Opioids with benzodiazepines and gabapentinoids: the sedation and breathing risk

Opioids such as morphine, codeine and tramadol act on receptors that control pain and also slow breathing. Benzodiazepines such as diazepam enhance a calming chemical in the brain. Gabapentin and pregabalin dampen nerve activity. None of these effects is dangerous in isolation at a prescribed dose for most people, but together they can reduce the drive to breathe, particularly during sleep.

The MHRA drug safety update on gabapentin, based on reports of severe breathing problems, states that patients with reduced lung function, respiratory or neurological disease, kidney impairment, older age or concomitant use of central nervous system depressants may be at higher risk.

The NHS morphine page lists sedative medicines that help with insomnia and anxiety, such as diazepam, nerve pain medicines such as gabapentin and other opioids such as codeine and co-codamol among medicines that may not mix well. The NHS gabapentin page says strong painkillers such as morphine can make you very tired and dizzy when you start gabapentin.

The NHS codeine page lists other opioid painkillers, some antihistamines and anti-nausea medicines among those that may not mix well, and the tramadol page says to tell the doctor about medicines that help you sleep or reduce tension or anxiety. Alcohol is also flagged on the morphine and codeine pages.

• Opioids: morphine, codeine, tramadol, co-codamol.

• Benzodiazepines such as diazepam, and other sleeping or anti-anxiety tablets.

• Gabapentin and pregabalin.

• Alcohol and some antihistamines.

The MHRA update lists people with compromised breathing, respiratory or neurological disease, kidney problems and older adults. Starting a new combination, increasing a dose or taking a dose after a gap also raises risk. People with sleep apnoea or chronic lung disease should be especially cautious, and the prescriber should know about them.

Kidney impairment matters for gabapentin because it is cleared by the kidneys, which is why dose adjustment is part of its prescribing. Our guide to benzodiazepine dependence and long-term use describes other risks of regular sedative use.

The MHRA says to seek immediate medical attention for any trouble breathing or shallow breaths. Other signs include extreme sleepiness, being difficult to wake, confusion, blue lips and slow or irregular breathing. These are emergencies: call 999. Our opioid overdose guide describes what to do while waiting.

If someone has taken a combination and is simply very drowsy but easy to rouse, contact NHS 111 for advice. Do not leave them alone and do not give further doses.

The MHRA advises prescribers to be aware of the risk of CNS depression with gabapentin, consider dose adjustments in higher-risk patients and report suspected reactions through the Yellow Card scheme. In practice this means starting low, reviewing early, and avoiding unnecessary combinations.

A medication review can check whether each sedating medicine is still needed. Ask whether your painkiller, sleeping tablet and nerve pain medicine could be simplified.

Take medicines exactly as prescribed and avoid alcohol with them unless your prescriber says otherwise. Tell every professional about all sedating products, including over-the-counter antihistamines for allergy or sleep. Avoid driving if you feel drowsy. Never share medicines.

Keep a medicine list on your phone. If you are unsure about a combination, a community pharmacist can check it the same day without an appointment.