Bayer Healthcare Pharmaceuticals Inc.

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Bayer Healthcare Pharmaceuticals Inc. Drugs

Fluoxetine

Fluoxetine

• Apply and gently massage a thin layer of FINACEA Gel into the affected areas on the face twice daily (morning and evening). • Use only very mild soaps or soapless cleansing lotion before application of FINACEA Gel. • Cosmetics may be applied after the application of FINACEA Gel has dried. • Avoid the use of occlusive dressings or wrappings. • Instruct patients to avoid spicy foods, thermally hot foods and drinks, alcoholic beverages. • Patients should be reassessed if no improvement is observed upon completing 12 weeks of therapy. • Not for oral, ophthalmic or intravaginal use.
Feridex

Feridex

Dose

The recommended dosage of Feridex I.V. is 0.56 milligrams of iron (0.05 mL Feridex I.V.) per kilogram of body weight, that is diluted in 100 mL of 5% dextrose solution and given over 30 minutes. (SeeDrug Preparation Section). The diluted drug is administered through a 5 micron filter at a rate of 2 to 4 milliliters per minute.

Feridex I.V. should not be administered undiluted.

Drug Preparation
The vial should be used at room temperature. Mix by inverting the vial 10 to 20 times. Draw up the appropriate dose of Feridex I.V. into a sterile syringe. Dilute Feridex I.V. by injecting it into 100 mL of 5% dextrose solution (D5W). The bag should be inverted two or three times to assure dilution. The drug product should be administered within 8 hours following dilution.
Imaging

Post-contrast imaging may begin immediately after the dose is infused and may be performed up to 3.5 hours after the end of the infusion. T2-weighted pulse sequences provide the maximum contrast effect.
Ultravist

Ultravist

• Visually inspect ULTRAVIST for particulate matter and/or discoloration, whenever solution and container permit. Do not administer ULTRAVIST if particulate matter and/or discoloration is observed. • Determine the volume and concentration of ULTRAVIST Injection to be used taking into account factors such as age, body weight, size of the vessel and the rate of blood flow within the vessel; consider also extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed. Specific dose adjustments for age, gender, weight and renal function have not been studied for ULTRAVIST Injection. As with all iodinated contrast agents, lower doses may have less risk. The efficacy of ULTRAVIST Injection below doses recommended has not been established. • The maximum recommended total dose of iodine in adults is 86 grams; a maximum recommended total dose of iodine has not been established for pediatric patients. • Hydrate patients adequately prior to and following the administration of ULTRAVIST. [See Warnings and Precautions (5.2).]
2.1 Intra-Arterial Procedures

The volume and rate of injection of the contrast agent will vary depending on the injection site and the area being examined. Inject contrast at rates approximately equal to the flow rate in the vessel being injected.
• Cerebral Arteriography (300 mg I/mL), Coronary Arteriography and Left Ventriculography (370 mg I/mL), Peripheral Arteriography (300 mg I/mL): see Table 1. • Aortography and Visceral Angiography (370 mg I/mL): Use a volume and rate of contrast injection proportional to the blood flow and related to the vascular and pathological characteristics of the specific vessels being studied. Do not exceed 225 mL as total dose for the procedure.
Table 1: Suggested Single Injection Doses for Adult Intra-Arterial Procedures

Cerebral Arteriography

(300 mg I/mL)

Peripheral Arteriography

(300 mg I/mL)

Coronary Arteriography and Left Ventriculography

(370 mg I/mL)
Intra-Arterial Injection Sites
Carotid Arteries

Vertebral Arteries

Aortic Arch Injection (4 vessel study)

3–12 mL

4–12 mL

20–50 mL

-

-

-

-

-

-

Right Coronary Artery

Left Coronary Artery

Left Ventricle

-

-

-

-

-

-

3–14 mL

3–14 mL

30–60 mL

Subclavian or Femoral Artery

Aortic Bifurcation (distal runoff)

-

-

5–40 mL

25–50 mL

-

-

Maximum Total Dose

150 mL

250 mL

225 mL

2.2 Intravenous Procedures
• Peripheral Venography (240 mg I/mL): Inject the minimum volume necessary to visualize satisfactorily the structures under examination. Do not exceed 250 mL as total dose for the procedure. • Contrast Computed Tomography (CT) (300 mg I/mL and 370 mg I/mL) and Excretory Urography (300 mg I/mL): see Table 2.
Table 2: Suggested ULTRAVIST Injection Dosing for Adult Intravenous Contrast Administration

Excretory Urography (300 mg I/mL)

Contrast Computed Tomography (300 mg I/mL)

Contrast Computed Tomography (370 mg I/mL)

Excretory Urography

Approximately 300 mg I/kg body wt. (Adults with normal renal function)

-

-

Head

-

50–200 mL

41–162 mL

Body

Bolus Injection

50–200 mL

41–162 mL

Rapid Infusion

100–200 mL

81–162 mL

Maximum Total Dose

100 mL

200 mL (60 g iodine)

162 mL (60 g iodine)

2.3 Pediatric Dosing

The recommended dose in children over 2 years of age for the following evaluations is:
• Intra-arterial:
Cardiac chambers and related arteries (370 mg I/mL):

Inject 1 to 2 milliliters per kilogram (mL/kg). Do not exceed 4 mL/kg as total dose.
• Intravenous:
Contrast Computerized Tomography or Excretory Urography (300 mg I/mL):

Inject 1 to 2 mL/kg. Do not exceed 3 mL/kg as total dose.

The safety and efficacy relationships of other doses, concentrations or procedures have not been established [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].
Precose

Precose

There is no fixed dosage regimen for the management of diabetes mellitus with PRECOSE or any other pharmacologic agent. Dosage of PRECOSE must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dose of 100 mg t.i.d. PRECOSE should be taken three times daily at the start (with the first bite) of each main meal. PRECOSE should be started at a low dose, with gradual dose escalation as described below, both to reduce gastrointestinal side effects and to permit identification of the minimum dose required for adequate glycemic control of the patient. If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.

During treatment initiation and dose titration (see below), one-hour postprandial plasma glucose may be used to determine the therapeutic response to PRECOSE and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately three months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of PRECOSE, either as monotherapy or in combination with sulfonylureas, insulin or metformin.

Initial Dosage

The recommended starting dosage of PRECOSE is 25 mg given orally three times daily at the start (with the first bite) of each main meal. However, some patients may benefit from more gradual dose titration to minimize gastrointestinal side effects. This may be achieved by initiating treatment at 25 mg once per day and subsequently increasing the frequency of administration to achieve 25 mg t.i.d.

Maintenance Dosage

Once a 25 mg t.i.d. dosage regimen is reached, dosage of PRECOSE should be adjusted at 4–8 week intervals based on one-hour postprandial glucose or glycosylated hemoglobin levels, and on tolerance. The dosage can be increased from 25 mg t.i.d. to 50 mg t.i.d. Some patients may benefit from further increasing the dosage to 100 mg t.i.d. The maintenance dose ranges from 50 mg t.i.d. to 100 mg t.i.d. However, since patients with low body weight may be at increased risk for elevated serum transaminases, only patients with body weight > 60 kg should be considered for dose titration above 50 mg t.i.d. (see PRECAUTIONS). If no further reduction in postprandial glucose or glycosylated hemoglobin levels is observed with titration to 100 mg t.i.d., consideration should be given to lowering the dose. Once an effective and tolerated dosage is established, it should be maintained.

Maximum Dosage:

The maximum recommended dose for patients ≤ 60 kg is 50 mg t.i.d. The maximum recommended dose for patients > 60 kg is 100 mg t.i.d.

Patients Receiving Sulfonylureas or Insulin:

Sulfonylurea agents or insulin may cause hypoglycemia. PRECOSE given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the potential for hypoglycemia. If hypoglycemia occurs, appropriate adjustments in the dosage of these agents should be made.
Atracurium Besylate

Atracurium Besylate

2.1 How to Take Yasmin

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive effectiveness, Yasmin must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start Yasmin

Instruct the patient to begin taking Yasmin either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of Yasmin use, instruct the patient to take one yellow Yasmin daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one yellow Yasmin daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. Yasmin should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Yasmin can be taken without regard to meals. If Yasmin is first taken later than the first day of the menstrual cycle, Yasmin should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Yasmin use, instruct the patient to take one yellow Yasmin daily, beginning on the first Sunday after the onset of her menstrual period. She should take one yellow Yasmin daily for 21 consecutive days, followed by one white tablet daily on Days 22 through 28. Yasmin should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Yasmin can be taken without regard to meals. Yasmin should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of Yasmin on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her yellow tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Yasmin is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a yellow Yasmin daily for seven consecutive days.

When switching from a different birth control pill

When switching from another birth control pill, Yasmin should be started on the same day that a new pack of the previous oral contraceptive would have been started.

When switching from a method other than a birth control pill

When switching from a transdermal patch or vaginal ring, Yasmin should be started when the next application would have been due. When switching from an injection, Yasmin should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Yasmin should be started on the day of removal.

Withdrawal bleeding usually occurs within 3 days following the last yellow tablet. If spotting or breakthrough bleeding occurs while taking Yasmin, instruct the patient to continue taking Yasmin by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if Yasmin is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Yasmin if pregnancy is confirmed.

The risk of pregnancy increases with each active yellow tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the FDA-Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking a new cycle of yellow tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start Yasmin no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts Yasmin postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Yasmin for 7 consecutive days.

2.3 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 occurs within 3-4 hours after tablet-taking, this can be regarded as a missed tablet.
Natazia

Natazia

2.1 How to Take Natazia

To achieve maximum contraceptive effectiveness, Natazia must be taken exactly as directed. Take one tablet by mouth at the same time every day. Tablets must be taken in the order directed on the blister pack. Tablets should not be skipped or intake delayed by more than 12 hours. For patient instructions for missed pills, see FDA-Approved Patient Labeling.

2.2 How to Start Natazia

Instruct the patient to begin taking Natazia on Day 1 of her menstrual cycle (that is, the first day of her menstrual bleeding). See FDA-Approved Patient Labeling. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 9 days.

For postpartum women who do not breastfeed or after a second trimester abortion, start Natazia no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Natazia postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Natazia for 9 consecutive days. The possibility of ovulation and conception prior to initiation of medication should also be considered.

If the patient is switching from a combination hormonal method such as:
• Another pill • Vaginal ring • Patch • Instruct her to take the first dark yellow pill on the first day of her withdrawal bleed. She should not continue taking the pills from her previous birth control pack. If she does not have a withdrawal bleed, rule out pregnancy before starting Natazia. • If she previously used a vaginal ring or transdermal patch, she should start using Natazia on the day the ring or patch is removed. • Instruct the patient to use a non-hormonal back-up method such as a condom or spermicide for the first 9 days.
If the patient is switching from a progestin-only method such as a:
• Progestin-only pill • Implant • Intrauterine system • Injection • Instruct her to take the first dark yellow pill on the day she would have taken her next progestin-only pill or on the day of removal of her implant or intrauterine system or on the day when she would have had her next injection. • Instruct the patient to use a non-hormonal back-up method such as a condom or spermicide for the first 9 days.
2.3 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 3-4 hours after taking a colored tablet, this can be regarded as a missed tablet.
Beyaz

Beyaz

2.1 How to Take Beyaz

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive and PMDD effectiveness, Beyaz must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start Beyaz

Instruct the patient to begin taking Beyaz either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of Beyaz use, instruct the patient to take one pink Beyaz daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one pink Beyaz daily for 24 consecutive days, followed by one light orange tablet daily on Days 25 through 28. Beyaz should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Beyaz can be taken without regard to meals. If Beyaz is first taken later than the first day of the menstrual cycle, Beyaz should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Beyaz use, instruct the patient to take one pink Beyaz daily, beginning on the first Sunday after the onset of her menstrual period. She should take one pink Beyaz daily for 24 consecutive days, followed by one light orange tablet daily on Days 25 through 28. Beyaz should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Beyaz can be taken without regard to meals. Beyaz should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of Beyaz on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her pink tablets on the next day after ingestion of the last light orange folate tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Beyaz is started later than the day following administration of the last light orange tablet, the patient should use another method of contraception until she has taken a pink Beyaz daily for seven consecutive days.

When switching from a different birth control pill

When switching from another birth control pill, Beyaz should be started on the same day that a new pack of the previous oral contraceptive would have been started.

When switching from a method other than a birth control pill

When switching from a transdermal patch or vaginal ring, Beyaz should be started when the next application would have been due. When switching from an injection, Beyaz should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Beyaz should be started on the day of removal.

Withdrawal bleeding usually occurs within 3 days following the last pink tablet. If spotting or breakthrough bleeding occurs while taking Beyaz, instruct the patient to continue taking Beyaz by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if Beyaz is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Beyaz if pregnancy is confirmed.

The risk of pregnancy increases with each active pink tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the FDA Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more light orange tablets, she should still be protected against pregnancy provided she begins taking a new cycle of pink tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start Beyaz no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Beyaz postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Beyaz for 7 consecutive days.

2.3 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 occurs within 3-4 hours after tablet-taking, this can be regarded as a missed tablet.

2.4 Folate Supplementation

The U.S. Preventive Services Task Force recommends that women of childbearing age consume supplemental folic acid in a dose of at least 0.4 mg (400 mcg) daily.1 Consider other folate supplementation that a woman may be taking before prescribing Beyaz. Ensure that folate supplementation is maintained if a woman discontinues Beyaz due to pregnancy.
Safyral

Safyral

2.1 How to Take Safyral

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive effectiveness, Safyral must be taken as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start Safyral

Instruct the patient to begin taking Safyral either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of Safyral use, instruct the patient to take one orange Safyral daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one orange Safyral daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Safyral should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Safyral can be taken without regard to meals. If Safyral is first taken later than the first day of the menstrual cycle, Safyral should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Safyral use, instruct the patient to take one orange Safyral daily, beginning on the first Sunday after the onset of her menstrual period. She should take one orange Safyral daily for 21 consecutive days, followed by one light orange tablet, containing levomefolate alone, daily on Days 22 through 28. Safyral should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Safyral can be taken without regard to meals. Safyral should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of Safyral on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her orange tablets on the next day after ingestion of the last light orange folate tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Safyral is started later than the day following administration of the last light orange tablet, the patient should use another method of contraception until she has taken an orange Safyral daily for seven consecutive days.

