CONTRAINDICATIONS
HYFTOR is contraindicated in patients with a history of hypersensitivity to sirolimus or any other component of HYFTOR.
WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis, have been associated with the oral administration of sirolimus. The concomitant use of HYFTOR with other drugs known to cause angioedema, such as angiotensin-converting enzyme (ACE) inhibitors, may increase the risk of developing angioedema. Elevated sirolimus levels may also potentiate angioedema. Discontinue HYFTOR immediately if symptoms occur.
• Serious Infection: Serious infections, including opportunistic infections, have been reported after oral administration of sirolimus. Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been reported in patients treated with oral sirolimus. Discontinue HYFTOR immediately if symptoms of infection occur.
• Malignancy: Lymphoma and other malignancies, particularly of the skin, have been observed after oral administration of sirolimus. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using HYFTOR. If patients need to be outdoors, they should wear protective clothing and discuss other sun protection measures with their physician.
• Hyperlipidemia: Increased serum cholesterol and triglycerides requiring treatment have been observed with oral administration of sirolimus. Monitor for hyperlipidemia during treatment.
• Interstitial Lung Disease/Non-Infectious Pneumonitis: Cases of interstitial lung disease (ILD) (including pneumonitis, bronchiolitis obliterans organizing pneumonia [BOOP], and pulmonary fibrosis), some fatal, with no identified infectious etiology have occurred in patients receiving oral sirolimus. Discontinue HYFTOR immediately if symptoms of ILD occur.
• Immunizations: During treatment with HYFTOR, vaccinations may be less effective. Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with HYFTOR. The use of live vaccines should be avoided during treatment with HYFTOR.
• Embryo-Fetal Toxicity: Based on animal studies and the mechanism of action, oral sirolimus can cause fetal harm when administered to a pregnant woman. In animal studies, oral sirolimus caused embryo-fetal toxicity when administered during the period of organogenesis at maternal exposures that were equal to or less than human exposures at the recommended lowest starting dose. HYFTOR is systemically absorbed after topical administration and may result in fetal exposure. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to avoid becoming pregnant. They should use effective contraception prior to, throughout treatment and for 12 weeks after the final dose of HYFTOR.
• Male Infertility: Azoospermia or oligospermia has been observed after oral administration of sirolimus. Advise males that HYFTOR may impair fertility.

ADVERSE REACTIONS
The most common adverse reactions (≥1%) are dry skin, application site irritation, pruritus, acne, acneiform dermatitis, ocular hyperemia, skin hemorrhage, and skin irritation.

USE IN SPECIFIC POPULATIONS

• Pregnancy: 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.
• Lactation: Breastfeeding is not recommended during treatment with HYFTOR.
• Infertility: Based on clinical findings and animal studies, male and female fertility may be compromised by the treatment with sirolimus.

Please see full Prescribing Information for additional safety information.