Pyrazinamid is most probably neither an inducer nor an inhibitor of CYP enzymes. Risk for gastrointestinal adverse events in the form of nausea, vomiting, anorexia and abdominal pain motivates vigilance against insufficient intake of food, especially of carbohydrate.

Pyrazinamide is a part of a combination therapy which also consists of rifampicin and isoniazid. The Summary of Product Characteristics of this combination product has listed porphyria as a contraindication. 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 nausea, vomiting, anorexia and abdominal pain.

Pyrazinamid is hydrolysed by microsomal deaminases to the active metabolite pyrazinoic acid and then metabolized to 5-hydroxypyrazinoic acid by xanthine oxidase (Lacroix 1987 and SPC). Other metabolites are 5-hydroxy-pyrazinamide and pyrazinuric acid (Lacroix 1989). The half-life elimination is 10 hours. In vitro studies indicate that pyrazinamide does not have any significant effects on any CYP activities (Nishimura 2004). There are observed drug-drug interactions with pyrazinamide in combination with a known CYP inducer, rifampicin (Ahn 2003), which makes it difficult to know if pyrazinamide is contributing to the inducing effect. Apart from this there are observed no drug-drug interactions involving CYP enzymes with pyrazinamide as a perpetrator (DRUID and Interaktionsdatabasen), which may indicate that pyrazinamide is not an inhibitor or inducer of CYP enzymes.

Pyrazinamide is reported to be unsafe and to exacerbate porphyria (Disler 1982, Gorchein 1997, Kalman 1998, Moore 1997and Rifkind 1976), but this is anecdotal information without support in clinical data. A study in rats also warns against this drug (Treece 1976) but due to the huge differences between man and rats in drug metabolism this investigation is not considered relevant.