When switching from a different birth control pill

When switching from another birth control pill, Safyral should be started on the same day that a new pack of the previous oral contraceptive would have been started.

When switching from a method other than a birth control pill

When switching from a transdermal patch or vaginal ring, Safyral should be started when the next application would have been due. When switching from an injection, Safyral should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Safyral should be started on the day of removal.

Withdrawal bleeding usually occurs within 3 days following the last orange tablet. If spotting or breakthrough bleeding occurs while taking Safyral, instruct the patient to continue taking Safyral by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if Safyral is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Safyral if pregnancy is confirmed.

The risk of pregnancy increases with each active orange tablet missed. For additional patient instructions regarding missed pills, see the “WHAT TO DO IF YOU MISS PILLS” section in the FDA-Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more light orange tablets, she should still be protected against pregnancy provided she begins taking a new cycle of orange tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start Safyral no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts Safyral postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Safyral for 7 consecutive days.

2.3 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 occurs within 3-4 hours after tablet-taking, this can be regarded as a missed tablet.

2.4 Folate Supplementation

The U.S. Preventive Services Task Force recommends that women of childbearing age consume supplemental folic acid in a dose of at least 0.4 mg (400 mcg) daily.1 Consider other folate supplementation that a woman may be taking before prescribing Safyral. Ensure that folate supplementation is maintained if a woman discontinues Safyral due to pregnancy.
Adalat Cc

Adalat Cc

Dosage should be adjusted according to each patient’s needs. It is recommended that Adalat CC be administered orally once daily on an empty stomach. Adalat CC is an extended release dosage form and tablets should be swallowed whole, not bitten or divided. In general, titration should proceed over a 7-14 day period starting with 30 mg once daily. Upward titration should be based on therapeutic efficacy and safety. The usual maintenance dose is 30 mg to 60 mg once daily. Titration to doses above 90 mg daily is not recommended.

If discontinuation of Adalat CC is necessary, sound clinical practice suggests that the dosage should be decreased gradually with close physician supervision.

Co-administration of nifedipine with grapefruit juice is to be avoided (See CLINICAL PHARMACOLOGY and PRECAUTIONS).

Care should be taken when dispensing Adalat CC to assure that the extended release dosage form has been prescribed.
Betapace

Betapace

As with other antiarrhythmic agents, Betapace should be initiated and doses increased in a hospital with facilities for cardiac rhythm monitoring and assessment (see INDICATIONS AND USAGE). Betapace should be administered only after appropriate clinical assessment (see INDICATIONS AND USAGE), and the dosage of Betapace must be individualized for each patient on the basis of therapeutic response and tolerance. Proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment.

Adults

Dosage of Betapace should be adjusted gradually, allowing 3 days between dosing increments in order to attain steady-state plasma concentrations, and to allow monitoring of QT intervals. Graded dose adjustment will help prevent the usage of doses which are higher than necessary to control the arrhythmia. The recommended initial dose is 80 mg twice daily. This dose may be increased, if necessary, after appropriate evaluation to 240 or 320 mg/day (120-160 mg twice daily). In most patients, a therapeutic response is obtained at a total daily dose of 160 to 320 mg/day, given in two or three divided doses. Some patients with life-threatening refractory ventricular arrhythmias may require doses as high as 480-640 mg/day; however, these doses should only be prescribed when the potential benefit outweighs the increased risk of adverse events, in particular proarrhythmia. Because of the long terminal elimination half-life of Betapace, dosing on more than a BID regimen is usually not necessary.

Children

As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.

For children aged about 2 years and greater

For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children (see CLINICAL PHARMACOLOGY) is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended.

For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steadystate plasma concentrations of sotalol in patients with age-adjusted normal renal function.

For children aged about 2 years or younger

For children aged about 2 years or younger. the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in months.

For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.

In all children, individualization of dosage is required. As in adults Betapace (sotalol hydrochloride) should be used with particular caution in children if the QTc is greater than 500 msec on therapy, and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 msec.

Dosage in Renal Impairment

Adults

Because sotalol is excreted predominantly in urine and its terminal elimination half-life is prolonged in conditions of renal impairment, the dosing interval (time between divided doses) of sotalol should be modified (when creatinine clearance is lower than 60 mL/min) according to the following table.
* The initial dose of 80 mg and subsequent doses should be administered at these intervals. See following paragraph for dosage escalations.
Creatinine Clearance mL/min

Dosing* Interval (hours)

> 60

12

30-59

24

10-29

36-48

< 10

Dose should be individualized

Since the terminal elimination half-life of Betapace (sotalol hydrochloride) is increased in patients with renal impairment, a longer duration of dosing is required to reach steady-state. Dose escalations in renal impairment should be done after administration of at least 5-6 doses at appropriate intervals (see table above). Extreme caution should be exercised in the use of sotalol in patients with renal failure undergoing hemodialysis. The half-life of sotalol is prolonged (up to 69 hours) in anuric patients. Sotalol, however, can be partly removed by dialysis with subsequent partial rebound in concentrations when dialysis is completed. Both safety (heart rate, QT interval) and efficacy (arrhythmia control) must be closely monitored.

Children

The use of Betapace (sotalol hydrochloride) in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.

Transfer to Betapace

Before starting Betapace, previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2-3 plasma half-lives if the patient's clinical condition permits (see Drug Interactions). Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, Betapace should not be initiated until the QT interval is normalized (see WARNINGS).

Preparation of Extemporaneous Oral Solution

Betapace Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
1. Measure 120 mL of Simple Syrup. 2. Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle. 3. Add five (5) Betapace 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup. 4. Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved. 5. Allow the tablets to hydrate for at least two hours. 6. After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.

This compounding procedure results in a solution containing 5 mg/mL of sotalol HCI. The fine solid particles are the water-insoluble inactive ingredients of the tablets.

This extemporaneously prepared oral solution of sotalol HCI (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.

Stability studies indicate that the suspension is stable for three months when stored at controlled room temperature (15°-30°C/59°-86°F) and ambient humidity.

Transfer to Betapace AF from Betapace

Patients with a history of symptomatic AFIB/AFL who are currently receiving Betapace for the maintenance of normal sinus rhythm should be transferred to Betapace AF because of the significant differences in labeling (i.e., patient package insert for Betapace AF, dosing administration, and safety information).
Betapace Af

Betapace Af

Dosing and Administration in Adults
• Therapy with Betapace AF must be initiated (and, if necessary, titrated) in a setting that provides continuous electrocardiographic (ECG) monitoring and in the presence of personnel trained in the management of serious ventricular arrhythmias. Patients should continue to be monitored in this way for a minimum of 3 days on the maintenance dose. In addition, patients should not be discharged within 12 hours of electrical or pharmacological conversion to normal sinus rhythm. • The QT interval is used to determine patient eligibility for Betapace AF treatment and for monitoring safety during treatment. The baseline QT interval must be ≤450 msec in order for a patient to be started on Betapace AF therapy. During initiation and titration, the QT interval should be monitored 2-4 hours after each dose. If the QT interval prolongs to 500 msec or greater, the dose must be reduced or the drug discontinued. • The dose of Betapace AF must be individualized according to calculated creatinine clearance. In patients with a creatinine clearance >60 mL/min Betapace AF is administered twice daily (BID) while in those with a creatinine clearance between 40 and 60 mL/min, the dose is administered once daily (QD). In patients with a creatinine clearance less than 40 mL/min Betapace AF is contraindicated. The recommended initial dose of Betapace AF is 80 mg and is initiated as shown in the dosing algorithm described below. The 80 mg dose can be titrated upward to 120 mg during initial hospitalization or after discharge on 80 mg in the event of recurrence, by rehospitalization and repeating the same steps used during the initiation of therapy (see Upward Titration of Dose). • Patients with atrial fibrillation should be anticoagulated according to usual medical practice. Hypokalemia should be corrected before initiation of Betapace AF therapy (see WARNINGS, Ventricular Arrhythmia). • Patients to be discharged on Betapace AF therapy from an in-patient setting should have an adequate supply of Betapace AF, to allow uninterrupted therapy until the patient can fill a Betapace AF prescription.
Initiation of Betapace AF Therapy

Step 1. Electrocardiographic assessment: Prior to administration of the first dose, the QT interval must be determined using an average of 5 beats. If the baseline QT is greater than 450 msec (JT ≥330 msec if QRS over 100 msec), Betapace AF is contraindicated.

Step 2. Calculation of creatinine clearance: Prior to the administration of the first dose, the patient's creatinine clearance should be calculated using the following formula:

creatinine clearance (male) =

(140-age) x body weight in kg

72 x serum creatinine (mg/dL)

creatinine clearance (female) =

(140-age) x body weight in kg x 0.85

72 x serum creatinine (mg/dL)

When serum creatinine is given in μmol/L, divide the value by 88.4 (1 mg/dL = 88.4 μmol/L).

Step 3. Starting Dose: The starting dose of Betapace AF is 80 mg twice daily (BID) if the creatinine clearance is >60 mL/min, and 80 mg once daily (QD) if the creatinine clearance is 40-60 mL/min. If the creatinine clearance is <40 mL/min Betapace AF is contraindicated.

Step 4. Administer the appropriate daily dose of Betapace AF and begin continuous ECG monitoring with QT interval measurements 2-4 hours after each dose.

Step 5. If the 80 mg dose level is tolerated and the QT interval remains <500 msec after at least 3 days (after 5 or 6 doses if patient receiving QD dosing), the patient can be discharged. Alternatively, during hospitalization, the dose can be increased to 120 mg bid and the patient followed for 3 days on this dose (followed for 5 or 6 doses if patient receiving QD doses).

The steps described above are summarized in the following diagram:

Place Patient on Telemetry

Check Baseline QT

If QT >450 msec Betapace AF is CONTRAINDICATED

If QT ≤450 msec, proceed

Calculate Creatine Clearance (Clcr)

If Clcr is <40 mL/min Betapace AF is CONTRAINDICATED

If Clcr is 40-60 mL/min start Betapace AF 80 mg QD

If Clcr is >60 mL/min start Betapace AF 80 mg BID

Monitor QT 2-4 hours after each dose.

If QT ≥500 msec discontinue Betapace AF

If QT <500 msec after 3 days (after 5th or 6th dose if

patient receiving QD dosing)

discharge patient on current treatment. Alternatively, during

hospitalization, the dose can be increased to 120 mg BID

and the patient followed for 3 days on this dose (followed for 5 or

6 doses if patient receiving QD doses).

Upward Titration of Dose

If the 80 mg dose level (given BID or QD depending upon the creatinine clearance) does not reduce the frequency of relapses of AFIB/AFL and is tolerated without excessive QT interval prolongation (i.e., ≥520 msec), the dose level may be increased to 120 mg (BID or QD depending upon the creatinine clearance). As proarrhythmic events can occur not only at initiation of therapy, but also with each upward dosage adjustment, Steps 2 through 5 used during initiation of Betapace AF therapy should be followed when increasing the dose level. In the U.S. multicenter dose-response study, the 120 mg dose (BID or QD) was found to be the most effective in prolonging the time to ECG documented symptomatic recurrence of AFIB/AFL. If the 120 mg dose does not reduce the frequency of early relapse of AFIB/AFL and is tolerated without excessive QT interval prolongation (≥520 msec), an increase to 160 mg (BID or QD depending upon the creatinine clearance), can be considered. Steps 2 through 5 used during the initiation of therapy should be used again to introduce such an increase.

Maintenance of Betapace AF Therapy

Renal function and QT should be re-evaluated regularly if medically warranted. If QT is 520 msec or greater (JT 430 msec or greater if QRS is > 100 msec), the dose of Betapace AF therapy should be reduced and patients should be carefully monitored until QT returns to less than 520 msec. If the QT interval is ≥520 msec while on the lowest maintenance dose level (80 mg) the drug should be discontinued. If renal function deteriorates, reduce the daily dose in half by administering the drug once daily as described in Initiation of Betapace AF Therapy, Step 3.

Special Considerations

The maximum recommended dose in patients with a calculated creatinine clearance greater than 60 mL/min is 160 mg BID, doses greater than 160 mg BID have been associated with an increased incidence of Torsade de Pointes and are not recommended.

A patient who misses a dose should NOT double the next dose. The next dose should be taken at the usual time.

Dosing and Administration in Children

As in adults the following precautionary measures should be considered when initiating sotalol treatment in children: initiation of treatment in the hospital after appropriate clinical assessment; individualized regimen as appropriate; gradual increase of doses if required; careful assessment of therapeutic response and tolerability; and frequent monitoring of the QTc interval and heart rate.

For children aged about 2 years and greater

For children aged about 2 years and greater, with normal renal function, doses normalized for body surface area are appropriate for both initial and incremental dosing. Since the Class III potency in children (see CLINICAL PHARMACOLOGY) is not very different from that in adults, reaching plasma concentrations that occur within the adult dose range is an appropriate guide. From pediatric pharmacokinetic data the following is recommended.

For initiation of treatment, 30 mg/m2 three times a day (90 mg/m2 total daily dose) is approximately equivalent to the initial 160 mg total daily dose for adults. Subsequent titration to a maximum of 60 mg/m2 (approximately equivalent to the 360 mg total daily dose for adults) can then occur. Titration should be guided by clinical response, heart rate and QTc, with increased dosing being preferably carried out in-hospital. At least 36 hours should be allowed between dose increments to attain steady-state plasma concentrations of sotalol in patients with age-adjusted normal renal function.

For children aged about 2 years or younger

For children aged about 2 years or younger, the above pediatric dosage should be reduced by a factor that depends heavily upon age, as shown in the following graph, age plotted on a logarithmic scale in months.

For a child aged 20 months, the dosing suggested for children with normal renal function aged 2 years or greater should be multiplied by about 0.97; the initial starting dose would be (30 X 0.97)=29.1 mg/m2, administered three times daily. For a child aged 1 month, the starting dose should be multiplied by 0.68; the initial starting dose would be (30 X 0.68)=20 mg/m2, administered three times daily. For a child aged about 1 week, the initial starting dose should be multiplied by 0.3; the starting dose would be (30 X 0.3)=9 mg/m2. Similar calculations should be made for increased doses as titration proceeds. Since the half-life of sotalol decreases with decreasing age (below about 2 years), time to steady-state will also increase. Thus, in neonates the time to steady-state may be as long as a week or longer.

