Acitretin

Indications

Acitretin is indicated in severe extensive psoriasis which is resistant to other forms of therapy, palmo-plantar pustular psoriasis, severe congenital ichthyosis, severe Darier’s disease (keratosis follicularis).

Pharmacology

Acitretin is a retinoid, an aromatic analogue of vitamin A. The mechanism of action of acitretin is unknown, however, evidence exists for a wide range of actions at various cellular and subcellular levels. These include regulation of RNA/DNA synthesis, modulation of factors which influence epidermal proliferation, modification of glycoprotein synthesis and modulation of the immune response. Whatever the exact mechanism of action, the most prominent effect of acitretin is a modulation of cellular differentiation in the epidermis which re-establishes a more normal pattern of cell growth.

Dosage & Administration

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.

Interaction

Existing data suggests that concurrent intake of acitretin with ethanol led to the formation of etretinate. Concomitant administration of methotrexate, tetracyclines or vitamin A and other retinoids with acitretin is contraindicated. In concurrent treatment with phenytoin, it must be remembered that Acitretin partially reduces the protein binding of phenytoin. Low dose progesterone-only products (minipills) may be an inadequate method of contraception during acitretin therapy, Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.

Contraindications

Acitretin is highly teratogenic and must not be used by women who are pregnant. The same applies to women of childbearing potential unless strict contraception is practiced 4 weeks before, during and for 2 years after treatment. The use of Acitretin is contra-indicated in women who are breast feeding.Acitretin is contraindicated in patients with severe hepatic or renal impairment and in patients with chronic abnormally elevated blood lipid values. Concomitant administration of Acitretin with other retinoids or Vitamin A is contra-indicated due to the risk of hypervitaminosis A. Acitretin is contra-indicated in cases of hypersensitivity to the preparation (acitretin or excipients) or to other retinoids. Patients with rare glucose-galactosemalabsorption should not take this medicine.

Side Effects

Adverse effects are seen in most patients receiving acitretin. Most of the clinical side-effects of Acitretin are dose-related and are usually well-tolerated at the recommended dosages. However, the toxic dose of Acitretin is close to the therapeutic dose and most patients experience some side-effects during theinitial period whilst dosage is being adjusted. The skin and mucous membranes are most commonly affected. An initial worsening of psoriasis symptoms issometimes seen at the beginning of the treatment period.

Pregnancy & Lactation

Acitretin is contraindicated in pregnant women or nursing mother. It is highly teratogenic. Its use is contraindicated in women who might become pregnant during or within 2 years of the cessation of treatment.

Precautions & Warnings

The risk of giving birth to a deformed child is exceptionally high if Acitretin is taken before or during pregnancy, no matter for how long or at what dosage. Women of childbearing potential must not receive blood from patients being treated with acitretin. Donation of blood by a patient being treated with acitretin is prohibited during and for two years after completion of treatment with acitretin. The effects of UV light are enhanced by retinoid therapy; therefore patients should avoid excessive exposure to sunlight. Hepatic function should be checked before starting treatment with Acitretin, every 1-2 weeks for the first 2 months after commencement and then every 3 months during treatment. Serum cholesterol and serum triglycerides (fasting values) must be monitored before starting treatment, one month after the commencement and then every 3 months during treatment, especially in high-risk patients and during long-term treatment. Retinoids can alter glucose tolerance, blood sugar levels should therefore be checked. Patients should be warned of the possibility of alopecia. Decreased night vision has been reported with acitretin therapy. Patients with severe headache, nausea, vomiting, and visual disturbances should discontinue acitretin immediately.

Overdose Effects

Manifestations of acute Vitamin A toxicity include severe headache, vertigo, nausea or vomiting, drowsiness, irritability and pruritus. Signs and symptoms of accidental or deliberate overdosage with Acitretin would probably be similar. Specific treatment is unnecessary because of the low acute toxicity of the preparation.

Therapeutic Class

Oral Retinoid preparations

Storage Conditions

Store in a cool & dry place, protected from light. Do not store above 25°C.