Paroxetine is not an inhibitor or an inducer of CYP3A4, CYP2C9 and CYP2C19 in vivo. Risk for gastrointestinal adverse events in the form of loss of appetite, obstipation, diarrhoea and vomiting motivates vigilance against insufficient intake of food, especially of carbohydrate.

Paroxetine is indicated for the treatment of major depressive episode, obsessive compulsive disorder, panic disorder with and without agoraphobia, social anxiety disorders/social phobia, generalised anxiety disorder and post-traumatic stress disorder. 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 loss of appetite, obstipation, diarrhoea and vomiting. Other common side effects are dizziness, tremor, headache, somnolence and insomnia. A very common side effect is nausea.

Probably significant

Paroxetine is metabolised by CYP2D6 (Norsk legemiddelhåndbok). Half-life elimination is approximately 24 hours. Paroxetine is listed as a competitive inhibitor of CYP2C9 and CYP2C19 in vitro (Isoherranen 2008). Studies also indicate that it is not a time-dependent inhibitor of CYP3A in vitro (Zimmerlin 2011). Paroxetine caused no changes in the plasma concentration of carbamazepine, valproate or phenytoin (Andersen 1991). Carbamazepine is a substrate of CYP3A4 while valproate and phenytoin are substrates of CYP2C9 and CYP2C19 (Norsk legemiddelhåndbok). Paroxetine did not have any effect on the pharmacokinetics parameters of etravirine, a substrate of CYP3A4, CYP2C9 and CYP2C19, when co-administrated (Kakuda 2011). These data indicate that paroxetine is not an inhibitor or an inducer of CYP3A4, CYP2C9 and CYP2C19 in vivo. Paroxetine is a strong (FDA and Grimm 2009) mechanism-based (Isoherranen 2009) inhibitor of CYP2D6 in vivo (Hisaka 2010, Pelkonen 2008 and SPC). The relative abundance of CYP2D6 in the liver is less than 5 per cent of the total CYP isoforms (Mouly 2009 and Pelkonen 2008). The mechanism-based inhibition of CYP2D6 may lead to increased de novo synthesis of CYP2D6, but with the very low relative abundance of CYP2D6 the potential effect on the total heme biosynthetic flux is expected to be minimal. The use of paroxetine is, therefore, not expected to significantly influence the level of ALA and PGB in patients with an acute porphyria.

C. Andersson: 1 report of safe use.

Uneventful use reported in 11 patients with acute porphyria.