Version July 2025
Note: Complete all vaccinations (per current immunization guideline recommendations) prior to initiation of topical sirolimus treatment.
Facial angiofibroma associated with tuberous sclerosis: Topical: Apply twice daily (in the morning and at bedtime) to the affected facial skin; the maximum recommended daily dose is 800 mg (2.5 cm). If symptoms do not improve within 12 weeks, re-evaluate the need for continuing therapy.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
Hypersensitivity symptoms: Immediately discontinue topical sirolimus.
Infection (symptoms of serious infection): Immediately discontinue topical sirolimus.
Interstitial lung disease symptoms: Immediately discontinue topical sirolimus.
Refer to adult dosing.
(For additional information see "Sirolimus gel (topical): Pediatric drug information")
Note: Complete all age-appropriate vaccinations according to current immunization guidelines prior to initiating therapy.
Facial angiofibroma associated with tuberous sclerosis: Note: If no improvement occurs within 12 weeks, reevaluate the need for continued therapy.
Children ≥6 to 11 years: Topical: Apply to affected area of the face twice daily; maximum daily dose: 600 mg (2 cm)/day.
Children ≥12 years and Adolescents: Topical: Apply to affected area of the face twice daily; maximum daily dose: 800 mg (2.5 cm)/day.
Dosage adjustment for toxicity:
Hypersensitivity symptoms: Immediately discontinue topical sirolimus.
Infection (symptoms of serious infection): Immediately discontinue topical sirolimus.
Interstitial lung disease symptoms: Immediately discontinue topical sirolimus.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults.
>10%:
Dermatologic: Pruritus (17%), xeroderma (40%)
Local: Application-site irritation (37%)
1% to 10%:
Dermatologic: Acne vulgaris (7%), acneiform eruption (3%), dermal hemorrhage (3%), skin irritation (3%)
Ophthalmic: Ocular hyperemia (3%)
Hypersensitivity (eg, anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, hypersensitivity vasculitis) to sirolimus or any component of the formulation.
Concerns related to adverse effects:
• Hyperlipidemia: Serum cholesterol and triglyceride elevations requiring treatment have been observed with oral sirolimus.
• Hypersensitivity: Hypersensitivity reactions (including anaphylactic/anaphylactoid reactions, angioedema, exfoliative dermatitis, and hypersensitivity vasculitis) have been associated with oral sirolimus. Concurrent use of topical sirolimus with other medications known to cause angioedema (eg, angiotensin-converting enzyme [ACE] inhibitors) may increase the risk of angioedema. Elevated sirolimus levels (± concurrent ACE inhibitors) may also potentiate angioedema.
• Infection: Serious infections (including opportunistic infections) have been reported with oral sirolimus. Cases of progressive multifocal leukoencephalopathy (sometimes fatal) have been reported with oral sirolimus.
• Malignancy: Lymphoma and other malignancies, particularly skin malignancies, have been observed following oral sirolimus treatment.
• Pulmonary toxicity: Cases (some fatal) of interstitial lung disease (ILD), including pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary fibrosis, with no identified infectious etiology have occurred in patients receiving oral sirolimus. ILD resolved upon oral sirolimus discontinuation or dosage reduction in some cases.
Concurrent drug therapy issues:
• Immunizations: Vaccinations may be less effective during topical sirolimus treatment. Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating topical sirolimus treatment. Avoid the use of live vaccines during topical sirolimus treatment.
Other warnings/precautions:
• Photosensitivity: Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) during topical sirolimus treatment. Patients should wear protective clothing and utilize sun protection if outdoors while on topical sirolimus treatment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, External:
Hyftor: 0.2% (10 g) [contains alcohol, usp, trolamine (triethanolamine)]
No
Gel (Hyftor External)
0.2% (per gram): $242.40
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Topical: Apply to affected skin of the face in the morning and at bedtime. Do not use with occlusive dressings. Do not cover treated skin with bandages, dressings, or wraps. Wash hands before and after application. For topical use only; not for oral, ophthalmic, or intravaginal use.
Topical: For external use only. Not for oral, ophthalmic, or intravaginal use. Wash hands before and after application. Apply to the affected area in the morning and at bedtime. Do not use occlusive dressing, wrap, bandage, or covering over treated area. Limit exposure to natural or artificial sunlight; protective clothing should be worn.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Facial angiofibroma associated with tuberous sclerosis: Treatment of facial angiofibroma associated with tuberous sclerosis in adults and pediatric patients ≥6 years of age.
Sirolimus (topical) may be confused with pimecrolimus, sirolimus (conventional [oral]), sirolimus (protein bound), tacrolimus (topical).
Substrate of CYP3A4 (Minor), P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Therapeutic Immunosuppressant Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Sirolimus (Topical). Risk C: Monitor
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate 2 to 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Pimecrolimus. Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to starting immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Therapeutic Immunosuppressant Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Patients who could become pregnant should use effective contraception prior to, during therapy, and for at least 12 weeks after the last dose of topical sirolimus.
Azoospermia and oligospermia were observed following use of oral sirolimus; fertility may be impaired following topical use.
Refer to the Sirolimus (Conventional) monograph for additional information.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to oral sirolimus may cause fetal harm. Topical sirolimus is systemically absorbed; fetal exposure may occur.
Refer to the Sirolimus (Conventional) monograph for additional information.
It is not known if sirolimus is present in breast milk following topical administration; however, sirolimus is present in breast milk following oral use.
Sirolimus is systemically absorbed following topical administration. Due to the potential for serious adverse events in the breastfed infant, breastfeeding is not recommended by the manufacturer. Refer to the Sirolimus (Conventional) monograph for additional information.
Monitor for hyperlipidemia (during treatment). Monitor for signs/symptoms of hypersensitivity; infection; pulmonary toxicity (interstitial lung disease, pneumonitis, bronchiolitis obliterans organizing pneumonia, pulmonary fibrosis); and malignancy.
Sirolimus inhibits mammalian target of rapamycin (mTOR) activation; although the mechanism 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 mTOR activation.
Absorption: Adults: Following 12 weeks of topical therapy, sirolimus blood concentrations ranged from undetectable to 0.5 ng/mL after multiple topical sirolimus doses; periodic sirolimus samples from a 52-week trial demonstrated a maximum sirolimus concentration (at any time) of 3.27 ng/mL.
Distribution: There is no evidence in patients with tuberous sclerosis that sirolimus accumulates systemically (based on blood concentrations) with topical application for periods of up to 1 year.
Metabolism: Oral sirolimus: Extensively metabolized in intestinal wall and hepatically.
Half-life elimination: Oral sirolimus: ~62 hours (± 16 hours).
Excretion: Oral sirolimus: Feces (91%); urine (~2%).
