Chlorprothixene is possibly an inhibitor of CYP3A4, but is not listed as a mechanism-based inhibitor. Risk for gastrointestinal adverse events in the form of obstipation, dyspepsia and nausea motivates vigilance against insufficient intake of food, especially of carbohydrate.

Thioxantene derivative

Chlorprothixene is indicated for the treatment of psychoses. Common side effects that can be potentially porphyrinogenic through reduction in carbohydrate intake and that also can be confused with an acute porphyria attack are obstipation, dyspepsia and nausea. Another common side effect is myalgia. Less common side effects are vomiting and diarrhoea. Abrupt discontinuation of zuclopenthixol may be accompanied by withdrawal symptoms. The most common symptoms are nausea, vomiting, anorexia, diarrhoea, rhinorrhoea, sweating, myalgias, paraesthesias, insomnia, restlessness, anxiety, and agitation. Patients may also experience vertigo, alternate feelings of warmth and coldness, and tremor. Symptoms generally begin within 1 to 4 days of withdrawal and abate within 7 to 14 days (SPC).

Chlorprothixene is a substrate of CYP2D6 (Hiemke 2012) and is metabolised to chlorprothixene-sulfoxide, N-desmethyl-chlorprothixene-sulfoxide and chlorprothixene-sulfoxide-N-oxide (Raaflaub 1975). The metabolites are psychopharmacological inactive (SPC). Half-life elimination is 15 hours. A case report showed that the concentration of risperidone increased when it was co-administrated with chlorprothixene (Bader 2008). Risperidone is a substrate of CYP2D6 and CYP3A4 (SPC), which indicates that chlorprothixene can inhibit CYP2D6 or CYP3A4, or both of them. Risperidone is however, not listed as a mechanism-based inhibitor.

Thunell: 1 observation of safe use.

Uneventful use reported in 1 patient with acute porphyria.