Acitretin

Introduction

Acitretin is an oral retinoid primarily used in the treatment of severe psoriasis and other keratinization disorders. It is a second-generation retinoid that helps to normalize skin cell growth and reduce scaling and inflammation.

Uses

Acitretin is indicated for the treatment of severe cases of psoriasis, particularly pustular and erythrodermic psoriasis. It is also used to treat other keratinization disorders such as ichthyosis and palmoplantar keratoderma.

Brand Name	Acitretin
Type
Weight
Generic	Acitretin
Manufacturer
Available in	English বাংলা

Mechanism of Action

Acitretin modulates the proliferation and differentiation of epidermal cells by binding to nuclear retinoic acid receptors. This regulation results in a normalization of keratinocyte growth and differentiation, reducing the scaling and thickening of the skin seen in psoriasis and other related skin conditions.

How Long Does It Take to Work?

Improvements in psoriasis symptoms with acitretin typically begin within 2-4 weeks, though it may take up to 3-6 months for full therapeutic effects. Patients must adhere to the treatment regimen for sustained benefit.

Absorption

Acitretin is well absorbed after oral administration, particularly when taken with food, which can increase its bioavailability. Its absorption can be erratic, with peak plasma concentrations occurring 2-5 hours after dosing.

Route of Elimination

Acitretin is primarily eliminated via the liver, with about 50% excreted in feces and 35% excreted in urine. It undergoes extensive hepatic metabolism.

Dosage

Adult and elderly: Initial daily dose should be 25 mg or 30 mg for 2 to 4 weeks. After this initial treatment period the involved areas of the skin should show a marked response and/or side-effects should be apparent. In general, a daily dosage of 25-50 mg taken for a further 6 to 8 weeks to achieve optimal therapeutic results. However, it may be necessary in some cases to increase the dose up to a maximum of 75 mg/day.

In patients with Darier’s disease a starting dose of 10 mg may be appropriate. The dose should be increased cautiously as isomorphic reactions may occur. Patients with severe congenital ichthyosis and severe Darier’s disease may require therapy beyond 3 months. The lowest effective dosage, not exceeding 50mg/day, should be given. Continuous use beyond 6 months is contra-indicated as only limited clinical data are available on patients treated beyond this length of time.

Children: The daily dosage is about 0.5mg/kg. Higher doses (up to 1mg/kg daily) may be necessary in some cases for limited periods, but only up to a maximum of 35 mg/day.

The typical starting dose for adults is 25-50 mg taken orally once daily. Dosage can be adjusted based on clinical response and tolerance. In psoriasis, the dose is gradually increased, with the maximum recommended dose being 75 mg/day.

Administration

Acitretin is administered orally and should be taken with food to improve absorption. It is recommended to follow the prescribed dosage and not exceed the maximum dose of 75 mg/day.

Side Effects

Common side effects include:

• Dry skin, lips, and eyes
• Hair loss
• Increased blood lipids
• Liver enzyme abnormalities
• Photosensitivity (increased sensitivity to sunlight)

Serious side effects include liver toxicity, severe dryness, and teratogenic effects (birth defects if taken during pregnancy).

Toxicity

Acitretin has significant toxicity, particularly related to hepatotoxicity and hyperlipidemia. It is also highly teratogenic, posing serious risks to fetal development. Overdose may lead to excessive retinoid toxicity, with symptoms including headache, dizziness, nausea, and dry skin.

Precautions

Precautions when using acitretin include:

• Monitoring liver function tests and lipid levels regularly
• Avoiding use in women of childbearing potential unless stringent contraceptive measures are followed
• Avoiding alcohol consumption, as it can lead to the formation of etretinate, a longer-acting teratogenic metabolite
• Using sunscreen and protective clothing due to increased photosensitivity

Interaction

Acitretin may interact with:

• Alcohol, leading to the formation of etretinate, which prolongs its teratogenic risk
• Tetracyclines, increasing the risk of intracranial hypertension
• Methotrexate, increasing the risk of liver damage
• Vitamin A or other retinoids, increasing the risk of toxicity

Disease Interaction

Acitretin should be used cautiously in patients with:

• Liver disease
• Hyperlipidemia
• Renal impairment
• Diabetes, as it may alter blood sugar levels

Drug Interaction

Significant drug interactions include:

• Alcohol, which converts acitretin into the longer-lasting etretinate
• Other hepatotoxic drugs, which can increase the risk of liver damage
• Concomitant use with vitamin A supplements or other retinoids, increasing toxicity risk
• Warfarin, increasing the risk of bleeding

Food Interactions

Acitretin should be taken with food to improve absorption. Alcohol consumption should be avoided as it can extend the teratogenic effects of the drug.

Pregnancy Use

Acitretin is highly teratogenic and classified as pregnancy category X. It must not be used during pregnancy or in women planning to become pregnant within three years of stopping treatment. Women of childbearing age must use effective contraception during treatment and for at least three years after discontinuation.

Lactation Use

It is unknown whether acitretin is excreted in breast milk. However, due to the potential for serious adverse effects in nursing infants, breastfeeding is contraindicated during acitretin therapy.

Acute Overdose

In the event of an overdose, symptoms of hypervitaminosis A may occur, including severe headache, nausea, vomiting, and dry skin. Treatment is supportive and symptomatic. Immediate medical attention is required.

Contraindication

Acitretin is contraindicated in:

• Pregnant women or women planning to become pregnant within three years
• Severe liver or kidney impairment
• Chronic alcoholism
• Patients taking other retinoids or vitamin A supplements

Use Direction

Acitretin should be taken with food at the prescribed dose. Women of childbearing potential must use two forms of contraception during and after treatment. Alcohol consumption should be avoided to prevent the formation of etretinate.

Storage Conditions

Acitretin should be stored at room temperature, away from light and moisture, and kept in its original container. The medication should be kept out of reach of children.

Volume of Distribution

The volume of distribution for acitretin is approximately 9 liters/kg, indicating extensive tissue distribution, particularly in lipid-rich tissues.

Half Life

The elimination half-life of acitretin is approximately 49 hours. However, if it converts to etretinate (due to alcohol consumption), the half-life extends to several weeks, significantly prolonging the teratogenic risk.

Clearance

Acitretin is cleared primarily via hepatic metabolism. Its clearance can be impaired in patients with liver dysfunction, necessitating dose adjustments or discontinuation in severe cases.

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Some Frequently Asked Questions About Acitretin