HYFTOR sirolimus 2 mg/g Gel
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🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Kinase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- Sirolimus comes in a few different forms, and each one has its own approved use. The oral tablets and liquid are mainly used to prevent kidney transplant rejection and to treat a r...
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- Yes, it matters — but not in the way you might think. You don't have to eat with it, but you do need to be consistent. Food, especially a high-fat meal, can increase how much sirol...
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 3K9958V90M
A liquid solvent derived from fermentation or chemical synthesis. In medicines, alcohol dissolves active ingredients, helps preserve the product, and improves how the body absorbs certain drugs.
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UNII 4Q93RCW27E
A synthetic polymer made from acrylic acid that's crosslinked for stability. It acts as a thickener and gelling agent in creams and gels, helping the medicine spread evenly and maintain its texture.
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UNII 9O3K93S3TK
Trolamine is an alkaline compound used as a pH buffer and emulsifier in medicines. It helps neutralize acids, stabilize formulations, and enable mixing of oil and water-based ingredients.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
4 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per g | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $196.71 | $1,967.14 / 10 g |
| Medicare drug plans payPart D · Q2 2026 | $213.02 | $2,130.25 / 10 g |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Hyftor 2 mg/gthis 73683-0101-10 | Nobelpharma | 1 tube | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Code | What it grants | Expires |
|---|---|---|
| ODE-391 | Orphan Drug Exclusivity (7-year) | Mar 22, 2029 |
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 73683-0101-10 You're viewing this | 1 TUBE in 1 CARTON (73683-101-10) / 10 g in 1 TUBE | 2022-03-23 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE HYFTOR is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older. HYFTOR is an mTOR inhibitor immunosuppressant indicated for the treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients 6 years of age and older. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to HYFTOR initiation [see Warning and Precautions (5.6) ] . Apply HYFTOR to the skin of the face affected with angiofibroma twice daily in the morning and at bedtime. The maximum recommended daily dosage is: 600 mg (2 cm) for pediatric patients 6 to 11 years of age 800 mg (2.5 cm) for adults and pediatric patients 12 years of age and older If symptoms do not improve within 12 weeks of treatment, reevaluate the need for continuing HYFTOR.
Do not use HYFTOR with occlusive dressings. For topical use only. Not for oral, ophthalmic, or intravaginal use.
Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to HYFTOR initiation. ( 2 ) Apply to the skin of the face affected with angiofibroma twice daily. ( 2 ) The maximum daily dosage is: 600 mg (2 cm) for patients 6 to 11 years of age.
( 2 ) 800 mg (2.5 cm) for patients 12 years of age and older. ( 2 ) Do not use with occlusive dressings. ( 2 ) For topical use only.
Not for oral, ophthalmic, or intravaginal use. ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Topical gel , 0.2%: Each gram contains 2 mg of sirolimus in a colorless and transparent gel in 10-gram tubes. Topical gel, 0.2%: 2 mg of sirolimus per gram. ( 3 )
⛔ 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 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Oral sirolimus has been associated with hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis. Discontinue HYFTOR immediately if symptoms of hypersensitivity occur. ( 5.1 ) Serious Infection : Serious infections, including opportunistic infections and latent viral infections, such as progressive multifocal leukoencephalopathy, have been reported with oral sirolimus.
Discontinue HYFTOR immediately if symptoms of infection occur. ( 5.2 ) Malignancy : Oral sirolimus has been associated with malignancy, including lymphoma and skin cancer. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using HYFTOR.
( 5.3 ) Hyperlipidemia : Oral sirolimus has been associated with increased serum cholesterol and triglycerides requiring treatment. Monitor for hyperlipidemia during treatment. ( 5.4 ) Interstitial Lung Disease (ILD)/Non-infectious Pneumonitis : Oral sirolimus has been associated with ILD, sometimes fatal.
