"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
Sandimmune® (cyclosporine) is indicated for the prophylaxis of organ rejection in kidney, liver, and heart allogeneic transplants. It is always to be used with adrenal corticosteroids. The drug may also be used in the treatment of chronic rejection in patients previously treated with other immunosuppressive agents.
Because of the risk of anaphylaxis, Sandimmune® Injection (cyclosporine injection, USP) should be reserved for patients who are unable to take the soft gelatin capsules or oral solution.
DOSAGE AND ADMINISTRATION
Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP) and Sandimmune® Oral Solution (cyclosporine oral solution, USP)
Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP) and Sandimmune® Oral Solution (cyclosporine oral solution, USP) have decreased bioavailability in comparison to Neoral® Soft Gelatin Capsules (cyclosporine capsules, USP) MODIFIED and Neoral® Oral Solution (cyclosporine oral solution, USP) MODIFIED. Sandimmune® and Neoral® are not bioequivalent and cannot be used interchangeably without physician supervision.
The initial oral dose of Sandimmune® (cyclosporine) should be given 4-12 hours prior to transplantation as a single dose of 15 mg/kg. Although a daily single dose of 14-18 mg/kg was used in most clinical trials, few centers continue to use the highest dose, most favoring the lower end of the scale. There is a trend towards use of even lower initial doses for renal transplantation in the ranges of 10-14 mg/kg/day. The initial single daily dose is continued postoperatively for 1-2 weeks and then tapered by 5% per week to a maintenance dose of 5-10 mg/kg/day. Some centers have successfully tapered the maintenance dose to as low as 3 mg/kg/day in selected renal transplant patients without an apparent rise in rejection rate.
(See Blood Concentration Monitoring, below.)
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)
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)
In pediatric usage, the same dose and dosing regimen may be used as in adults although in several studies, children have required and tolerated higher doses than those used in adults.
Adjunct therapy with adrenal corticosteroids is recommended. Different tapering dosage schedules of prednisone appear to achieve similar results. A dosage schedule based on the patient's weight started with 2.0 mg/kg/day for the first 4 days tapered to 1.0 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. Another center started with an initial dose of 200 mg tapered by 40 mg/day until reaching 20 mg/day. After 2 months at this dose, a further reduction to 10 mg/day was made. Adjustments in dosage of prednisone must be made according to the clinical situation.
To make Sandimmune® Oral Solution (cyclosporine oral solution, USP) more palatable, the oral solution may be diluted with milk, chocolate milk, or orange juice preferably at room temperature. Patients should avoid switching diluents frequently. Sandimmune® Soft Gelatin Capsules and Oral Solution should be administered on a consistent schedule with regard to time of day and relation to meals.
Take the prescribed amount of Sandimmune® (cyclosporine) from the container using the dosage syringe supplied after removal of the protective cover, and transfer the solution to a glass of milk, chocolate milk, or orange juice. Stir well and drink at once. Do not allow to stand before drinking. It is best to use a glass container and rinse it with more diluent to ensure that the total dose is taken. After use, replace the dosage syringe in the protective cover. Do not rinse the dosage syringe with water or other cleaning agents either before or after use. If the dosage syringe requires cleaning, it must be completely dry before resuming use. Introduction of water into the product by any means will cause variation in dose.
Sandimmune® Injection (cyclosporine injection, USP)
FOR INFUSION ONLY
Note: Anaphylactic reactions have occurred with Sandimmune® Injection (cyclosporine injection, USP). (See WARNINGS)
Patients unable to take Sandimmune® Soft Gelatin Capsules or Oral Solution pre- or postoperatively may be treated with the I.V. concentrate. Sandimmune® Injection (cyclosporine injection, USP) is administered at 1/3 the oral dose. The initial dose of Sandimmune® Injection (cyclosporine injection, USP) should be given 4-12 hours prior to transplantation as a single I.V. dose of 5-6 mg/kg/day. This daily single dose is continued postoperatively until the patient can tolerate the soft gelatin capsules or oral solution. Patients should be switched to Sandimmune® Soft Gelatin Capsules or Oral Solution as soon as possible after surgery. In pediatric usage, the same dose and dosing regimen may be used, although higher doses may be required.
Adjunct steroid therapy is to be used. (See aforementioned.)
Immediately before use, the I.V. concentrate should be diluted 1 mL Sandimmune® Injection (cyclosporine injection, USP) in 20 mL-100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection and given in a slow intravenous infusion over approximately 2-6 hours.
Diluted infusion solutions should be discarded after 24 hours.
The Cremophor® EL (polyoxyethylated castor oil) contained in the concentrate for intravenous infusion can cause phthalate stripping from PVC.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Blood Concentration Monitoring
Several study centers have found blood concentration monitoring of cyclosporine useful in patient management. While no fixed relationships have yet been established, in one series of 375 consecutive cadaveric renal transplant recipients, dosage was adjusted to achieve specific whole blood 24-hour trough concentrations of 100-200 ng/mL as determined by high-pressure liquid chromatography (HPLC).
Of major importance to blood concentration analysis is the type of assay used. The above concentrations are specific to the parent cyclosporine molecule and correlate directly to the new monoclonal specific radioimmunoassays (mRIA-sp). Nonspecific assays are also available which detect the parent compound molecule and various of its metabolites. Older studies often cited concentrations using a nonspecific assay which were roughly twice those of specific assays. Assay results are not interchangeable and their use should be guided by their approved labeling. If plasma specimens are employed, concentrations will vary with the temperature at the time of separation from whole blood. Plasma concentrations may range from 1/2-1/5 of whole blood concentrations. Refer to individual assay labeling for complete instructions. In addition, Transplantation Proceedings (June 1990) contains position papers and a broad consensus generated at the Cyclosporine-Therapeutic Drug Monitoring conference that year. Blood concentration monitoring is not a replacement for renal function monitoring or tissue biopsies.
Sandimmune® Soft Gelatin Capsules (cyclosporine capsules, USP)
25 mg: Oblong, pink, branded “78/240”. Unit dose packages of 30 capsules, 3 blister cards of 10 capsules .NDC 0078-0240-15
100 mg: Oblong, dusty rose, branded “78/241”. Unit dose packages of 30 capsules, 3 blister cards of 10 capsules .NDC 0078-0241-15
Store and Dispense
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].
An odor may be detected upon opening the unit dose container, which will dissipate shortly thereafter. This odor does not affect the quality of the product.
Sandimmune® Oral Solution (cyclosporine oral solution, USP)
Supplied in 50 mL bottles containing 100 mg of cyclosporine per mL …………………. NDC 0078-0110-22
A dosage syringe is provided for dispensing.
Store and Dispense
In the original container at temperatures below 30°C (86°F). Do not store in the refrigerator. Protect from freezing. Once opened, the contents must be used within 2 months.
Sandimmune® Injection (cyclosporine injection, USP)
FOR INTRAVENOUS INFUSION
Supplied as a 5 mL sterile ampul containing 50 mg of cyclosporine per mL, in boxes of 10 ampuls ..NDC 0078-0109-01 Store and Dispense: At temperatures below 30°C (86°F). Protect from light. FOR INFUSION ONLY
Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936
Last reviewed on RxList: 5/17/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Sandimmune Information
Sandimmune - User Reviews
Sandimmune User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.