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Active ingredient: Acitretin - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Keratolytic Agents

Dosage Forms

  • 10 mg and 25 mg gelatin capsules for oral administration

Brands / Synonyms

Acetretin; Soriatane; Soriatane

Indications

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) in the skin which help normalize the growth cycle of skin cells.

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.

Toxicity

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

Biotrnasformation / Drug Metabolism

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.

Contraindications

Pregnancy Category X.

Soriatane is contraindicated in patients with severely impaired liver or kidney function and in patients with chronic abnormally elevated blood lipid values.

An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with Soriatane is also contraindicated.

Since both Soriatane and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated.

Soriatane is contraindicated in cases of hypersensitivity to the preparation (acitretin or excipients) or to other retinoids.

Drug Interactions

Ethanol:Clinical evidence has shown that etretinate can be formed with concurrent ingestion of acitretin and ethanol.

Glibenclamide: In a study of 7 healthy male volunteers, acitretin treatment potentiated the blood glucose lowering effect of glibenclamide (a sulfonylurea similar to chlorpropamide) in 3 of the 7 subjects. Repeating the study with 6 healthy male volunteers in the absence of glibenclamide did not detect an effect of acitretin on glucose tolerance. Careful supervision of diabetic patients under treatment with Soriatane is recommended.

Hormonal Contraceptives: It has not been established if there is a pharmacokinetic interaction between acitretin and combined oral contraceptives. However, it has been established that acitretin interferes with the contraceptive effect of microdosed progestin "minipill" preparations. Microdosed "minipill" progestin preparations are not recommended for use with Soriatane. It is not known whether other progestational contraceptives, such as implants and injectables, are adequate methods of contraception during acitretin therapy.

Methotrexate: An increased risk of hepatitis has been reported to result from combined use of methotrexate and etretinate. Consequently, the combination of methotrexate with acitretin is also contraindicated.

Phenytoin: If acitretin is given concurrently with phenytoin, the protein binding of phenytoin may be reduced.

Tetracyclines: Since both acitretin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated.

Vitamin A and oral retinoids: Concomitant administration of vitamin A and/or other oral retinoids with acitretin must be avoided because of the risk of hypervitaminosis A.

Other: There appears to be no pharmacokinetic interaction between acitretin and cimetidine, digoxin, or glyburide. Investigations into the effect of acitretin on the protein binding of anticoagulants of the coumarin type (warfarin) revealed no interaction.

Laboratory Tests

If significant abnormal laboratory results are obtained, either dosage reduction with careful monitoring or treatment discontinuation is recommended, depending on clinical judgement.

Blood Sugar: Some patients receiving retinoids have experienced problems with blood sugar control. In addition, new cases of diabetes have been diagnosed during retinoid therapy, including diabetic ketoacidosis. In diabetics, blood-sugar levels should be monitored very carefully.

Lipids: In clinical studies, the incidence of hypertriglyceridemia was 66%, hypercholesterolemia was 33% and that of decreased HDL was 40%. Pretreatment and follow-up measurements should be obtained under fasting conditions. It is recommended that these tests be performed weekly or every other week until the lipid response to Soriatane has stabilized.

Liver Function Tests: Elevations of AST (SGOT), ALT (SGPT) or LDH were experienced by approximately 1 in 3 patients treated with Soriatane. It is recommended that these tests be performed prior to initiation of Soriatane therapy, at 1- to 2-week intervals until stable and thereafter at intervals as clinically indicated.

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