In all children, individualization of dosage is required. As in adults Betapace AF (sotalol hydrochloride) should be used with particular caution in children if the QTc is greater than 500 msec on therapy and serious consideration should be given to reducing the dose or discontinuing therapy when QTc exceeds 550 msec.

The use of Betapace AF (sotalol hydrochloride) in children with renal impairment has not been investigated. Sotalol elimination is predominantly via the kidney in the unchanged form. Use of sotalol in any age group with decreased renal function should be at lower doses or at increased intervals between doses. Monitoring of heart rate and QTc is more important and it will take much longer to reach steady-state with any dose and/or frequency of administration.

Transfer to Betapace AF from Betapace

Patients with a history of symptomatic AFIB/AFL who are currently receiving Betapace for the maintenance of normal sinus should be transferred to Betapace AF because of the significant differences in labeling (i.e., patient package insert, dosing administration, and safety information).

Transfer to Betapace AF from Other Antiarrhythmic Agents

Before starting Betapace AF, previous antiarrhythmic therapy should generally be withdrawn under careful monitoring for a minimum of 2-3 plasma half-lives if the patient's clinical condition permits (see Drug Interactions). Treatment has been initiated in some patients receiving I.V. lidocaine without ill effect. After discontinuation of amiodarone, Betapace AF should not be initiated until the QT interval is normalized (see WARNINGS).

Preparation of Extemporaneous Oral Solution

Betapace AF Syrup 5 mg/mL can be compounded using Simple Syrup containing 0.1% sodium benzoate (Syrup, NF) available from Humco Laboratories as follows:
1. Measure 120 mL of Simple Syrup 2. Transfer the syrup to a 6-ounce amber plastic (polyethylene terephthalate [PET]) prescription bottle. NOTE: An oversized bottle is used to allow for a headspace, so that there will be more effective mixing during shaking of the bottle. 3. Add five (5) Betapace AF 120 mg tablets to the bottle. These tablets are added intact; it is not necessary to crush the tablets. NOTE: The addition of the tablets can also be done first. The tablets can also be crushed if preferred. If the tablets are crushed, care should be taken to transfer the entire quantity of tablet powder into the bottle containing the syrup. 4. Shake the bottle to wet the entire surface of the tablets. If the tablets have been crushed, shake the bottle until the endpoint is achieved. 5. Allow the tablets to hydrate for approximately two hours. 6. After at least two hours have elapsed, shake the bottle intermittently over the course of at least another two hours until the tablets are completely disintegrated. NOTE: The tablets can be allowed to hydrate overnight to simplify the disintegration process.
The endpoint is achieved when a dispersion of fine particles in the syrup is obtained.

This compounding procedure results in a solution containing 5 mg/mL of sotalol HCl. The fine solid particles are the water-insoluble inactive ingredients of the tablets.

This extemporaneously prepared oral solution of sotalol HCl (with suspended inactive particles) must be shaken well prior to administration. This is to ensure that the amount of inactive solid particles per dose remains constant throughout the duration of use.

Stability studies indicate that the suspension is stable when stored at controlled room temperature (15°-30°C/59°-86°F) and ambient humidity for three (3) months.
Carisoprodol

Carisoprodol

Skyla contains 13.5 mg of levonorgestrel (LNG) released in vivo at a rate of approximately 14 mcg/day after 24 days. This rate decreases progressively to 5 mcg/day after 3 years. The average in vivo release rate of LNG is approximately 6 mcg/day over a period of 3 years.

Skyla must be removed by the end of the third year and can be replaced at the time of removal with a new Skyla if continued contraceptive protection is desired.

Skyla is supplied within an inserter in a sterile package (see Figure 1) that must not be opened until required for insertion [see Description (11)]. Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions (5.3)].

2.1. Insertion Instructions
• A complete medical and social history should be obtained to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LNG IUS) for contraception . If indicated, perform a physical examination, and appropriate tests for any forms of genital or other sexually transmitted infections. [See Contraindications (4) and Warnings and Precautions (5.10).] • Follow the insertion instructions exactly as described in order to ensure proper placement and avoid premature release of Skyla from the inserter. Once released, Skyla cannot be re-loaded. • Skyla should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Skyla. • Insertion may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, bradycardia) or seizure in an epileptic patient, especially in patients with a predisposition to these conditions. Consider administering analgesics prior to insertion.
Timing of Insertion
• Insert Skyla into the uterine cavity during the first seven days of the menstrual cycle or immediately after a first trimester abortion. Back up contraception is not needed when Skyla is inserted as directed. • Postpone postpartum insertion and insertions following second trimester abortions a minimum of six weeks or until the uterus is fully involuted. If involution is delayed, wait until involution is complete before insertion [see Warnings and Precautions (5.6, 5.7)].
Tools for Insertion

Preparation
• Gloves • Speculum • Sterile uterine sound • Sterile tenaculum • Antiseptic solution, applicator
Procedure
• Sterile gloves • Skyla with inserter in sealed package • Instruments and anesthesia for paracervical block, if anticipated • Consider having an unopened backup Skyla available • Sterile, sharp curved scissors
Preparation for insertion
• Exclude pregnancy and confirm that there are no other contraindications to the use of Skyla. • Ensure that the patient understands the contents of the Patient Information Booklet and obtain the signed patient informed consent located on the last page of the Patient Information Booklet. • With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape and position of the uterus. • Gently insert a speculum to visualize the cervix. • Thoroughly cleanse the cervix and vagina with a suitable antiseptic solution. • Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with a tenaculum forceps and gently apply traction to stabilize and align the cervical canal with the uterine cavity. Perform a paracervical block if needed. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. The tenaculum should remain in position and gentle traction on the cervix should be maintained throughout the insertion procedure. • Gently insert a uterine sound to check the patency of the cervix, measure the depth of the uterine cavity in centimeters, confirm cavity direction, and detect the presence of any uterine anomaly. If you encounter difficulty or cervical stenosis, use dilatation, and not force, to overcome resistance. If cervical dilatation is required, consider using a paracervical block.
Insertion Procedure

Proceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Skyla. Ensure use of aseptic technique throughout the entire procedure.

Step 1–Opening of the package
• Open the package (Figure 1). The contents of the package are sterile.
Figure 1: Opening the Skyla Package
• Using sterile gloves, lift the handle of the sterile inserter and remove from the sterile package.
Step 2–Load Skyla into the insertion tube
• Push the slider forward as far as possible in the direction of the arrow thereby moving the insertion tube over the Skyla T-body to load Skyla into the insertion tube (Figure 2). The tips of the arms will meet to form a rounded end that extends slightly beyond the insertion tube.
Figure 2: Move slider all the way to the forward position to load Skyla
• Maintain forward pressure with your thumb or forefinger on the slider . DO NOT move the slider downward at this time as this may prematurely release the threads of Skyla. Once the slider is moved below the mark, Skyla cannot be re-loaded .
Step 3–Setting the Flange
• Holding the slider in this forward position, set the upper edge of the flange to correspond to the uterine depth (in centimeters) measured during sounding (Figure 3).
Figure 3: Setting the flange

Figure 3: Setting the flange

Step 4–Skyla is now ready to be inserted
• Continue holding the slider in this forward position. Advance the inserter through the cervix until the flange is approximately 1.5–2 cm from the cervix and then pause (Figure 4).
Figure 4: Advancing insertion tube until flange is 1.5 to 2 cm from the cervix

Do not force the inserter. If necessary, dilate the cervical canal.

Step 5–Open the arms
• While holding the inserter steady, move the slider down to the mark to release the arms of Skyla (Figure 5). Wait 10 seconds for the horizontal arms to open completely.
Figure 5: Move the slider back to the mark to release and open the arms

Step 6–Advance to fundal position

Advance the inserter gently towards the fundus of the uterus until the flange touches the cervix. If you encounter fundal resistance do not continue to advance. Skyla is now in the fundal position (Figure 6). Fundal positioning of Skyla is important to prevent expulsion.

Figure 6: Move Skyla into the fundal position

Figure 6. Move Skyla into the fundal position

Step 7–Release Skyla and withdraw the inserter
• Holding the entire inserter firmly in place, release Skyla by moving the slider all the way down (Figure 7).
Figure 7: Move the slider all the way down to release Skyla from the insertion tube
• Continue to hold the slider all the way down while you slowly and gently withdraw the inserter from the uterus. • Using a sharp, curved scissor, cut the threads perpendicular, leaving about 3 cm visible outside of the cervix [cutting threads at an angle may leave sharp ends (Figure 8)]. Do not apply tension or pull on the threads when cutting to prevent displacing Skyla.
.

Figure 8: Cutting the threads
Skyla insertion is now complete. Prescribe analgesics, if indicated. Keep a copy of the Consent Form with lot number for your records.
Important information to consider during or after insertion
• If you suspect that Skyla is not in the correct position, check placement (for example, using transvaginal ultrasound). Remove Skyla if it is not positioned completely within the uterus. A removed Skyla must not be re-inserted. • If there is clinical concern, exceptional pain or bleeding during or after insertion, appropriate steps should be taken immediately to exclude perforation, such as physical examination and ultrasound.
2.2 Patient Follow-up
• Patients should be reexamined and evaluated 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.
2.3 Removal of Skyla

Timing of Removal
• Skyla should not remain in the uterus after 3 years. • If pregnancy is not desired, the removal should be carried out during menstruation, provided the woman is still experiencing regular menses. If removal will occur at other times during the cycle, consider starting a new contraceptive method a week prior to removal. If removal occurs at other times during the cycle and the woman has had intercourse in the week prior to removal, she is at risk of pregnancy. [See Dosage and Administration (2.4).]
Tools for Removal

Preparation
• Gloves • Speculum
Procedure
• Sterile forceps
Removal Procedure
• Remove Skyla by applying gentle traction on the threads with forceps (Figure 9).
Figure 9: Removal of Skyla
• If the threads are not visible, determine location of Skyla by ultrasound [see Warnings and Precautions (5.10)]. • If Skyla is found to be in the uterine cavity on ultrasound exam, it may be removed using a narrow forceps, such as an alligator forceps. This may require dilation of the cervical canal. After removal of Skyla, the system should be examined to ensure that it is intact. • Removal may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, or a seizure in an epileptic patient).
2.4 Continuation of Contraception after Removal
• If pregnancy is not desired and if a woman wishes to continue using Skyla, a new system can be inserted immediately after removal any time during the cycle. • If a patient with regular cycles wants to start a different birth control method, time removal and initiation of new method to ensure continuous contraception. Either remove Skyla during the first 7 days of the menstrual cycle and start the new method or start the new method at least 7 days prior to removing Skyla if removal is to occur at other times during the cycle. • If a patient with irregular cycles or amenorrhea wants to start a different birth control method, start the new method at least 7 days before removal.
Dandruff

Dandruff

Mirena contains 52 mg of levonorgestrel (LNG). Initially, LNG is released at a rate of approximately 20 mcg/day. This rate decreases progressively to half that value after 5 years.

Mirena must be removed by the end of the fifth year and can be replaced at the time of removal with a new Mirena if continued contraceptive protection is desired.

Mirena is supplied within an inserter in a sterile package (see Figure 1Figure 1) that must not be opened until required for insertion [see Description (11.2)]. Do not use if the seal of the sterile package is broken or appears compromised. Use strict aseptic techniques throughout the insertion procedure [see Warnings and Precautions (5.3)].

2.1. Insertion Instructions
• A complete medical and social history should be obtained to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system (LNG IUS) for contraception. If indicated, perform a physical examination, and appropriate tests for any forms of genital or other sexually transmitted infections. [See Contraindications ( 4) and Warnings and Precautions ( 5.10).] • Follow the insertion instructions exactly as described in order to ensure proper placement and avoid premature release of Mirena from the inserter. Once released, Mirena cannot be re-loaded. • Mirena should be inserted by a trained healthcare provider. Healthcare providers should become thoroughly familiar with the insertion instructions before attempting insertion of Mirena. • Insertion may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, bradycardia), or with seizure in an epileptic patient, especially in patients with a predisposition to these symptoms. Consider administering analgesics prior to insertion.
Timing of Insertion

Insert Mirena into the uterine cavity during the first seven days of the menstrual cycle or immediately after a first trimester abortion. Back up contraception is not needed when Mirena is inserted as directed.

Postpone postpartum insertion and insertions following second trimester abortions a minimum of six weeks or until the uterus is fully involuted. If involution is delayed, wait until involution is complete before insertion [see Warnings and Precautions (5.6, 5.7)].

Tools for Insertion

Preparation
• Gloves • Speculum • Sterile uterine sound • Sterile tenaculum • Antiseptic solution, applicator
Procedure
• Sterile gloves • Mirena with inserter in sealed package • Instruments and anesthesia for paracervical block, if anticipated • Consider having an unopened backup Mirena available • Sterile, sharp curved scissors
Preparation for insertion
• Exclude pregnancy and confirm that there are no other contraindications to the use of Mirena. • Ensure that the patient understands the contents of the Patient Information Booklet and obtain the signed patient informed consent located on the last page of the Patient Information Booklet. With the patient comfortably in lithotomy position, do a bimanual exam to establish the size, shape and position of the uterus. • Gently insert a speculum to visualize the cervix. • Thoroughly cleanse the cervix and vagina with a suitable antiseptic solution. • Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with a tenaculum forceps and gently apply traction to stabilize and align the cervical canal with the uterine cavity. Perform a paracervical block if needed. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. The tenaculum should remain in position and gentle traction on the cervix should be maintained throughout the insertion procedure. • Gently insert a uterine sound to check the patency of the cervix, measure the depth of the uterine cavity in centimeters, confirm cavity direction, and detect the presence of any uterine anomaly. If you encounter difficulty or cervical stenosis, use dilatation, and not force, to overcome resistance. If cervical dilatation is required, consider using a paracervical block. • The uterus should sound to a depth of 6 to 10 cm. Insertion of Mirena into a uterine cavity less than 6 cm by sounding may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy.
Insertion Procedure

Proceed with insertion only after completing the above steps and ascertaining that the patient is appropriate for Mirena. Ensure use of aseptic technique throughout the entire procedure.

