Anti-diarrheal

Cyclosporine Capsules USP MODIFIED, soft gelatin capsules, has increased bioavailability in comparison to Sandimmune (Cyclosporine Capsules USP). Cyclosporine Capsules USP MODIFIED and Sandimmune (Cyclosporine Capsules USP) are not bioequivalent and cannot be used interchangeably without physician supervision.

The daily dose of Cyclosporine Capsules USP MODIFIED should always be given in two divided doses (BID). It is recommended that Cyclosporine Capsules USP MODIFIED be administered on a consistent schedule with regard to time of day and relation to meals. Grapefruit and grapefruit juice affect metabolism, increasing blood concentration of cyclosporine, thus should be avoided.

Renal Impairment in Kidney, Liver, and Heart Transplantation

Cyclosporine undergoes minimal renal elimination and its pharmacokinetics do not appear to be significantly altered in patients with end-stage renal disease who receive routine hemodialysis treatments (see CLINICAL PHARMACOLOGY). However, due to its nephrotoxic potential (see WARNINGS), careful monitoring of renal function is recommended; cyclosporine dosage should be reduced if indicated (see WARNINGS and PRECAUTIONS).

Renal Impairment in Rheumatoid Arthritis and Psoriasis

Patients with impaired renal function should not receive cyclosporine (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).

The clearance of cyclosporine may be significantly reduced in severe liver disease patients (see CLINICAL PHARMACOLOGY). Dose reduction may be necessary in patients with severe liver impairment to maintain blood concentrations within the recommended target range (see WARNINGS and PRECAUTIONS).

The initial oral dose of Cyclosporine Capsules USP MODIFIED can be given 4 to 12 hours prior to transplantation or be given postoperatively. The initial dose of Cyclosporine Capsules USP MODIFIED varies depending on the transplanted organ and the other immunosuppressive agents included in the immunosuppressive protocol. In newly transplanted patients, the initial oral dose of Cyclosporine Capsules USP MODIFIED is the same as the initial oral dose of Sandimmune (Cyclosporine Capsules USP). Suggested initial doses are available from the results of a 1994 survey of the use of Sandimmune (Cyclosporine Capsules USP) in US transplant centers. The mean ± SD initial doses were 9 ± 3 mg/kg/day for renal transplant patients (75 centers), 8 ± 4 mg/kg/day for liver transplant patients (30 centers), and 7 ± 3 mg/kg/day for heart transplant patients (24 centers). Total daily doses were divided into two equal daily doses. The Cyclosporine Capsules USP MODIFIED dose is subsequently adjusted to achieve a pre-defined cyclosporine blood concentration (see Blood Concentration Monitoring in Transplant Patients, below). If cyclosporine trough blood concentrations are used, the target range is the same for Cyclosporine Capsules USP MODIFIED as for Sandimmune (Cyclosporine Capsules USP). Using the same trough concentration target range for Cyclosporine Capsules USP MODIFIED as for Sandimmune (Cyclosporine Capsules USP) results in greater cyclosporine exposure when Cyclosporine Capsules USP MODIFIED are administered (see Pharmacokinetics, Absorption). Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower Cyclosporine Capsules USP MODIFIED doses may be sufficient as maintenance therapy.

Adjunct therapy with adrenal corticosteroids is recommended initially. Different tapering dosage schedules of prednisone appear to achieve similar results. A representative dosage schedule based on the patient’s weight started with 2 mg/kg/day for the first 4 days tapered to 1 mg/kg/day by 1 week, 0.6 mg/kg/day by 2 weeks, 0.3 mg/kg/day by 1 month, and 0.15 mg/kg/day by 2 months and thereafter as a maintenance dose. Steroid doses may be further tapered on an individualized basis depending on status of patient and function of graft. Adjustments in dosage of prednisone must be made according to the clinical situation.

