[Prolonged diminished effect of coumarin derivatives after use of rifampicin].
A 73-year-old woman with endocarditis was treated with flucloxacillin and rifampicin. She already used the anticoagulant acenocoumarol because of a recent heart valve replacement. After starting rifampicin therapy the sensitivity for the acenocoumarol was reduced. The international normalised ratio (INR) did not exceed 2.0, while values of 2.5-3.5 were required. Increase of the daily dose of acenocoumarol with a factor 6 compared to the dose which resulted in a therapeutic INR before hospitalisation, proved insufficient to obtain a therapeutic INR during long-term rifampicin therapy. 21 days after rifampicin discontinuation the INR finally responded to high coumarin dosages. The breakdown of coumarins in the liver is increased by rifampicin due to induction of several isoenzymes of the cytochrome P450-system. This case illustrates that sensitivity to coumarins can be decreased profoundly even after discontinuation of rifampicin therapy. INR should be monitored closely not only at the start and discontinuation of rifampicin therapy, but also during the weeks after discontinuation of rifampicin treatment.
Harmsze
A M
AM
St. Antonius Ziekenhuis, Postbus 2500, 3430 EM, Nieuwegein. a.harmsze@antoniusmesosgroep.nl
Deneer
V H M
VH
Wiltink
E H
EH
D000074:Acenocoumarol / Q000493:pharmacokinetics / Q000494:pharmacology*; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004696:Endocarditis / Q000188:drug therapy; D005260:Female; D006350:Heart Valve Prosthesis; D006801:Humans; D019934:International Normalized Ratio; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D012293:Rifampin / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000925:Anticoagulants; D000074:Acenocoumarol; D012293:Rifampin