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RAPAMUNE

SIROLIMUS · by PFIZER

IMMUNOSUPPRESSANTS Non-calcineurin inhibiting immunosuppressant PFIZER

Composition

Cap 0.5 mg/1 mg: Sirolimus 0.5 mg/1 mg

Indications & Dosage

Prophylaxis of organ rejection in kidney allograft recipients: Adult: Initially 6 mg for 1 dose, after surgery once wound has healed, then 2 mg once daily; in combination with ciclosporin and corticosteroid for 2-3 months dose to be adjusted according to whole blood-sirolimus trough concentration.

Precautions

Sirolimus doses should be given 4 hours after ciclosporin, ciclosporin should then be withdrawn over 4-8 weeks (if not possible, sirolimus should be discontinued and an alternate immunosuppressive regimen used), increased risk of infections (especially urinary tract infection), hyperlipidaemia, increased susceptibility to lymphoma and other malignancies, particularly of the skin, avoid exposure to UV light. Precaution in mild to moderate hepatic impairment, dose adjustment is required in severe hepatic impairment; decrease dose by half and monitor whole blood-sirolimus trough concentration every 5-7 days.

Interactions

Antiarrhythmics (amiodarone, dronedarone) Antiepileptics (carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone) Antifungals, azoles, Macrolides, aprepitant, bosentan, Calcium channel blockers (diltiazem, verapamil), HIV-protease inhibitors, Live vaccines, Monoclonal antibodies, other immunosuppressants, Grapefruit juice increases the concentration of sirolimus

Pregnancy

Contraindicated, use contraceptives during treatment and for 12 weeks after the last dose.

Lactation

Contraindicated discontinue breast-feeding

Side Effects

Anaemia, headache, fever, abdominal pain, nausea, diarrhoea, constipation, arthralgia, ascites, diabetes mellitus, dyslipidaemia, electrolyte imbalance, embolism and thrombosis, hypertension, haemorrhage, haemolytic uraemic syndrome, hyperglycaemia, leucopenia, lymphatic vessel disorders, menstrual cycle irregularities, ovarian cyst, neoplasms, neutropenia, oedema, osteonecrosis, pancreatitis, pericardial effusion, proteinuria, respiratory disorders, sepsis, skin reactions, stomatitis, tachycardia, thrombocytopenia. Rare: focal segmental glomerulosclerosis, nephrotic syndrome, pancytopenia, post transplant lymphoproliferative disorder and posterior reversible encephalopathy syndrome (PRES)