CYCLOSPORINE

It is a cyclic polypeptide containing 11 amino acids. It suppresses humoral immunity and to a great extent, cell-mediated reactions. This action is due to a specific and reversible inhibition of immunocompetent lymphocytes in the G0 or G1 phases of cell cycle. T-helper cells are the main target but T-suppressor cells are also suppressed. Cyclosporine also inhibits lympholine production and release.

Indications

Orally used for prevention of graft rejection after kidney, liver, heart, lung, pancreas. By IV infusion used in bone marrow transplant.

Dosage

Oral: First dose given 4-12 hrs. before the transplantation, 10-15 mg/kg. This dose in continued daily for 1-2 weeks after which a maintenance dose of 2-6 mg/kg/day is continued. IV infusion: Starting dose one day before the transplantation 3-5 mg/kg/day. Continue for 2 weeks after transplant. Then oral maintenance dose of 12.5 mg/kg/day in 2 divided doses for 6 months to a year.

Contra-Indications

Hypersensitivity, lactation.

Special Precautions

Dose should be carefully titrated. Renal and/or hepatic impairment, possibility of hyperkalaemia, hypertension, vaccinations are less effective. Paediatrics: Use with caution. Pregnancy: Safety has not been established. Lactation: Safety has not been established. Elderly: Reduced dose may be necessary.

Side Effects

Kidney damage, convulsions, hypertension, liver damage, tremor, hirsutism, gingival hypertrophy, hyperkalaemia, fluid retention, increased susceptibility to infectons, GI symptoms.

Drug Interactions

Additive nephrotoxicity due to aminoglycosides, amphotericin B, ciprofloxacin, colchicine, melphalan, co-trimoxazole, NSAIDs. Cyclosporine blood levels increased by diltiazem, doxycycline, erythromycin, ketoconazole, methyl-prednisolone, nicardipine, verapamil, oral contraceptives. Carbamazepine, isoniazid, phenobarbitone, phenytoin, rifampicin reduce cyclosporine levels.