Metoclopramide

Intramuscular, Intravenous
Diabetic gastric stasis

Intramuscular, Intravenous
Prophylaxis of postoperative nausea and vomiting

Intramuscular, Intravenous
Nausea and vomiting, Prophylaxis of nausea and vomiting associated with radiation therapy

Intravenous
Prophylaxis of delayed chemotherapy-induced nausea and vomiting

Intravenous
Prophylaxis of chemotherapy-induced nausea and vomiting

Intravenous
Postoperative nausea and vomiting

Intravenous
Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract

Nasal
Diabetic gastric stasis

Oral
Nausea and vomiting, Prophylaxis of nausea and vomiting associated with radiation therapy

Oral
Gastro-oesophageal reflux disease

Oral
Diabetic gastric stasis

Oral
Prophylaxis of delayed chemotherapy-induced nausea and vomiting

Oral
Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract

Oral:
GERD:
Patients taking strong CYP2D6 inhibitors (e.g. quinidine, bupropion, fluoxetine, paroxetine): 5 mg 4 times daily given 30 minutes before each meal and at bedtime or 10 mg tid. Max: 30 mg daily.

Diabetic gastric stasis:
Patients taking strong CYP2D6 inhibitors (e.g. quinidine, bupropion, fluoxetine, paroxetine): 5 mg 4 times daily given 30 minutes before each meal and at bedtime. Max: 20 mg daily.

Nasal:
Diabetic gastric stasis:
Patients taking strong CYP2D6 inhibitors (e.g. quinidine, bupropion, fluoxetine, paroxetine): Not recommended.

Pharmacogenomics:

Metoclopramide is partially metabolised by the CYP2D6 isoenzyme into monodeethylmetoclopramide and N-hydroxy and N-deethyl metabolites. Individuals who are poor metabolisers of CYP2D6 may have increased exposure to metoclopramide, therefore possibly increasing the risk of adverse reactions including acute dystonia. The prevalence of CYP2D6 poor metabolisers is estimated at approx 1% in Asians and 5-10% among white populations.

The US Food and Drug Administration recommends reducing the oral dosage for CYP2D6 poor metabolisers. Dosing recommendations are indicated below.

GERD:
5 mg 4 times daily given 30 minutes before each meal and at bedtime or 10 mg tid. Max: 30 mg daily.

Diabetic gastric stasis:
5 mg 4 times daily given 30 minutes before each meal and at bedtime. Max: 20 mg daily.

Oral:
Nausea and vomiting; Prophylaxis of nausea and vomiting associated with radiation therapy; Prophylaxis of delayed chemotherapy-induced nausea and vomiting:

CrCl (mL/min)	Dosage
<15	Reduce dose by 75%.
15-60	Reduce dose by 50%.

Diabetic gastric stasis:
ESRD (including haemodialysis and continuous ambulatory peritoneal dialysis patient): 5 mg bid. Max: 10 mg daily.

CrCl (mL/min)	Dosage
<60	5 mg 4 times daily given 30 minutes before each meal and at bedtime. Max: 20 mg daily.

GERD:
ESRD (haemodialysis and continuous ambulatory peritoneal dialysis patient): 5 mg 4 times daily given 30 minutes before each meal and at bedtime or 10 mg bid. Max: 20 mg daily.

CrCl (mL/min)	Dosage
≤60	5 mg 4 times daily given 30 minutes before each meal and at bedtime or 10 mg tid. Max: 30 mg daily.

Intubation of the small intestine; Premedication for radiologic examination of the upper gastrointestinal tract:
Dose reduction may be needed.

Intravenous:
Intubation of the small intestine; Premedication for radiologic examination of the upper gastrointestinal tract:
Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

CrCl (mL/min)	Dosage
<40	Initiate at approx 1/2 of the recommended dose; may increase or decrease according to clinical efficacy and safety.

