Intravenous Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: Loading dose: 2-4 mg/kg via continuous infusion over 15-20 minutes. Maintenance: 3-5 mg/kg infused over 8-12 hours. Alternatively, initial dose of up to 2 mg/kg via intermittent infusion over at least 15 minutes, may be given before cancer therapy and repeated at 2-hourly intervals. Max total: 10 mg/kg in 24 hours. Child: As 2nd line option: Usual dose: 1-18 years 0.1-0.15 mg/kg up to tid. 1-<3 years 10-14 kg: 1 mg; 3-<5 years 15-19 kg: 2 mg; 5-<9 years 20-29 kg: 2.5 mg; 9-18 years 30 kg-60 kg: 5 mg; 15-18 years >60 kg: Same as adult dose. All doses to be given up to tid. Max: 0.5 mg/kg in 24 hours. Max duration: 5 days. Elderly: Dosage reduction may be needed.
Intravenous Nausea and vomiting, Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: 10 mg up to tid. Max: 30 mg or 0.5mg/kg daily. Child: As 2nd line option: Usual dose: 1-18 years 0.1-0.15 mg/kg up to tid. 1-<3 years 10-14 kg: 1 mg; 3-<5 years 15-19 kg: 2 mg; 5-<9 years 20-29 kg: 2.5 mg; 9-18 years 30 kg-60 kg: 5 mg; 15-18 years >60 kg: Same as adult dose. All doses to be given up to tid. Max: 0.5 mg/kg in 24 hours. Max duration: 5 days. Elderly: Dosage reduction may be needed.
Intravenous Prophylaxis of postoperative nausea and vomiting
Adult: 10 mg as a single dose. Child: As 2nd line option: Usual dose: 1-18 years 0.1-0.15 mg/kg up to tid. 1-<3 years 10-14 kg: 1 mg; 3-<5 years 15-19 kg: 2 mg; 5-<9 years 20-29 kg: 2.5 mg; 9-18 years 30 kg-60 kg: 5 mg; 15-18 years >60 kg: Same as adult dose. Dose to be given after termination of surgery. Max treatment duration: 48 hours. Elderly: Dosage reduction may be needed.
Intravenous Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract
Adult: 10 mg as a single dose, given over 1-2 minutes. Child: <6 years 0.1 mg/kg; 6-14 years 2.5-5 mg; >14 years Same as adult dose. All doses to be given as single dose.
Oral Nausea and vomiting, Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: 10 mg up to tid. Max: 30 mg or 0.5 mg/kg daily. Recommended Max treatment duration: 5 days. Elderly: Dosage reduction may be needed.
Oral Diabetic gastric stasis
Adult: For early manifestations: 10 mg 30 minutes before each meal and at bedtime for 2-8 weeks. Max: 40 mg daily. Elderly: 5 mg 4 times daily. Max: 40 mg daily.
Oral Gastroesophageal reflux disease
Adult: 10-15 mg up to 4 times daily given 30 minutes before each meal and at bedtime, depending on severity of symptoms. If occurrence of symptoms is intermittent, may give doses up to 20 mg as a single dose prior to provoking situation. Max: 60 mg daily. Max treatment duration: 12 weeks. Elderly: 5 mg up to 4 times daily. Max: 60 mg daily.
Oral Prophylaxis of chemotherapy-induced nausea and vomiting
Adult: 10 mg up to tid. Max: 30 mg or 0.5 mg/kg daily. Recommended Max treatment duration: 5 days. Child: As 2nd line option: Usual dose: 1-18 years 0.1-0.15 mg/kg tid. 1-<3 years 10-14 kg: 1 mg; 3-<5 years 15-19 kg: 2 mg; 5-<9 years 20-29 kg: 2.5 mg; 9-18 years 30 kg-60 kg: 5 mg; 15-18 years >60 kg: Same as adult dose. All doses to be given up to tid. Max: 0.5 mg/kg in 24 hours. Recommended Max treatment duration: 5 days. Elderly: Dosage reduction may be needed.
Oral Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract
Adult: 10 or 20 mg as a single dose given before examination. Elderly: Initiate at lowest recommended dose.
Parenteral Diabetic gastric stasis
Adult: Severe cases: 10 mg up to 4 times daily via IM or slow IV inj over 1-2 minutes up to 10 days and may shift to oral therapy once possible.
Special Patient Group
Patients taking strong CYP2D6 inhibitors (e.g. quinidine, bupropion, fluoxetine): Oral: 5 mg up to 4 times daily or 10 mg up to tid.
