Hyftor (sirolimus)
Macrolide Immunosuppressants - Topical Topical Gel (Gram)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is an immunosuppressive agent.
The precise mechanism of action of sirolimus in the treatment of angiofibroma associated with tuberous sclerosis is uncertain. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by TSC1 or TSC2 mutations, which lead to the constitutive activation of mammalian target of rapamycin (mTOR). Sirolimus inhibits mTOR activation.
Following 12 weeks of treatment with sirolimus topical gel in adult and pediatric subjects >=6 years of age, sirolimus blood concentrations ranged from undetectable to 0.50 ng/mL after multiple doses. There was 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.
Sirolimus is a substrate for cytochrome P-450 (CYP) isoenzyme 3A4 and P-glycoprotein and is extensively metabolized in the liver by O-demethylation and/or hydroxylation. While 7 major metabolites of sirolimus have been identified, sirolimus is the principal species in whole blood and is responsible for greater than 90% of immunosuppressive activity.
USES: Sirolimus is used to treat clusters of bumps on the face (facial angiofibroma) in people with a certain genetic disorder (tuberous sclerosis). This medication belongs to a class of drugs known as immunosuppressants. It works by weakening your body's defense system (immune system).
Generic name: sirolimus
Pronunciation: (sir-OH-li-mus)
Drug class: Macrolide Immunosuppressants - Topical
Therapeutic class: Dermatological
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Hyftor
Indications
The following indications are listed for Hyftor:
- Facial Angiofibroma Associated With Tuberous Sclerosis Complex
Also known as: Facial Angiofibroma Due To Tuberous Sclerosis, Facial Angiofibroma Of Tuberous Sclerosis, Tuberous Sclerosis Complex-Related Facial Angiofibroma.
Dosing
No dosing information is available for this tab.
Sirolimus is applied topically to the skin as a gel. The topical gel is for external use only and not for oral, ophthalmic, or intravaginal use.
The safety of sirolimus topical gel under occlusion, which may promote systemic exposure, has not been evaluated. Do not use sirolimus gel with occlusive dressings.
Hands should be washed prior to and following application of the cream.
Sirolimus topical gel should be refrigerated at 2-8degreesC. Refrigerate immediately after application. Protect from light.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Hyftor 0.2% Gel | Maintenance | Apply 1.25 centimeters (400 mg) to the affected area of the face by topical route 2 times per day. |
No dosing information is available for this tab.
Drug interactions
Drug interaction studies with sirolimus gel have not been conducted. Sirolimus is a known substrate for cytochrome P-450 (CYP) isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp).
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of hypersensitivity to sirolimus or any ingredient in the formulation.
- Lactation
- Interstitial lung disease
- Malignancy
- Pregnancy
- Hyperlipidemia
- Male infertility
Adverse reactions
Most common adverse reactions (>=1%) with sirolimus gel in adults and pediatric patients >=6 years of age are dry skin, application site irritation, pruritus, acne, acneiform dermatitis, ocular hyperemia, skin hemorrhage, and skin irritation.
Less Frequent
- Influenza
More Frequent
- Acne vulgaris
- Acneiform eruption
- Bleeding skin
- Dry skin
- Ocular redness
- Pruritus of skin
- Skin irritation
Less Frequent
- Contact dermatitis
- Ocular irritation
- Skin photosensitivity
Precautions
No enhanced messaging available.
The safety and effectiveness of sirolimus topical gel have been established in pediatric patients >=6 years of age for the treatment of facial angiofibroma associated with tuberous sclerosis. Use of sirolimus gel in this age group is supported by data from a randomized, vehicle-controlled, double-blind 12-week trial along with additional efficacy and long-term safety data from a 104-week open label safety trial. A total of 13 pediatric patients 6 to 17 years of age received sirolimus gel in the phase 3 clinical trial along with 48 pediatric patients 3 to 17 years of age in the 104-week open label safety trial. Adverse reactions occurred with similar frequency in adult and pediatric subjects.
The safety and effectiveness of sirolimus topical gel for the topical treatment of facial angiofibroma associated with tuberous sclerosis have not been established in pediatric patients <6 years of age.
Based on animal studies and mechanism of action, oral sirolimus can cause fetal harm when administered to a pregnant woman. Sirolimus topical gel is systemically absorbed after topical administration and may result in fetal exposure. The available data from case reports on sirolimus topical gel 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 sirolimus topical gel. In an animal reproduction study with oral sirolimus, embryolethality occurred when sirolimus was administered orally to pregnant rats during the period of organogenesis. 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 sirolimus gel.
There are no available data on the presence of sirolimus in human milk; it is not known whether the drug has any effects on the breast-fed infant or on milk production. After oral administration, sirolimus was present in the milk of lactating rats. Because of the potential for serious adverse reactions in the breast-fed infant, the manufacturer states that breast-feeding is not recommended during treatment with sirolimus gel.
Clinical studies of sirolimus topical gel did not include sufficient numbers of patients >=65 years of age to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
ICD codes
| Code | Type | Description |
|---|---|---|
| Facial angiofibroma associated with tuberous sclerosis complex | ||
| D23.39 | ICD10CM | Other benign neoplasm of skin of other parts of face |
| Q85.1 | ICD10CM | Tuberous sclerosis |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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