In transplanted patients who are considered for conversion to Cyclosporine Capsules USP MODIFIED from Sandimmune (Cyclosporine Capsules USP), Cyclosporine Capsules USP MODIFIED should be started with the same daily dose as was previously used with Sandimmune (Cyclosporine Capsules USP) (1:1 dose conversion). The Cyclosporine Capsules USP MODIFIED dose should subsequently be adjusted to attain the pre-conversion cyclosporine blood trough concentration. Using the same trough concentration target range for Cyclosporine Capsules USP MODIFIED as for Sandimmune (Cyclosporine Capsules USP) results in greater cyclosporine exposure when Cyclosporine Capsules USP MODIFIED are administered (see Pharmacokinetics, Absorption). Patients with suspected poor absorption of Sandimmune (Cyclosporine Capsules USP) require different dosing strategies (see Transplant Patients with Poor Absorption of Sandimmune (Cyclosporine Capsules USP), below). In some patients, the increase in blood trough concentration is more pronounced and may be of clinical significance.

Until the blood trough concentration attains the pre-conversion value, it is strongly recommended that the cyclosporine blood trough concentration be monitored every 4 to 7 days after conversion to Cyclosporine Capsules USP MODIFIED. In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored every two weeks during the first two months after conversion. If the blood trough concentrations are outside the desired range and/or if the clinical safety parameters worsen, the dosage of Cyclosporine Capsules USP MODIFIED must be adjusted accordingly.

Patients with lower than expected cyclosporine blood trough concentrations in relation to the oral dose of Sandimmune (Cyclosporine Capsules USP) may have poor or inconsistent absorption of cyclosporine from Sandimmune (Cyclosporine Capsules USP). After conversion to Cyclosporine Capsules USP MODIFIED, patients tend to have higher cyclosporine concentrations. Due to the increase in bioavailability of cyclosporine following conversion to Cyclosporine Capsules USP MODIFIED, the cyclosporine blood trough concentration may exceed the target range. Particular caution should be exercised when converting patients to Cyclosporine Capsules USP MODIFIED at doses greater than 10 mg/kg/day. The dose of Cyclosporine Capsules USP MODIFIED should be titrated individually based on cyclosporine trough concentrations, tolerability, and clinical response. In this population the cyclosporine blood trough concentration should be measured more frequently, at least twice a week (daily, if initial dose exceeds 10 mg/kg/day) until the concentration stabilizes within the desired range.

The initial dose of Cyclosporine Capsules USP MODIFIED is 2.5 mg/kg/day, taken twice daily as a divided (BID) oral dose. Salicylates, NSAIDs, and oral corticosteroids may be continued (see WARNINGS and PRECAUTIONS, Drug Interactions). Onset of action generally occurs between 4 and 8 weeks. If insufficient clinical benefit is seen and tolerability is good (including serum creatinine less than 30% above baseline), the dose may be increased by 0.5 to 0.75 mg/kg/day after 8 weeks and again after 12 weeks to a maximum of 4 mg/kg/day. If no benefit is seen by 16 weeks of therapy, Cyclosporine Capsules USP MODIFIED therapy should be discontinued.

Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension elevations in serum creatinine (30% above patient’s pretreatment level) or clinically significant laboratory abnormalities (see WARNINGS and PRECAUTIONS).

If dose reduction is not effective in controlling abnormalities or if the adverse event or abnormality is severe, Cyclosporine Capsules USP MODIFIED should be discontinued. The same initial dose and dosage range should be used if Cyclosporine Capsules USP MODIFIED are combined with the recommended dose of methotrexate. Most patients can be treated with Cyclosporine Capsules USP MODIFIED doses of 3 mg/kg/day or below when combined with methotrexate doses of up to 15 mg/week (see CLINICAL PHARMACOLOGY, Clinical Trials).

There is limited long-term treatment data. Recurrence of rheumatoid arthritis disease activity is generally apparent within 4 weeks after stopping cyclosporine.

The initial dose of Cyclosporine Capsules USP MODIFIED should be 2.5 mg/kg/day. Cyclosporine Capsules USP MODIFIED should be taken twice daily, as a divided (1.25 mg/kg BID) oral dose. Patients should be kept at that dose for at least 4 weeks, barring adverse events. If significant clinical improvement has not occurred in patients by that time, the patient’s dosage should be increased at 2 week intervals. Based on patient response, dose increases of approximately 0.5 mg/kg/day should be made to a maximum of 4 mg/kg/day.

Dose decreases by 25% to 50% should be made at any time to control adverse events, e.g., hypertension, elevations in serum creatinine (≥ 25% above the patient’s pretreatment level), or clinically significant laboratory abnormalities. If dose reduction is not effective in controlling abnormalities, or if the adverse event or abnormality is severe, Cyclosporine Capsules USP MODIFIED should be discontinued (see Special Monitoring for Psoriasis Patients).

