ingenol mebutate topical

Action and Spectrum

Actions and spectrum: 

• Keratolytic Action: ingenol mebutate works as a keratolytic agent, meaning it helps to remove and shed the abnormal, thickened skin cells that are characteristic of actinic keratosis. It promotes the exfoliation of the damaged skin cells, leading to their removal. 
• Cytotoxic Effects: ingenol mebutate also has cytotoxic effects on the abnormal cells. It induces cell death (apoptosis) in the actinic keratosis cells, resulting in their elimination. 
• Local Immune Response: ingenol mebutate stimulates a local immune response in the skin, which helps to clear the actinic keratosis lesions. It activates certain immune cells and releases inflammatory mediators that contribute to the destruction of the abnormal cells. 

The spectrum of ingenol mebutate is primarily limited to the treatment of actinic keratosis, a condition caused by long-term sun exposure. It is not indicated for other skin conditions or cancers. The topical formulation allows for targeted application directly to the affected areas, reducing systemic exposure and potential side effects. 

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

extremities/trunk application 

• Irritation at application site (4%) 
• pain at application site (2%) 
• pruritus at application site (8%) 
• Nasopharyngitis (2%) 

scalp/face application 

• infection at application site (3%) 
• Headache (2%) 
• pruritus at application site (8%) 
• Periorbital edema (3%)

>10% 

extremities/trunk application 

• Flaking/scaling (90%) 
• Swelling (64%) 
• Erosion/ulceration (26%) 
• Erythema (92%) 
• Crusting (74%) 
• Vesiculation/pustulation (44%) 

scalp/face application 

• Flaking/scaling (85%) 
• Swelling (79%) 
• Erosion/ulceration (32%) 
• Erythema (94%) 
• Crusting (80%) 
• Vesiculation/pustulation (56%) 
• pain at application site (15%)

Frequency not defined 

Eye pain 

Eyelid edema 

Chemical conjunctivitis  

Post marketing Reports 

Herpes Zoster 

Eye injuries 

scarring at application site 

Hypersensitivity 

Allergic contact dermatitis 

Corneal burn 

pigmentation changes at application site 

Stevens-Johnson syndrome 

Skin Non-melanoma cancer 

Black Box Warning

Black Box Warning: 

There is no black box warning associated with ingenol mebutate topical. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: It is contraindicated in individuals who have a known hypersensitivity or allergy to ingenol mebutate or any of the ingredients in the topical formulation. Hypersensitivity reactions can range from mild skin irritation to severe allergic reactions. 
• Viral Skin Infections: It is contraindicated in patients with viral skin infections, such as herpes simplex virus (HSV) or varicella-zoster virus (VZV) infections. The application of ingenol mebutate topical can potentially exacerbate or spread these infections. 
• Open Wounds, Ulcerations, or Broken Skin: It should not be applied to open wounds, ulcerations, or areas of broken skin. The presence of such conditions may increase the absorption of ingenol mebutate, leading to systemic exposure and potential adverse effects. 
• Photosensitivity Disorders: ingenol mebutate topical is contraindicated in individuals with known photosensitivity disorders or a history of phototoxic reactions. It can cause increased sensitivity to sunlight, leading to severe sunburn or other adverse skin reactions.

Caution: 

• Eye Exposure: Avoid contact with the eyes, as ingenol mebutate can cause severe eye irritation. In case of accidental contact, rinse the eyes thoroughly with water. 
• Application Site Reactions: Skin reactions such as redness, swelling, burning sensation, and blistering may occur at the application site.  
• Sun Exposure: ingenol mebutate topical can make the treated skin more sensitive to sunlight.  
• Concurrent Skin Treatments: Avoid using other topical medications or treatments on the same area concurrently with ingenol mebutate. Combining multiple topical treatments may increase the risk of skin irritation. 
• Systemic Absorption: Although ingenol mebutate is a topical medication, there is a potential for systemic absorption. This can result in systemic side effects, especially if large areas of the body are treated or if there are open wounds or broken skin. 
• Pregnancy and Lactation: The safety of ingenol mebutate topical during pregnancy and lactation has not been established.

