What is Ingenol Mebutate used for?

**Introduction to Ingenol Mebutate**

Ingenol Mebutate, often marketed under trade names such as Picato, is a topical medication primarily used to treat actinic keratosis. Actinic keratosis is a rough, scaly patch on the skin that develops from years of exposure to the sun. If untreated, it can lead to more serious skin conditions, including squamous cell carcinoma. Ingenol Mebutate was originally derived from the plant Euphorbia peplus, commonly known as milkweed. The drug is a diterpene ester and has gained attention for its unique dual mechanism of action. Research institutions worldwide have been involved in studying Ingenol Mebutate's efficacy and safety, resulting in its approval by various regulatory agencies. However, recent developments have seen a decline in its usage due to safety concerns, which we will explore later in this blog.

The drug is particularly indicated for the topical treatment of actinic keratosis in both the face and scalp regions. Ingenol Mebutate has been extensively studied through clinical trials, where its effectiveness in clearing up lesions has been well documented. Despite its promising results, the drug has faced scrutiny due to associated side effects, leading to its market withdrawal in some regions.

**Ingenol Mebutate Mechanism of Action**

Ingenol Mebutate works through a dual mechanism that targets both the immune response and cell death. Firstly, it induces rapid cell death in the hyperproliferative cells that make up actinic keratosis lesions. This process is known as primary necrosis and occurs within hours of application. Unlike traditional chemotherapeutic agents that target DNA replication or metabolic pathways, Ingenol Mebutate disrupts the cell membrane, leading to an influx of calcium and other ions, which triggers cell death.

Secondly, Ingenol Mebutate promotes an immune response against the treated area. It activates protein kinase C (PKC) isoforms, which then trigger the release of pro-inflammatory cytokines and chemokines. This phase recruits neutrophils and other immune cells to the site, which helps to clear the dead cells and possibly target any malignant cells that might be present. This dual-action approach not only removes the visible lesions but also helps to treat the underlying pathology that could lead to future lesions.

**How to Use Ingenol Mebutate**

Ingenol Mebutate is intended for topical use only and comes in gel form, with two different concentrations: 0.015% for the face and scalp, and 0.05% for the trunk and extremities. The application process is straightforward but must be followed carefully to avoid complications.

For facial and scalp lesions, the 0.015% gel is applied once daily for three consecutive days. For lesions on the trunk and extremities, the 0.05% gel is applied once daily for two consecutive days. The gel should be applied to the affected area and allowed to dry for 15 minutes before washing hands. The treated area should not be touched or washed for at least six hours after application. It's advisable to apply the medication at the same time each day to maintain consistent drug levels.

The onset of action for Ingenol Mebutate is typically rapid. Users may start to notice redness and swelling within a day of the first application, indicating the drug is working. Full healing and lesion clearance can take several weeks, during which the treated area may go through phases of redness, blistering, and crusting before new skin forms.

**What are Ingenol Mebutate Side Effects**

While Ingenol Mebutate is effective in treating actinic keratosis, it is not without its side effects. Common side effects include localized skin reactions such as redness, swelling, peeling, and crusting. These are generally expected and indicate that the drug is working. More severe side effects can include pain, itching, and infection at the application site. Users should monitor the treated area closely and consult their healthcare provider if severe symptoms occur.

One of the significant concerns with Ingenol Mebutate is its potential to cause severe allergic reactions, although this is rare. Symptoms may include rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, and difficulty breathing. If any of these symptoms occur, immediate medical attention is required.

Contraindications for using Ingenol Mebutate include hypersensitivity to the drug or any of its components. Additionally, it is not recommended for use on areas with broken skin, mucous membranes, or around the eyes. Due to insufficient data on its safety, Ingenol Mebutate should also be avoided in pregnant or breastfeeding women unless absolutely necessary and prescribed by a healthcare provider.

**What Other Drugs Will Affect Ingenol Mebutate**

Ingenol Mebutate is used topically, which generally limits its interactions with systemic medications. However, caution should still be exercised. Concurrent use of other topical treatments on the same area should be avoided to prevent compounded skin irritation or unpredictable drug interactions. This includes other medications for actinic keratosis, corticosteroids, and emollients that might alter the skin barrier and affect drug absorption.

Patients should inform their healthcare provider of all medications they are currently taking, including over-the-counter drugs, vitamins, and herbal supplements. Although systemic absorption of Ingenol Mebutate is minimal, theoretical drug interactions could still occur.

In conclusion, Ingenol Mebutate represents a significant advancement in the treatment of actinic keratosis with its dual mechanism of action. However, its associated side effects and potential risks cannot be ignored. Patients considering this treatment should have a thorough discussion with their healthcare provider to weigh the benefits against the risks. Despite its promising initial results, the decline in its usage due to safety concerns serves as a reminder of the complexities involved in dermatological treatments.