Patients generally show some improvement in the clinical manifestations of psoriasis in 2 weeks. Satisfactory control and stabilization of the disease may take 12 to 16 weeks to achieve. Results of a dose-titration clinical trial with Cyclosporine Capsules USP MODIFIED indicate that an improvement of psoriasis by 75% or more (based on PASI) was achieved in 51% of the patients after 8 weeks and in 79% of the patients after 16 weeks. Treatment should be discontinued if satisfactory response cannot be achieved after 6 weeks at 4 mg/kg/day or the patient’s maximum tolerated dose. Once a patient is adequately controlled and appears stable the dose of Cyclosporine Capsules USP MODIFIED should be lowered, and the patient treated with the lowest dose that maintains an adequate response (this should not necessarily be total clearing of the patient). In clinical trials, cyclosporine doses at the lower end of the recommended dosage range were effective in maintaining a satisfactory response in 60% of the patients. Doses below 2.5 mg/kg/day may also be equally effective.

Upon stopping treatment with cyclosporine, relapse will occur in approximately 6 weeks (50% of the patients) to 16 weeks (75% of the patients). In the majority of patients rebound does not occur after cessation of treatment with cyclosporine. Thirteen cases of transformation of chronic plaque psoriasis to more severe forms of psoriasis have been reported. There were 9 cases of pustular and 4 cases of erythrodermic psoriasis. Long term experience with Cyclosporine Capsules USP MODIFIED in psoriasis patients is limited and continuous treatment for extended periods greater than one year is not recommended. Alternation with other forms of treatment should be considered in the long term management of patients with this life long disease.

Transplant centers have found blood concentration monitoring of cyclosporine to be an essential component of patient management. Of importance to blood concentration analysis are the type of assay used, the transplanted organ, and other immunosuppressant agents being administered. While no fixed relationship has been established, blood concentration monitoring may assist in the clinical evaluation of rejection and toxicity, dose adjustments, and the assessment of compliance.

Various assays have been used to measure blood concentrations of cyclosporine. Older studies using a nonspecific assay often cited concentrations that were roughly twice those of the specific assays. Therefore, comparison between concentrations in the published literature and an individual patient concentration using current assays must be made with detailed knowledge of the assay methods employed. Current assay results are also not interchangeable and their use should be guided by their approved labeling. A discussion of the different assay methods is contained in Annals of Clinical Biochemistry 1994;31:420-446. While several assays and assay matrices are available, there is a consensus that parent-compound-specific assays correlate best with clinical events. Of these, HPLC is the standard reference, but the monoclonal antibody RIAs and the monoclonal antibody FPIA offer sensitivity, reproducibility, and convenience. Most clinicians base their monitoring on trough cyclosporine concentrations. Applied Pharmacokinetics, Principles of Therapeutic Drug Monitoring (1992) contains a broad discussion of cyclosporine pharmacokinetics and drug monitoring techniques. Blood concentration monitoring is not a replacement for renal function monitoring or tissue biopsies.

Glimepiride tablets should be administered with breakfast or the first main meal of the day.

The recommended starting dose of glimepiride tablet is 1 mg or 2 mg once daily. Patients at increased risk for hypoglycemia (e.g., the elderly or patients with renal impairment) should be started on 1 mg once daily [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.5, 8.6)].

After reaching a daily dose of 2 mg, further dose increases can be made in increments of 1 mg or 2 mg based upon the patient’s glycemic response. Uptitration should not occur more frequently than every 1 to 2 weeks. A conservative titration scheme is recommended for patients at increased risk for hypoglycemia [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.5, 8.6)].

The maximum recommended dose is 8 mg once daily.

Patients being transferred to glimepiride from longer half-life sulfonylureas (e.g., chlorpropamide) may have overlapping drug effect for 1 to 2 weeks and should be appropriately monitored for hypoglycemia.

When colesevelam is coadministered with glimepiride, maximum plasma concentration and total exposure to glimepiride is reduced. Therefore, glimepiride should be administered at least 4 hours prior to colesevelam.

Dissolve one (1) strip under the tongue daily. It may take up to 15 doses to start relief.

drink plenty of clear fluids to help prevent dehydration,which may accompany diarrhea

Wet hands thoroughly. Rub product into hands and allow to dry. Do not rinse. Wash hands with water and hand cleanser after every 7-9 applications. For use when hands are not visibly soiled.

