Sirolimus

RAPAMUNE

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What it ismTOR inhibitor; transplant, lymphangioleiomyomatosis and vascular anomalies.

Why it mattersIts anti-lymphangiogenic effect makes it disease-modifying therapy for lymphangioleiomyomatosis, a role everolimus does not share.

What it changesImpaired wound healing, so it is avoided immediately post-transplant. Hyperlipidemia, pneumonitis and mouth ulcers.

FDA-approved for

transplant immunosuppression (1999)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Immunosuppression → increased infection and malignancy (incl. lymphoma) risk; not recommended in liver transplant (excess mortality, graft loss, hepatic artery thrombosis) or lung transplant (bronchial anastomotic dehiscence)

FDA dosing	Population	Start	Target	Max
Renal transplant rejection prophylaxis (low–moderate immunologic risk)	Adults	6 mg loading dose day 1, then 2 mg QD	Adjust to trough concentration	40 mg/day
Renal transplant rejection prophylaxis (high immunologic risk)	Adults	Up to 15 mg loading dose day 1, then 5 mg QD	Adjust to trough concentration	40 mg/day
Lymphangioleiomyomatosis (LAM)	Adults	2 mg QD	Trough 5–15 ng/mL	40 mg/day

Titration Continue new maintenance dose for at least 7–14 days before further dose adjustment (long half-life)

Renal Undefined

Hepatic Reduce maintenance dose in hepatic impairment

Maximum dose on any day should not exceed 40 mg

Instructions

Take orally once daily, consistently with or without food
Do not crush, chew, or split tablets; patients unable to take tablets should use the oral solution
Take 4 hours after cyclosporine (renal transplant)
Therapeutic drug monitoring recommended for all patients

Cautions

Increased susceptibility to infection and possible lymphoma/malignancy
Hypersensitivity reactions and angioedema
Fluid accumulation and impaired wound healing
Hyperlipidemia
Decline in renal function with long-term cyclosporine combination
Proteinuria
Interstitial lung disease / non-infectious pneumonitis
Embryo-fetal toxicity
Not recommended in liver or lung transplant

Adverse reactions

Peripheral edema
Hypertriglyceridemia
Hypertension
Hypercholesterolemia
Increased creatinine
Abdominal pain
Diarrhea
Headache
Fever
Urinary tract infection
Anemia
Nausea
Arthralgia
Thrombocytopenia

Pregnancy Can cause fetal harm; use highly effective contraception during treatment and for 12 weeks after final dose

Lactation Breastfeeding not recommended (potential for serious adverse effects in breastfed infants based on mechanism of action)

⚠ BOXED WARNINGS

Immunosuppression, infection and lymphoma
Not recommended in liver or lung transplantation

Cost, est. cash$50–$10,000/month or cycle

Generic entry2014

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk3 / 4

Legacy pregnancy categoryD

Defining liabilityMyelosuppression, dyslipidemia, impaired healing, pneumonitis and interaction burden.

Mechanism of action: Sirolimus ballicule

Sirolimus ballicule: receptor binding, kinetics and half-life diagram

Open Sirolimus in the interactive console ↗

Memory aids: mascots and interaction avatars

Sirolimus RAPAMUNE mascot mnemonic cartoon — **“Wrap a mice in Zero limas”**
studied as an anti-aging therapy

CYP3A4 substrate

P-gp substrate (sensitive)

Open Sirolimus in the interactive console ↗