Discontinue HYFTOR if ILD symptoms occur. ( 5.5 ) Immunizations: During treatment with HYFTOR, vaccinations may be less effective. Avoid use of live vaccines during treatment with HYFTOR.
( 5.6 ) Embryo-Fetal Toxicity : Based on animal studies, HYFTOR can cause fetal harm. Use of effective contraception is recommended for females of reproductive potential prior to and throughout treatment, and for 12 weeks after final dose of HYFTOR. ( 5.7 , 8.1 , 8.3 ) Male Infertility : Oral sirolimus has been associated with azoospermia and oligospermia.
Advise males that HYFTOR may impair fertility. ( 5.8 , 8.3 , 13.1 )
5.1Hypersensitivity 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 (with or without concomitant ACE inhibitors) may also potentiate angioedema.
Discontinue HYFTOR immediately if symptoms of hypersensitivity occur.
5.2Serious 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.
5.3Malignancy 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 while using HYFTOR, they should wear protective clothing and discuss other sun protection measures with their physician.
5.4Hyperlipidemia Increased serum cholesterol and triglycerides requiring treatment have been observed with oral administration of sirolimus. Monitor for hyperlipidemia during treatment with HYFTOR.
5.5Interstitial 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. In some cases, the ILD has resolved upon discontinuation or dosage reduction of oral sirolimus. Discontinue HYFTOR immediately if symptoms of ILD occur.
5.6Immunizations 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 avoide…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS Most common adverse reactions (≥1%) are dry skin, application site irritation, pruritus, acne, acneiform dermatitis, ocular hyperemia, skin hemorrhage, and skin irritation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Nobelpharma America, LLC at 1 (877) 375-0825 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a randomized, double-blind, vehicle-controlled trial, subjects aged 6 years and older with facial angiofibroma associated with tuberous sclerosis applied HYFTOR twice daily for 12 weeks. A total of 30 subjects were treated with HYFTOR and 32 with the vehicle.
The majority of the subjects were female (54.8%). A total of 40.3% were less than 18 years of age. The most common adverse reactions reported by ≥1% of subjects treated with HYFTOR and more frequently than in subjects treated with vehicle are presented in Table 1.
Adverse reactions occurred with similar frequency in pediatric subjects 6 years of age and older. Table 1: Adverse Reactions in ≥1% of Subjects Aged 6 Years and Older with Facial Angiofibroma Associated with Tuberous Sclerosis Through Week 12 Preferred Term HYFTOR N = 30 Vehicle N = 32 Dry skin Dry skin includes dry skin and asteatosis 12 (40%) 4 (13%) Application site irritation 11 (37%) 9 (28%) Pruritus 5 (17%) 4 (13%) Acne 2 (7%) 0 (0%) Acneiform dermatitis 1 (3%) 0 (0%) Ocular hyperemia 1 (3%) 0 (0%) Skin hemorrhage 1 (3%) 0 (0%) Skin irritation 1 (3%) 0 (0%) In a 104-week, open-label safety trial, the most common adverse reactions associated with HYFTOR application were application site irritation (31%), dry skin (28%), acne (20%), pruritus (9%), eye irritation (9%), erythema (7%), acneiform dermatitis (6%), contact dermatitis (5%), solar dermatitis (1%), and photosensitivity reaction (1%).
Adverse reactions occurred with similar frequency in adult and pediatric subjects 6 years of age and older.
🔄 Drug Interactions ▾
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 )
7.1Effects 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.
7.2Effects 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Lactation : Breastfeeding not recommended. ( 8.2 )
8.1Pregnancy 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 0.5 mg/kg/day, the highest dose tested.
8.2Lactation Risk Summary There are no available data on the presence of sirolimus in human milk, the effects on the breastfed infant, or the effects 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 breastfed infant, breastfeeding is not recommended during treatment with HYFTOR.
