Prokinetic / antiemetic (dopamine antagonist)
Metoclopramide is a prokinetic and antiemetic medicine, used for the short-term treatment of symptomatic, documented gastroesophageal reflux that has failed conventional therapy, and for the relief of symptoms in acute and recurrent diabetic gastroparesis in adults. It can cause extrapyramidal effects and tardive dyskinesia, so use is time-limited.
Also known as: Primperan, Maxolon, metoclopramide
Metoclopramide increases gastric motility and may reduce levothyroxine absorption, decreasing its effect.
Metoclopramide increases gastric peristalsis and accelerates gastric emptying, which may reduce the dissolution and absorption time of levothyroxine in the proximal duodenum. The metoclopramide label documents that "increased GI motility by metoclopramide may impact absorption of other drugs, leading to a decrease" thereof. Although levothyroxine is not explicitly listed, the mechanism is applicable to drugs absorbed in the proximal duodenum that depend on adequate contact time. This interaction is mild and variable between patients, but may be clinically relevant in patients with borderline hypothyroidism or who have recently had their levothyroxine dose adjusted. Separate the doses (metoclopramide after meals, levothyroxine on an empty stomach) and monitor TSH if malabsorption or worsening of hypothyroidism is suspected.
Metoclopramide + levothyroxine: accelerated gastric emptying by metoclopramide shortens the contact time of levothyroxine with the absorptive mucosa. Monitor TSH.
Accelerated gastric emptying shortens levothyroxine contact time with the absorptive mucosa.
Monitor TSH and hypothyroidism symptoms (fatigue, weight gain).
Decompensated hypothyroidism.
Separate administration times and monitor TSH when starting or stopping metoclopramide.
DailyMed (FDA) — approved Metoclopramide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d31d815-50fa-4e78-8ebd-affc2514ce78 ; approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Metoclopramide may reduce digoxin absorption and, in some patients, delay its therapeutic effect.
Metoclopramide accelerates gastric emptying and intestinal transit, which can increase the rate and extent of digoxin absorption (especially slow-release formulations) and transiently raise plasma levels. The effect is usually modest, but relevant in patients with borderline levels or reduced renal function. Monitor digoxin levels when metoclopramide is started or stopped and watch for digitalis toxicity signs; separate dosing when possible.
Metoclopramide accelerates gastric emptying and can increase digoxin absorption and levels. Monitor digoxin levels in stable patients.
Metoclopramide-induced faster intestinal transit reduces digoxin absorption time.
Monitor the antiarrhythmic/rate-control response and heart failure symptoms.
Loss of rhythm/heart failure control.
Monitor clinical response and consider dose adjustment or an alternative schedule.
DailyMed (FDA) — approved Metoclopramide label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5d31d815-50fa-4e78-8ebd-affc2514ce78 ; approved Digoxin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e61d2108-d871-44c0-b12a-2e61fbb56967 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Metoclopramide should be taken before meals to optimise the prokinetic effect.
Take 30 minutes before meals.
EMC-UK (MHRA) — approved Metoclopramide SmPC: https://www.medicines.org.uk/emc/product/6213/smpc
Metoclopramide may cause severe hypertensive crises in patients with phaeochromocytoma.
Do not use in patients with phaeochromocytoma.
EMC-UK (MHRA) — approved Metoclopramide SmPC: https://www.medicines.org.uk/emc/product/6213/smpc
Metoclopramide may lower the seizure threshold.
Use with caution and monitor neurological signs.
EMC-UK (MHRA) — approved Metoclopramide SmPC: https://www.medicines.org.uk/emc/product/6213/smpc
Metoclopramide is a dopamine antagonist and may worsen parkinsonian symptoms.
Do not use in patients with Parkinson's disease.
EMC-UK (MHRA) — approved Metoclopramide SmPC: https://www.medicines.org.uk/emc/product/6213/smpc
Metoclopramide is used in pregnancy (hyperemesis), but should be used with caution in the 1st trimester and at low doses.
Use the lowest effective dose for the shortest time possible.
Excreted into breast milk in small amounts; occasional use is probably compatible.
No specific additional contraception.
EMC-UK (MHRA) — approved Metoclopramide SmPC: https://www.medicines.org.uk/emc/product/6213/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Prokinetic and antiemetic (dopamine D2 antagonist and 5-HT4 agonist/5-HT3 antagonist), indicated for the short-term treatment of nausea and vomiting, diabetic gastroparesis and gastro-oesophageal reflux disease. Increases lower oesophageal sphincter tone and accelerates gastric emptying. Risk of extrapyramidal effects (including tardive dyskinesia) with prolonged use — limit treatment duration.
Stimulates motility of the upper GI tract without stimulating gastric, biliary or pancreatic secretions: increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and duodenal bulb and increases peristalsis of the duodenum and jejunum, accelerating gastric emptying and intestinal transit; increases resting lower oesophageal sphincter tone. It seems to sensitise tissues to the action of acetylcholine; the effect is abolished by anticholinergic drugs.
Absolute oral bioavailability of 80% ± 15.5% (relative to a 20 mg IV dose); peak plasma concentrations about 1-2 hours after an oral dose. Not extensively bound to plasma proteins (~30%); high volume of distribution (~3.5 L/kg), suggesting extensive tissue distribution.
Metabolised in the liver by oxidation and by glucuronide and sulphate conjugation; the major oxidative metabolite (monodeethylmetoclopramide) is formed primarily by CYP2D6, an enzyme subject to genetic variability. Approximately 85% of the radioactivity of an oral dose appears in urine within 72 hours; only 18-22% is recovered as free metoclopramide within 36 hours.
Mean elimination half-life of 5-6 hours in subjects with normal renal function (pharmacokinetics are linear between 20-100 mg). Severe renal impairment prolongs the half-life and reduces clearance — reduce the dose. Half-life may be prolonged in hepatic impairment (lower clearance).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