Pharmacogenomics:
CYP2D6 poor metabolisers:
Metoclopramide is primarily metabolised by CYP2D6. Individuals who are poor metabolisers of CYP2D6 may have an increased exposure to metoclopramide, resulting to increased risk of adverse effects including acute dystonia. Dosage reduction is recommended. The prevalence of CYP2D6 poor metabolisers is estimated at approx 1% in Asians and 5-10% among white populations.
Renal Impairment
Oral Prophylaxis of nausea and vomiting associated with radiation therapy; Nausea and vomiting; Prophylaxis of chemotherapy-induced nausea and vomiting
Intravenous: Nausea and vomiting; Prophylaxis of nausea and vomiting associated with radiation therapy;Prophylaxis of postoperative nausea and vomiting; Prophylaxis of chemotherapy-induced nausea and vomiting
CrCl (mL/min)
Dosage
<15
Reduce dose by 75%.
15-60
Reduce dose by 50%.
Intubation of the small intestine; Premedication for radiologic examination of the upper gastrointestinal tract
CrCl (mL/min)
Dosage
<40
Reduce dose by 50%
Parenteral Diabetic gastric stasis
CrCl (mL/min)
Dosage
<40
Reduce dose by 50%
Hepatic Impairment
Oral: Prophylaxis of nausea and vomiting associated with radiation therapy; Nausea and vomiting; Prophylaxis of chemotherapy-induced nausea and vomiting Severe: Reduce dose by 50%.
Diabetic gastric stasis
Moderate to severe: 5 mg 4 times daily. Max: 20 mg daily.
Administration
Should be taken on an empty stomach. Take 30 min before meals.
Reconstitution
Inj: Doses >10 mg: Dilute in 50 mL of compatible solution (e.g. 0.9% NaCl).
Incompatibility
Incompatible with cefalotin Na, chloramphenicol Na, and Na bicarbonate.
Contraindications
Patient with gastrointestinal perforation, haemorrhage or mechanical obstruction, suspected or known pheochromocytoma or other catecholamine-releasing paragangliomas, history of neuroleptic or drug-induced tardive dyskinesia, seizure disorder (e.g. epilepsy), Parkinson’s disease, known history of methaemoglobinaemia with metoclopramide or nicotinamide adenine dinucleotide-cytochrome b5 reductase (NADH-Cyb5R) deficiency. Concomitant use with drugs which may cause extrapyramidal reactions (e.g. antipsychotics, levodopa). Children <1 year.
Special Precautions
Patient with underlying neurological conditions, Parkinson’ s disease, cardiac conduction disturbances or sick sinus syndrome, hypertension, uncorrected electrolyte imbalance, bradycardia, heart failure with coexisting renal impairment, risk factors of fluid overload (e.g. HF, cirrhosis), history of atopy (including asthma), porphyria, diabetes, disorders associated with delayed gastric emptying, history of depression. CYP2D6 poor metabolisers. Renal and hepatic impairment. Children and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: Dystonic reactions, akathisia, parkinsonian symptoms, tardive dyskinesia, methaemoglobinaemia, circulatory collapse, severe bradycardia, cardiac arrest, QT prolongation, sinus arrest, torsades de pointes. depression, suicidal ideation; gynaecomastia, galactorrhoea, amenorrhoea and impotence secondary to hyperprolactinaemia, Blood and lymphatic system disorders: Rarely, agranulocytosis, leucopenia, neutropenia, sulfhaemoglobinaemia. Cardiac disorders: Supraventricular tachycardia, acute CHF, AV block. Eye disorders: Visual disturbance. Gastrointestinal disorders: Diarrhoea, nausea, vomiting, bowel disturbance. General disorders and admin site conditions: Asthenia, fatigue. Hepatobiliary disorders: Rarely, hepatoxicity. Immune system disorders: Hypersensitivity, rarely, angioedema. Investigations: Increased plasma aldosterone levels. Metabolism and nutrition disorders: Fluid retention, porphyria. Nervous system disorders: Somnolence, restlessness, headache, dizziness, seizure, rarely, tremor. Psychiatric disorders: Insomnia. Rarely, anxiety, agitation, confusion, hallucinations. Renal and urinary disorders: Urinary incontinence or urgency. Reproductive system and breast disorders: Priapism. Respiratory, thoracic and mediastinal disorders: Bronchospasm, rarely, laryngospasm, laryngeal oedema. Skin and subcutaneous tissue disorders: Rarely, rash, urticaria. Vascular disorders: Hypotension (IV), hypertension, flushing. Potentially Fatal: Rarely, neuroleptic malignant syndrome characterised by muscle rigidity, hyperthermia, altered consciousness, autonomic instability.
This drug may cause drowsiness, dizziness, involuntary movements, if affected, do not drive or operate machinery.
Monitoring Parameters
Monitor for signs and symptoms of tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal manifestations.
