Alitretinoin

Alitretinoin is a first-generation member of the retinoid family, which also includes retinol, retina, tretinoin, isotretinoin and acitretin. the retinoids They are all related to vitamin A. Alitretinoin is not yet available in New Zealand.

What is alitretinoin used for?

• Alitretinoin gel 0.1% (Panretin®) is used to treat skin lesions resulting from Kaposi sarcoma (KS), a Cancer of the cells that cover blood vessels and is seen more frequently in patients with HIV/AIDS.
• Alitretinoin (Toctino®) capsules are used to treat severe chronic hand dermatitis/ /eczema that does not respond to powerful current corticosteroid therapy.

How does alitretinoin work?

• Retinoids play a role in regulating normal cell growth and cell death.
• Alitretinoin binds to retinoid receptors on the cell. core and activates the receptors.
• Activated receptors regulate the expression of genes that control cell differentiation and growth in both normal and abnormal cells.
• In this way, alitretinoin is capable of inhibit The growth of Kaposi sarcoma cells.
• The mechanism of action of alitretinoin in chronic hand eczema is unknown.
• Alitretinoin has been shown immunomodulator and antiinflammatory effects that are relevant to the skin inflammation.

How is alitretinoin administered?

Alitretinoin Gel 0.1%

• Alitretinoin gel is usually applied directly to AIDS-related KS lesions twice a day.
• It can be applied three or four times a day if tolerated.
• If side effects occur, the frequency of application should be decreased.
• The affected skin is thoroughly cleaned with mild soap or cleanser and water. Avoid medicated or abrasive soap, or soap that dries the skin.
• Clean fingertips, gauze, or a cotton swab can be used to apply the medication.
• The gel should not be applied to skin outside of KS lesions.
• The gel is allowed to dry for at least 3 to 5 minutes before putting on clothing.
• Dressings, bandages, cosmetics, lotions or other skin medications should not be applied to the area to be treated.
• Response to treatment has been seen within two weeks in some patients, however longer treatment periods (8-14 weeks) may be required in other patients.
• It is best to avoid applying the gel near mucous membrane Surfaces such as eyes, nostrils, mouth, lips, vagina, tip of the penis, rectum or anus.

• Insect repellents containing diethyltoluamide (DEET) should be avoided due to potential interaction and increased toxicity.

Alitretinoin capsules

• Alitretinoin capsules should only be prescribed by dermatologists or doctors experienced in using systemic retinoids, and have a complete understanding of the risks of systemic retinoid therapy and the requirements for regular monitoring.
• The medication is usually taken with a meal.
• Alitretinoin is teratogenic (causes birth deformities). A negative pregnancy test must be confirmed before starting treatment.
• The recommended starting dose is 30 mg once a day.
• A dose reduction to 10 mg once daily may be considered in patients with unacceptable side effects at the higher dose.
• A course of alitretinoin treatment is usually 12 to 24 weeks, depending on response.
• Treatment should be discontinued in patients who continue to have severe disease after the initial 12 weeks of treatment.
• If dermatitis recurs, patients may benefit from additional treatment with alitretinoin.
• Alitretinoin should not be prescribed if the patient's dermatitis can be adequately controlled by standard measures, including skin protection, avoidance Allergens and irritantsand treatment with potent topical corticosteroids.
• The use of alitretinoin is not recommended in patients under 18 years of age.
• Licensing requirements may mean that alitretinoin prescriptions for women of childbearing potential are limited to 30 days and continued treatment requires a new prescription.

Link to key evidence from clinical trials on alitretinoin

Possible drug interactions with alitretinoin

• Alitretinoin is metabolized by cytochrome P450 3A4 (CYP3A4; a liver enzyme involved in drugs metabolism)
• CYP3A4 inhibitors such as ketoconazole increase the plasma oral alitretinoin level and dose reduction may be necessary.
• A 16% reduction in simvastatin plasma levels has been observed when taken with oral alitretinoin.
• It is not known if there is any interaction between topical alitretinoin and systemically administered medications for KS.
• To date, topical alitretinoin has not been reported to interact with systemic antiretroviral medications, azole antifungals, and macrolide antibiotics.
• Not pharmacokinetics Interactions have been observed when taking oral alitretinoin with cyclosporine or the oral contraceptive ethinyl estradiol and norgestimate.

Than adverse events Can alitretinoin cause?

Alitretinoin Gel 0.1%

Adverse events related to the use of alitretinoin gel in patients with AIDS-related KS occur almost exclusively at the application site. These include:

• mild heat or itching of the skin
• lightening or darkening of the skin
• red, climbing skin
• eruption
• swelling, blisters or crust of the skin
• pain at application site
• Itch
• sensitivity to the sun on the treated site.

Alitretinoin capsules

• Headache
• Increased levels of triglycerides and blood cholesterol
• Blood cell disorders: decreased coagulation, decreased number of red and white blood cells.
• Thyroid problems: decreased levels of thyroid hormones
• Eye problems: inflammation of the eye (conjunctivitis) and eyelid area; eyes feel dry and irritated
• Muscle and joint pain
• Skin and hair problems: dry skin, especially on the lips and face, inflamed skin, hair loss
• Increased risk of sunburn.
• Increased liver levels. enzymes have been seen in blood tests
• Depression, anxiety, aggressive tendencies, mood disturbances, and very rarely, suicidal ideation have been reported in patients treated with systemic retinoids, including oral alitretinoin.
• Allergic reactions affecting the skin, including anaphylaxis and vasculitis have been rarely reported.

Use in pregnancy

• Alitretinoin gel can harm the fetus if it is absorbed through the skin.
• Women of childbearing potential should avoid becoming pregnant when using the gel or taking the capsules.
• It is not known whether the risk increases with the application of alitretinoin gel to ulcerated lesions.
• Women of childbearing age should not take alitretinoin capsules for hand eczema unless strict contraceptive precautions are followed.
• To exclude the possibility of pregnancy, a pregnancy test should be performed and its date and result recorded before prescribing alitretinoin capsules.
• The need to repeat pregnancy tests every month depends on the patient's sexual activity and recent menstrual history.
• Five weeks after stopping treatment, women should undergo a final pregnancy test to exclude pregnancy.

Use in nursing mothers

• It is not known whether alitretinoin is excreted in human milk.
• Because many drugs are excreted in human milk, mothers should stop breastfeeding before using alitrethionin.

Use in children

The safety and effectiveness of alitretinoin have not been established in children.

Use in the elderly

Safety and effectiveness of alitretinoin in patients 65 years and older have not been evaluated.

Cautions

• Exposure of skin treated with alitretinoin gel to sunlight and sunlamps should be minimized to avoid photosensitivity.
• Patients treated with oral alitretinoin should be observed for signs of depression and referred for appropriate treatment if necessary.
• In case of adverse effects, the medication may be discontinued or the dose may be reduced.