Advice for healthcare professionals:
- benzodiazepines (and benzodiazepine-like drugs) and opioid medicines (opioids) can both cause respiratory depression; when used together, additive effects on the central nervous system increase the risks of sedation, respiratory depression, coma, and death
- only prescribe benzodiazepines (or benzodiazepine-like drugs) and opioids together if there is no alternative
- if a decision is made to co-prescribe, use the lowest doses possible for the shortest duration of time and carefully monitor patients for signs of respiratory depression
- if there is any change in prescribing such as new interactions or dose adjustments, re-introduce close monitoring of the patient
- if co-prescribing methadone with a benzodiazepine or benzodiazepine-like drug, closely monitor for respiratory depression for at least 2 weeks following initiation or changes to prescribing because the respiratory depression effect of methadone may be delayed
- advise patients of the symptoms of respiratory depression and sedation and the need to seek immediate medical attention if these occur
- report suspected adverse drug reactions to any medicines to the Yellow Card Scheme
Reminder of risk of respiratory depression when co-prescribed
The MHRA recently received a report from a Coroner following death by respiratory arrest of a man given the benzodiazepine clonazepam, and among other drugs, the opioid methadone.
We remind healthcare professionals that benzodiazepines and benzodiazepine-like drugs and opioids can both cause respiratory depression. When co-prescribed, the depressive effect on the central nervous system is additive. Therefore, they should only be co-prescribed if there is no alternative. Warnings about the risks of co-prescribing these products were reviewed in Europe in 2018.
Reminder of advice to minimise risk
If co-prescribing of these drugs is considered necessary, the lowest effective doses should be used and for the shortest duration. All patients should be closely monitored. If methadone is prescribed, the respiratory depression effects could be delayed. Monitoring should continue for at least 2 weeks following initiation or changes to prescribing such as increased dose or the addition of a new medicine that may interact with opioids.
Advice to supply to patients
Advise patients to always read the leaflet for the medicines that they have been supplied.
For benzodiazepines or related drugs and opioids, the patient information leaflet advises that these medicines increase the risk of drowsiness, difficulties in breathing (respiratory depression), and coma, and that these effects may be life-threatening. Therefore, patients should seek medical advice if these symptoms occur.
Patients are advised to inform their prescribers about any opioids or sedative medicines they are taking, and to follow any dose recommendation closely. The leaflet advises them that it may be helpful to inform friends or relatives of the signs and symptoms of respiratory depression and sedation and be aware of the need to seek medical attention if they occur.
Report adverse drug reactions on a Yellow Card
Healthcare professionals are asked to report any suspected adverse drug reactions (ADRs) to drugs to the Yellow Card Scheme.
It is easiest and quickest to report ADRs online via the Yellow Cards website or via the Yellow Card app. Download the app via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices. You can also view recent alerts from the MHRA and read Drug Safety Updates through the App newsfeed.
Article citation: Drug Safety Update volume 13, issue 8: March 2020: 5.