Overdosage
Symptoms: Extrapyramidal disorders, drowsiness, headache, vertigo, restlessness, weakness decreased level of consciousness, anxiety, confusion, hallucination, nausea, vomiting, xerostomia, constipation, hypotension and cardio-respiratory arrest. Rarely, AV block. Methaemoglobinaemia and generalised seizures may also occur in premature and full-term neonates. Management: Symptomatic and supportive treatment. Extrapyramidal reactions may be controlled by administration of anticholinergic agents (e.g. diphenhydramine, benztropine). Administer IV methylene blue in cases of methaemoglobinaemia however, the use of methylene blue in patients with G6PD deficiency is not recommended due to an increased risk of haemolytic anaemia which may be fatal. Monitor CV and respiratory functions.
Drug Interactions
Additive sedative effects with CNS depressants (e.g. morphine derivatives, anxiolytics, H1-receptor blockers, sedative antidepressants, barbiturates, clonidine). Increased risk of extrapyramidal disorders with other neuroleptic agents or centrally-acting drugs (e.g. phenothiazines, tetrabenazine). May increase the risk of serotonin syndrome associated with serotonergic drugs (e.g. SSRIs). May decrease the bioavailability of digoxin. May increase the absorption of ciclosporin, aspirin and paracetamol. May prolong the duration of action of neuromuscular blocking agents (e.g. mivacurium, suxamethonium). Increased serum concentrations with strong CYP2D6 inhibitors (e.g. fluoxetine, paroxetine). Plasma concentrations of atovaquone may be reduced by metoclopramide. Increased risk of QT prolongation with other agents known to prolong QT interval (e.g. class IA and III antiarrhythmics, TCAs, macrolides, antipsychotics). May alter the effects of central stimulants (e.g. sympathomimetics. Increased risk of hypertension with MAO inhibitors. May diminish the effect of antidiabetic agents. Potentially Fatal: Concomitant administration with levodopa or dopamine agonists (e.g. bromocriprine) may result in mutual antagonism.
Food Interaction
Additive sedative effects with alcohol.
Action
Description: Metoclopramide is a substituted benzamide with prokinetic and antiemetic properties. It stimulates the motility of the upper gastrointestinal tract and accelerates gastric peristalsis without stimulating gastric, biliary or pancreatic secretions, leading to increased gastric emptying and intestinal transit time. It blocks dopamine receptors and serotonin receptors (at higher doses) in chemoreceptor trigger zone of the CNS. Onset: 30-60 minutes (oral); 1-3 minutes (IV); 10-15 minutes (IM). Duration: 1-2 hours. Pharmacokinetics: Absorption: Rapidly and almost completely from the gastrointestinal tract after oral administration. Absolute bioavailability: 80±15.5%. Time to peak plasma concentration: Approx 1-2 hours (oral). Distribution: Extensively distributed to body tissues. Crosses the blood-brain barrier and placenta and enters breast milk at low level. Volume of distribution: Approx 3.5 L/kg. Plasma protein binding: Approx 30%. Metabolism: Metabolised in the liver by CYP2D6 via oxidation and glucuronide and sulfate conjugation to major metabolite, monodeethylmetoclopramide. Undergoes hepatic first-pass metabolism. Excretion: Via urine (approx 85%, with approx 50% as free or conjugated metoclopramide); faeces (approx 5%). Elimination half-life: 2.5-6 hours.
Chemical Structure
Metoclopramide Source: National Center for Biotechnology Information. PubChem Database. Metoclopramide, CID=4168, https://pubchem.ncbi.nlm.nih.gov/compound/Metoclopramide (accessed on Jan. 22, 2020)
A03FA01 - metoclopramide ; Belongs to the class of propulsives. Used in the treatment of functional gastrointestinal disorders.
References
Camilleri M and Shin A. Lessons from Pharmacogenetics and Metoclopramide: Towards the Right Dose of the Right Drug for the Right Patient. J Clin Gastroenterol. 2012 Jul;46(6):437-439. doi: 10.1097/MCG.0b013e3182549528. Accessed 01/08/2019Anon. Metoclopramide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 15/07/2019.Buckingham R (ed). Metoclopramide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/07/2019.McEvoy GK, Snow EK, Miller J et al (eds). Metoclopramide Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 18/02/2015.Metoclopramide Hydrochloride Tablet (Par Pharmaceutical Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/02/2015.Metoclopramide Oral Solution (VistaPharm, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 15/07/2019.Metoclopramide Solution for Injection (Hospira, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 15/07/2019.Metoclopramide Tablet (Impax Generics). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 15/07/2019.Metoclopramide. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 17/07/2019.Reglan Tablets (Ani Pharmaceuticals, Inc.). U.S. FDA. https://www.fda.gov/. Accessed 17/07/2019.
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