Step 1–Opening of the package
• Open the package ( Figure 1Figure 1). The contents of the package are sterile.
Figure 1 Opening the Mirena Package
• Using sterile gloves lift the handle of the sterile inserter and remove from the sterile package.
Step 2–Load Mirena into the insertion tube
• Push the slider forward as far as possible in the direction of the arrow thereby moving the insertion tube over the Mirena T-body to load Mirena into the insertion tube ( Figure 2Figure 2). The tips of the arms will meet to form a rounded end that extends slightly beyond the insertion tube.
Figure 2 Move slider all the way to the forward position to load Mirena
• Maintain forward pressure with your thumb or forefinger on the slider. DO NOT move the slider downward at this time as this may prematurely release the threads of Mirena. Once the slider is moved below the mark, Mirena cannot be re-loaded.
Step 3–Setting the flange
• Holding the slider in this forward position, set the upper edge of the flange to correspond to the uterine depth (in centimeters) measured during sounding ( Figure 3Figure 3).
Figure 3 Setting the flange

Step 4–Mirena is now ready to be inserted
• Continue holding the slider in this forward position. Advance the inserter through the cervix until the flange is approximately 1.5–2 cm from the cervix and then pause ( Figure 4Figure 4).
Figure 4 Advancing insertion tube until flange is 1.5 to 2 cm from the cervix

Do not force the inserter. If necessary, dilate the cervical canal.

Step 5–Open the arms

While holding the inserter steady, move the slider down to the mark to release the arms of Mirena (Figure 5Figure 5). Wait 10 seconds for the horizontal arms to open completely.

Figure 5 Move the slider back to the mark to release and open the arms

Step 6–Advance to fundal position
• Advance the inserter gently towards the fundus of the uterus until the flange touches the cervix. If you encounter fundal resistance do not continue to advance. Mirena is now in the fundal position ( Figure 6Figure 6). Fundal positioning of Mirena is important to prevent expulsion.
Figure 6 Move Mirena into the fundal position

Step 7–Release Mirena and withdraw the inserter
• Holding the entire inserter firmly in place, release Mirena by moving the slider all the way down ( Figure 7Figure 7).
Figure 7 Move the slider all the way down to release Mirena from the insertion tube
• Continue to hold the slider all the way down while you slowly and gently withdraw the inserter from the uterus. • Using a sharp, curved scissor, cut the threads perpendicular, leaving about 3 cm visible outside of the cervix [cutting threads at an angle may leave sharp ends ( Figure 8Figure 8)]. Do not apply tension or pull on the threads when cutting to prevent displacing Mirena.
Figure 8 Cutting the threads

Mirena insertion is now complete. Prescribe analgesics, if indicated. Keep a copy of the Consent Form with lot number for your records.

Important information to consider during or after insertion
• If you suspect that Mirena is not in the correct position, check placement (for example, using transvaginal ultrasound). Remove Mirena if it is not positioned completely within the uterus. A removed Mirena must not be re-inserted. • If there is clinical concern, exceptional pain or bleeding during or after insertion, appropriate steps (such as physical examination and ultrasound) should be taken immediately to exclude perforation.
2.2 Patient Follow-up
• Reexamine and evaluate patients 4 to 6 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.
2.3 Removal of Mirena

Timing of Removal
• Mirena should not remain in the uterus after 5 years. • If pregnancy is not desired, the removal should be carried out during menstruation, provided the woman is still experiencing regular menses. If removal will occur at other times during the cycle, consider starting a new contraceptive method a week prior to removal. If removal occurs at other times during the cycle and the woman has had intercourse in the week prior to removal, she is at risk of pregnancy. [See Dosage and Administration ( 2.4) .]
Tools for Removal

Preparation
• Gloves • Speculum
Procedure
• Sterile forceps
Removal Procedure
• Remove Mirena by applying gentle traction on the threads with forceps. ( Figure 9Figure 9).
Figure 9 Removal of Mirena
• If the threads are not visible, determine location of Mirena by ultrasound [see Warnings and Precautions ( 5.10)]. • If Mirena is found to be in the uterine cavity on ultrasound exam, it may be removed using a narrow forceps, such as an alligator forceps. This may require dilation of the cervical canal. After removal of Mirena, examine the system to ensure that it is intact. • Removal may be associated with some pain and/or bleeding or vasovagal reactions (for example, syncope, or a seizure in an epileptic patient).
2.4 Continuation of Contraception after Removal
• If pregnancy is not desired and if a woman wishes to continue using Mirena, a new system can be inserted immediately after removal any time during the cycle. • If a patient with regular cycles wants to start a different birth control method, time removal and initiation of new method to ensure continuous contraception. Either remove Mirena during the first 7 days of the menstrual cycle and start the new method immediately thereafter or start the new method at least 7 days prior to removing Mirena if removal is to occur at other times during the cycle. • If a patient with irregular cycles or amenorrhea wants to start a different birth control method, start the new method at least 7 days before removal.
Angeliq

Angeliq

Each pack of Angeliq covers 28 days of treatment. Treatment is continuous, which means that the next pack follows immediately without a break. The tablets are to be swallowed whole with some liquid irrespective of food intake and should preferably be taken at the same time every day. In case a tablet is forgotten, it should be taken as soon as possible. If more than 24 hours have elapsed, the missed tablet should not be taken. If several tablets are forgotten, bleeding may occur.

Women who do not take estrogens or women who change from a continuous combination product may start treatment at any time. Women changing from a continuous sequential or cyclic hormone therapy (HT) should complete the current cycle of therapy before initiating Angeliq therapy.

Use of estrogen, alone or in combination with a progestin, should be limited to the lowest effective dose available and for the shortest duration consistent with treatment goals and risks for the individual woman. Patients should be reevaluated periodically as clinically appropriate to determine if treatment is still necessary [see Boxed Warning].

2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

The dosage is one Angeliq 0.25 mg DRSP/0.5 mg E2 tablet or one Angeliq 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily.

2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause

The dosage is one Angeliq 0.5 mg DRSP/1 mg E2 tablet taken by mouth once daily.

When prescribing solely for the treatment of symptoms of vulvar and vaginal atrophy, topical vaginal products should be considered.
Mirena

Mirena

Mirena contains 52 mg of levonorgestrel. Initially, levonorgestrel is released at a rate of approximately 20 mcg/day. This rate decreases progressively to half that value after 5 years.

Mirena is packaged sterile within an inserter. Information regarding insertion instructions, patient counseling and record keeping, patient follow-up, removal of Mirena and continuation of contraception after removal is provided below.

2.1. Insertion Instructions
• NOTE: Mirena should be inserted by a trained healthcare provider. Healthcare providers are advised to become thoroughly familiar with the insertion instructions before attempting insertion of Mirena. • Mirena is inserted with the provided inserter ( Figure 1a) into the uterine cavity within seven days of the onset of menstruation or immediately after a first trimester abortion by carefully following the insertion instructions. It can be replaced by a new Mirena at any time during the menstrual cycle.
Figure 1a. Mirena and inserter

Preparation for insertion
• Ensure that the patient understands the contents of the Patient Information Booklet and obtain consent. A consent form that includes the lot number is on the last page of the Patient Information Booklet. • Confirm that there are no contraindications to the use of Mirena. • Perform a urine pregnancy test, if indicated. • With the patient comfortably in lithotomy position, gently insert a speculum to visualize the cervix and rule out genital contraindications to the use of Mirena. • Do a bimanual exam to establish the size and position of the uterus, to detect other genital contraindications, and to exclude pregnancy. • Thoroughly cleanse the cervix and vagina with a suitable antiseptic solution. Perform a paracervical block, if needed. • Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with a tenaculum forceps and apply gentle traction to align the cervical canal with the uterine cavity. If the uterus is retroverted, it may be more appropriate to grasp the lower lip of the cervix. Note that the tenaculum forceps should remain in position throughout the insertion procedure to maintain gentle traction on the cervix. • Gently insert a uterine sound to check the patency of the cervix, measure the depth of the uterine cavity, confirm its direction and exclude the presence of any uterine anomaly. If you encounter cervical stenosis, use dilatation, not force, to overcome resistance. • The uterus should sound to a depth of 6 to 10 cm. Insertion of Mirena into a uterine cavity less than 6 cm by sounding may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy. • After ascertaining that the patient is appropriate for Mirena, open the carton containing Mirena.
Insertion Procedure

Ensure use of sterile technique throughout the entire procedure.

Step 1–Opening of the sterile package
• Open the sterile package completely ( Figure 1b). • Place sterile gloves on your hands. • Pick up the handle of the inserter containing Mirena and carefully release the threads so that they hang freely.
Place your thumb or forefinger on the slider. Make sure that the slider is in the furthest position away from you, for example, at the top of the handle towards the insertion tube (Figure 1b). NOTE: Keep your thumb or forefinger on the slider until insertion is complete.
• With the centimeter scale of the insertion tube facing up, check that the arms of Mirena are in a horizontal position. If they are not, align them on a flat, sterile surface, for example, the sterile package (Figures 1b and 1c).
Figure 1b. Aligning the arms with the slider in the furthest position

Figure 1c. Checking that the arms are horizontal and aligned with respect to the scale

Step 2–Load Mirena into the insertion tube
• Holding the slider in the furthest position, pull on both threads to load Mirena into the insertion tube ( Figure 2a) . • Note that the knobs at the ends of the arms now meet to close the open end of the insertion tube ( Figure 2b). If the knobs do not meet properly
If the knobs do not meet properly, release the arms by pulling the slider back to the mark (raised horizontal line on the handle) (Figure 6a) . Re-load Mirena by aligning the open arms on a sterile surface (Figure 1b). Return the slider to its furthermost position and pull on both threads. Check for proper loading (Figure 2b).

Figure 2a. Loading Mirena into the insertion tube

Figure 2b. Properly loaded Mirena with knobs closing the end of the insertion tube

Step 3–Secure the threads

Secure the threads in the cleft at the bottom end of the handle to keep Mirena in the loaded position (Figure 3).

Figure 3. Threads are secured in the cleft

Step 4–Setting the flange

Set the upper edge of the flange to the depth measured during the uterine sounding (Figure 4).

Figure 4. Setting the flange to the uterine depth

Step 5–Mirena is now ready to be inserted
• Continue to hold the slider with the thumb or forefinger firmly in the furthermost position. Grasp the tenaculum forceps with your other hand and apply gentle traction to align the cervical canal with the uterine cavity. • While maintaining traction on the cervix, gently advance the insertion tube through the cervical canal and into the uterine cavity until the flange is 1.5 to 2 cm from the external cervical os. • CAUTION: do not advance flange to the cervix at this step. Maintaining the flange 1.5 to 2 cm from the cervical os allows sufficient space for the arms to open (when released) within the uterine cavity (Figures 5 and 6b). NOTE! Do not force the inserter. If necessary, dilate the cervical canal.
Figure 5. Advancing insertion tube until flange is 1.5 to 2 cm from cervical os

Step 6–Release the arms
• While holding the inserter steady, release the arms of Mirena by pulling the slider back until the top of the slider reaches the mark (raised horizontal line on the handle) ( Figure 6a) . • Wait approximately 10 seconds to allow the horizontal arms of Mirena to open and regain its T-shape ( Figure 6b).
Figure 6a. Pulling the slider back to reach the mark

Figure 6b. Releasing the arms of Mirena

Step 7–Advance to fundal position

Gently advance the inserter into the uterine cavity until the flange meets the cervix and you feel fundal resistance. Mirena should now be in the desired fundal position (Figure 7).

Figure 7. Mirena in the fundal position

Step 8–Release Mirena and withdraw the inserter
• While holding the inserter steady, pull the slider all the way down to release Mirena from the insertion tube ( Figure 8). The threads will release automatically from the cleft. • Check that the threads are hanging freely and gently withdraw the inserter from the uterus. Be careful not to pull on the threads as this will displace Mirena.
Figure 8. Releasing Mirena from the insertion tube

Step 9–Cut the threads
• Cut the threads perpendicular to the thread length, for example, with sterile curved scissors, leaving about 3 cm visible outside the cervix ( Figure 9). NOTE: Cutting threads at an angle may leave sharp ends.
Figure 9. Cutting the threads

Mirena insertion is now complete.

Important information to consider during or after insertion
• If you suspect that Mirena is not in the correct position, check placement (for example, with transvaginal ultrasound). Remove Mirena if it is not positioned completely within the uterus. A removed Mirena must not be reinserted. • If there is clinical concern and/or exceptional pain or bleeding during or after insertion, appropriate and timely measures and assessments, for example ultrasound, should be performed to exclude perforation.
2.2 Patient Counseling and Record Keeping
• Keep a copy of the consent form and lot number for your records. • Counsel the patient on what to expect following Mirena insertion. Give the patient the Follow-up Reminder Card that is provided with the product. Discuss expected bleeding patterns during the first months of Mirena use. [See Patient Counseling Information (17.1).] • Prescribe analgesics, if indicated.
2.3 Patient Follow-up
• Patients should be reexamined and evaluated 4 to 12 weeks after insertion and once a year thereafter, or more frequently if clinically indicated.
2.4 Removal of Mirena
• Remove Mirena by applying gentle traction on the threads with forceps. The arms will fold upward as it is withdrawn from the uterus. Mirena should not remain in the uterus after 5 years. • Removal may be associated with some pain and/or bleeding or neurovascular episodes. • If the threads are not visible and Mirena is in the uterine cavity, it may be removed using a narrow forceps, such as an alligator forceps. This may require dilation of the cervical canal [see Warnings and Precautions ( 5.13)]. • After removal of Mirena, verify that the system is intact. • During difficult removals, the hormone cylinder may slide over and cover the horizontal arms. This situation generally does not require further intervention once the system is verified to be intact. • If Mirena is removed mid-cycle and the woman has had intercourse within the preceding week, she is at a risk of pregnancy unless a new Mirena is inserted immediately following removal.
2.5 Continuation of Contraception after Removal
• You may insert a new Mirena immediately following removal. • If a patient with regular cycles wants to start a different birth control method, remove Mirena during the first 7 days of the menstrual cycle and start the new method. • If a patient with irregular cycles or amenorrhea wants to start a different birth control method, or if you remove Mirena after the seventh day of the menstrual cycle, start the new method at least 7 days before removal.
Betaseron

Betaseron

2.1 Dosing Information

The recommended starting dose is 0.0625 mg (0.25 mL) subcutaneously every other day, with dose increases over a six week period to the recommended dose of 0.25 mg (1 mL) every other day (see Table 1).
Table 1 Schedule for Dose Titration * Dosed every other day, subcutaneously
Betaseron

Dose*

Percentage of

recommended dose

Volume

Weeks 1-2

0.0625 mg

25%

0.25 mL

Weeks 3-4

0.125 mg

50%

0.5 mL

Weeks 5-6

0.1875 mg

75%

0.75 mL

Week 7 and thereafter

0.25 mg

100%

1 mL

2.2 Reconstitution of the Lyophilized Powder

(a) Prior to reconstitution, verify that the vial containing lyophilized Betaseron is not cracked or damaged. Do not use cracked or damaged vials.

