Medication Pearls For Practice: Methadone And Sleep Apnea

"Medication Pearls For Practice" is a new column to be a regular feature here at Onco-PRN. With my role in the Pain and Paliative Care Clinic, expect a lot of pain and symtom control related medication topics. Of course, oncology medications will also be featured.

In this post, key points taken from the Pharmacist's Letter are in bold and italicized.

From: Canadian Pharmacist's Letter 2008; 15(10):241007

Medications that Can Exacerbate Sleep Apnea

“A number of medications, especially CNS depressants such as opioids, benzodiazepines, and muscle relaxants can potentially exacerbate sleep apnea.

*Recently, central sleep apnea has been reported with chronic opioid use and up to 30% of stable methadone maintenance treatment patients have central sleep apnea. In one study (n=50), patients on methadone maintenance therapy were found to have significantly less rapid eye movement (REM) sleep. Central sleep apnea occurred more often in non-REM sleep in methadone maintenance therapy patients. In contrast, respiratory disturbances occur more often during REM sleep with obstructive apnea. These patients had normal resting cardiac function.

*In another study (n=140), the association of methadone, non-methadone opioids, and benzodiazepines with sleep apnea was examined. In the study, patients taking methadone and benzodiazepines concomitantly were found to have a significantly higher rate of central sleep apnea. In the 33% of patients taking methadone, the median daily dosage of morphine equivalents was 187.5 mg/day. The median daily dosage of sustained-release opioids other than methadone in morphine equivalents was 187.5 mg/day. In 36% of patients taking benzodiazepines, the median daily dosage in diazepam equivalents was 15 mg/day. Results of the study showed that 75% of the patients had apnea/hypopnea episodes during sleep. Thirty-nine percent had obstructive sleep apnea, 4% had sleep apnea of an indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea. Increased dosage of methadone was associated with a higher incidence of central sleep apnea. In contrast, equivalent doses of non-methadone opioids were not found to be associated with increased risk for sleep apnea. The combination of methadone and benzodiazepine also caused significantly more sleep apnea. There are data suggesting that benzodiazepines could possibly inhibit methadone metabolism, prolonging its effect; therefore, this combination should be used cautiously.

In both of these studies presentation of central sleep apnea was atypical compared to those with chronic heart failure (no Cheyne-Stokes respiration, no crescendo-decrescendo pattern of tidal volume).

The cause of central sleep apnea associated with chronic opioid use is likely multifactorial, involving the change of sleep architecture (REM, non-REM, sleep stages, etc) and respiratory depression effect.

Patients with sleep apnea are more likely to experience exacerbation of symptoms when treated with opioids. It is especially important to use caution when titrating opioid analgesic doses in this patient population. The use of patient controlled analgesia (PCA) should be monitored closely in this patient population.”

Feel free to comment below and if you would like to contribute to this featured column topic, "Medication Pearls For Practice", email me at: chrisral@albertahealthservices.ca