8.3Females and Males of Reproductive Potential Contraception Based on animal studies with oral sirolimus, HYFTOR may cause fetal harm when administered to pregnant women. Females of reproductive potential are recommended to avoid becoming pregnant and to use an effective contraceptive method. Effective contraception should be initiated before HYFTOR therapy and used throughout treatment and for 12 weeks after the final dose of HYFTOR [see Warnings and Precautions (5.7) , Use in Specific Populations (8.1) ] .
Infertility Based on clinical findings and findings in animal studies, male and female fertility may be compromised by the treatment with sirolimus [see Warnings and Precautions (5.8) , Nonclinical Toxicology (13.1) ]. Ovarian cysts and menstrual disorders (including amenorrhea and menorrhagia) have been reported in females with the use of oral sirolimus. Azoospermia h…
🤰 Pregnancy ▾
8.1Pregnancy 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 0.5 mg/kg/day, the highest dose tested.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of HYFTOR have been established in pediatric patients aged 6 years and older for the topical treatment of facial angiofibroma associated with tuberous sclerosis. Use of HYFTOR 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 subjects aged 6 years to 17 years received HYFTOR in the Phase 3 clinical trial along with 48 pediatric subjects aged 3 years to 17 years in the 104-week open label safety trial.
Adverse reactions occurred with similar frequency in adult and pediatric subjects [see Adverse Reaction (6.1) , Clinical Studies (14) ]. The safety and effectiveness of HYFTOR for this indication have not been established in pediatric patients less than 6 years of age.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of HYFTOR did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of sirolimus in the treatment of angiofibroma associated with tuberous sclerosis is unknown. Tuberous sclerosis is associated with genetic defects in TSC1 and TSC2 which leads to the constitutive activation of mammalian target of rapamycin (mTOR). Sirolimus inhibits mTOR activation.
12.3Pharmacokinetics Absorption Following 12 weeks of treatment with HYFTOR in adult and pediatric subjects aged 6 years and older, sirolimus blood concentrations ranged from undetectable to 0.50 ng/mL after multiple doses of HYFTOR in the Phase 3 trial. Periodic blood samples were obtained in the 52-week trial and the maximum sirolimus concentration measured at any time in adult subjects was 3.27 ng/mL and the maximum sirolimus concentration measured at any time in pediatric subjects was 1.80 ng/mL. Distribution 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.
Elimination Metabolism Studies evaluating the metabolism of HYFTOR have not been conducted. Sirolimus is a substrate for both CYP3A4 and P-gp. Sirolimus is extensively metabolized after oral administration in the intestinal wall and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen.
Inhibitors of CYP3A4 and P-gp increase sirolimus concentrations. Inducers of CYP3A4 and P-gp decrease sirolimus concentrations. Sirolimus is extensively metabolized by O-demethylation and/or hydroxylation.
Seven (7) major metabolites, including hydroxy, demethyl, and hydroxydemethyl, are identifiable in whole blood. Some of these metabolites are also detectable in plasma, fecal, and urine samples. Sirolimus is the major component in human whole blood and contributes to more than 90% of the immunosuppressive activity.
Excretion Studies evaluating the excretion of HYFTOR have not been conducted. After a single dose of [ 14 C] sirolimus oral solution in healthy volunteers, the majority (91%) of radioactivity was recovered from the feces, and only a minor amount (2.2%) was excreted in urine. The mean ± SD terminal elimination half-life (t½) of sirolimus after multiple dosing in stable renal transplant patients was estimated to be about 62 ± 16 hours.
Drug Interaction Studies Drug interaction studies with HYFTOR have not been conducted. Sirolimus is known to be a substrate for both cytochrome P-450 3A4 (CYP3A4) and p-glycoprotein (P-gp). [see Drug Interactions (7.1 , 7.2) ] .
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of sirolimus in the treatment of angiofibroma associated with tuberous sclerosis is unknown. Tuberous sclerosis is associated with genetic defects in TSC1 and TSC2 which leads to the constitutive activation of mammalian target of rapamycin (mTOR). Sirolimus inhibits mTOR activation.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied HYFTOR ® (sirolimus topical gel) 0.2% is a colorless and transparent gel supplied as 10 g in aluminum tubes (NDC 73683-101-10). Each gram contains 2 mg of sirolimus. Storage and Handling Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light.
