Losartan Rifampicin

ANGIOTENSIN II RECEPTOR ANTAGONISTS - LOSARTAN RIFAMPICIN i antihypertensive effect of losartan Rifampicin induces CYP2C9 Monitor BP at least weekly until stable... 

A study in 10 healthy volunteers has suggested that rifampicin interacts with losartan (31). The AUCs of both losartan and its active metabolite were markedly reduced (about 30 and 40% respectively) when rifampicin 300 mg bd was given for 1 week. 

Ten healthy subjects were given losartan 50 mg daily for a week and then, after a 6-day washout period, losartan 50 mg daily with rifampicin 300 mg twice daily for a week. It was found that rifampicin reduced the AUC of losartan by 36%, reduced its half-life from 2 to 0.9 hours, and increased its clearance by 60%. The AUC of the active metabolite, E3174, was reduced by 41% and its half-life was reduced from 5.1 to 2.5 hours. Diastolic blood pressure was significantly reduced by losartan alone, but not by the combination. The presumed reason for this interaction is that rifampicin (a recognised enzyme inducer) increases the metabolism of losartan to its active metabolite by the cytochrome P450 isoenzyme CYP2C9. 

The clinical importance of this interaction still awaits assessment, but it would seem likely that the antihypertensive effects of losartan would be reduced by rifampicin. If both drugs are used, be alert for the need to increase the losartan dosage. More study is needed. There seems to be no information regarding other angiotensin II receptor antagonists, but note that irbesartan, and to a limited extent candesartan, are also metabolised by CYP2C9 (see the introduction , (p.l2)). 

Rifampicin increases the metabolism of losartan and its active metabolite, E-3174, which may result in reduced antihypertensive effects. 

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