Acute Porphyria Drugs

Acute Porphyria Drug Database

J04AK01 - Pyrazinamide
Propably not porphyrinogenic
PNP
Rationale
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.
Therapeutic characteristics
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.
Metabolism and pharmakokinetics
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.
Published experience
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.

References

  1. Scientific articles
  2. Ahn HC, Lee YC. The clearance of theophylline is increased during the initial period of tuberculosis treatment. Int J Tuberc Lung Dis. 2003 Jun;7(6):587-91. PMID 12797703. #1730
  3. Disler PB, Blekkenhorst GH, et al. Guidelines for drug prescription in patients with the acute porphyrias. S Afr Med J. 1982 May 1;61(18):656-60. PMID 6123155. #4518
  4. Gorchein A. Drug treatment in acute porphyria. Br J Clin Pharmacol. 1997 Nov;44(5):427-34. PMID 9384458. #1733
  5. Kalman DR and Bonkovsky HL. Management of acute attacks in the porphyrias. Clin Dermatol. 1998 Mar-Apr;16(2):299-306. #1738
  6. Lacroix C, Hoang TP, et al. Pharmacokinetics of pyrazinamide and its metabolites in healthy subjects. Eur J Clin Pharmacol. 1989;36(4):395-400. #1740
  7. 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
  8. Nishimura Y, Kurata N, et al. Inhibitory effect of antituberculosis drugs on human cytochrome P450-mediated activities. Epub 2004 Nov 5. #1736
  9. Rifkind AB. Drug-induced exacerbations of porphyria. Prim Care. 1976 Dec;3(4):665-85. PMID 13442. #1739
  10. Treece GL, Magnussen CR, et al. Exacerbation of porphyria during treatment of pulmonary tuberculosis. Am Rev Respir Dis. 1976 Feb;113(2):233-7. PMID 1247237. #4524
  11. Drug interaction databases
  12. DRUID. Pyrazinamide #1734
  13. Interaktionsdatabasen. Pyraznamide #1735
  14. Summary of Product Characteristics
  15. Norwegian medicines agency. Summary of Product Characteristics (SPC). Rimcure. #1737
Similar drugs
Explore alternative drugs in similar therapeutic classes J04A / J04AK or go back.
 
© NAPOS 2024
An unhandled error has occurred. Reload 🗙