(b) To reconstitute lyophilized Betaseron for injection, attach the prefilled syringe containing the diluent (Sodium Chloride, 0.54% Solution) to the Betaseron vial using the vial adapter.

(c) Slowly inject 1.2 mL of diluent into the Betaseron vial.

(d) Gently swirl the vial to dissolve the lyophilized powder completely; do not shake. Foaming may occur during reconstitution or if the vial is swirled or shaken too vigorously. If foaming occurs, allow the vial to sit undisturbed until the foam settles.

(e) 1 mL of reconstituted Betaseron solution contains 0.25 mg of interferon beta-1b.

(f) After reconstitution, if not used immediately, refrigerate the reconstituted Betaseron solution at 2 to 8°C (35 to 46°F) and use within three hours. Do not freeze.

2.3 Important Administration Instructions

(a) Perform the first Betaseron injection under the supervision of an appropriately qualified healthcare professional. If patients or caregivers are to administer Betaseron, train them in the proper subcutaneous injection technique and assess their ability to inject subcutaneously to ensure the proper administration of Betaseron.

(b) Visually inspect the reconstituted Betaseron solution before use; discard if it contains particulate matter or is discolored.

(c) Keeping the syringe and vial adapter in place, turn the assembly over so that the vial is on top. Withdraw the appropriate dose of Betaseron solution. Remove the vial from the vial adapter before injecting Betaseron.

(d) Use safe disposal procedures for needles and syringes.

(e) Do not re-use needles or syringes.

(f) Advise patients and caregivers to rotate sites for subcutaneous injections to minimize the likelihood of severe injection site reactions, including necrosis or localized infection.

2.4 Premedication for Flu-like Symptoms

Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with Betaseron use [see Warnings and Precautions (5.7)].
Xofigo

Xofigo

2.1 Recommended Dosage

The dose regimen of Xofigo is 50 kBq (1.35 microcurie) per kg body weight, given at 4 week intervals for 6 injections. Safety and efficacy beyond 6 injections with Xofigo have not been studied.

The volume to be administered to a given patient should be calculated using the:
• Patient’s body weight (kg) • Dosage level 50 kBq/kg body weight or 1.35 microcurie/kg body weight • Radioactivity concentration of the product (1,000 kBq/mL; 27 microcurie/mL) at the reference date • Decay correction factor to correct for physical decay of radium-223.
The total volume to be administered to a patient is calculated as follows:

Volume to be administered (mL)

=

Body weight in kg × 50 kBq/kg body weight

Decay factor × 1,000 kBq/mL

or

Volume to be administered (mL)

=

Body weight in kg × 1.35 microcurie/kg body weight

Decay factor × 27 microcurie/mL
Table 1: Decay Correction Factor Table
Days from Reference Date

Decay Factor

Days from Reference Date

Decay Factor

-14

2.296

0

0.982

-13

2.161

1

0.925

-12

2.034

2

0.870

-11

1.914

3

0.819

-10

1.802

4

0.771

-9

1.696

5

0.725

-8

1.596

6

0.683

-7

1.502

7

0.643

-6

1.414

8

0.605

-5

1.330

9

0.569

-4

1.252

10

0.536

-3

1.178

11

0.504

-2

1.109

12

0.475

-1

1.044

13

0.447

14

0.420

The Decay Correction Factor Table is corrected to 12 noon Central Standard Time (CST). To determine the decay correction factor, count the number of days before or after the reference date. The Decay Correction Factor Table includes a correction to account for the 7 hour time difference between 12 noon Central European Time (CET) at the site of manufacture and 12 noon US CST, which is 7 hours earlier than CET.

Immediately before and after administration, the net patient dose of administered Xofigo should be determined by measurement in an appropriate radioisotope dose calibrator that has been calibrated with a National Institute of Standards and Technology (NIST) traceable radium-223 standard (available upon request from Bayer) and corrected for decay using the date and time of calibration. The dose calibrator must be calibrated with nationally recognized standards, carried out at the time of commissioning, after any maintenance procedure that could affect the dosimetry and at intervals not to exceed one year.

2.2 Administration

Administer Xofigo by slow intravenous injection over 1 minute.

Flush the intravenous access line or cannula with isotonic saline before and after injection of Xofigo.

2.3 Instructions for Use / Handling

General warning

Xofigo (an alpha particle-emitting pharmaceutical) should be received, used and administered only by authorized persons in designated clinical settings. The receipt, storage, use, transfer and disposal Xofigo are subject to the regulations and/or appropriate licenses of the competent official organization.

Xofigo should be handled by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken.

Radiation protection

The administration of Xofigo is associated with potential risks to other persons (e.g., medical staff, caregivers and patient’s household members) from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations.

For drug handling

Follow the normal working procedures for the handling of radiopharmaceuticals and use universal precautions for handling and administration such as gloves and barrier gowns when handling blood and bodily fluids to avoid contamination. In case of contact with skin or eyes, the affected area should be flushed immediately with water. In the event of spillage of Xofigo, the local radiation safety officer should be contacted immediately to initiate the necessary measurements and required procedures to decontaminate the area. A complexing agent such as 0.01 M ethylene-diamine-tetraacetic acid (EDTA) solution is recommended to remove contamination.

For patient care

Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. When handling bodily fluids, simply wearing gloves and hand washing will protect caregivers. Clothing soiled with Xofigo or patient fecal matter or urine should be washed promptly and separately from other clothing.

Radium-223 is primarily an alpha emitter, with a 95.3% fraction of energy emitted as alpha-particles. The fraction emitted as beta-particles is 3.6%, and the fraction emitted as gamma-radiation is 1.1%. The external radiation exposure associated with handling of patient doses is expected to be low, because the typical treatment activity will be below 8,000 kBq (216 microcurie). In keeping with the As Low As Reasonably Achievable (ALARA) principle for minimization of radiation exposure, it is recommended to minimize the time spent in radiation areas, to maximize the distance to radiation sources, and to use adequate shielding. Any unused product or materials used in connection with the preparation or administration are to be treated as radioactive waste and should be disposed of in accordance with local regulations.

The gamma radiation associated with the decay of radium-223 and its daughters allows for the radioactivity measurement of Xofigo and the detection of contamination with standard instruments.

Instructions for preparation

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

Xofigo is a ready-to-use solution and should not be diluted or mixed with any solutions. Each vial is for single use only.

Dosimetry

The absorbed radiation doses in major organs were calculated based on clinical biodistribution data in five patients with castration-resistant prostate cancer. Calculations of absorbed radiation doses were performed using OLINDA/EXM (Organ Level INternal Dose Assessment/EXponential Modeling), a software program based on the Medical Internal Radiation Dose (MIRD) algorithm, which is widely used for established beta and gamma emitting radionuclides. For radium-223, which is primarily an alpha particle-emitter, assumptions were made for intestine, red marrow and bone/osteogenic cells to provide the best possible absorbed radiation dose calculations for Xofigo, considering its observed biodistribution and specific characteristics.

The calculated absorbed radiation doses to different organs are listed in Table 2. The organs with highest absorbed radiation doses were bone (osteogenic cells), red marrow, upper large intestine wall, and lower large intestine wall. The calculated absorbed doses to other organs are lower.
Table 2: Calculated Absorbed Radiation Doses to Organs Target Organ Mean (Gy/MBq) Mean (rad/mCi) Coefficient of Variation (%) * LLI: lower large intestine † ULI: upper large intestine
Adrenals

0.00012

0.44

56

Brain

0.00010

0.37

80

Breasts

0.00005

0.18

120

Gallbladder wall

0.00023

0.85

14

LLI* wall

0.04645

171.88

83

Small intestine wall

0.00726

26.87

45

Stomach wall

0.00014

0.51

22

ULI† wall

0.03232

119.58

50

Heart wall

0.00173

6.40

42

Kidneys

0.00320

11.86

36

Liver

0.00298

11.01

36

Lungs

0.00007

0.27

90

Muscle

0.00012

0.44

41

Ovaries

0.00049

1.80

40

Pancreas

0.00011

0.41

43

Red marrow

0.13879

513.51

41

Osteogenic cells

1.15206

4262.60

41

Skin

0.00007

0.27

79

Spleen

0.00009

0.33

54

Testes

0.00008

0.31

59

Thymus

0.00006

0.21

109

Thyroid

0.00007

0.26

96

Urinary bladder wall

0.00403

14.90

63

Uterus

0.00026

0.94

28

Whole body

0.02311

85.50

16
Promethazine Vc With Co...

Promethazine Vc With Codeine

CIPRO Tablets and Oral Suspension should be administered orally as described in the appropriate Dosage Guidelines tables.

2.1 Dosage in Adults

The determination of dosage and duration for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function.
Table 1: Adult Dosage Guidelines * Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). † Used in conjunction with metronidazole. ‡ Begin drug administration as soon as possible after suspected or confirmed exposure. Infection Dose Frequency Usual Durations * Urinary Tract 250–500 mg every 12 hours 7 to 14 days Acute Uncomplicated Cystitis 250 mg every 12 hours 3 days Chronic Bacterial Prostatitis 500 mg every 12 hours 28 days Lower Respiratory Tract 500–750 mg every 12 hours 7 to 14 days Acute Sinusitis 500 mg every 12 hours 10 days Skin and Skin Structure 500–750 mg every 12 hours 7 to 14 days Bone and Joint 500–750 mg every 12 hours 4 to 8 weeks Complicated Intra–Abdominal † 500 mg every 12 hours 7 to 14 days Infectious Diarrhea 500 mg every 12 hours 5 to 7 days Typhoid Fever 500 mg every 12 hours 10 days Uncomplicated Urethral and Cervical Gonococcal Infections 250 mg single dose single dose Inhalational anthrax (post-exposure) ‡ 500 mg every 12 hours 60 days Plague ‡ 500–750 mg every 12 hours 14 days
Conversion of IV to Oral Dosing in Adults

Patients whose therapy is started with CIPRO IV may be switched to CIPRO Tablets or Oral Suspension when clinically indicated at the discretion of the physician (Table 2) [see Clinical Pharmacology (12.3)].
Table 2: Equivalent AUC Dosing Regimens
CIPRO Oral Dosage

Equivalent CIPRO IV Dosage

250 mg Tablet every 12 hours

200 mg intravenous every 12 hours

500 mg Tablet every 12 hours

400 mg intravenous every 12 hours

750 mg Tablet every 12 hours

400 mg intravenous every 8 hours

2.2 Dosage in Pediatric Patients

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection. CIPRO should be administered as described in Table 3.
Table 3: Pediatric Dosage Guidelines Infection Dose Frequency Total Duration * The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). † Begin drug administration as soon as possible after suspected or confirmed exposure. ‡ Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis.
Complicated Urinary Tract or Pyelonephritis (patients from 1 to 17 years of age)*

10 mg/kg to 20 mg/kg

(maximum 750 mg per dose; not to be exceeded even in patients weighing more than 51 kg)

Every 12 hours

10–21 days

Inhalational Anthrax (Post-Exposure)†

15 mg/kg

(maximum 500 mg per dose)

Every 12 hours

60 days

Plague†, ‡

15 mg/kg

(maximum 500 mg per dose)

Every 12 to 8 hours

10–21 days

2.3 Dosage Modifications in Patients with Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in Table 4.
Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal Function
Creatinine Clearance (mL/min)

Dose

> 50

See Usual Dosage.

30–50

250–500 mg every12 hours

5–29

250–500 mg every 18 hours

Patients on hemodialysis or Peritoneal dialysis

250–500 mg every 24 hours (after dialysis)

When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance:

Men - Creatinine clearance (mL/min) =

Weight (kg) x (140–age)

72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals noted above. Patients should be carefully monitored.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m2).

2.4 Important Administration Instructions

With Multivalent Cations

Administer CIPRO at least 2 hours before or 6 hours after magnesium/aluminum antacids; polymeric phosphate binders (for example, sevelamer, lanthanum carbonate) or sucralfate; Videx® (didanosine) chewable/buffered tablets or pediatric powder for oral solution; other highly buffered drugs; or other products containing calcium, iron or zinc.

With Dairy Products

Concomitant administration of CIPRO with dairy products (like milk or yogurt) or calcium-fortified juices alone should be avoided since decreased absorption is possible; however, CIPRO may be taken with a meal that contains these products.

Hydration of Patients Receiving CIPRO

Assure adequate hydration of patients receiving CIPRO to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones.

Instruct the patient of the appropriate CIPRO administration [see Patient Counseling Information (17)].

2.5 Directions for Reconstitution of the CIPRO Microcapsules for Oral Suspension

CIPRO Oral Suspension is supplied in 5% (5 g ciprofloxacin in 100 mL) and 10% (10 g ciprofloxacin in 100 mL) strengths. CIPRO oral suspension is composed of two components (microcapsules and diluent) that must be combined prior to dispensing.
Table 5: Appropriate Dosing Volumes of the Reconstituted Oral Suspensions
Dose

5%

10%

250 mg

5 mL

2.5 mL

500 mg

10 mL

5 mL

750 mg

15 mL

7.5 mL

Preparation of the suspension:

Step 5: Write the expiration date of the re-constituted oral suspension on the bottle label.

Reconstituted product may be stored below 30 °C (86°F) for 14 days. Protect from freezing.

