Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension.
Article Details
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Pulido T, Sandoval J, Roquet I, Gutierrez R, Rueda T, Pena H, Santos E, Miranda MT, Lupi E
Interaction of acenocoumarol and sitaxentan in pulmonary arterial hypertension.
Eur J Clin Invest. 2009 Jun;39 Suppl 2:14-8. doi: 10.1111/j.1365-2362.2009.02116.x.
- PubMed ID
- 19335742 [ View in PubMed]
- Abstract
BACKGROUND: Sitaxentan inhibits the metabolism of warfarin, resulting in a need for adjustment of warfarin dose when both drugs are coadministered. We report the long-term effects on bleeding of acenocoumarol co-administered as part of conventional therapy for pulmonary hypertension with sitaxentan in a subset of patients enrolled in the Sitaxentan To Relieve ImpaireD Exercise-3 (STRIDE-3) study. MATERIALS AND METHODS: STRIDE-3 is an ongoing, long-term, open-label trial, evaluating the safety and efficacy of sitaxentan, 100 mg once daily, in patients with pulmonary arterial hypertension. Information on bleeding events was collected prospectively, including the type of event, severity, anticoagulant use and investigator attribution of causality. Coagulation tests were performed on a monthly basis. A clinically significant interaction was defined as an international normalized ratio (INR) >/= 5.0, or any minor bleeding event plus an INR > 2.0 and < 5.0. RESULTS: Of 55 patients enrolled in STRIDE-3, 50 received acenocoumarol. Average follow-up was 158.6 +/- 57.6 weeks. The average dose of anticoagulant therapy was 3.9 +/- 1.3 mg week(-1) (range, 1.5-7.0 mg week(-1)). Following treatment, an INR >/= 5 in at least one INR determination was observed in 13 patients, although none of these patients had a clinically significant bleeding event. Dose reductions in acenocoumarol were performed to adjust target INR to 1.5-2.0. Two patients died of massive haemoptysis, but these episodes were not attributed to a drug interaction. Four patients with an INR > 2.0 and < 5.0 experienced a minor bleeding event (nosebleeds/gingivitis). CONCLUSIONS: No clinically significant bleeding events were recorded with coadministration of sitaxentan and acenocoumarol in this patient subgroup. These results suggest that coadministration of sitaxentan and acenocoumarol is clinically manageable and well tolerated.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Sitaxentan Cytochrome P450 2C9 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAcenocoumarolSitaxentan The serum concentration of Acenocoumarol can be increased when it is combined with Sitaxentan. WarfarinSitaxentan The serum concentration of Warfarin can be increased when it is combined with Sitaxentan.