Sirolimus (topical)
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From MedlinePlus, U.S. National Library of Medicine
Handling and access
NIOSH hazardous drug
Table 2NIOSH lists sirolimus as a hazardous drug. AHFS class: 92:44 immunosuppressive agents.
- Meets the NIOSH definition of a hazardous drug (carcinogenicity, developmental or reproductive toxicity, organ toxicity at low doses, or genotoxicity) without MSHI or a Group 1 or 2A carcinogen classification.
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Kinase Inhibitor, mTOR Inhibitor Immunosuppressant
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Drug interactions
Check sirolimus (topical) against a medication listLabel text (3 paragraphs)
7 DRUG INTERACTIONS CYP3A4 Inhibitors: During concomitant use of HYFTOR with CYP3A4 inhibitors, monitor for adverse reactions of HYFTOR. ( 7.1 ) Substrates and Inhibitors of CYP3A : During concomitant use of HYFTOR with drugs that are both substrates and inhibitors of CYP3A, monitor for adverse reactions of the CYP3A substrate and inhibitor. ( 7.2 )
7.1 Effects of Other Drugs on HYFTOR Table 2 presents clinically significant drug interactions involving drugs that affect HYFTOR. Table 2: Effects of CYP3A4 Inhibitors on HYFTOR Clinical Impact Concomitant use of HYFTOR with inhibitors of CYP3A4 has the potential to increase the systemic exposure of sirolimus and increase the risk of HYFTOR adverse reactions. Intervention Monitor for adverse reactions of HYFTOR.
7.2 Effects of HYFTOR on Other Drugs Systemic exposure of drugs that are both substrates and inhibitors of CYP3A could be increased with coadministration with HYFTOR. Monitor for adverse reactions of such co-administered drugs.
Contraindications
4 CONTRAINDICATIONS HYFTOR is contraindicated in patients with a history of hypersensitivity to sirolimus or any other component of HYFTOR. Reactions to sirolimus have included anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis [see Warning and Precautions (5.1) ] . History of hypersensitivity to sirolimus or any other component of HYFTOR. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
CLikelihood score C: Probable rare cause of clinically apparent liver injury.
Sirolimus is macrocyclic antibiotic with potent immunosuppressive activity that is used alone or in combination with calcineurin inhibitors and corticosteroids to prevent cellular rejection after renal transplantation. Sirolimus therapy can be associated with mild serum enzyme elevations and it has been linked to rare instances of clinically apparent cholestatic liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on animal studies and mechanism of action, oral sirolimus can cause fetal harm when administered to a pregnant woman. HYFTOR is systemically absorbed after topical administration and may result in fetal exposure. The available data from case reports on HYFTOR use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with HYFTOR.
In an animal reproduction study, oral administration of 0.5 mg/kg/day sirolimus caused embryo-fetal lethality in pregnant rats when administered during the period of organogenesis (see Data ). The available data do not allow the calculation of relevant comparisons between the systemic exposure of sirolimus observed in animal studies to the systemic exposure that would be expected in humans after topical use of HYFTOR. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In embryo-fetal development studies in rats, oral administration of sirolimus to pregnant rats during the period of organogenesis (gestation days 6 -15) induced embryo-fetal lethality at 0.5 mg/kg/day, reduced fetal body weight at 1.0 mg/kg/day and caused maternal toxicity at 2.0 mg/kg/day. No treatment related embryo-fetal developmental effects were observed at 0.1 mg/kg/day.
In embryo-fetal development studies in rabbits, oral administration of sirolimus to pregnant rabbits during the period of organogenesis (gestation days 6 -18) induced maternal toxicity (decreased body weight) at 0.05 mg/kg/day, which was associated with embryo-fetal loss or early resorption. No treatment related developmental effects were observed at 0.025 mg/kg/day. In a pre- and postnatal development toxicity study, oral administration of sirolimus to pregnant rats during gestation and lactation (gestation day 6 through lactation day 20) increased the incidence of dead pups, resulting in reduced live litter size at 0.5 mg/kg/day.
No treatment related developmental effects were observed at 0.1 mg/kg/day. Sirolimus did not cause maternal toxicity or affect developmental parameters in the surviving offspring (morphological development, motor activity, learning, or fertility assessment) at…
Breastfeeding (LactMed)
Information from one mother indicates that the amount of sirolimus in milk is very low. Additionally, the oral bioavailability of the drug is poor, so systemic exposure in the infant is likely very low. A few infants have reportedly been breastfed during maternal sirolimus therapy. Until more data become available, sirolimus should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Sirolimus is undetectable in the bloodstream after application to the skin, so use of topical sirolimus is unlikely to affect a nursing infant. Avoid application to the nipple area and ensure that the infant’s skin does not come into direct contact with the areas of skin that have been treated.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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