No additions should be made to the mixed final ciprofloxacin suspension. CIPRO Oral Suspension should not be administered through feeding or NG (nasogastric) tubes due to its physical characteristics.
Cipro

Cipro

2.1 Dosage

CIPRO XR and ciprofloxacin immediate-release tablets are not interchangeable. Cipro XR should be administered orally once daily (Table 1).
Table 1: Dosage Guidelines
Indication

Dose

Frequency

Usual Duration

Uncomplicated Urinary Tract Infection (Acute Cystitis)

500 mg

every 24 hours

3 Days

Complicated Urinary Tract Infection and Acute Uncomplicated Pyelonephritis

1000 mg

every 24 hours

7–14 Days

Patients whose therapy is started with CIPRO IV for UTIs may be switched to CIPRO XR when clinically indicated at the discretion of the physician.

2.2 Administration
• CIPRO XR tablets should be taken whole and not split, crushed, or chewed. • CIPRO XR should be administered at least 2 hours before or 6 hours after antacids containing magnesium or aluminum, polymeric phosphate binders (for example, sevelamer, lanthanum carbonate), as well as sucralfate, VIDEX ® (didanosine) chewable/buffered tablets or pediatric powder, other highly buffered drugs, metal cations such as iron, and multivitamin preparations with zinc [see Drug Interactions (7)]. • Concomitant administration of Cipro XR with dairy products (like milk or yogurt) or with calcium-fortified products alone should be avoided since decreased absorption is possible. A 2-hour window between substantial calcium intake (greater than 800 mg) and dosing with CIPRO XR is recommended [see Patient Counseling Information (17)].
Adequate hydration of patients receiving CIPRO XR should be maintained to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones [see Warnings and Precautions (5.12), Adverse Reactions (6.1) and Patient Counseling Information (17)].

2.3 Impaired Renal Function
• In patients with cUTI and acute uncomplicated pyelonephritis with a creatinine clearance of ≤ 30 mL/min, the dose of CIPRO XR should be reduced from 1000 mg to 500 mg daily. The use of Ciprofloxacin 1000 mg XR tablets is not recommended in this patient population. • For patients on hemodialysis or peritoneal dialysis, administer CIPRO XR after the dialysis procedure is completed (maximum dose should be Ciprofloxacin 500 mg XR every 24 hours). The use of Ciprofloxacin 1000 mg XR is not recommended in this patient population. [See Use in Specific Populations (8.6) and Clinical Pharmacology (12.3).] • For patients on continuous ambulatory peritoneal dialysis (CAPD), the maximum dose should be 500 mg every 24 hours.
Climara

Climara

Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer. A woman without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.14)].

Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals.

2.2 Treatment of Moderate to Severe Symptoms of Vulvar and Vaginal Atrophy due to Menopause

Start therapy with 0.025 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to taper or discontinue the medication should be made at 3 to 6 month intervals.

2.3 Treatment of Hypoestrogenism due to Hypogonadism, Castration, or Primary Ovarian Failure

Start therapy with 0.025 mg per day applied to the skin once weekly. The dose should be adjusted as necessary to control symptoms. Clinical responses (relief of symptoms) at the lowest effective dose should be the guide for establishing administration of the Climara transdermal system, especially in women with an intact uterus.

2.4 Prevention of Postmenopausal Osteoporosis

Start therapy with 0.025 mg per day applied to the skin once weekly.

2.5 Application of the Climara Transdermal System

Site Selection
• The adhesive side of Climara should be placed on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. • Climara should not be applied to or near the breasts. • The sites of application must be rotated, with an interval of at least 1-week allowed between applications to the same site. • The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the transdermal system off. • Application to areas where sitting would dislodge Climara should also be avoided.
Application
• Climara should be applied immediately after opening the pouch and removing the protective liner. • Climara should be pressed firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges. • If the system lifts, apply pressure to maintain adhesion. • In the event that a system should fall off reapply it to a different location. If the system cannot be reapplied, a new system should be applied for the remainder of the 7-day dosing interval. • Only one system should be worn at any one time during the 7-day dosing interval. • Swimming, bathing, or using a sauna while using Climara has not been studied, and these activities may decrease the adhesion of the system and the delivery of estradiol.
2.6 Removal of the Climara Transdermal System
• Removal of Climara should be done carefully and slowly to avoid irritation of the skin. • Should any adhesive remain on the skin after removal of the Climara system, allow the area to dry for 15 minutes. Then gently rubbing the area with an oil-based cream or lotion should remove the adhesive residue. • Used patches still contain some active hormones. Each patch should be carefully folded in half so that it sticks to itself before throwing it away.
Nexavar

Nexavar

2.1 Recommended Dose for Hepatocellular Carcinoma, Renal Cell Carcinoma, and Differentiated Thyroid Carcinoma

The recommended daily dose of NEXAVAR is 400 mg (2 x 200 mg tablets) taken twice daily without food (at least 1 hour before or 2 hours after a meal). Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs.

2.2 Dose Modifications for Suspected Adverse Drug Reactions

Temporary interruption of NEXAVAR is recommended in patients undergoing major surgical procedures [see Warnings and Precautions (5.7)].

Temporary interruption or permanent discontinuation of NEXAVAR may be required for the following:
• Cardiac ischemia or infarction [see Warnings and Precautions (5.1)] • Hemorrhage requiring medical intervention [see Warnings and Precautions (5.2)] • Severe or persistent hypertension despite adequate anti-hypertensive therapy [see Warnings and Precautions (5.3)] • Gastrointestinal perforation [see Warnings and Precautions (5.5)] • QTc prolongation [see Warnings and Precautions (5.9)] • Severe drug-induced liver injury [see Warnings and Precautions (5.10)]
Dose modifications for Hepatocellular Carcinoma and Renal Cell Carcinoma

When dose reduction is necessary, the NEXAVAR dose may be reduced to 400 mg once daily. If additional dose reduction is required, NEXAVAR may be reduced to a single 400 mg dose every other day [see Warnings and Precautions (5)].

Suggested dose modifications for dermatologic toxicities are outlined in Table 1.
Table 1: Suggested Dose Modifications for Dermatologic Toxicities in Patients with Hepatocellular or Renal Cell Carcinoma
Dermatologic Toxicity Grade

Occurrence

Suggested Dose Modification

Grade 1: Numbness, dysesthesia, paresthesia, tingling, painless swelling, erythema or discomfort of the hands or feet which does not disrupt the patient’s normal activities

Any occurrence

Continue treatment with NEXAVAR and consider topical therapy for symptomatic relief

Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities

1st occurrence

Continue treatment with NEXAVAR and consider topical therapy for symptomatic relief

If no improvement within 7 days, see below

No improvement within 7 days or 2nd or 3rd occurrence

Interrupt NEXAVAR treatment until toxicity resolves to Grade 0–1

When resuming treatment, decrease NEXAVAR dose by one dose level (400 mg daily or 400 mg every other day)

4th occurrence

Discontinue NEXAVAR treatment

Grade 3: Moist desquamation, ulceration, blistering or severe pain of the hands or feet, or severe discomfort that causes the patient to be unable to work or perform activities of daily living

1st or 2nd occurrence

Interrupt NEXAVAR treatment until toxicity resolves to Grade 0–1

When resuming treatment, decrease NEXAVAR dose by one dose level (400 mg daily or 400 mg every other day)

3rd occurrence

Discontinue NEXAVAR treatment

Dose modifications for Differentiated Thyroid Carcinoma
Table 2: Recommended Doses for Patients with Differentiated Thyroid Carcinoma Requiring Dose Reduction
Dose Reduction

NEXAVAR Dose

First Dose Reduction

600 mg daily dose

400 mg and 200 mg 12 hours apart (2 tablets and 1 tablet 12 hours apart – either dose can come first)

Second Dose Reduction

400 mg daily dose

200 mg twice daily (1 tablet twice daily)

Third Dose Reduction

200 mg daily dose

200 mg once daily (1 tablet once daily)

When dose reduction is necessary for dermatologic toxicities, reduce the NEXAVAR dose as indicated in Table 3 below.
Table 3: Recommended Dose Modifications for Dermatologic Toxicities for Patients with Differentiated Thyroid Carcinoma
Dermatologic Toxicity Grade

Occurrence

NEXAVAR Dose Modification

Grade 1: Numbness, dysesthesia, paresthesia, tingling, painless swelling, erythema or discomfort of the hands or feet which does not disrupt the patient’s normal activities

Any occurrence

Continue treatment with NEXAVAR

Grade 2: Painful erythema and swelling of the hands or feet and/or discomfort affecting the patient’s normal activities

1st occurrence

Decrease NEXAVAR dose to 600 mg daily

If no improvement within 7 days, see below

No improvement within 7 days at reduced doseor 2nd occurrence

Interrupt NEXAVAR until resolved or improved to grade 1

If NEXAVAR is resumed, decrease dose (see Table 2)

3rd occurrence

Interrupt NEXAVAR until resolved or improved to grade 1

If NEXAVAR is resumed, decrease dose (see Table 2)

4th occurrence

Discontinue NEXAVAR permanently

Grade 3:

Moist desquamation, ulceration, blistering, or severe pain of the hands or feet, resulting in inability to work or perform activities of daily living

1st occurrence

Interrupt NEXAVAR until resolved or improved to grade 1

If NEXAVAR is resumed, decrease dose by one dose level (see Table 2)

2nd occurrence

Interrupt NEXAVAR until resolved or improved to grade 1

When NEXAVAR is resumed, decrease dose by 2 dose levels (see Table 2)

3rd occurrence

Discontinue NEXAVAR permanently

Following improvement of Grade 2 or 3 dermatologic toxicity to Grade 0–1 after at least 28 days of treatment on a reduced dose of NEXAVAR, the dose of NEXAVAR may be increased one dose level from the reduced dose. Approximately 50% of patients requiring a dose reduction for dermatologic toxicity are expected to meet these criteria for resumption of the higher dose and roughly 50% of patients resuming the previous dose are expected to tolerate the higher dose (that is, maintain the higher dose level without recurrent Grade 2 or higher dermatologic toxicity)
Betaseron

Betaseron

2.1 Dosing Information

The recommended starting dose is 0.0625 mg (0.25 mL) subcutaneously every other day, with dose increases over a six-week period to the recommended dose of 0.25 mg (1 mL) every other day (see Table 1).
Table 1: Schedule for Dose Titration * Dosed every other day, subcutaneously
BETASERON

Dose*

Percentage of

recommended dose

Volume

Weeks 1-2

0.0625 mg

25%

0.25 mL

Weeks 3-4

0.125 mg

50%

0.5 mL

Weeks 5-6

0.1875 mg

75%

0.75 mL

Week 7 and thereafter

0.25 mg

100%

1 mL

If a dose of BETASERON is missed, then it should be taken as soon as the patient remembers or is able to take it. The patient should not take BETASERON on two consecutive days. The next injection should be taken about 48 hours (two days) after that dose. If the patient accidentally takes more than their prescribed dose, or takes it on two consecutive days, they should be instructed to call their healthcare provider immediately.

2.2 Reconstitution of the Lyophilized Powder

(a) Prior to reconstitution, verify that the vial containing lyophilized BETASERON is not cracked or damaged. Do not use cracked or damaged vials.

(b) To reconstitute lyophilized BETASERON for injection, attach the pre-filled syringe containing the diluent (Sodium Chloride, 0.54% Solution) to the BETASERON vial using the vial adapter.

(c) Slowly inject 1.2 mL of diluent into the BETASERON vial.

(d) Gently swirl the vial to dissolve the lyophilized powder completely; do not shake. Foaming may occur during reconstitution or if the vial is swirled or shaken too vigorously. If foaming occurs, allow the vial to sit undisturbed until the foam settles.

(e) 1 mL of reconstituted BETASERON solution contains 0.25 mg of interferon beta-1b.

(f) After reconstitution, if not used immediately, refrigerate the reconstituted BETASERON solution at 35°F to 46°F (2°C to 8°C) and use within three hours. Do not freeze.

2.3 Important Administration Instructions

(a) BETASERON is intended for use under the guidance and supervision of a physician. If patients or caregivers are to administer BETASERON, train them in the proper technique for self‐administering subcutaneous injections using the prefilled syringe or the optional injection device. The BETACONNECT autoinjector has three adjustable injection depth settings; the healthcare provider should determine the proper depth setting and injection technique. Use only the syringes in the BETASERON packaging with the BETACONNECT autoinjector.

The initial BETASERON injection should be performed under the supervision of an appropriately qualified healthcare provider. Users should demonstrate competency in all aspects of the BETASERON injection prior to independent use. If a patient is to self‐administer BETASERON, the physical and cognitive ability of that patient to self‐administer and properly dispose of syringes should be assessed. Patients with severe neurological deficits should not self‐administer injections without assistance from a trained caregiver.

Appropriate instruction for self‐injection or injection by another person should be provided to the patient or their caregiver, including careful review of the BETASERON Medication Guide, the prefilled syringe Instructions for Use, and the BETACONNECT autoinjector Instructions for Use that accompanies the product.

(b) Visually inspect the reconstituted BETASERON solution before use; discard if it contains particulate matter or is discolored.

(c) Keeping the syringe and vial adapter in place, turn the assembly over so that the vial is on top. Withdraw the appropriate dose of BETASERON solution. Remove the vial from the vial adapter before injecting BETASERON.

(d) Use safe disposal procedures for needles and syringes.

(e) Do not re-use needles or syringes.

(f) Advise patients and caregivers to rotate sites for subcutaneous injections to minimize the likelihood of severe injection site reactions, including necrosis or localized infection.

2.4 Premedication for Flu-like Symptoms

Concurrent use of analgesics and/or antipyretics on treatment days may help ameliorate flu-like symptoms associated with BETASERON use [see Warnings and Precautions (5.7)].
Climara Pro

Climara Pro

Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual women. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

One Climara Pro transdermal system is available for use.

Initiation of Therapy

Women not currently using continuous estrogen-alone therapy or estrogen plus progestin therapy may start therapy with Climara Pro at any time. However, women currently using continuous estrogen-alone therapy or estrogen plus progestin therapy should complete the current cycle of therapy before initiating Climara Pro therapy. Women often experience withdrawal bleeding at the completion of the cycle. The first day of this bleeding would be an appropriate time to begin Climara Pro therapy.

