Info

Brand Name

Rapamune®

Company

Wyeth-Ayerst

Class

• Kinase inhibitor macrocyclic lactone antibiotic with immunosup-pressant properties

Mechanism of Action

• Binds to an immunophilin protein to form a complex which inhibits the activation of the mammalian Target of Rapamycin (mTOR)ulatory kinase. This inhibits T lymphocyte activation and proliferation by IL-2, IL-4, and IL-5.

Indications

• The prophylaxis of organ rejection in patients receiving renal transplants.

Contraindications

• Hypersensitivity to sirolimus or its derivatives or any component of the drug product.

Warnings

• Increased risk of infection and lymphomas.

Special Precautions

• Increased serum cholesterol and triglycerides.

• Lymphocele

• Impaired renal function in combination with cyclosporine

• Pregnancy Category C

Adverse Reactions

• Hypokalemia • Thrombocytopenia

• Leukopenia • Fever

Drug Interactions

• Sirolimus is known to be a substrate for both cytochrome CYP3A4 and P-glycoprotein.

Drugs that Increase Sirolimus Levels

• Cyclosporine (amount affected by coadministration schedule and formulation).

• Diltiazem • Ketoconazole

Drugs that may Increase Sirolimus Levels Include:

• Calcium channel blockers: nicardipine, verapamil

• Antifungal agents: clotrimazole, fluconazole, itraconazole

• Macrolide antibiotics: clarithromycin, erythromycin, troleandomycin

• Gastrointestinal prokinetic agents: cisapride, metoclopramide

• Other drugs: bromocriptine, cimetidine, danazol, HIV-protease inhibitors (e.g., ritonavir, indinavir)

• Grapefruit and grapefruit juice may increase sirolimus concentrations.

Drugs that may Decrease Sirolimus Levels Include:

• Anticonvulsants: carbamazepine, phenobarbital, phenytoin

• Antibiotics: rifabutin, rifapentine

• Herbal preparations: St. John's Wort (hypericum perforatum) could result in reduced sirolimus levels.

Formulations

• Oral solution in a concentration of 1 mg/ml in:

2 oz (60 ml fill) amber glass bottles 5 oz (150 ml fill) amber glass bottles

• Cartons containing 30 unit-of-use laminated aluminum pouches of 1 ml, 2 ml and 5 ml

• 1 mg tablets supplied in a bottle of 100 tablets

• 1 mg tablets supplied in a carton of 100 tablets (10 blister cards of 10 tablets each)

Dosage

• De novo transplant recipients, a loading dose of sirolimus of 3 times the maintenance dose should be given. A daily maintenance dose of 2 mg is recommended for use in renal transplant patients, with a loading dose of 6mg.

• The initial dose in patients >12 years old, who weigh less than 40 kg the loading dose should be 3 mg/m2 followed by 1 mg/m2/day.

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