Dosing & Uses
Dosage Forms & Strengths
topical gel
- 0.2%
Facial Angiofibroma
Indicated for treatment of facial angiofibroma associated with tuberous sclerosis
Apply thin layer to affected skin BID (morning and bedtime)
Not to exceed 800 mg/day (2.5 cm/day)
If symptoms do not improve within 12 weeks, reevaluate need for continued treatment
Dosing Considerations
Complete all age-appropriate vaccinations as recommended by current immunization guidelines before initiating
Females of reproductive potential should avoid pregnancy; initiate effective contraceptive before starting treatment, during therapy, and for 12 weeks after the final dose
Dosage Forms & Strengths
topical gel
- 0.2%
Facial Angiofibroma
Indicated for treatment of facial angiofibroma associated with tuberous sclerosis in children aged ≥6 years
<6 years: Safety and efficacy not established
≥6 years
- Apply thin layer to affected skin BID (morning and bedtime)
- 6-11 years: Not to exceed 600 mg/day (2 cm/day)
- ≥12 years: Not to exceed 800 mg/day (2.5 cm/day)
- If symptoms do not improve within 12 weeks, reevaluate need for continued treatment
Dosing Considerations
Complete all age-appropriate vaccinations as recommended by current immunization guidelines before initiating
Females of reproductive potential should avoid pregnancy; initiate effective contraceptive before starting treatment, during therapy, and for 12 weeks after the final dose
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (0)
Minor (0)
Adverse Effects
>10%
Dry skin (28-40%)
Skin irritation (31-37%)
Acne (7-20%)
Pruritus (9-17%)
1-10%
Eye irritation (9%)
Erythema (7%)
Acneiform dermatitis (3-6%)
Contact dermatitis (5%)
Ocular hyperemia (3%)
Skin hemorrhage (3%)
Skin irritation (3%)
Solar dermatitis (1%)
Photosensitivity (1%)
Warnings
Contraindications
Hypersensitivity to sirolimus or any other component
Cautions
Lymphoma and other malignancies, particularly skin, observed after oral sirolimus; instruct patients to minimize or avoid exposure to natural or artificial sunlight, including wearing protective clothing and sunscreen
Cases of interstitial lung disease (ILD) including pneumonitis, bronchiolitis obliterans organizing pneumonia (BOOP), and pulmonary fibrosis, some fatal, with no identified infectious etiology, reported with oral sirolimus; in some cases, ILD resolved upon discontinuation or dosage reduction; discontinue therapy immediately if symptoms of ILD occur
Increased serum cholesterol and triglycerides, requiring treatment, observed with oral sirolimus; monitor for hyperlipidemia during treatment
Based on animal studies and mechanism of action, oral sirolimus can cause fetal harm when administered to pregnant females
May impair male fertility
Hypersensitivity reactions
- Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis have been associated with oral sirolimus
- Elevated sirolimus levels (with or without concomitant ACE inhibitors) may also potentiate angioedema
- Discontinue immediately if hypersensitivity symptoms occur
Serious infections
- Serious infections, including opportunistic infections, reported after oral sirolimus
- Progressive multifocal leukoencephalopathy (PML) reports, including cases of fatal PML
- Discontinue immediately if symptoms of infection occur
Drug interaction overview
- Drug interaction studies for sirolimus topical have not been conducted
- Sirolimus is a substrate of CYP3A4 and p-glycoprotine (P-gp)
-
Immunizations
- Complete all age-appropriate vaccinations as recommended by current immunization guidelines before initiating
- Avoid use of live vaccines during treatment
- Sirolimus may decrease vaccine efficacy
-
CYP3A4 inhibitors
- Monitor for sirolimus adverse effects
- Coadministration of sirolimus with CYP3A4 inhibitors may increase sirolimus systemic exposure
-
Drugs that are both substrates and inhibitors of CYP3A
- Monitor
- Systemic exposure of drugs that are both substrates and inhibitors of CYP3A may increase when coadministered with sirolimus
Pregnancy & Lactation
Pregnancy
Based on animal studies and mechanism of action, oral sirolimus can cause fetal harm when administered to pregnant females
Sirolimus topical is systemically absorbed and may result in fetal exposure
Available data from case reports on sirolimus topical use in pregnant females are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal studies
- Animal reproduction studies have not been conducted with sirolimus topical
- Oral sirolimus 0.5 mg/kg/day caused embryo-fetal lethality in pregnant rats when administered during organogenesis
- Available data do not allow calculation of relevant comparisons between systemic exposure of sirolimus observed in animal studies to systemic exposure that would be expected in humans after topical use
Contraception
- Based on animal studies with oral sirolimus, may cause fetal harm when administered to pregnant females
- Females of reproductive potential are recommended to avoid becoming pregnant
- Initiate effective contraceptive before starting therapy, during treatment, and for 12 weeks after the final dose
Infertility
- Based on clinical findings and findings in animal studies, male and female fertility may be compromised by sirolimus treatment
- Ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) reported in females with oral sirolimus
- Azoospermia reported in males with oral sirolimus; reversible upon discontinuation of sirolimus in most cases
Lactation
Data are not available on presence in human milk, effects on breastfed infants, or effects on milk production
After oral administration, sirolimus was present in the milk of lactating rats
Breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Topical mammalian target of rapamycin (mTOR) inhibitor
A germline mutation of the TSC1 or TSC2 gene, leading to activation of mTOR pathway, accounts for the pathogenesis of TSC-associated angiofibroma
Sirolimus inhibits mTOR activation by inhibition of phosphatidylinositol-3-kinase (PI3K)-like serine/threonine protein kinase
Absorption
Blood concentrations
- Following 12 weeks of administration: Undetectable to 0.5 ng/mL
- Maximum concentration with period samples during 52-week trial: 3.27 ng/mL (adults); 1.8 ng/mL (pediatrics)
Distribution
No evidence based on blood concentrations that sirolimus accumulates systemically upon topical application in patients with tuberous sclerosis for periods of up to 1 year
Metabolism
Metabolism studies for sirolimus topical have not been conducted
Sirolimus is a substrate for both CYP3A4 and P-gp
Extensively metabolized after oral administration in intestinal wall and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen
Elimination
Excretion studies for sirolimus topical have not been conducted
Single oral dose
- Half-life: 62 hr (stable renal transplant recipients)
- Excretion: Feces (91%); urine (2.2%)
Administration
Topical Administration
For topical use only; not for oral, ophthalmic, or intravaginal use
Wash hands before and after application
Instruct patient on how to correctly measure dose
Apply thin layer to affected skin; gently and completely rub in minimum amount of gel
Limit application to areas of involvement with angiofibroma
Do not use with occlusive dressing; safety of gel under occlusion, which may promote systemic exposure, has not been evaluated
Storage
Refrigerate at 2-8ºC (36-46ºF)
Protect from light
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