indication

For the treatment of severe psoriasis in adults.

pharmacology

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 acitretin is unknown, however it is believed to work by targeting specific receptors (retinoid receptors such as RXR and RAR) in the skin which help normalize the growth cycle of skin cells.

toxicity

Oral, rat: LD₅₀ = >4000 mg/kg. Symptoms of overdose include headache and vertigo.

biotransformation

Following oral absorption, acitretin undergoes extensive metabolism and interconversion by simple isomerization to its 13-cis form (cis-acitretin). Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted.

absorption

Oral absorption of acitretin is optimal when given with food, and is linear and proportional with increasing doses from 25 to 100 mg. Approximately 72% (range 47% to 109%) of the administered dose was absorbed after a single 50 mg dose of acitretin was given to 12 healthy subjects.

half life

49 hours (range 33 to 96 hours)

route of elimination

Both parent compound and isomer are further metabolized into chain-shortened breakdown products and conjugates, which are excreted. The chain-shortened metabolites and conjugates of acitretin and cis-acitretin are ultimately excreted in the feces (34% to 54%) and urine (16% to 53%).

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.

Norethindrone: Acitretine may cause a loss of contraceptive effect

Oxytetracycline: Increased risk of intracranial hypertension

Rolitetracycline: Increased risk of intracranial hypertension

Tetracycline: Increased risk of intracranial hypertension

Vitamin A: Acitretin increases the risk of vitamin A toxicity. Avoid vitamin A supplementation while taking acitretin.