2.1 Treatment of Moderate to Severe Vasomotor Symptoms due to Menopause

Climara Pro 0.045 mg per day/0.015 mg per day applied to the skin once weekly. Therapy should be started at the lowest effective dose and the shortest duration consistent with the treatment goals. Attempts to discontinue the medication should be made at 3 to 6 month intervals.

2.2 Prevention of Postmenopausal Osteoporosis

Climara Pro 0.045 mg per day/0.015 mg per day applied to the skin once weekly.

2.3 Application of the Transdermal System

Site Selection
• The adhesive side of Climara Pro should be placed on a smooth (fold free), clean, dry area of the skin on the lower abdomen or the upper quadrant of the buttock. • Climara Pro should not be applied to or near the breasts. • The area selected should not be oily (which can impair adherence of the system), damaged, or irritated. • The waistline should be avoided, since tight clothing may rub Climara Pro off or modify drug delivery. • Application to areas where sitting would dislodge Climara Pro should also be avoided. • The sites of application must be rotated, with an interval of at least 1-week allowed between applications to the same site.
Application
• Climara Pro should be applied immediately after opening the pouch and removing the protective lining. • Climara Pro should be pressed firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges. • If the system lifts, apply pressure to maintain adhesion. • In the event that a system should fall off, the same system may be reapplied to another area of the lower abdomen. If the system cannot be reapplied, a new system may be applied, in which case, the original treatment schedule should be continued. • Only one system should be worn at any one time during 7-day dosing interval. • Once in place, the transdermal system should not be exposed to the sun for prolonged periods of time. • Swimming, bathing, or using a sauna while using Climara Pro has not been studied, and these activities may decrease the adhesion of the system and the delivery of the estrogen and progestin.
2.4 Removal of the Transdermal System
• Removal of Climara Pro should be done carefully and slowly to avoid irritation of the skin. • Should any adhesive remain on the skin after removal of the system, allow the area to dry for 15 minutes. • Then gently rubbing the area with an oil-based cream or lotion should remove the adhesive residue. • Used patches still contain some active hormones. Each patch should be carefully folded in half so that it sticks to itself before throwing it away
Balziva

Balziva

• Visually inspect ULTRAVIST for particulate matter and/or discoloration, whenever solution and container permit. Do not administer ULTRAVIST if particulate matter and/or discoloration is observed. • Determine the volume and concentration of ULTRAVIST Injection to be used taking into account factors such as age, body weight, size of the vessel and the rate of blood flow within the vessel; consider also extent of opacification required, structure(s) or area to be examined, disease processes affecting the patient, and equipment and technique to be employed. Specific dose adjustments for age, gender, weight and renal function have not been studied for ULTRAVIST Injection. As with all iodinated contrast agents, lower doses may have less risk. The efficacy of ULTRAVIST Injection below doses recommended has not been established. • The maximum recommended total dose of iodine in adults is 86 grams; a maximum recommended total dose of iodine has not been established for pediatric patients. • Hydrate patients adequately prior to and following the administration of ULTRAVIST [see Warnings and Precautions ( 5.2)]. • Warming ULTRAVIST to body temperature shortly before administration may help improve tolerability and ease of injection [see How Supplied/Storage and Handling (16)].
2.1 Intra-Arterial Procedures

The volume and rate of injection of the contrast agent will vary depending on the injection site and the area being examined. Inject contrast at rates approximately equal to the flow rate in the vessel being injected.
• Cerebral Arteriography (300 mg I/mL), Coronary Arteriography and Left Ventriculography (370 mg I/mL), Peripheral Arteriography (300 mg I/mL), Intra-arterial Digital Subtraction Angiography (IA-DSA) (150 mg I/mL): see Table 1. • Aortography and Visceral Angiography (370 mg I/mL): Use a volume and rate of contrast injection proportional to the blood flow and related to the vascular and pathological characteristics of the specific vessels being studied. Do not exceed 225 mL as total dose for the procedure.
Table 1: Suggested Single Injection Doses for Adult Intra-Arterial Procedures

IA-DSA*

(150 mg I/mL)

Cerebral Arteriography

(300 mg I/mL)

Peripheral Arteriography

(300 mg I/mL)

Coronary Arteriography andLeft Ventriculography

(370 mg I/mL)
Intra-Arterial Injection Sites
Carotid Arteries

Vertebral Arteries

Aortic Arch Injection (4 vessel study)

6–10 mL

4–8 mL

-

3–12 mL

4–12 mL

20–50 mL

-

-

-

-

-

-

Right Coronary Artery

Left Coronary Artery

Left Ventricle

-

-

-

-

-

-

-

-

-

3–14 mL

3–14 mL

30–60 mL

Aorta

Major Branches of the Abdominal Aorta

20–50 mL

2–20 mL

-

-

-

-

-

-

Subclavian or Femoral Artery

Aortic Bifurcation (distal runoff)

-

-

-

-

5–40 mL

25–50 mL

-

-

Maximum Total Dose

250 mL

150 mL

250 mL

225 mL

2.2 Intravenous Procedures
• Peripheral Venography (240 mg I/mL): Inject the minimum volume necessary to visualize satisfactorily the structures under examination. Do not exceed 250 mL as total dose for the procedure. • Contrast Computed Tomography (CT) (300 mg I/mL and 370 mg I/mL) and Excretory Urography (300 mg I/mL): see Table 2.
Table 2: Suggested ULTRAVIST Injection Dosing for Adult Intravenous Contrast Administration

Excretory Urography (300 mg I/mL)

Contrast Computed Tomography (300 mg I/mL)

Contrast Computed Tomography (370 mg I/mL)

Excretory Urography

Approximately 300 mg I/kg body wt. (Adults with normal renal function)

-

-

Head

-

50–200 mL

41–162 mL

Body
Bolus Injection
50–200 mL

41–162 mL
Rapid Infusion
100–200 mL

81–162 mL

Maximum Total Dose

100 mL (30 g iodine)

200 mL (60 g iodine)

162 mL (60 g iodine)

2.3 Pediatric Dosing

The recommended dose in children over 2 years of age for the following evaluations is:
• Intra-arterial:
Cardiac chambers and related arteries (370 mg I/mL):

Inject 1 to 2 milliliters per kilogram (mL/kg). Do not exceed 4 mL/kg as total dose.
• Intravenous:
Contrast Computerized Tomography or Excretory Urography (300 mg I/mL):

Inject 1 to 2 mL/kg. Do not exceed 3 mL/kg as total dose.

The safety and efficacy relationships of other doses, concentrations or procedures have not been established [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].
Simvastatin

Simvastatin

2.1 How to Take Yaz

Take one tablet by mouth at the same time every day. The failure rate may increase when pills are missed or taken incorrectly.

To achieve maximum contraceptive and PMDD effectiveness, Yaz must be taken exactly as directed, in the order directed on the blister pack. Single missed pills should be taken as soon as remembered.

2.2 How to Start Yaz

Instruct the patient to begin taking Yaz either on the first day of her menstrual period (Day 1 Start) or on the first Sunday after the onset of her menstrual period (Sunday Start).

Day 1 Start

During the first cycle of Yaz use, instruct the patient to take one light pink Yaz daily, beginning on Day 1 of her menstrual cycle. (The first day of menstruation is Day 1.) She should take one light pink Yaz daily for 24 consecutive days, followed by one white inert tablet daily on Days 25 through 28. Yaz should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Yaz can be taken without regard to meals. If Yaz is first taken later than the first day of the menstrual cycle, Yaz should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

Sunday Start

During the first cycle of Yaz use, instruct the patient to take one light pink Yaz daily, beginning on the first Sunday after the onset of her menstrual period. She should take one light pink Yaz daily for 24 consecutive days, followed by one white inert tablet daily on Days 25 through 28. Yaz should be taken in the order directed on the package at the same time each day, preferably after the evening meal or at bedtime with some liquid, as needed. Yaz can be taken without regard to meals. Yaz should not be considered effective as a contraceptive until after the first 7 consecutive days of product administration. Instruct the patient to use a non-hormonal contraceptive as back-up during the first 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered.

The patient should begin her next and all subsequent 28-day regimens of Yaz on the same day of the week that she began her first regimen, following the same schedule. She should begin taking her light pink tablets on the next day after ingestion of the last white tablet, regardless of whether or not a menstrual period has occurred or is still in progress. Anytime a subsequent cycle of Yaz is started later than the day following administration of the last white tablet, the patient should use another method of contraception until she has taken a light pink Yaz daily for seven consecutive days.

When switching from a different birth control pill

When switching from another birth control pill, Yaz should be started on the same day that a new pack of the previous oral contraceptive would have been started.

When switching from a method other than a birth control pill
When switching from a transdermal patch or vaginal ring, Yaz should be started when the next application would have been due. When switching from an injection, Yaz should be started when the next dose would have been due. When switching from an intrauterine contraceptive or an implant, Yaz should be started on the day of removal.
Withdrawal bleeding usually occurs within 3 days following the last light pink tablet. If spotting or breakthrough bleeding occurs while taking Yaz, instruct the patient to continue taking Yaz by the regimen described above. Counsel her that this type of bleeding is usually transient and without significance; however, advise her that if the bleeding is persistent or prolonged, she should consult her healthcare provider.

Although the occurrence of pregnancy is low if Yaz is taken according to directions, if withdrawal bleeding does not occur, consider the possibility of pregnancy. If the patient has not adhered to the prescribed dosing schedule (missed one or more active tablets or started taking them on a day later than she should have), consider the possibility of pregnancy at the time of the first missed period and take appropriate diagnostic measures. If the patient has adhered to the prescribed regimen and misses two consecutive periods, rule out pregnancy. Discontinue Yaz if pregnancy is confirmed.

The risk of pregnancy increases with each active light pink tablet missed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the FDA Approved Patient Labeling. If breakthrough bleeding occurs following missed tablets, it will usually be transient and of no consequence. If the patient misses one or more white tablets, she should still be protected against pregnancy provided she begins taking a new cycle of light pink tablets on the proper day.

For postpartum women who do not breastfeed or after a second trimester abortion, start Yaz no earlier than 4 weeks postpartum due to the increased risk of thromboembolism. If the patient starts on Yaz postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken Yaz for 7 consecutive days.

2.3 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 occurs within 3–4 hours after tablet-taking, this can be regarded as a missed tablet.
Up And Up Nicotine

Up And Up Nicotine

Generally, when estrogen is prescribed for a postmenopausal woman with a uterus, a progestin should also be considered to reduce the risk of endometrial cancer. It is recommended that women who have a uterus and are treated with Menostar receive a progestin for 14 days every 6 to 12 months and undergo an endometrial biopsy at yearly intervals or as clinically indicated in order to detect any endometrial stimulation which might require further clinical action. A women without a uterus does not need a progestin. In some cases, however, hysterectomized women with a history of endometriosis may need a progestin [see Warnings and Precautions (5.2, 5.14)].

Use of estrogen-alone, or in combination with a progestin, should be with the lowest effective dose and for the shortest duration consistent with treatment goals and risks for the individual woman. Postmenopausal women should be re-evaluated periodically as clinically appropriate to determine if treatment is still necessary.

2.1 Prevention of Postmenopausal Osteoporosis

Menostar 14 mcg per day applied to a clean dry area of the lower abdomen once weekly.

2.2 Application of the Menostar Transdermal System

Site Selection
• The adhesive side of Menostar should be placed on a clean, dry area of the lower abdomen or the upper quadrant of the buttock. • Menostar should not be applied to or near the breasts. • The sites of application must be rotated, with an interval of at least 1-week allowed between applications to a same site. • The area selected should not be oily, damaged, or irritated. The waistline should be avoided, since tight clothing may rub the transdermal system off. Application to areas where sitting would dislodge Menostar should also be avoided.
Application
• Menostar should be applied immediately after opening the pouch and removing the protective liner. • Menostar should be pressed firmly in place with the fingers for at least 10 seconds, making sure there is good contact, especially around the edges. • If the system lifts, apply pressure to maintain adhesion. • In the event that a system should fall off reapply it to a different location. If the system cannot be reapplied, a new system should be applied for the remainder of the 7-day dosing interval. • Only one system should be worn at any one time during the 7-day dosing interval. Swimming, bathing, or using a sauna while using Menostar has not been studied, and these activities may decrease the adhesion of the system and the delivery of estradiol.
2.3 Removal of the Menostar Transdermal System
• Removal of the system should be done carefully and slowly to avoid irritation of the skin. • Should any adhesive remain on the skin after removal of the system, allow the area to dry for 15 minutes. Then gently rubbing the area with an oil-based cream or lotion should remove the adhesive residue. Used patches still contain some active hormones. Each patch should be carefully folded in half so that it sticks to itself before throwing it away
Gadavist

Gadavist

2.1 Recommended Dose

The recommended dose of Gadavist for adult and pediatric patients (including term neonates) is 0.1 mL/kg body weight (0.1 mmol/kg). Refer to Table 1 to determine the volume to be administered.
Table 1: Volume of Gadavist Injection by Body Weight
Body Weight

Volume to be Administered, mL

lb

kg

5.5

2.5

0.25

11

5

0.5

22

10

1

33

15

1.5

44

20

2

55

25

2.5

66

30

3

77

35

3.5

88

40

4

99

45

4.5

110

50

5

132

60

6

154

70

7

176

80

8

198

90

9

220

100

10

242

110

11

264

120

12

286

130

13

308

140

14

2.2 Administration Guidelines
• Gadavist is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration. Closely examine Table 1 to determine the volume to be administered.
Use sterile technique when preparing and administering Gadavist.
• Administer Gadavist as an intravenous bolus injection, manually or by power injector, at a flow rate of approximately 2 mL/second. • Follow Gadavist injection with a normal saline flush to ensure complete administration of the contrast. • Contrast-enhanced MRI can commence immediately following contrast administration.
2.3 Drug Handling
• Visually inspect Gadavist for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged. • Do not mix Gadavist with other medications and do not administer Gadavist in the same intravenous line simultaneously with other medications because of the potential for chemical incompatibility. • Instructions of the device manufacturer must be followed.
Pharmacy Bulk Package Preparation
• Pharmacy Bulk Packages are not for use in direct intravenous infusions. • After the Pharmacy Bulk Package has been opened, Gadavist remains stable for 24 hours at 20–25°C (68–77°F). • The Pharmacy Bulk Package contains many single doses and is used with an appropriate transfer device for filling empty sterile syringes. • The transfer of Gadavist from the Pharmacy Bulk Package must be performed in an aseptic work area, such as a laminar flow hood, using aseptic technique. • Once the Pharmacy Bulk Package is punctured, it should not be removed from the aseptic work area during the entire 24 hour period of use. • IV tubing and syringes used to administer Gadavist must be discarded at the conclusion of the radiological examination.
The contents of the Pharmacy Bulk Package after initial puncture should be used within 24 hours. Discard any unused portion in accordance with regulations dealing with the disposal of such materials.
Magnevist

Magnevist

The recommended dosage of Magnevist injection is 0.2 mL/kg (0.1 mmol/kg) administered intravenously, at a rate not to exceed 10 mL per 15 seconds. Dosing for patients in excess of 286 lbs has not been studied systematically.

