PALM SPRINGS, CA — Morning (vs. evening) dosing of extended-release (ER) hydromorphone appears to be associated with fewer respiratory events in patients with low-back pain and sleep-disordered breathing, according to a presentation at the American Academy of Pain Medicine 28th Annual Meeting.
Lynn Webster, MD, of Lifetree Clinical Research, Salt Lake City, UT, and colleagues studied the effect of a.m. or p.m. dosing time of 24-hour hydromorphone ER on sleep physiology in patients with low-back pain in a Phase 4 trial. Chronic opioid exposure has been associated with sleep-disordered breathing, they noted.
The double-blind, placebo-controlled, single-center, crossover study enrolled patients were initiated into an open-label, immediate-release hydromorphone titration phase. Upon completion, patients entered the study’s placebo-controlled, double-blind phase and were randomized to either a.m. or p.m. dosing of hydromorphone ER.
Patients were stabilized on once-daily hydromorphone ER 8mg (n=10), 12mg (n=2), or 16mg (n=3) for at least 14 days, then crossed over to the alternate dosing regimen. Overnight sleep studies were performed at baseline, after immediate-release hydromorphone titration, and following each hydromorphone ER dosing period.
Efficacy was evaluated using polysomnography (PSG)-related assessments, short-form McGill Pain Questionnaire (SF-MPQ), modified Medical Outcomes Study (MOS) Sleep scale, and patient-reported responses in a Daily Diary including the Numeric Pain Rating Scale (NPRS) and Sleep Diary. Patients were also assessed for adverse events, vital signs, oxygen saturation, 12-lead ECG, clinical laboratory tests (hematology, chemistry, and urinalysis), and physical-examination findings.
Mean Apnea-Hypopnea Index scores were 12.9 for a.m. dosing and 17.1 for p.m. dosing (P=0.1248), indicating that a.m. dosing produced fewer nighttime respiratory events than p.m. dosing. Apnea episodes were also less frequent: 52.9 events for a.m. dosing vs. 62.3 for p.m. dosing (P=0.0829). Oxygen desaturation events with a.m. dosing were less than half those observed with p.m. dosing, 33.8 vs. 71.6 (P=0.087), as was oxygen saturation time below 88%, 17.7 vs. 40.8 minutes (P=0.270).
The a.m. and p.m. ER hydromorphone dosing groups were comparable for pain control and showed no effect on subjective sleep scores, quality of life, or use of rescue medications.