sirolimus topical

Action and Spectrum

Actions and spectrum: 

sirolimus topical is an immunosuppressive agent with both antiproliferative and anti-inflammatory actions. It works by inhibiting the activity of mTOR (mammalian target of rapamycin), a protein kinase involved in cell growth and immune response.

sirolimus topical is primarily used in the treatment of certain dermatological conditions, such as facial angiofibromas in tuberous sclerosis complex and cutaneous manifestations of graft-versus-host disease.

Its spectrum of action is limited to the targeted areas of application and does not have systemic effects like oral or systemic administration of sirolimus. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Erythema (7%) 

Contact dermatitis (5%) 

Skin hemorrhage (3%) 

Solar dermatitis (1%) 

Eye irritation (9%) 

Acneiform dermatitis (3-6%) 

Ocular hyperemia (3%) 

Skin irritation (3%) 

Photosensitivity (1%)   

>10% 

Skin irritation (31-37%) 

Pruritus (9-17%) 

Dry skin (28-40%) 

Acne (7-20%) 

Black Box Warning

Black Box Warning: 

sirolimus topical does not have a black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Individuals with known hypersensitivity or allergic reactions to sirolimus or any of its components should avoid using sirolimus topical. 
• Open Wounds or Broken Skin: sirolimus topical should not be applied tobroken skin, open wounds, or areas with active infections. 
• Immunocompromised Individuals: sirolimus topical may not be suitable for individuals with compromised immune systems, as it may affect the body’s ability to fight infections locally. 
• Pregnancy and Lactation: The use of sirolimus topical during pregnancy and breastfeeding is not recommended.

Caution: 

• Skin Sensitivity: sirolimus topical may cause skin irritation or allergic reactions in some individuals. It should be monitored forsigns of redness, itching, or rash, and discontinue use if such reactions occur. 
• Application to Mucous Membranes: sirolimus topical is intended for only external use and not to be applied to mucous membranes such as the eyes, mouth, or genitals. 
• Immunosuppression: sirolimus is an immunosuppressive medication, and although the systemic absorption of sirolimus topical is minimal, caution should be exercised in individuals with compromised immune systems or those taking other immunosuppressive medications. 
• Drug Interactions: sirolimus may interact with other medications. It is important to inform healthcare provider about all the medications, including over-the-counter drugs and supplements, that you are currently taking.

Comorbidities: 

• Immunocompromised Conditions: sirolimus is an immunosuppressive medication, and individuals with underlying immunocompromised conditions, such as HIV/AIDS or organ transplant recipients, may be at an increased risk of infections when using sirolimus topical. 
• Skin Infections: sirolimus topical should be used with caution in individuals with existing skin infections. The immunosuppressive effects of sirolimus may potentially hinder the ability body’s to fight off infections or delay wound healing. 
• Allergic Reactions: Individuals with a known hypersensitivity or allergy to sirolimus or its ingredients should avoid using sirolimus topical. 
• Bleeding Disorders: sirolimus can have an anticoagulant effect, and caution should be exercised in individuals with bleeding disorders or those taking medications that affect blood clotting. 
• Liver or Kidney Dysfunction: sirolimus is primarily metabolized in the liver and gets excreted by the kidneys. Individuals with impaired liver or kidney function may require dosage adjustments or closer monitoring when using sirolimus topical. 

Pregnancy / Lactation

Pregnancy consideration: N/A 

Lactation: N/A  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

sirolimus topical, also known as rapamycin, belongs to a class of medications called mammalian target of rapamycin (mTOR) inhibitors. It exerts its pharmacological effects by inhibiting the activity of mTOR, a protein kinase involved in cell growth and proliferation. By blocking mTOR signaling, sirolimus inhibits the proliferation of certain cells, including T lymphocytes and fibroblasts. 

In dermatology, sirolimus topical is primarily used for its immunosuppressive and antiproliferative properties. It is thought to reduce inflammation and suppress the immune response, making it beneficial in the treatment of certain skin conditions such as facial angiofibromas in tuberous sclerosis, cutaneous T-cell lymphoma, and other dermatoses. 

Pharmacodynamics: 

The pharmacodynamics of sirolimus topical primarily involves inhibition of the mammalian target of rapamycin (mTOR). sirolimus topical exhibits immunosuppressive and antiproliferative properties. It reduces the activity of T lymphocytes, inhibiting their proliferation and cytokine production. This immunosuppressive effect helps to alleviate inflammatory skin conditions and prevent excessive immune response. 

sirolimus also inhibits fibroblast proliferation and collagen synthesis, which can be beneficial in certain dermatoses characterized by abnormal fibroblast activity, such as facial angiofibromas in tuberous sclerosis.  

Pharmacokinetics: 

Absorption 

sirolimus is absorbed through the skin when applied topically. However, the extent of absorption is generally low, and systemic exposure is minimal. 

Distribution 

Once absorbed, sirolimus may distribute within the skin and underlying tissues. It may also undergo some systemic distribution, although to a lesser extent compared to oral or intravenous administration. 

Metabolism 

sirolimus undergoes metabolism in the liver, primarily by the enzyme cytochrome P450 3A4 (CYP3A4). Metabolism of sirolimus may also occur locally within the skin. The metabolites formed are generally less active than the parent compound. 

Elimination and excretion 

The elimination of sirolimus and its metabolites primarily occurs through the feces. 

Adminstartion

Administration: 

• Clean the affected skin area: Wash the area with soap and water, and make a pat it dry with a clean towel. 
• Apply a thin layer: Take a sufficient amount of sirolimus cream or ointment and spread it evenly over the affected skin area. Gently rub the medication into the skin until it is absorbed. 
• Follow dosing instructions: The specific dosing instructions may vary based on the condition treated and the formulation of sirolimus topical. 
• Frequency of application: sirolimus topical is usually applied once daily. However, the frequency may vary based on the individual’s condition and the recommendation of the healthcare provider. 
• Avoid contact with eyes, nose, and mouth: Be cautious to avoid getting sirolimus topical into your eyes, nose, or mouth. If accidental contact occurs, rinse with water. 
• Wash hands after application: After applying sirolimus topical, thoroughly wash hands with water and soap to remove any residual medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: sirolimus topical 

Pronounced: (sigh-roh-LYE-mus TOP-i-kal)  

Why do we use sirolimus topical? 

• Treatment of Facial Angiofibromas: sirolimus topical is approved for the treatment of facial angiofibromas, which are raised red bumps or nodules on the face, typically seen in individuals with TSC. It helps reduce the size and appearance of these facial lesions. 
• Treatment of Cutaneous T-cell Lymphoma (CTCL): Sirolimus topical may be used as an off-labelled treatment for CTCL, a type of non-Hodgkin lymphoma that affects the skin. It can help reduce the severity of skin lesions, itching, and inflammation associated with CTCL. 
• Treatment of Other Dermatological Conditions: sirolimus topical is being investigated for its potential use in other skin conditions, such as psoriasis, and various inflammatory skin disorders.