Version May 2024
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): $226.20
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.
Sirolimus is a hazardous agent (NIOSH 2016 [group 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 2016; 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).
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (minor), P-glycoprotein/ABCB1 (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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG Products: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Sirolimus (Topical). Risk C: Monitor therapy
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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 enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 diminish the therapeutic effect 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect 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 combination
Typhoid Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 2 to 3 months after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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%).
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