What it's for (Indications)
- Acitretin is a systemic retinoid primarily indicated for the treatment of severe psoriasis in adults, particularly for forms that are recalcitrant to other therapies.
- This includes debilitating conditions such as erythrodermic psoriasis, characterized by widespread inflammation and scaling covering a significant portion of the body surface, and generalized pustular psoriasis (von Zumbusch type), which presents with acute flares of widespread sterile pustules.
- It is also approved for other severe disorders of keratinization that are unresponsive to conventional therapeutic approaches, such as congenital ichthyosis and Darier's disease.
- The efficacy of acitretin stems from its ability to normalize the epidermal cell growth and differentiation, which is severely dysregulated in these conditions.
- Its use is generally reserved for patients who have not responded adequately to, or who cannot tolerate, other systemic treatments due to the potential for significant adverse effects.
- This therapeutic approach aims to reduce erythema, scaling, and induration, thereby improving the patient's quality of life significantly when severe disease impacts daily functioning and overall well-being.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Dosage must be individualized due to pharmacokinetic variability, clinical efficacy, and dose-related side effects. Initial therapy typically begins at 25 to 50 mg per day, administered as a single dose with the main meal. Maintenance doses of 25 to 50 mg per day are adjusted based on individual patient response to initial treatment. Relapses should be treated following the same guidelines as initial therapy. When acitretin is used with phototherapy, the phototherapy dose should be decreased based on the patient’s individual response. Females previously treated with etretinate (TEGISON) must continue to adhere to its contraceptive recommendations. |
Safety & Warnings
Common Side Effects
- Commonly reported side effects include dry skin, dermatitis, sticky skin, and erythema.
- More severe or systemic adverse reactions, resembling hypervitaminosis A syndrome, can affect mucocutaneous, musculoskeletal, hepatic, neuropsychiatric, and central nervous systems.
- Postmarketing reports have identified acute myocardial infarction, thromboembolism, stroke, hypersensitivity reactions (including angioedema and urticaria), and myopathy with peripheral neuropathy.
Serious Warnings
- Black Box Warning: WARNING: TERATOGENICITY. Acitretin is highly teratogenic. It is absolutely contraindicated in females who are pregnant, or who intend to become pregnant during therapy or at any time for at least 3 years following discontinuation of therapy. Acitretin also must not be used by females who may not use reliable contraception while undergoing treatment and for at least 3 years following discontinuation of treatment. Acitretin is a metabolite of etretinate (TEGISON), and major human fetal abnormalities have been reported.
- Pregnancy: Acitretin is highly teratogenic and must not be used by females who are pregnant or who intend to become pregnant during therapy or for at least 3 years following discontinuation.
- Females must use reliable contraception during treatment and for at least 3 years post-treatment.
- Lactation: Should not be used by breastfeeding mothers.
- Liver Function: Patients with pre-existing liver disease or severely impaired liver function should consult their doctor and generally should not use acitretin, due to an increased risk of hepatotoxicity.
- Kidney Function: Patients with kidney diseases or severely impaired kidney function should not use acitretin.
- Cardiovascular/Lipids: Patients with chronic abnormally elevated blood lipid values should be monitored due to possible cardiovascular effects, as acitretin can increase blood lipids.
- Alcohol: The use of alcohol should be limited or avoided.
- Hypersensitivity: Patients with known allergies to acitretin or its components should consult a doctor.
- Other: If taking any vitamins (especially in high doses, due to risk of congenital disabilities), nutritional supplements, or herbal products, consult a doctor.
- Patients should seek immediate medical advice if swelling is experienced.
- Driving: Its intake has not shown any risks during driving, but individual response should be considered.
How it Works (Mechanism of Action)
Acitretin is a synthetic, orally administered retinoid, an active metabolite of etretinate, belonging to the class of aromatic retinoids. Its therapeutic effects are primarily mediated through its interaction with nuclear retinoic acid receptors (RARs), specifically RAR-alpha, RAR-beta, and RAR-gamma. These RARs are ligand-activated transcription factors that, upon binding with acitretin, form a complex which then binds to specific DNA sequences known as retinoid response elements (RAREs) in the promoter regions of target genes. This binding event modulates gene expression, leading to a profound impact on cellular processes. In conditions like psoriasis and other severe keratinization disorders, where there is an aberrant proliferation and differentiation of keratinocytes, acitretin works to normalize these cellular functions. It effectively reduces the hyperproliferation of epidermal cells and promotes their proper differentiation, thereby correcting the underlying pathology of keratinization disorders. Furthermore, acitretin exhibits anti-inflammatory and immunomodulatory properties by influencing the production of cytokines and other inflammatory mediators, which contribute to its overall efficacy in managing severe inflammatory dermatoses and alleviating the associated symptoms of erythema and scaling.