Source: DGNews  |  Posted 4 years ago

By Ed Susman

SAN FRANCISCO, CA -- September 10, 2007 -- The investigational factor Xa inhibitor apixaban -- which is in development for treatment of thromboembolic disease -- does not have an important drug-drug adverse interaction with digoxin.

"We anticipate that when apixaban receives marketing approval it will be used in conjunction with a number of other drugs, including digoxin," said Charles Frost, PharmD, Associate Director for Clinical Discovery, Bristol-Myers Squibb, Princeton, New Jersey, United States.

Apixaban, now in phase 3 clinical testing, and digoxin could be coadministered in some patients, especially those who may suffer from atrial fibrillation, said Dr. Frost during a poster presentation here on September 9 at the 36th annual meeting of the American College of Clinical Pharmacology (ACCP). Apixaban may be indicated for treatment and prevented of deep vein thrombosis, he added.

Dr. Frost and his colleagues recruited 24 healthy men into the open-label, two-treatment, single-sequence crossover study; 22 completed the study. Study participants were given daily doses of digoxin for 10 days and then underwent serial measurements of digoxin at baseline and then at 30 minutes, 1 hour, 90 minutes, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 16 hours, and 24 hours.

Participants were confined to the testing facility for the duration of the study. Ten days after enrolment, they underwent serial blood measurements after taking both digoxin and apixaban.

The pharmacokinetics of digoxin in the blood was virtually superimposable with and without coadministration of apixaban, Dr. Frost reported. "Coadministration of apixaban 20 mg once a day for 10 days did not affect the pharmacokinetics of digoxin," he said.

"Coadministration of apixaban 20 mg once a day and digoxin 0.25 mg once a day for 10 days was safe and well tolerated in these healthy subjects," he added.

There were 27 adverse events reported by the subjects, all of which were mild to moderate and resolved without treatment. Elevated liver enzymes occurred in three patients -- two reported in the digoxin group prior to apixaban administration. One patient discontinued for that reason. One subject withdrew consent.

One subject reported gingival bleeding on day 18 of the study, but it resolved after 4 days. Bruising at the catheter site was noted in one patient but no intervention was required.

Funding for this study was provided by Bristol-Myers Squibb.

[Presentation title: Apixaban Does Not Affect the Pharmacokinetics of Digoxin. Poster 60]