Acute Porphyria Drug Database

N05AF01 - Flupentixol
Propably not porphyrinogenic
PNP

Rationale
Flupentixol is metabolised by CYP2D6 and is not listed as inducer or inhibitor of any major CYP enzymes. Risk for gastrointestinal adverse events in the form of obstipation, dyspepsia, vomiting and diarrhoea motivates vigilance against insufficient intake of food, especially of carbohydrate.
Chemical description
Thioxantene derivative. The active isomere is cis-(Z)-flupentixol.
Therapeutic characteristics
Flupentixol is indicated for the treatment of schizophrenia and other 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, vomiting and diarrhoea. Other common side effects are myalgia, headache and tachycardia. A less common side effect is loss of appetite. 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).
Metabolism and pharmakokinetics
Flupentixol is a substrate of CYP2D6 (Hiemke 2012 and Pirmohamed 2003). Cis-(Z)-cisflupentixol is metabolised via sulfoxidation and N-dealkylation and glucuronacidconjugation. None of the metabolites are psychopharmacological active (SPC). Half-life elimination is 35 hours. Flupentixol is not listed as an inducer or inhibitor of any major CYP enzymes (Isoherranen 2009 and Pelkonen 2008).
Personal communication
Thunell: 1 report of uneventful use.
Published experience
Flupentixol is listed to be unsafe for use in acute porphyria because it has been shown to be porphyrinogenic in animals or in vitro systems (Moore 1997).
IPNet drug reports
Uneventful use reported in 1 patient with acute porphyria.

References

  1. Scientific articles
  2. Hiemke C. , Pfuhlmann B. (2012). Interactions and monitoring of antipsychotic drugs. PMID 23129335. #4669
  3. Isoherranen N, Hachad H, et al. Qualitative analysis of the role of metabolites in inhibitory drug-drug interactions: literature evaluation based on the metabolism and transport drug interaction database. Chem Res Toxicol. 2009 Feb;22(2):294-8. #1005
  4. Moore MR, Hift RJ. Drugs in the acute porphyrias--toxicogenetic diseases. Cell Mol Biol (Noisy-le-grand). 1997 Feb;43(1):89-94. PMID 9074793. #1110
  5. Pelkonen O, Turpeinen M, et al. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008 Oct;82(10):667-715. PMID 18618097. #4347
  6. Pirmohamed M, Park BK. Cytochrome P450 enzyme polymorphisms and adverse drug reactions. Toxicology. 2003 Oct 1;192(1):23-32. PMID 14511900. #2646

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