📋 Indications & Clinical 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 & Warnings
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then be withdrawn over 4-8 weeks (if not possible,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.
🔄 Drug 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
⚠️ Adverse Reactions / 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)
🤰 Pregnancy & Lactation Safety
Pregnancy Risk:
Contraindicated, use contraceptives
during treatment and for 12 weeks after the last
dose.
Lactation / Breastfeeding:
Contraindicated discontinue
breast-feeding
📚 Official Regulatory & Clinical References
- Drug Regulatory Authority of Pakistan (DRAP): Drug Registration, S.R.O. Price Gazettes & National Essential Medicines List (NEML).
- World Health Organization (WHO): Collaborating Centre for Drug Statistics Methodology (ATC/DDD Index).
- Formulary Standards: British National Formulary (BNF) & Pakistan National Formulary (PNF) guidelines.