Opioids learning module

4.8. Important drug interactions

As a group, the most important interactions of opioids are with other sedating drugs and result in enhanced CNS depression. Where further sedation and CNS depressant effects are undesirable, concomitant use of such drugs should be avoided or, if this is not possible, monitor the patient for effects such as respiratory depression, hypotension, bradycardia, and excessive drowsiness.

Consult summaries of product characteristics and other sources for information on the interactions of individual opioids

Interacting drug or drug class Effect of interaction Risk-reduction measures
Alcohol Additive effect on blood pressure reduction, sedation and possibly respiratory depression Avoid increasing alcohol intake or excessive use of alcohol
Antihistamines (sedating, eg chlorphenamine, hydroxyzine, promethazine) Increased sedation Monitor patient for CNS depressant effect; consider using non-sedating antihistamine
Antimuscarinics (eg aclidinium, atropine, darifenacin, dicycloverine, fesoterodine, flavoxate, glycopyrronium, hyoscine, ipratropium, orphenadrine, oxybutynin, procyclidine, propantheline, propiverine, solifenacin, tiotropium, tolterodine, trihexyphenidyl, trospium) Increased risk of constipation and of urinary retention Monitor the patient for constipation and for bladder dysfunction
Antipsychotics Additive effect on blood pressure reduction and sedation Monitor patient for CNS depressant effect and for excessive reduction of blood pressure
Anxiolytics and hypnotics (eg buspirone, zolpidem, zopiclone) Increased sedation and possibly respiratory depression Monitor patient for CNS depressant effects
Barbiturates (eg phenobarbital) Increased sedation and CNS depressant effects, including respiratory depression Monitor patient for CNS depressant effects
Benzodiazepines (eg chlordiazepoxide, diazepam, lorazepam, nitrazepam, temazepam) Increased sedation and possibly respiratory depressant effect Monitor patient for CNS depressant effects
Domperidone Opioids antagonise the gastrointestinal effect of domperidone and metoclopramide Consider selecting another antiemetic
General anaesthetics (intravenous and inhaled) Increased effects of anaesthetic Monitor the patient closely
Metoclopramide Opioids antagonise the gastrointestinal effect of metoclopramide and domperidone Consider selecting another antiemetic
Monoamine oxidase inhibitors (MAOIs), including moclobemide CNS excitation or depression (with hypertension or hypotension) have been reported. Interaction more likely with opioids which inhibit serotonin reuptake: dextropropoxyphene, pethidine and tramadol Avoid concomitant use of an MAOI with dextropropoxyphene, pethidine and tramadol (MAOI should be stopped at least 2 weeks before starting opioid). Preferably avoid concomitant use of an MAOI with other opioids and if used concomitantly, opioid dosage may need to be adjusted
Rifampicin Rifampicin might reduce the effect of opioids such as alfentanil, codeine, methadone, morphine and oxycodone, by increasing their metabolism. Monitor effect of opioids when initiating or withdrawing rifampicin—adjust opioid dose if necessary
Sodium oxybate Increased CNS depressant effects Avoid concomitant use
Tricyclic and related antidepressants (eg amitriptyline, clomipramine, dosulepin, trazodone) Increased sedation Monitor patient for CNS depressant effects

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Page last modified: 17 February 2015