Table 1 (Recommended Dosages) summarizes the recommended volumes and concentrations of Xylocaine Injection for various types of anesthetic procedures.  The dosages suggested in this table are for normal healthy adults and refer to the use of epinephrine-free solutions.  When larger volumes are required, only solutions containing epinephrine should be used except in those cases where vasopressor drugs may be contraindicated.

There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures.  Xylocaine is not approved for this use (see WARNINGS and DOSAGE AND ADMINISTRATION).

These recommended doses serve only as a guide to the amount of anesthetic required for most routine procedures.  The actual volumes and concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required, duration of anesthesia required, and the physical condition of the patient.  In all cases the lowest concentration and smallest dose that will produce the desired result should be given.  Dosages should be reduced for children and for the elderly and debilitated patients and patients with cardiac and/or liver disease.

The onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are proportional to the volume and concentration (ie, total dose) of local anesthetic used.  Thus, an increase in volume and concentration of Xylocaine Injection will decrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increase the segmental spread of anesthesia.  However, increasing the volume and concentration of Xylocaine Injection may result in a more profound fall in blood pressure when used in epidural anesthesia.  Although the incidence of side effects with lidocaine HCl is quite low, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directly proportional to the total dose of local anesthetic agent injected.

For intravenous regional anesthesia, only the 50 mL single dose vial containing Xylocaine (lidocaine HCl) 0.5% Injection should be used.

For epidural anesthesia, only the following dosage forms Xylocaine Injection are recommended:

1% without epinephrine                         10 mL Plastic Ampule

1% without epinephrine                         30 mL single dose solutions

1% with epinephrine   1:200,000           30 mL single dose solutions

1.5% without epinephrine                      10 mL Plastic Ampule

1.5% without epinephrine                      20 mL Plastic Ampule

1.5% with epinephrine  1:200,000          30 mL ampules, 30 mL single dose solutions

2% without epinephrine                         10 mL Plastic Ampule

2% with epinephrine   1:200,000           20 mL ampules, 20 mL single dose solutions

Although these solutions are intended specifically for epidural anesthesia, they may also be used for infiltration and peripheral nerve block, provided they are employed as single dose units.  These solutions contain no bacteriostatic agent. 

In epidural anesthesia, the dosage varies with the number of dermatomes to be anesthetized (generally 2 to 3 mL of the indicated concentration per dermatome).

As a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space, a test dose such as 2 to 3 mL of 1.5% lidocaine HCl should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block.  The test dose should be repeated if the patient is moved in a manner that may have displaced the catheter.  Epinephrine, if contained in the test dose (10 to 15 mcg have been suggested), may serve as a warning of unintentional intravascular injection.  If injected into a blood vessel, this amount of epinephrine is likely to produce a transient “epinephrine response” within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient.  The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds.  Patients on beta blockers may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in systolic blood pressure.  Adequate time should be allowed for onset of anesthesia after administration of each test dose.  The rapid injection of a large volume of Xylocaine Injection through the catheter should be avoided, and, when feasible, fractional doses should be administered.

In the event of the known injection of a large volume of local anesthetic solution into the subarachnoid space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural catheter.

For epidural anesthesia, only the following dosage forms Xylocaine Injection are recommended:

1% without epinephrine                         10 mL Plastic Ampule

1% without epinephrine                         30 mL single dose solutions

1% with epinephrine   1:200,000           30 mL single dose solutions

1.5% without epinephrine                      10 mL Plastic Ampule

1.5% without epinephrine                      20 mL Plastic Ampule

1.5% with epinephrine  1:200,000          30 mL ampules, 30 mL single dose solutions

2% without epinephrine                         10 mL Plastic Ampule

2% with epinephrine   1:200,000           20 mL ampules, 20 mL single dose solutions

Although these solutions are intended specifically for epidural anesthesia, they may also be used for infiltration and peripheral nerve block, provided they are employed as single dose units.  These solutions contain no bacteriostatic agent. 

In epidural anesthesia, the dosage varies with the number of dermatomes to be anesthetized (generally 2 to 3 mL of the indicated concentration per dermatome).

