to relief of pain and depending upon tolerability. ULTRAM ER should not be administered at a dose exceeding 300 mg per day.

Patients Currently on Tramadol Immediate-Release Products

For patients maintained on tramadol IR products, calculate the 24-hour tramadol IR dose and initiate a total daily dose of ULTRAM ER rounded down to the next lowest 100 mg increment. The dose may subsequently be individualized according to patient need. Due to limitations in flexibility of dose selection with ULTRAM ER, some patients maintained on tramadol IR products may not be able to convert to ULTRAM ER. ULTRAM ER should not be administered at a dose exceeding 300 mg per day. The concomitant use of ULTRAM ER with other tramadol products is not recommended (see WARNINGS).

Individualization of Dose

Good pain management practice dictates that the dose be individualized according to patient need using the lowest beneficial dose. Start at the lowest possible dose and titrate upward as tolerated to achieve an adequate effect. Clinical studies of ULTRAM ER have not demonstrated a clinical benefit at a total daily dose exceeding 300 mg.

In general, dosing of an elderly patient (over 65 years of age) should be initiated cautiously, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. ULTRAM ER should be administered with even greater caution in patients over 75 years, due to the greater frequency of adverse events seen in this population.
Axert

Axert

2.1 Acute Treatment of Migraine Attacks

The recommended dose of AXERT® (almotriptan malate) in adults and adolescents age 12 to 17 years is 6.25 mg to 12.5 mg, with the 12.5 mg dose tending to be a more effective dose in adults. As individuals may vary in their response to different doses of AXERT®, the choice of dose should be made on an individual basis.

If the headache is relieved after the initial AXERT® dose but returns, the dose may be repeated after 2 hours. The effectiveness of a second dose has not been established in placebo-controlled trials. The maximum daily dose should not exceed 25 mg. The safety of treating an average of more than four migraines in a 30-day period has not been established.

2.2 Hepatic Impairment

The recommended starting dose of AXERT® in patients with hepatic impairment is 6.25 mg. The maximum daily dose should not exceed 12.5 mg over a 24-hour period [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.3)].

2.3 Renal Impairment

The recommended starting dose of AXERT® in patients with severe renal impairment is 6.25 mg. The maximum daily dose should not exceed 12.5 mg over a 24-hour period [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.3)].
Duragesic

Duragesic

2.1 Initial Dosing

DURAGESIC should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Due to the risk of respiratory depression, DURAGESIC is only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning DURAGESIC therapy. As DURAGESIC is only for use in opioid-tolerant patients, do not begin any patient on DURAGESIC as the first opioid.

Patients considered opioid-tolerant are those who are taking at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)]. Monitor patients closely for respiratory depression, especially within the first 24–72 hours of initiating therapy with DURAGESIC when serum concentrations from the initial patch will peak [see Warnings and Precautions (5.2)].

The recommended starting dose when converting from other opioids to DURAGESIC is intended to minimize the potential for overdosing patients with the first dose.

Discontinue all other around-the-clock opioid drugs when DURAGESIC therapy is initiated.

While there are useful tables of opioid equivalents readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient's 24-hour fentanyl requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour fentanyl requirements which could result in adverse reactions. In a DURAGESIC clinical trial, patients were converted from their prior opioid to DURAGESIC using Table 1 as a guide for the initial DURAGESIC dose.

