NEOTIGASON

What it is

Neotigason (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

**Adults.** 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. This may be less than 20 mg and should not exceed 50 mg daily. **Children.** The dosage should be established on a weight basis. The daily dosage is about 0.5 mg/kg. Higher doses up to 1 mg/kg or 35 mg daily may be necessary in some cases for limited periods.

Key safety warnings

**Teratogenicity.** Neotigason is highly teratogenic, inducing a high frequency of severe and life threatening birth defects. Neotigason 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. Women of childbearing potential must use effective contraception, without interruption, 1 month before starting treatment, throughout the entire duration of treatment and for 3 years after the end of treatment. At least one highly effective method of contraception (i.e. a user-independent form) or two complementary user-dependent forms of contraception should be used. **Psychiatric effects.** 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. **Pseudotumour cerebri.** Neotigason 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 Neotigason immediately and be referred for neurologic evaluation and care. **Bone changes.** Maintenance treatment may result in progression of existing spinal hyperostosis, in appearance of new hyperostotic lesions and in extraskeletal calcification, as has been observed in long-term systemic treatment with retinoids. In adults, especially elderly, receiving long-term treatment with Neotigason, appropriate examinations should be periodically performed in view of possible ossification abnormalities. **Lipid abnormalities.** Approximately 65% of patients receiving Neotigason during clinical trials experienced an elevation in triglycerides. Approximately 30% developed a decrease in high density lipoproteins (HDL). Serum cholesterol and serum triglycerides (fasting values) must be monitored, before starting treatment, one month after the commencement and then every 3 months during treatment especially in high-risk patients. **Hepatic function.** Hepatic function should be monitored before and every one to two weeks for the first two months after starting treatment with Neotigason and then every three months during treatment.

Contraindications

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

PBS listing

Neotigason capsule 10 mg is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$89.52. Neotigason capsule 25 mg is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$182.05.

Regulatory history

Neotigason acitretin 10 mg and 25 mg capsules were first listed on the Australian Register of Therapeutic Goods on 26 May 1995.