📦 Storage and Handling ▾
Storage and Handling Store refrigerated at 2° to 8°C (36° to 46°F). Protect from light.
📋 Description ▾
11 DESCRIPTION HYFTOR ® (sirolimus topical gel) 0.2% is an mTOR inhibitor immunosuppressant for topical use. Each gram contains 2 mg of sirolimus, which is solubilized in a gel consisting of alcohol 51%, Carbomer 940, purified water, and trolamine. Chemically, sirolimus is designated as (3 S ,6 R ,7 E ,9 R ,10 R ,12 R ,14 S ,15 E ,17 E ,19 E ,21 S ,23 S ,26 R ,27 R ,34a S )-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-9,27-dihydroxy-3-[(1 R )-2-[(1 S ,3 R ,4 R )-4-hydroxy-3-methoxycyclohexyl]-1-methylethyl]-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3 H -pyrido[2,1- c ][1,4]oxaazacyclohentriacontine-1,5,11,28,29(4 H ,6 H ,31 H )-pentone.
It has the following structural formula: Sirolimus is a white to off-white powder and is insoluble in water, but freely soluble in chloroform, acetone and acetonitrile. Sirolimus has a molecular formula of C 51 H 79 NO 13 and a molecular weight of 914.19. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Hypersensitivity Inform patients that oral sirolimus has been associated with hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis. Advise patients to discontinue HYFTOR immediately and seek medical attention if symptoms occur [see Warnings and Precautions (5.1) ] .
Serious Infections Inform patients that oral sirolimus has been associated with increased susceptibility to infections, including opportunistic infections and latent viral infections, such as progressive multifocal leukoencephalopathy (PML). Advise patients to discontinue HYFTOR immediately and seek medical attention if symptoms occur [see Warnings and Precautions (5.2) ] . Malignancy Inform patients that oral sirolimus has been associated with malignancy, including lymphoma and skin cancer.
Advise patients to minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment), and to use protective measures if exposure cannot be avoided, while using HYFTOR [see Warnings and Precautions (5.3) ] . Hyperlipidemia Inform patients that oral sirolimus has been associated with increased serum cholesterol and triglycerides requiring treatment and that periodic laboratory monitoring may be needed [see Warnings and Precautions (5.4) ] . Interstitial Lung Disease Inform patients that oral sirolimus has been associated with interstitial lung disease [ILD] sometimes fatal, with no identified infectious etiology.
Advise patients to discontinue HYFTOR immediately and seek medical attention if symptoms (e.g. shortness of breath) occur [see Warnings and Precautions (5.5) ] . Immunization Inform patients that during treatment with HYFTOR, vaccinations may be less effective. Instruct patients that vaccination with live vaccines should be avoided during treatment with HYFTOR and to inform the healthcare practitioner that they are using HYFTOR prior to a potential vaccination [see Warnings and Precautions (5.6) ] .
Pregnancy HYFTOR may cause fetal harm if used during pregnancy. Advise female patients of reproductive potential to avoid becoming pregnant and to use effective contraception prior to, throughout treatment, and for 12 weeks after the final dose of HYFTOR. Advise pregnant women of the potential risk to a fetus [see Warnings and Precautions (5.7) , Use in Specific Populations (8.1 , 8.3) ].
Lactation Advise lactating women that breastfeeding is not recommended during treatment with HYFTOR [see Use in Specific Populations (8.2) ]. Infertility Inform male and female patients that HYFTOR may impair fertility [see Warnings and Precautions (5.8) , Use in Specific Populations (8.3) , Nonclinical Toxicology (13.1) ]. Administration Information Inform patients that the skin being treated with HYFTOR should not be covered with bandages, dressings or wraps [see Dosage and Administration (2) ].