Generic Name and Formulations:
Sirolimus 1mg/mL; contains alcohol.

Company:
Pfizer Inc.
Indications for RAPAMUNE ORAL SOLUTION:
Organ rejection prophylaxis in renal transplant patients, in combination with cyclosporine and corticosteroids.

Adult:
Tabs and oral soln are interchangeable up to 2mg. Dilute soln with water or orange juice only. Take once daily, consistently with or without food (absorption increased by high-fat meals). Swallow tabs whole. Give as soon as possible after transplantation in combination with cyclosporine and corticosteroids, 4 hours after cyclosporine dose. Low- to moderate-immunologic risk (≥13yrs): Loading dose: 6mg, maintenance dose: initially 2mg/day. Adjust maintenance dose at 7‒14 day intervals to achieve trough concentration target range (see literature); max 40mg/day. May give loading dose in addition to new maintenance dose when increasing trough levels; give loading dose over 2 days if maintenance dose plus loading dose is >40mg/day. Withdraw cyclosporine 2‒4 months after transplantation progressively over 4‒8 weeks; adjust sirolimus dose to achieve trough concentration target range 16‒24ng/mL for first year, then 12‒20ng/mL thereafter. High-immunologic risk (≥18yrs): Loading dose: 15mg on day 1, maintenance dose starting on day 2: initially 5mg/day; obtain trough level between days 5‒7, adjust dose to achieve trough concentration target range 10‒15ng/mL. Hepatic impairment (mild or moderate): reduce maintenance dose by ⅓; severe: reduce maintenance dose by ½. Low body weight (<40kg): Loading dose: 3mg/m2; maintenance dose: initially 1mg/m2/day.

Children:
<13yrs: not recommended.

See Also:
RAPAMUNE

Pharmacological Class:
Immunosuppressant.

Warnings/Precautions:
Liver or lung transplants: not recommended. Increased risk of infections, lymphomas and other malignancies (eg, skin). Avoid sun, UV light. Hepatic impairment. Monitor sirolimus blood concentrations (obtain trough level 3‒4 days after a loading dose), renal function, lipids, urine protein and for viral infections (eg, BK virus-associated nephropathy). Antimicrobial prophylaxis for PCP and CMV: see literature. Delayed would healing (esp. BMI >30kg/m2). Pregnancy (Cat.C; use effective contraception before, during, and for 12 weeks after therapy), nursing mothers: not recommended.

Interactions:
Avoid live vaccines. Potentiated by cyclosporine, separate dose by 4 hours; increase sirolimus dose after cyclosporine withdrawal. Increased risk of angioedema with ACE-inhibitors. Potentiated by CYP3A4 and/or P-glycoprotein inhibitors (eg, cimetidine, diltiazem, protease inhibitors, verapamil, grapefruit juice); avoid strong inhibitors (eg, azole antifungals, erythromycin, telithromycin, clarithromycin). Antagonized by CYP3A4 and/or P-glycoprotein inducers (eg, carbamazepine, phenobarbital, phenytoin, St. Johns wort); avoid strong inducers (eg, rifampin, rifabutin). Potentiates verapamil. Additive nephrotoxicity with cyclosporine, aminoglycosides, amphotericin B. Increased risk of hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, thrombotic microangiopathy with concomitant calcineurin inhibitor.

Adverse Reactions:
Peripheral edema, hyperlipidemia, increased creatinine, hypertension, constipation, abdominal pain, diarrhea, headache, fever, urinary tract infection, anemia, nausea, arthralgia, pain, thrombocytopenia; infections (eg, viral), interstitial lung disease, hypersensitivity reactions, angioedema, proteinuria, impaired wound healing, progressive multifocal leukoencephalopathy, malignancies (eg, lymphomas, skin).

How Supplied:
Tabs—100
Soln—60mL (w. oral syringe)