Consider the following when using the information in Table 1:
This is not a table of equianalgesic doses. The conversion doses in this table are only for the conversion from one of the listed oral or parenteral opioid analgesics to DURAGESIC. The table cannot be used to convert from DURAGESIC to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.
To convert patients from oral or parenteral opioids to DURAGESIC, use Table 1. Do not use Table 1 to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative and will overestimate the dose of the new agent.
Table 1*: DOSE CONVERSION TO DURAGESIC Current Analgesic Daily Dosage (mg/day) Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the conversion methodology outlined above with Table 2. * Table 1 should not be used to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative. Use of Table 1 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible [see Dosage and Administration (2.3)]. Oral morphine 60–134 135–224 225–314 315–404 Intramuscular or Intravenous morphine 10–22 23–37 38–52 53–67 Oral oxycodone 30–67 67.5–112 112.5–157 157.5–202 Oral codeine 150–447 Oral hydromorphone 8–17 17.1–28 28.1–39 39.1–51 Intravenous hydromorphone 1.5–3.4 3.5–5.6 5.7–7.9 8–10 Intramuscular meperidine 75–165 166–278 279–390 391–503 Oral methadone 20–44 45–74 75–104 105–134 ⇓ ⇓ ⇓ ⇓ Recommended DURAGESIC Dose 25 mcg/hour 50 mcg/hour 75 mcg/hour 100 mcg/hour
Alternatively, for adult and pediatric patients taking opioids or doses not listed in Table 1, use the following methodology:
1. Calculate the previous 24-hour analgesic requirement. 2. Convert this amount to the equianalgesic oral morphine dose using a reliable reference.
Refer to Table 2 for the range of 24-hour oral morphine doses that are recommended for conversion to each DURAGESIC dose. Use this table to find the calculated 24-hour morphine dose and the corresponding DURAGESIC dose. Initiate DURAGESIC treatment using the recommended dose and titrate patients upwards (no more frequently than 3 days after the initial dose and every 6 days thereafter) until analgesic efficacy is attained.
3. Do not use Table 2 to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative and will overestimate the dose of the new agent. Table 2*: RECOMMENDED INITIAL DURAGESIC DOSE BASED UPON DAILY ORAL MORPHINE DOSE Oral 24-hourMorphine(mg/day) DURAGESICDose(mcg/hour) NOTE: In clinical trials, these ranges of daily oral morphine doses were used as a basis for conversion to DURAGESIC. * Table 2 should not be used to convert from DURAGESIC to other therapies because this conversion to DURAGESIC is conservative. Use of Table 2 for conversion to other analgesic therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is possible [see Dosage and Administration (2.5)]. 60–134 25 135–224 50 225–314 75 315–404 100 405–494 125 495–584 150 585–674 175 675–764 200 765–854 225 855–944 250 945–1034 275 1035–1124 300
For delivery rates in excess of 100 mcg/hour, multiple systems may be used.

Hepatic Impairment

Avoid the use of DURAGESIC in patients with severe hepatic impairment. In patients with mild to moderate hepatic impairment, start with one half of the usual dosage of DURAGESIC. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.14), Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

Renal Impairment

Avoid the use of DURAGESIC in patients with severe renal impairment. In patients with mild to moderate renal impairment, start with one half of the usual dosage of DURAGESIC. Closely monitor for signs of sedation and respiratory depression, including at each dosage increase [see Warnings and Precautions (5.15), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

2.2 Titration and Maintenance of Therapy

Individually titrate DURAGESIC to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving DURAGESIC to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During chronic therapy, periodically reassess the continued need for opioid analgesics.

The dosing interval for DURAGESIC is 72 hours. Do not increase the DURAGESIC dose for the first time until at least 3 days after the initial application. Titrate the dose based on the daily dose of supplemental opioid analgesics required by the patient on the second or third day of the initial application.

It may take up to 6 days for fentanyl levels to reach equilibrium on a new dose [see Clinical Pharmacology (12.3)]. Therefore, evaluate patients for further titration after no less than two 3-day applications before any further increase in dosage is made.

Base dosage increments on the daily dosage of supplementary opioids, using the ratio of 45 mg/24 hours of oral morphine to a 12 mcg/hour increase in DURAGESIC dose.

If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

A small proportion of adult patients may not achieve adequate analgesia using a 72-hour dosing interval and may require systems to be applied at 48 hours rather than at 72 hours, only if adequate pain control cannot be achieved using a 72-hour regimen. An increase in the DURAGESIC dose should be evaluated before changing dosing intervals in order to maintain patients on a 72-hour regimen.

Dosing intervals less than every 72 hours were not studied in children and adolescents and are not recommended.

2.3 Administration of DURAGESIC

DURAGESIC patches are for transdermal use, only.

Proper handling of DURAGESIC is necessary in order to prevent serious adverse outcomes, including death, associated with accidental secondary exposure to DURAGESIC [see Warnings and Precautions (5.3)].

Application and Handling Instructions
Patients should apply DURAGESIC to intact, non-irritated, and non-irradiated skin on a flat surface such as the chest, back, flank, or upper arm. In young children and persons with cognitive impairment, adhesion should be monitored and the upper back is the preferred location to minimize the potential of inappropriate patch removal. Hair at the application site may be clipped (not shaved) prior to system application. If the site of DURAGESIC application must be cleansed prior to application of the patch, do so with clear water. Do not use soaps, oils, lotions, alcohol, or any other agents that might irritate the skin or alter its characteristics. Allow the skin to dry completely prior to patch application. Patients should apply DURAGESIC immediately upon removal from the sealed package. The patch must not be altered (e.g., cut) in any way prior to application. DURAGESIC should not be used if the pouch seal is broken or if the patch is cut or damaged. The transdermal system is pressed firmly in place with the palm of the hand for 30 seconds, making sure the contact is complete, especially around the edges. Each DURAGESIC patch may be worn continuously for 72 hours. The next patch is applied to a different skin site after removal of the previous transdermal system. If problems with adhesion of the DURAGESIC patch occur, the edges of the patch may be taped with first aid tape. If problems with adhesion persist, the patch may be overlayed with a transparent adhesive film dressing. If the patch falls off before 72 hours, dispose of it by folding in half and flushing down the toilet. A new patch may be applied to a different skin site. Patients (or caregivers who apply DURAGESIC) should wash their hands immediately with soap and water after applying DURAGESIC. Contact with unwashed or unclothed application sites can result in secondary exposure to DURAGESIC and should be avoided. Examples of accidental exposure include transfer of a DURAGESIC patch from an adult's body to a child while hugging, sharing the same bed as the patient, accidental sitting on a patch and possible accidental exposure of a caregiver's skin to the medication in the patch while applying or removing the patch. Instruct patients, family members, and caregivers to keep patches in a secure location out of the reach of children and of others for whom DURAGESIC was not prescribed.
Avoidance of Heat

