Metoclopramide
Class: antiemetic – prokinetic – dopamine receptor antagonist
Indications: nausea and/or vomiting, restoration of tone in upper GI tract, hiccups
Contraindications/cautions: complete intestinal obstruction. Young persons (< 20 years old) are more prone to extrapyramidal side effects so use lower doses; caution also in the elderly, renal & hepatic impairment
Adverse reactions: less common: tardive dyskinesia – usually on prolonged use, extrapyramidal reactions e.g. Parkinsonism, akathisia (usually at doses > 30 mg/24 hours — switch to domperidone which enters the CNS to a lesser extent), diarrhoea, restlessness
Metabolism/clearance: metabolised in the liver partially by the metabolising enzyme CYP2D6 to inactive metabolites which are mainly excreted with some parent drug by the kidneys
Interactions:
- increased clinical effect/toxicity of metoclopramide (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. bupropion, fluoxetine, paroxetine, quinine
- faster onset of action of SR morphine may occur with concomitant metoclopramide
- prokinetic activity of metoclopramide may be affected by concomitant opioids, anticholinergics e.g. hyoscine
- increased risk of extrapyramidal effects and neurotoxicity with lithium
| Dosing: | |
|---|---|
| oral: | 10 mg 3 to 4 times a day (max. 0.5 mg/kg) (nausea, vomiting, hiccups) |
| subcut: | 30 to 60 mg over 24 hours (watch for extrapyramidal effects at > 30 mg/24 hours) |
| rectal: | 10 mg up to 3 times a day |
Syringe driver: see syringe driver compatibility chart
Mechanism of action: blocks dopamine receptors and perhaps affects 5HT receptors in the gastro-intestinal tract (increasing peristalsis), lowers oesophageal sphincter pressure, crosses BBB to CNS and chemoreceptor-trigger zone (CTZ)
Peak effect: oral/rectal: 1 to 3 hours
Notes:
- ‘High dose’ metoclopramide may work via 5HT3 antagonism (like ondansetron) but is associated with severe extrapyramidal effects
- most effective for nausea/vomiting due to gastric stasis. Some clinicians believe that metoclopramide is no better than placebo as an antiemetic but is useful as a prokinetic
- benztropine 2 mg may be used as an antidote
- the European Medicines Agency’s Committee recommends that metoclopramide should only be prescribed for short-term use (up to 5 days) and that it should only be used as a second-line