Alitretinoin

Products

Alitretinoin is commercially available in capsule form (Toctino) and was approved in many countries in 2009.

Structure and properties

Alitretinoin (C20H28O2, Mr = 300.4 g/mol) is a retinoid like the acne drugs isotretinoin (13- retinoic acid) or tretinoin (all-retinoic acid).

Effects

Alitretinoin (ATC D11AX19) has anti-inflammatory and immunomodulatory properties. Unlike other retinoids, it acts as an agonist at the retinoic acid receptor RAR as well as at the retinoid X receptor RXR. Alitretinoin is therefore also referred to as a pan-agonist. Retinoids have an effect on cell proliferation, cell differentiation, cell death, vascularization, keratinization, sebum secretion, and immunomodulation.

Indications

For the treatment of adults with refractory, severe chronic hand eczema who have received extended topical treatment for at least 4 weeks and have not responded.

Dosage

According to the SmPC. Capsules are taken once daily with a main meal. The duration of therapy is limited.

Contraindications

  • Pregnancy (harmful to fertility!)
  • Women of childbearing age, unless all conditions of the pregnancy prevention program are met.
  • Breastfeeding
  • Hypersensitivity
  • Hepatic insufficiency
  • Severe renal insufficiency
  • Uncontrolled hypercholesterolemia
  • Uncontrolled hypertriglyceridemia
  • Uncontrolled hypothyroidism
  • Hypervitaminosis A
  • Hereditary fructose intolerance
  • Treatment with tetracyclines or methotrexate

For complete precautions, see the drug label.

Interactions

Alitretinoin is metabolized and isomerized by CYP3A4, CYP2C8, and CYP2C9. Interactions with CYP inhibitors and P-gp inhibitors are possible. The drug should not be taken with vitamin A and other retinoids because of the risk of hypervitaminosis A. An increase in intracranial pressure has been reported with concomitant use of tetracyclines. Tetracyclines are contraindicated during treatment. Methotrexate may increase liver toxicity and is also contraindicated.

Adverse effects

The most common possible adverse effects include headache, skin flushing (erythema), facial flushing, nausea, and changes in laboratory values (triglycerides, cholesterol, TSH, T4).