Instruct patients to avoid exposing the DURAGESIC application site and surrounding area to direct external heat sources, such as heating pads or electric blankets, heat or tanning lamps, sunbathing, hot baths, saunas, hot tubs, and heated water beds, while wearing the system [see Warnings and Precautions (5. 11)].

2.4 Disposal Instructions

Failure to properly dispose of DURAGESIC has resulted in accidental exposures and deaths [see Warnings and Precautions (5.3)].

Patients should dispose of used patches immediately upon removal by folding the adhesive side of the patch to itself, then flushing down the toilet.

Unused patches should be removed from their pouches, the protective liners removed, the patches folded so that the adhesive side of the patch adheres to itself, and immediately flushed down the toilet.

Patients should dispose of any patches remaining from a prescription as soon as they are no longer needed.

2.5 Discontinuation of DURAGESIC

Significant amounts of fentanyl continue to be absorbed from the skin for 24 hours or more after the patch is removed [see Clinical Pharmacology (12.3)].

To convert patients to another opioid, remove DURAGESIC and titrate the dose of the new analgesic based upon the patient's report of pain until adequate analgesia has been attained. Upon system removal, 17 hours or more are required for a 50% decrease in serum fentanyl concentrations. Withdrawal symptoms are possible in some patients after conversion or dose adjustment [see Warnings and Precautions (5.17)].

Do not use Tables 1 and 2 to convert from DURAGESIC to other therapies to avoid overestimating the dose of the new agent resulting in overdose of the new analgesic and possibly death.

When discontinuing DURAGESIC and not converting to another opioid, use a gradual downward titration, such as halving the dose every 6 days, in order to reduce the possibility of withdrawal symptoms [see Warnings and Precautions (5.17)]. It is not known at what dose level DURAGESIC may be discontinued without producing the signs and symptoms of opioid withdrawal.
Tylenol With Codeine

Tylenol With Codeine

Dosage should be adjusted according to severity of pain and response of the patient.

The usual adult dosage is:
Single Doses (Range) Maximum 24-Hour Dose Codeine Phosphate 15 mg to 60 mg 360 mg Acetaminophen 300 mg to 1,000 mg 4,000 mg
Doses may be repeated up to every 4 hours.

The prescriber must determine the number of tablets per dose, and the maximum number of tablets per 24 hours, based upon the above dosage guidance. This information should be conveyed in the prescription.

It should be kept in mind, however, that tolerance to codeine can develop with continued use and that the incidence of untoward effects is dose related. Adult doses of codeine higher than 60 mg fail to give commensurate relief of pain but merely prolong analgesia and are associated with an appreciably increased incidence of undesirable side effects. Equivalently high doses in children would have similar effects.
Xarelto

Xarelto

Indication Dosage Reduction in Risk of Stroke in Nonvalvular Atrial Fibrillation (2.3) CrCl >50 mL/min: 20 mg once daily with the evening meal CrCl 15 to 50 mL/min: 15 mg once daily with the evening meal Treatment of DVT (2.4)Treatment of PE (2.4) 15 mg twice daily with food, for first 21 days ▼after 21 days, transition to ▼ 20 mg once daily with food, for remaining treatment Reduction in the Risk of Recurrence of DVT and of PE (2.4) 20 mg once daily with food Prophylaxis of DVT Following Hip or Knee Replacement Surgery (2.5) Hip replacement: 10 mg once daily for 35 days Knee replacement: 10 mg once daily for 12 days
2.1 Important Food Effect Information

The 15 mg and 20 mg XARELTO tablets should be taken with food, while the 10 mg tablet can be taken with or without food [see Clinical Pharmacology (12.3)].

In the nonvalvular atrial fibrillation efficacy study XARELTO was taken with the evening meal.

2.2 Switching to and from XARELTO

Switching from Warfarin to XARELTO - When switching patients from warfarin to XARELTO, discontinue warfarin and start XARELTO as soon as the International Normalized Ratio (INR) is below 3.0 to avoid periods of inadequate anticoagulation.

