A man with tuberculosis is treated with Rimactan (rifampicin), Zinamid (pyrazinamid) och Tibinide (

Fråga: A man with tuberculosis is treated with Rimactan (rifampicin), Zinamid (pyrazinamid) och Tibinide (isoniazid). The patient is also treated with Viagra (sildenafil).

Is there a risk for interaction?

Sammanfattning: There are no evidence that sildenafil influences the metabolism of rifampicin, pyrazinamide or isoniazid. However, a decreased effect of sildenafil can be expected when combined with both rifampicin and pyrazinamid through induction of the isoenzymes CYP3A4 and CYP2C9. This induction can be compensated for adjusting the sildenafil dose until satisfying effect is obtained.

Svar: No information concerning an interaction between sildenafil and the other drugs was found in the literature.

Rifampicin is known to induce different CYP 450 isoenzymes (1). Rifampicin in itself is metabolised in the liver by deacetylation and hydrolysis and is excreted in the bile and urine (2).

Isoniazid is metabolised in the liver by acetylation and is excreted in the urine. It is known to induce the isoenzyme CYP2E1 (1).

Pyrazinamide is metabolised primarily in the liver by deamination to the major active metabolite pyrazinoic acid which is subsequently hydroxylated to 5-hydroxypyrazinoic acid. It is excreted by the kidney mainly through glomerular filtration (3). When pyrazinamide is combined with cyclosporine decreased serum levels of cyclosporine have been seen indicating that pyrazinamide probably induces the CYP3A4 isoenzyme (4).

Viagra (sildenafil) is metabolised in the liver mainly by the isoenzyme CYP 3A4 and through a minor pathway by CYP 2C9 (5). In vitro studies have indicated that sildenafil is a weak inhibitor of the isoenzymes CYPs 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (5). 1 Grange JM, Winstanley PA, Davies PDO. Clinically significant drug interactions with antituberculosis agents. Drug Safety 1994; 11: 242-251

2 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1998. p. R32-R37
3 Reynolds JEF, editor. Martindale, The extra pharmacopoeia. 31st ed. London: Royal Pharmaceutical Society; 1996
4 Stockley IH. Drug interactions. 4th ed. London: The Pharmaceutical Press; 1996. p. 626

5 FASS 1998 (The Swedish Catalogue of Approved Medical Products)