Obstructive sleep apnea combination drug safe, reduces disorder severity over 1 month

Key takeaways:

• Obstructive sleep apnea severity at baseline improved with a combination drug.
• Side effects experienced with the drug matched the established side-effect profiles of both components.

A combination of atomoxetine and oxybutynin taken for 30 days lowered baseline obstructive sleep apnea severity, according to results published in Annals of the American Thoracic Society.

“The main findings of this study are that [atomoxetine-oxybutynin] administered in doses up to 80 mg/5 mg nightly before sleep for 1 month is safe and relatively well tolerated in people with obstructive sleep apnea,” Atqiya Aishah, BSc, PhD, of the University of New South Wales in Australia, and colleagues wrote.

In a randomized, placebo-controlled trial, Aishah and colleagues evaluated 39 patients (mean age, 51 years) with OSA to establish whether a nightly combination of atomoxetine, a noradrenergic, and oxybutynin, an antimuscarinic, was safe, effective and tolerable in patients receiving the treatment for 1 month.

As Healio recently reported, a combination of atomoxetine and aroxybutynin taken for 4 weeks lessened obstructive sleep apnea severity.

Researchers assessed three different doses of the drug combination — 80 mg of atomoxetine/5 mg of oxybutynin, 40 mg of atomoxetine/5 mg of oxybutynin and 40 mg of atomoxetine/2.5 mg of oxybutynin — against placebo.

To capture data on safety and efficacy, researchers had patients take part in laboratory sleep studies at baseline, night 1 of treatment and night 30 of treatment, during which they looked at changes in measures of alertness, memory, blood pressure, prostate function in men (International Prostate Symptom Score) and potential adverse events. Weekly phone calls also collected possible negative events on treatment.

Safety, tolerability

Of the total cohort, one patient from each drug combination dose withdrew from the study. Researchers observed high compliance, ranging from 94% to 97%, in the treatment groups.

According to researchers, patients taking the combination drug mostly experienced mild side effects that matched the established side effect profiles for each drug. Oxybutynin leading to more dry mouth with each additional dose is one example of a known side effect and was commonly experienced in those receiving the drug combination (80 mg/5 mg and 40 mg/5 mg, 78%; 40 mg/2.5 mg, 20%) compared with placebo (10%).

Researchers additionally reported that dyspepsia, constipation and fatigue were prevalent among those receiving a dosage of the drug combination.

Compared with placebo, patients receiving 80 mg of atomoxetine/5 mg of oxybutynin and 40 mg of atomoxetine/2.5 mg of oxybutynin experienced higher heart rates at night 30 (mean ± standard deviation: 80 mg/5 mg, 8 ± 10 beats per minute; P = .01; 40/2.5 mg, 9 ± 14 beats per minute; P = .02).

Other assessed measures, including blood pressure, prostate function, alertness and memory, did not differ across the treatment groups, according to researchers.

Disorder severity

Apnea-hypopnea index (AHI) with 4% desaturation (AHI₄) at baseline was higher among patients receiving the drug combination (80 mg/5 mg, 24 ± 18; 40 mg/5 mg, 22 ± 16; 40 mg/2.5 mg, 23 ± 24 events per hour) than patients receiving placebo (13 ± 12 events per hour) but was not significantly different. This was also true when evaluating baseline AHI₃, with less events per hour found in the placebo group (29 ± 14 events per hour) vs. the drug combination groups (80 mg/5 mg, 39 ± 19; 40 mg/5 mg, 35 ± 23; 40 mg/2.5 mg, 45 ± 24 events per hour).

When assessing changes in AHI₄ and hypoxic burden from baseline to night 1, researchers found that these measures decreased in patients receiving 80 mg of atomoxetine/5 mg of oxybutynin compared with patients receiving placebo (AHI₄, –12 ± 7 events per hour vs. 3 ± 8 events per hour; P < .01; –45% ± 37% minutes per hour vs. 7% ± 43% minutes per hour; P < .01).

In terms of evaluating changes from baseline to night 30 between these two groups, no significant reductions were found with the drug combination, according to researchers. Additionally, AHI₃ did not significantly differ between the 80 mg of atomoxetine/5 mg of oxybutynin group and the placebo group at night 1 or night 30.

However, among patients in the 80 mg of atomoxetine/5 mg of oxybutynin group, researchers found an approximate 50% drop in OSA severity at night 30 compared with their baseline measures (AHI₄, –8.5 events per hour; 95% CI, –18.3 to 1.3 events per hour; AHI₃, –8.2 events per hour; 95% CI, –22.5 to 6.2 events per hour).

“The high dose 80 mg/5 mg [atomoxetine-oxybutynin] combination appears to be the most promising combination to further investigate for OSA pharmacotherapy,” Aishah and colleagues wrote.