Switching from XARELTO to Warfarin - No clinical trial data are available to guide converting patients from XARELTO to warfarin. XARELTO affects INR, so INR measurements made during coadministration with warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue XARELTO and begin both a parenteral anticoagulant and warfarin at the time the next dose of XARELTO would have been taken.

Switching from XARELTO to Anticoagulants other than Warfarin - For patients currently taking XARELTO and transitioning to an anticoagulant with rapid onset, discontinue XARELTO and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next XARELTO dose would have been taken [see Drug Interactions (7.3)].

Switching from Anticoagulants other than Warfarin to XARELTO - For patients currently receiving an anticoagulant other than warfarin, start XARELTO 0 to 2 hours prior to the next scheduled evening administration of the drug (e.g., low molecular weight heparin or non-warfarin oral anticoagulant) and omit administration of the other anticoagulant. For unfractionated heparin being administered by continuous infusion, stop the infusion and start XARELTO at the same time.

2.3 Nonvalvular Atrial Fibrillation

For patients with creatinine clearance (CrCl) >50 mL/min, the recommended dose of XARELTO is 20 mg taken orally once daily with the evening meal. For patients with CrCl 15 to 50 mL/min, the recommended dose is 15 mg once daily with the evening meal [see Use in Specific Populations (8.7)].

2.4 Treatment of Deep Vein Thrombosis (DVT), Pulmonary Embolism (PE), and Reduction in the Risk of Recurrence of DVT and of PE

The recommended dose of XARELTO for the initial treatment of acute DVT and/or PE is 15 mg taken orally twice daily with food for the first 21 days. After this initial treatment period, the recommended dose of XARELTO is 20 mg taken orally once daily with food, at approximately the same time each day. The recommended dose of XARELTO for reduction in the risk of recurrence of DVT or PE is 20 mg taken orally once daily with food at approximately the same time each day [see Clinical Studies (14.2)].

2.5 Prophylaxis of Deep Vein Thrombosis Following Hip or Knee Replacement Surgery

The recommended dose of XARELTO is 10 mg taken orally once daily with or without food. The initial dose should be taken 6 to 10 hours after surgery provided that hemostasis has been established [see Dosage and Administration (2.6)].
For patients undergoing hip replacement surgery, treatment duration of 35 days is recommended. For patients undergoing knee replacement surgery, treatment duration of 12 days is recommended.
2.6 Discontinuation for Surgery and other Interventions

If anticoagulation must be discontinued to reduce the risk of bleeding with surgical or other procedures, XARELTO should be stopped at least 24 hours before the procedure to reduce the risk of bleeding [see Warnings and Precautions (5.2)]. In deciding whether a procedure should be delayed until 24 hours after the last dose of XARELTO, the increased risk of bleeding should be weighed against the urgency of intervention. XARELTO should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established, noting that the time to onset of therapeutic effect is short [see Warnings and Precautions (5.1)]. If oral medication cannot be taken during or after surgical intervention, consider administering a parenteral anticoagulant.

2.7 Missed Dose

If a dose of XARELTO is not taken at the scheduled time, administer the dose as soon as possible on the same day as follows:
For patients receiving 15 mg twice daily: The patient should take XARELTO immediately to ensure intake of 30 mg XARELTO per day. In this particular instance, two 15 mg tablets may be taken at once. The patient should continue with the regular 15 mg twice daily intake as recommended on the following day. For patients receiving 20 mg, 15 mg or 10 mg once daily: The patient should take the missed XARELTO dose immediately.
2.8 Administration Options

For patients who are unable to swallow whole tablets, 10 mg, 15 mg or 20 mg XARELTO tablets may be crushed and mixed with applesauce immediately prior to use and administered orally. After the administration of a crushed XARELTO 15 mg or 20 mg tablet, the dose should be immediately followed by food [see Dosage and Administration (2.1, 2.3, 2.4) and Clinical Pharmacology (12.3)].

Administration via nasogastric (NG) tube or gastric feeding tube: After confirming gastric placement of the tube, 10 mg, 15 mg or 20 mg XARELTO tablets may be crushed and suspended in 50 mL of water and administered via an NG tube or gastric feeding tube. Since rivaroxaban absorption is dependent on the site of drug release, avoid administration of XARELTO distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure. After the administration of a crushed XARELTO 15 mg or 20 mg tablet, the dose should then be immediately followed by enteral feeding [see Clinical Pharmacology (12.3)].

Crushed 10 mg, 15 mg or 20 mg XARELTO tablets are stable in water and in applesauce for up to 4 hours. An in vitro compatibility study indicated that there is no adsorption of rivaroxaban from a water suspension of a crushed XARELTO tablet to PVC or silicone nasogastric (NG) tubing.

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