Prophylaxis of chemotherapy-induced nausea and vomiting:
Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

CrCl (mL/min)	Dosage
<15	Reduce dose by 75%.
15-60	Reduce dose by 50%.

Intravenous/Intramuscular:
Diabetic gastric stasis:
Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

CrCl (mL/min)	Dosage
<40	Initiate at approx 1/2 of the recommended dose; may increase or decrease according to clinical efficacy and safety.

Nausea and vomiting; Prophylaxis of nausea and vomiting associated with radiation therapy; Prophylaxis of postoperative nausea and vomiting:
Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

CrCl (mL/min)	Dosage
<15	Reduce dose by 75%.
15-60	Reduce dose by 50%.

Nasal:
Haemodialysis and continuous ambulatory peritoneal dialysis patient: Not recommended.

CrCl (mL/min)	Dosage
<60	Not recommended.

Oral:
Nausea and vomiting; Prophylaxis of nausea and vomiting associated with radiation therapy; Prophylaxis of delayed chemotherapy-induced nausea and vomiting:
Severe: Reduce dose by 50%.

Diabetic gastric stasis:
Moderate or severe (Child-Pugh class B or C): 5 mg 4 times daily given 30 minutes before each meal and at bedtime. Max: 20 mg daily.

GERD:
Moderate or severe (Child-Pugh class B or C): 5 mg 4 times daily given 30 minutes before each meal and at bedtime or 10 mg tid. Max: 30 mg daily.

Intubation of the small intestine; Premedication for radiologic examination of the upper gastrointestinal tract:
Dose reduction may be needed.

Intravenous:
Prophylaxis of chemotherapy-induced nausea and vomiting:
Severe: Reduce by 50%. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

Intravenous/Intramuscular:
Nausea and vomiting; Prophylaxis of nausea and vomiting associated with radiation therapy; Prophylaxis of postoperative nausea and vomiting:
Severe: Reduce by 50%. Dosing recommendations may vary among individual products and between countries (refer to specific product guidelines).

Nasal:
Moderate or severe (Child-Pugh class B or C): Not recommended.

Should be taken on an empty stomach. Take 30 min before meals.

IV infusion: Dilute with appropriate volume of compatible solution. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).

Incompatible with cefalotin, chloramphenicol, and Na bicarbonate.

Gastrointestinal haemorrhage, perforation or mechanical obstruction; confirmed or suspected phaeochromocytoma or other catecholamine-releasing paragangliomas; seizure disorder (e.g. epilepsy), Parkinson's disease, history of neuroleptic or metoclopramide-induced tardive dyskinesia, known history of methaemoglobinaemia with metoclopramide or of nicotinamide adenine dinucleotide hydrogen (NADH)-cytochrome b₅ reductase deficiency. Children <1 year of age. Concomitant use with antipsychotics, levodopa or dopaminergic agonists.

Patient with underlying neurological conditions, history of atopy (including asthma) or porphyria, history of depression, hypertension, cardiac conduction disturbances (e.g. QT prolongation), uncorrected electrolyte imbalance, bradycardia, at risk of fluid overload (e.g. CHF, cirrhosis); sick sinus syndrome (IV). CYP2D6 poor metabolisers. Patients taking strong CYP2D6 inhibitors. Withhold for 3-4 days following gastrointestinal surgery (e.g. pyloroplasty, gut anastomosis). Moderate to severe renal and hepatic impairment. Children and elderly. Pregnancy and lactation.