Comorbidities: 

• Skin Conditions: If there are pre-existing skin conditions such as eczema, psoriasis, or skin infections, it is important to discuss the use of ingenol mebutate topical with your healthcare provider. Certain skin conditions may require special attention or caution when using this medication. 
• Sensitivity and Allergies: If there are known sensitivity or allergy to ingenol mebutate or any of its components, it is important to avoid using this medication. Inform your healthcare provider about any known allergies or sensitivities to medications or substances. 
• Immunocompromised State: If there is a weakened immune system due to HIV/AIDS, organ transplantation, or immunosuppressive therapy, it is important to discuss the use of ingenol mebutate topical with your healthcare provider. They can assess the potential risks and benefits of using this medication in your specific situation. 
• Open Wounds or Broken Skin: It is advised to avoid applying ingenol mebutate topical to open wounds or broken skin, as it may cause increased absorption and potential systemic side effects. Consult your healthcare provider for guidance if you have any concerns in this regard. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: C 

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: 

• Direct Cytotoxicity: ingenol mebutate directly affects the cells of actinic keratosis, causing cell death. It induces cell membrane rupture, leading to cellular swelling, disruption of cellular structures, and subsequent cell death. 
• Inflammatory Response: ingenol mebutate stimulates the local immune response, leading to the release of inflammatory mediators such as cytokines and chemokines. This immune response helps to clear the actinic keratosis lesions and initiate the healing process. 
• Vascular Effects: ingenol mebutate causes vasoconstriction of blood vessels, which may help to reduce inflammation and decrease the blood supply to the actinic keratosis lesions. 

Pharmacodynamics: 

• Cellular Destruction: ingenol mebutate directly induces cell death in actinic keratosis cells. It disrupts the cellular structures, leading to cell membrane rupture and subsequent cell death. This mechanism helps to eliminate the abnormal cells associated with actinic keratosis. 
• Inflammatory Response: ingenol mebutate stimulates an immune response on the skin, which leads to the release of inflammatory mediators like chemokines and cytokines. This immune response helps to eliminate the actinic keratosis cells and promote healing. 
• Selectivity: ingenol mebutate exhibits selectivity for actinic keratosis cells, sparing normal healthy skin cells. This targeted action minimizes the potential for damage to surrounding healthy tissue. 

Pharmacokinetics: 

Absorption 

ingenol mebutate is applied topically to the affected skin area. It is absorbed through skin and enters the underlying tissues. 

Distribution 

After absorption, ingenol mebutate is distributed within the skin layers, specifically targeting the actinic keratosis cells. Its distribution may be influenced by factors such as the blood flow to the skin and the binding affinity to skin proteins. 

Metabolism 

The metabolism of ingenol mebutate within the skin tissue is not well understood. It is primarily thought to undergo intracellular metabolism within the actinic keratosis cells. 

Elimination and excretion 

ingenol mebutate is not significantly excreted systemically as it acts locally within the skin. Any metabolites or traces of the drug that do enter systemic circulation are eliminated through normal metabolic and excretory processes. 

Adminstartion

Administration: 

• Preparation: Wash and dry the affected area before applying ingenol mebutate. make sure that the skin is dry, clean, and free from any other topical products. 
• Application: Open the tube or container of ingenol mebutate and squeeze out the prescribed amount of gel or cream onto your fingertip. Apply a thin layer to affected area, gently by rubbing it into the skin until it is fully absorbed. 
• Dosage: The specific dosage and duration of treatment with ingenol mebutate will be determined by your healthcare provider based on your condition and individual needs. Follow their instructions carefully and do not exceed the recommended dosage. 
• Avoid contact: Be cautious to avoid contact with healthy skin, mucous membranes, eyes, and lips. If accidentally contact occurs, rinse thoroughly with water. 
• Wash hands: After applying ingenol mebutate, wash your hands thoroughly to remove any residual medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ingenol mebutate topical 

Pronounced: (in-jen-ohl meh-BYOO-tate TOP-i-kal)  

Why do we use ingenol mebutate topical? 

The specific uses of ingenol mebutate topical include: 

• Actinic keratosis therapy on the face and scalp. 
• Actinic keratosis therapy on the trunk (chest, back) and extremities (arms, legs). 
• Prevention of actinic keratosis progression to squamous cell carcinoma.