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

Benzodiazepines1(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

1


  1. Class of medicines which have a sedating effect, most often used for anxiety and insomnia, but also used for muscle relaxation, managing convulsions, and as premedication for surgery and certain procedures. The class includes: chlordiazepoxide, diazepam, flurazepam, lorazepam, midazolam, nitrazepam, oxazepam, and tempazepam