Starting treatment with ambrisentan does not necessitate adjusting the dose of the oral anticoagulant phenprocoumon in patients with pulmonary hypertension (PH) who require both medications, report researchers.
Previous studies have shown that ambrisentan can be co-administered with warfarin without the need for warfarin dose-adjustment.
This is because ambrisentan is metabolized primarily by glucuronidation, and only partly by cytochrome P450, so does not interfere with warfarin metabolism, explain lead study author Natascha Sommer (Universities of Giessen and Marburg Lung Center, Germany) and co-workers.
Other available endothelin receptor antagonists have been shown to interfere with warfarin metabolism.
The team’s study included 42 PH patients, of whom 25 were prospectively enrolled. They had an average 6-minute walking distance of 331 m and 12%, 70% and 18% were in New York Heart Association functional classes II, III and IV, respectively. The patients were aged an average of 58 years when ambrisentan was added to pre-existing phenprocoumon.
The patients’ average international normalised ratio (INR) was 2.2 when measured 4 weeks before starting ambrisentan therapy and 2.3 when measured 8 weeks after initiation. The average phenprocoumon dose at these times was 12.3 mg and 13.5 mg, respectively.
There was also a strong correlation between INRs before and after starting ambrisentan and between individual phenprocoumon doses before and after.
Writing in Pulmonary Pharmacology & Therapeutics, Sommer et al note that their study was small, did not include a placebo, and cannot rule out long-term safety effects.
However, they say: “The phenprocoumon dose needed to achieve therapeutic INR levels in presence of ambrisentan treatment varied from the dose before ambrisentan treatment by less than 10%.
“Hence, there did not appear to be any clinically relevant interaction between these two drugs.”
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