ZETIN

What it is

Zetin (acitretin) is a retinoid for the oral treatment of severe cases of psoriasis and disorders of keratinisation. It is available as 10 and 25 mg capsules.

Approved indications Acitretin may be used for the treatment of:

— Severe intractable psoriasis in all its forms — Severe forms of disorders of keratinisation such as hyperkeratosis palmaris et plantaris — Pustulosis palmaris et plantaris — Ichthyosis — Keratosis follicularis (Darier's disease) — Lichen planus affecting the skin or the mucosae — Pityriasis rubra pilaris

Dosing overview

Because there are differences in the absorption and rate of metabolism of acitretin, the dosage must be individually adjusted. The capsules should be taken preferably once daily with meals, or with milk. An initial dosage of 25 mg or 30 mg for about two to four weeks may give satisfactory therapeutic results. In general, a daily dosage of 25–50 mg taken for a further six to eight weeks achieves optimal therapeutic results. In disorders of keratinisation, a continuous maintenance is mostly needed with the dose at the lowest possible level, which may be less than 20 mg and should not exceed 50 mg daily.

Key safety warnings

Zetin is highly teratogenic, inducing a high frequency of severe and life threatening birth defects, and must not be used by patients who are pregnant or who intend to become pregnant during therapy or for 3 years after cessation of therapy. Depression, depression aggravated, anxiety, mood alterations and psychotic disorders have been reported in patients treated with systemic retinoids, including acitretin. Particular care should be taken in patients with a history of depression. Patients should be monitored for signs of depression and referred for appropriate treatment if necessary. Zetin and other retinoids administered orally have been associated with cases of pseudotumour cerebri (benign intracranial hypertension). Early signs and symptoms include papilloedema, headache, nausea and vomiting, and visual disturbances. Patients with these signs and symptoms should be examined for papilloedema and, if present, should discontinue Zetin immediately and be referred for neurologic evaluation and care. Maintenance treatment may result in progression of existing spinal hyperostosis, in appearance of new hyperostotic lesions and in extraskeletal calcification. In adults, especially elderly, receiving long-term treatment with Zetin, appropriate examinations should be periodically performed in view of possible ossification abnormalities. Elevated transaminase and alkaline phosphatase levels have been noted in a number of patients receiving acitretin. Hepatic function should be monitored before and every one to two weeks for the first two months after starting treatment with Zetin and then every three months during treatment. Approximately 65% of patients receiving Zetin during clinical trials experienced an elevation in triglycerides. Approximately 30% developed a decrease in high density lipoproteins (HDL).

Contraindications

Zetin is strictly contraindicated in pregnant women and women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met. Zetin is contraindicated while breast feeding. Zetin is contraindicated in patients with severely impaired liver or kidney function and in patients with chronic abnormally elevated blood lipid values. Since both Zetin and tetracyclines can cause increased intracranial pressure, their combined use is contraindicated. The combination of methotrexate with Zetin is also contraindicated. Concomitant administration of Zetin and vitamin A or other retinoids is contraindicated due to the risk of hypervitaminosis A.

Regulatory history

Zetin was first included in the Australian Register of Therapeutic Goods on 26th May 1995. Zetin acitretin 25 mg capsule and 10 mg capsule (sponsored by Arrotex Pharmaceuticals) were listed on the ARTG on 23 May 2013.