A man with ventricular arrhythmias successfully treated with propafenone had a marked fall in his plasma propafenone level from 993 to 176 nanograms/mL within 12 days of starting to take rifampicin 450mg twice daily. Levels of two active metabolites of propafenone, 5-hydroxypropafenone and N-depropylpropafenone, changed from 195 to 64 nanograms/mL and from 110 to 192 nanograms/mL, respectively. His arrhythmias returned, but 2 weeks after stopping rifampicin his arrhythmias had disappeared and propafenone and its 5-hydroxy andN-depropyl metabolites had returned to acceptable levels (1411, 78 and 158 nanograms/mL respectively) (See reference number 1). In a study in young healthy subjects, rifampicin 600mg daily for 9 days reduced bioavailability of a single 300mg oral dose of propafenone from 30 to 10 % in CYP2D6 extensive metabolisers, and from 81 to 48 % in those with low levels of CYP2D6 (poor metabolisers). Consider Genetic factors,, for more information on metaboliser status. QRS prolongation decreased during enzyme induction. In contrast, in this study, rifampicin had no substantial effect on pharmacokinetics of propafenone given intravenously (See reference number 2). Similar findings were reported in a further study by same research group in healthy elderly subjects (See reference number 3).
Rifampicin induces CYP3A4/1A2-mediated metabolism and phase II glucuronidation of propafenone
An established and clinically relevant metabolic drug interaction. The dosage of oral propafenone will need increasing during concurrent use of rifampicin (See reference number 3). Alternatively, if possible, authors of case report(See reference number 1) advise use of another antibacterial, where possible, because of probable difficulty in adjusting propafenone dosage.
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