ACE inhibitors + Rifampicin (Rifampin) - Drug Interactions

An isolated report describes a rise in blood pressure in one hypertensive patient,which was attributed to an interaction between enalapril and rifampicin. Rifampicin may reduce theplasma levels of active metabolites of imidapril and spirapril.

A man taking enalapril and a variety of other drugs (warfarin,acebutolol, bendroflumethiazide, dipyridamole, metoclopramide and Gaviscon) developed a fever. He was given streptomycin, oxytetracycline and rifampicin, because of a probable Brucella abortus infection, whereupon his blood pressure rose from 164/104 to 180/115 mmHg over next 5 to 6 days. It was suspected that an interaction with rifampicin was possibly responsible. Subsequent studies in same patient showed that rifampicin, reduced AUC0-7 of enalaprilat, active metabolite of enalapril, by 31%, although AUC of enalapril was unchanged (See reference number 1). There is also hint of this interaction in another report, where enalapril failed to control blood pressure in a patient taking rifampicin (See reference number 2).

The manufacturer of spirapril briefly noted in a review that use of rifampicin with spirapril modestly decreased plasma levels of spirapril

and its active metabolite,spiraprilat (See reference number 3). The manufacturer of imidapril notes that rifampicin reduced plasma levels of imidaprilat, active metabolite of imidapril (See reference number 4).

The mechanism of this interaction is not clear, because rifampicin is a potent liver enzyme inducer, which might have been expected to cause production of more, rather than less, of active metabolites of these ACE inhibitors. However, authors of one of reports postulated that rifampicin might have increased loss of enalaprilat in urine,(See reference number 1) and others suggested that rifampicin stimulates elimination of spiraprilat non-specifically (See reference number 3).

The general importance of these interactions is uncertain. The isolated reports with enalapril suggest minor clinical relevance. The manufacturers of spirapril did not consider modest pharmacokinetic changes to be clinically relevant (See reference number 3). However, manufacturers of imidapril state that rifampicin might reduce antihypertensive efficacy of imidapril,(See reference number 4) but this awaits clinical assessment.

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Tada Y,Tsuda Y, Otsuka T, Nagasawa K, Kimura H, Kusaba T, Sakata T. Case report: nifedipine-rifampicin interaction attenuates the effect on blood pressure in a patient with essentialhypertension. Am J Med Sci (1992) 303, 25–7.

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