As a precaution against the adverse experience sometimes observed following unintentional penetration of the subarachnoid space, a test dose such as 2 to 3 mL of 1.5% lidocaine HCl should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block.  The test dose should be repeated if the patient is moved in a manner that may have displaced the catheter.  Epinephrine, if contained in the test dose (10 to 15 mcg have been suggested), may serve as a warning of unintentional intravascular injection.  If injected into a blood vessel, this amount of epinephrine is likely to produce a transient “epinephrine response” within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient.  The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds.  Patients on beta blockers may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in systolic blood pressure.  Adequate time should be allowed for onset of anesthesia after administration of each test dose.  The rapid injection of a large volume of Xylocaine Injection through the catheter should be avoided, and, when feasible, fractional doses should be administered.

In the event of the known injection of a large volume of local anesthetic solution into the subarachnoid space, after suitable resuscitation and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural catheter.

drink plenty of clear fluids to help prevent dehydration caused by diarrhea

find right dose on chart. If possible, use weight to dose; otherwise, use age.

Administer gabapentin oral solution orally with or without food.

If the gabapentin oral solution dose is reduced, discontinued, or substituted with an alternative medication, this should be done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the prescriber).

In adults with postherpetic neuralgia, gabapentin oral solution may be initiated on Day 1 as a single 300 mg dose, on Day 2 as 600 mg/day (300 mg two times a day), and on Day 3 as 900 mg/day (300 mg three times a day). The dose can subsequently be titrated up as needed for pain relief to a dose of 1800 mg/day (600 mg three times a day). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range; however, in these clinical studies, the additional benefit of using doses greater than 1800 mg/day was not demonstrated.

Patients 12 years of age and above

The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin oral solution is 300 mg to 600 mg three times a day. Dosages up to 2400 mg/day have been well tolerated in long-term clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a relatively short duration, and have been well tolerated. Administer gabapentin oral solution three times a day using 300 mg or 400 mg capsules, or 600 mg or 800 mg tablets. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years

The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the recommended maintenance dose reached by upward titration over a period of approximately 3 days. The recommended maintenance dose of gabapentin oral solution in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses. The recommended maintenance dose of gabapentin oral solution in patients 5 to 11 years of age is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Gabapentin oral solution may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. Dosages up to 50 mg/kg/day have been well tolerated in a long-term clinical study. The maximum time interval between doses should not exceed 12 hours.

Dosage adjustment in patients 12 years of age and older with renal impairment or undergoing hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in each indication):

TABLE 1. Gabapentin Oral SolutionDosage Based on Renal Function

Renal Function
Creatinine Clearance
(mL/min)

Total Daily
Dose Range
(mg/day)

Dose Regimen
(mg)

≥ 60

900 to 3600

300 TID

400 TID

600 TID

800 TID

1200 TID

>30 to 59

400 to 1400

200 BID

300 BID

400 BID

500 BID

700 BID

>15 to 29

200 to 700

200 QD

300 QD

400 QD

500 QD

700 QD

15a

100 to 300

100 QD

125 QD

150 QD

200 QD

300 QD

Post-Hemodialysis Supplemental Dose (mg)b

Hemodialysis

125b

150b

200b

250b

350b

TID = Three times a day; BID = Two times a day; QD = Single daily dose

a For patients with creatinine clearance <15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).

b Patients on hemodialysis should receive maintenance doses based on estimates of creatinine clearance as indicated in the upper portion of the table and a supplemental post-hemodialysis dose administered after each 4 hours of hemodialysis as indicated in the lower portion of the table.

Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

The use of gabapentin oral solution in patients less than 12 years of age with compromised renal function has not been studied.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.

The dose is one drop of dorzolamide hydrochloride ophthalmic solution in the affected eye(s) three times daily. Dorzolamide hydrochloride ophthalmic solution may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

age

dose

adults and children

12 years and over

10 mL

every 4 hours

children under 12 years

do not use

The dosage of EPANOVA is 2 grams (2 capsules) or 4 grams (4 capsules) once daily. The dosage should be individualized according to the patient’s response and tolerability. In clinical trials, EPANOVA was administered without regard to meals.

Patients should be advised to swallow EPANOVA capsules whole. Do not break open, crush, dissolve or chew EPANOVA.

adults and children
12 years and over

2 caplets after the first loose
stool; 1 caplet after each
subsequent loose stool; but
no more than 4 caplets in
24 hours