To ensure complete injection of Magnevist, administer 5-mL normal saline flush after the injection. The imaging procedure should be completed within 1 hour of injection of Magnevist injection.

Visually inspect for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.

Discard any unused portion in accordance with regulations dealing with the disposal of such materials.

DOSE AND DURATION OF MAGNEVIST INJECTION BY BODY WEIGHT

BODY WEIGHT

Total Volume, mL*

lb

kg

22

10

2

44

20

4

66

30

6

88

40

8

110

50

10

132

60

12

154

70

14

176

80

16

198

90

18

220

100

20

242

110

22

264

120

24

286

130

26

*Rate of injection: 10 mL/15 seconds

Pharmacy Bulk Package Preparation: NOT FOR DIRECT INFUSION

The Pharmacy Bulk Package contains many single doses and is used with an appropriate transfer device for filling empty sterile syringes.
a. The transfer of Magnevist Injection from the Pharmacy Bulk Package must be performed in an aseptic work area, such as a laminar flow hood, using aseptic technique. b. Once the Pharmacy Bulk Package is punctured, it should not be removed from the aseptic work area during the entire 24-hour period of use. c. The contents of the Pharmacy Bulk Package after initial puncture should be used within 24 hours. d. Any unused Magnevist Injection must be discarded 24 hours after the initial puncture of the bulk package.
IV tubing and syringes used to administer Magnevist Injection must be discarded at the conclusion of the radiological examination.

Any unused portion must be discarded in accordance with regulations dealing with the disposal of such material.
Magnevist

Magnevist

The recommended dosage of Magnevist injection is 0.2 mL/kg (0.1 mmol/kg) administered intravenously, at a rate not to exceed 10 mL per 15 seconds. Dosing for patients in excess of 286 lbs has not been studied systematically.

To ensure complete injection of Magnevist, administer 5-mL normal saline flush after the injection. The imaging procedure should be completed within 1 hour of injection of Magnevist injection.

Visually inspect for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.

Discard any unused portion in accordance with regulations dealing with the disposal of such materials.

DOSE AND DURATION OF MAGNEVIST INJECTION BY BODY WEIGHT

BODY WEIGHT

Total Volume, mL*

lb

kg

22

10

2

44

20

4

66

30

6

88

40

8

110

50

10

132

60

12

154

70

14

176

80

16

198

90

18

220

100

20

242

110

22

264

120

24

286

130

26

*Rate of Injection: 10 mL/15 seconds
Besivance

Besivance

CIPRO IV should be administered intravenously at dosages described in the appropriate Dosage Guidelines tables.

2.1 Dosage in Adults

The determination of dosage and duration for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of the patient’s host-defense mechanisms, and the status of renal and hepatic function.
Table 1: Adult Dosage Guidelines * Due to the designated pathogens (see Indications and Usage.) † Used in conjunction with metronidazole. ‡ Begin administration as soon as possible after suspected or confirmed exposure.
Infection*

Dose

Frequency

Usual Duration

Urinary Tract

200 mg to 400 mg

every 12 to every 8 hours

7–14 days

Lower Respiratory Tract

400 mg

every 12 to every 8 hours

7–14 days

Nosocomial Pneumonia

400 mg

every 8 hours

10–14 days

Skin and Skin Structure

400 mg

every 12 to every 8 hours

7–14 days

Bone and Joint

400 mg

every 12 to every 8 hours

4 to 8 weeks

Complicated Intra-Abdominal†

400 mg

every 12 hours

7–14 days

Acute Sinusitis

400 mg

every 12 hours

10 days

Chronic Bacterial prostatitis

400 mg

every 12 hours

28 days

Empirical Therapy In Febrile Neutropenic Patients

CIPRO IV

400 mg

and

every 8 hours

7–14 days

Piperacillin

50 mg/kg

every 4 hours

Inhalational anthrax(post-exposure)‡

400 mg

every 12 hours

60 days

Plague‡

400 mg

every 12 to 8 hours

14 days

Conversion of Intravenous to Oral Dosing in Adults

Patients whose therapy is started with CIPRO IV may be switched to CIPRO Tablets or Oral Suspension when clinically indicated at the discretion of the physician (Table 2) [see Clinical Pharmacology (12.3)].
Table 2:
CIPRO Oral DEquivalent AUC Dosing Regimensosage

Equivalent CIPRO IV Dosage

250 mg Tablet every 12 hours

200 mg intravenous every 12 hours

500 mg Tablet every 12 h

400 mg intravenous every 12 hours

750 mg Tablet every 12 hours

400 mg intravenous every 8 hours

2.2 Dosage in Pediatric Patients

Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined by the severity of the infection.
Table 3: Pediatric Dosage Guidelines * The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). † Begin drug administration as soon as possible after suspected or confirmed exposure. ‡ Begin drug administration as soon as possible after suspected or confirmed exposure to Y. pestis.
Infection

Dose

(mg/kg)

Frequency

Total Duration

Complicated Urinary Tract or Pyelonephritis

(patients from 1 to 17 years of age)*

6 mg/kg to 10 mg/kg

(maximum 400 mg per dose; not to be exceeded even in patients weighing more than 51 kg)

Every 8 hours

10–21 days

Inhalational Anthrax

(Post-Exposure)†

10 mg/kg

(maximum 400 mg per dose)

Every 12 hours

60 days

Plague†, ‡

10 mg/kg (maximum 400 mg per dose)

Every 12 to 8 hours

10–21 days

2.3 Dosage Modifications in Patients with Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. Dosage guidelines for use in patients with renal impairment are shown in Table 4.
Table 4: Recommended Starting and Maintenance Doses for Adult Patients with Impaired Renal Function
Creatinine Clearance (mL/min)

Dose

>30

See Usual Dosage.

5–29

200–400 mg every 18–24 hours

When only the serum creatinine concentration is known, the following formulas may be used to estimate creatinine clearance:

Men - Creatinine clearance (mL/min) =

Weight (kg) x (140 – age)

72 x serum creatinine (mg/dL)

Women - 0.85 x the value calculated for men.

The serum creatinine should represent a steady state of renal function.

In patients with severe infections and severe renal impairment and hepatic insufficiency, careful monitoring is suggested.

Pediatric patients with moderate to severe renal insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is available on dosing adjustments necessary for pediatric patients with moderate to severe renal insufficiency (that is, creatinine clearance of < 50 mL/min/1.73m2).

2.3 Preparation of CIPRO IV for Administration

Flexible Containers

CIPRO IV is available as a 0.2% premixed solution in 5% dextrose in flexible containers of 200 mL. The solutions in flexible containers do not need to be diluted and may be infused as described above.

2.4 Important Administration Instructions

Intravenous Infusion

CIPRO IV should be administered to by intravenous infusion over a period of 60 minutes. Slow infusion of a dilute solution into a larger vein will minimize patient discomfort and reduce the risk of venous irritation.

Hydration of Patients Receiving CIPRO IV

Adequate hydration of patients receiving CIPRO IV should be maintained to prevent the formation of highly concentrated urine. Crystalluria has been reported with quinolones [see Warnings and Precautions (5.12), Adverse Reactions (6.1), Nonclinical Toxicology (13.2) and Patient Counseling Information (17)].
Desonate

Desonate

Apply a thin layer to the affected areas two times daily and rub in gently. Discontinue use when control is achieved. If no improvement is seen within 4 weeks, reassessment of diagnosis may be necessary. Treatment beyond 4 consecutive weeks is not recommended. Do not use with occlusive dressings. Avoid contact with eyes or other mucous membranes.

For topical use only. Not for oral, ophthalmic, or intravaginal use.
Adempas

Adempas

2.1 Recommended Dosage in Adult Patients

The recommended starting dosage is 1 mg taken 3 times a day. For patients who may not tolerate the hypotensive effect of Adempas, consider a starting dose of 0.5 mg taken three times a day. If systolic blood pressure remains greater than 95 mmHg and the patient has no signs or symptoms of hypotension, up-titrate the dose by 0.5 mg taken three times a day. Dose increases should be no sooner than 2 weeks apart. The dose can be increased to the highest tolerated dosage, up to a maximum of 2.5 mg taken three times a day. If at any time, the patient has symptoms of hypotension, decrease the dosage by 0.5 mg taken three times a day.

2.2 Dosage Interruption

If a dose is missed, advise patients to continue with the next regularly scheduled dose.

In case Adempas is interrupted for 3 days or more, re-titrate Adempas.

2.3 Pregnancy Testing in Females of Reproductive Potential

Obtain pregnancy tests prior to initiation and monthly during treatment [see Use in Specific Populations (8.6)].

2.4 Use in Patients who Smoke

Consider titrating to dosages higher than 2.5 mg three times a day, if tolerated, in patients who smoke. A dose decrease may be required in patients who stop smoking. [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)].

2.5 Strong CYP and P-gp/BCRP Inhibitors

Consider a starting dose of 0.5 mg, three times a day when initiating Adempas in patients receiving strong cytochrome P450 (CYP) and P-glycoprotein/breast cancer resistance protein (P-gp/BCRP) inhibitors such as azole antimycotics (for example, ketoconazole, itraconazole) or HIV protease inhibitors (for example, ritonavir). Monitor for signs and symptoms of hypotension on initiation and on treatment with strong CYP and P-gp/BCRP inhibitors [see Warnings and Precautions (5.3), Drug Interactions (7.2) and Clinical Pharmacology (12.3)].
Eovist

Eovist

2.1 Recommended Dose

The recommended dose of EOVIST is 0.1 mL/kg body weight (0.025 mmol/kg body weight).

2.2 Drug Handling and Administration
• Use sterile technique when preparing and administering EOVIST • Visually inspect EOVIST, supplied in a single-use vial, for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or if particulate matter is present • Use EOVIST immediately after obtaining appropriate dose from vial. The rubber stopper should never be pierced more than once. Discard any unused portion of an EOVIST vial • Administer EOVIST undiluted as an intravenous bolus injection at a flow rate of approximately 2 mL/second • Do not mix EOVIST with other medications and do not administer EOVIST in the same intravenous line simultaneously with other medications • Flush the intravenous cannula with a normal saline solution after EOVIST injection • Imaging can commence immediately following EOVIST administration
2.3 Imaging
• Liver lesions are detected and characterized with pre-contrast MRI and EOVIST MRI obtained during dynamic and hepatocyte imaging phases. Perform a pre-contrast MRI, inject EOVIST and begin dynamic imaging approximately 15–25 seconds after completion of the injection. Dynamic imaging consists of the arterial, the porto-venous (approximately 60 seconds post-injection), and the blood equilibrium (approximately 120 seconds) phases. • Begin the hepatocyte imaging phase approximately 20 minutes post-injection. Hepatocyte phase imaging may be performed up to 120 minutes post-injection. • Elevated intrinsic levels of bilirubin (>3 mg/dL) or ferritin can reduce the hepatic contrast effect of EOVIST. Perform MR imaging no later than 60 minutes following EOVIST administration to patients with these laboratory abnormalities, including patients who have elevated ferritin levels due to hemodialysis [see Warnings and Precautions (5.6) and Use in Specific Populations (8.6, 8.7)]. • Lesions with no or minimal hepatocyte function (cysts, metastases, and the majority of hepatocellular carcinomas) generally will not accumulate EOVIST. Well-differentiated hepatocellular carcinoma may contain functioning hepatocytes and can show some enhancement in the hepatocyte imaging phase. Additional clinical information is therefore needed to support a diagnosis of hepatocellular carcinoma.
Stivarga

Stivarga

2.1 Recommended Dose

The recommended dose is 160 mg regorafenib (four 40 mg tablets) taken orally once daily for the first 21 days of each 28-day cycle. Continue treatment until disease progression or unacceptable toxicity.

Take Stivarga at the same time each day. Swallow tablet whole with water after a low-fat meal that contains less than 600 calories and less than 30% fat [see Clinical Pharmacology (12.3)]. Do not take two doses of Stivarga on the same day to make up for a missed dose from the previous day.

2.2 Dose Modifications

Interrupt Stivarga for the following:
• NCI CTCAE Grade 2 hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia (PPE)] that is recurrent or does not improve within 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 HFSR • Symptomatic Grade 2 hypertension • Any NCI CTCAE Grade 3 or 4 adverse reaction
Reduce the dose of Stivarga to 120 mg:
• For the first occurrence of Grade 2 HFSR of any duration • After recovery of any Grade 3 or 4 adverse reaction • For Grade 3 aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation; only resume if the potential benefit outweighs the risk of hepatotoxicity
Reduce the dose of Stivarga to 80 mg:
• For re-occurrence of Grade 2 HFSR at the 120 mg dose • After recovery of any Grade 3 or 4 adverse reaction at the 120 mg dose (except hepatotoxicity)
Discontinue Stivarga permanently for the following:
• Failure to tolerate 80 mg dose • Any occurrence of AST or ALT more than 20 times the upper limit of normal (ULN) • Any occurrence of AST or ALT more than 3 times ULN with concurrent bilirubin more than 2 times ULN • Re-occurrence of AST or ALT more than 5 times ULN despite dose reduction to 120 mg • For any Grade 4 adverse reaction; only resume if the potential benefit outweighs the risks

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