indication

For the treatment of severe psoriasis in adults.

pharmacology

The active metabolite responsible for etretinate's effects, acitretin, is a retinoid. Retinoids have a structure similar to vitamin A and are involved in the normal growth of skin cells. Acitretin works by inhibiting the excessive cell growth and keratinisation (process by which skin cells become thickened due to the deposition of a protein within them) seen in psoriasis. It therefore reduces the thickening of the skin, plaque formation and scaling.

mechanism of action

The mechanism of action of the active metabolite, acitretin, is unknown, however it is believed to work by targeting specific receptors (retinoid receptors) in the skin which help normalize the growth cycle of skin cells.

toxicity

Symptoms of overdose include headache and vertigo.

biotransformation

Extensively metabolized, with significant first-pass metabolism to the pharmacologically active acid form. Subsequent metabolism results in the inactive 13-cis acid form, chain-shortened breakdown products, and conjugates that are ultimately excreted.

absorption

Absorbed in the small intestine. Studies in normal volunteers indicate that the absorption of etretinate is greater in patients consuming whole milk or a high-fat diet than in patients in a fasting state.

half life

In one study, the apparent terminal half-life of etretinate after 6 months of therapy was approximately 120 days. In another study of 47 patients who had undergone chronic therapy with etretinate, 5 patients had detectable serum drug concentrations (0.5 to 12 ng/mL) 2.1 to 2.9 years after therapy was completed.

drug interactions

Demeclocycline: Increased risk of intracranial hypertension

Doxycycline: Increased risk of intracranial hypertension

Methacycline: Increased risk of intracranial hypertension

Methotrexate: Acitretin/etretinate increases the effect and toxicity of methotrexate

Minocycline: Increased risk of intracranial hypertension

Oxytetracycline: Increased risk of intracranial hypertension

Rolitetracycline: Increased risk of intracranial hypertension

Tetracycline: Increased risk of intracranial hypertension