Dronedarone

Additional information

Pharmacokinetics and dosing

It is reported that women compared to men have 30-90% higher plasma concentration of dronedarone and the metabolite N-debutyl [1]. In a double-blind, randomized and placebo-controlled study, it was found that dronedarone pharmacokinetics were affected by age. After 800 mg dronedarone, elderly men had an approximately 30% higher exposure than young men. Elderly women had 23% higher dronedarone exposure and 40% lower apparent clearance (CL/F) than elderly men. The apparent clearance of elderly men was approximately 20% lower than that of young men. Potentially, elderly women may have dronedarone exposure that is about 50% of that of young men[k1] . No young women were included in the study [2].

The observed sex differences in dronedarone pharmacokinetics do not appear to warrant dosing adjustments, as the difference in exposure is relatively small (~25%) and becomes statistically insignificant when correcting for body weight [2].

In the large placebo-controlled clinical trial of dronedarone ATHENA [3], no dosage alterations were made and the benefit of dronedarone over placebo was not significantly related to age or patient’s sex.

Effects

The large ATHENA clinical trial (2459 men, 2169 women) evaluated the use of dronedarone 400 mg twice a day in patients with atrial fibrillation. The effect of dronedarone on the primary outcome (first hospitalization due to cardiovascular events or death) was similar in men and women [3].

Adverse effects

Side effects reported in eight randomized clinical trials (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, DIONYSOS, PALLAS; totally 6487 men and 4118 women) were discussed in a review. Acute hepatic failure was reported in two participants, both women. Hepatocellular injury with an onset within 30 days of dronedarone initiation was reported in 17 women and 13 men [4-11].

Evaluation of patient specific factors on the frequency of adverse events showed an association between female sex and all adverse events and also for serious adverse events [1].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).