Significant: Tardive dyskinesia (potentially irreversible), extrapyramidal symptoms (particularly in children and young adults and/or high doses), parkinsonian symptoms (e.g. tremors, bradykinesia), motor restlessness (including feelings of anxiety, jitteriness), depression (including suicidal ideation), methaemoglobinaemia, elevated prolactin levels, fluid retention. IV: hypertension, serious CV effects (e.g. circulatory collapse, severe bradycardia, cardiac arrest, QT prolongation).
Blood and lymphatic system disorders: Agranulocytosis, neutropenia, leucopenia.
Eye disorders: Visual disturbance.
Gastrointestinal disorders: Diarrhoea, nausea; dysgeusia (nasal).
General disorders and administration site conditions: Asthenia, fatigue.
Immune system disorders: Hypersensitivity reactions, including bronchospasm, urticaria, rash, angioedema (glossal or laryngeal oedema).
Metabolism and nutrition disorders: Porphyria.
Nervous system disorders: Convulsive seizures, restlessness, somnolence.
Psychiatric disorders: Hallucinations, anxiety.
Vascular disorders: Hypotension (IV).
Potentially Fatal: Neuroleptic malignant syndrome.

IM/IV/Parenteral/PO: B

This drug may cause drowsiness, dizziness, dyskinesia and dystonias; if affected, do not drive or operate machinery.

Monitor for signs of tardive dyskinesia, extrapyramidal disorders, neuroleptic malignant syndrome; mental alertness.

Symptoms: Extrapyramidal disorders (muscle spasms, shuffling walk, jerky movements of head and face, trembling and shaking of hands), drowsiness, decreased level of consciousness, confusion, hallucinations, cardiorespiratory arrest, methaemoglobinaemia. Management: Symptomatic treatment. In case of extrapyramidal symptoms, administration of benzodiazepines in children and/or anticholinergic antiparkinsonian drugs in adults may be considered. Administer IV methylene blue to reverse methaemoglobinaemia. However, methylene blue may cause haemolytic anaemia in patients with G6PD deficiency, which can be fatal. Continuously monitor the CV and respiratory functions as needed.

May potentiate the sedative effects of CNS depressants (e.g. morphine derivatives, anxiolytics, sedative H₁ antihistamines, sedative antidepressants, barbiturates, clonidine). Additive effect with other neuroleptics on the occurrence of extrapyramidal disorders. May increase the risk of serotonin syndrome with serotonergic drugs (e.g. SSRIs). May decrease the bioavailability of digoxin. Increases the bioavailability of ciclosporin. May prolong the duration of action of neuromuscular blocking agents (e.g. mivacurium and suxamethonium). Increased plasma concentrations with strong CYP2D6 inhibitors (e.g. quinidine, bupropion, fluoxetine, paroxetine). May reduce the plasma concentrations of atovaquone. May accelerate the absorption of mexiletine. Concurrent use with extrapyramidal reaction-causing drugs (e.g. phenothiazines, tetrabenazine) may increase the frequency and severity of extrapyramidal side effects. Increased risk of hypertension with MAOIs.
Potentially Fatal: Concomitant use with levodopa or dopaminergic agonists may lead to mutual antagonism. Antipsychotics may increase the potential for additive effects, including increased frequency and severity of tardive dyskinesia, extrapyramidal symptoms and neuroleptic malignant syndrome.

Alcohol potentiates the sedative effect of metoclopramide; avoid concomitant use.

Description:
Mechanism of Action: Metoclopramide is a substituted benzamide with prokinetic and antiemetic properties. It accelerates gastric emptying and intestinal transit time by stimulating the motility of the upper gastrointestinal tract and increasing gastric peristalsis without stimulating gastric, biliary or pancreatic secretions. Additionally, it blocks dopamine receptors and serotonin receptors in the 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 absorbed from the gastrointestinal tract. Bioavailability: 80% ± 15.5% (oral); 47% (nasal). Time to peak plasma concentration: Approx 1-2 hours (oral).
Distribution: Widely distributed throughout the body. Readily crosses the blood-brain barrier and placenta; enters breast milk (low amounts). Volume of distribution: Approx 3.5 L/kg. Plasma protein binding: Approx 30%.
Metabolism: Metabolised in the liver via oxidation and glucuronide and sulfate conjugation. Metabolised partially by CYP2D6 into monodeethylmetoclopramide, a major oxidative metabolite. Undergoes hepatic first-pass metabolism.
Excretion: Mainly via urine (approx 85%; 20% as unchanged drug and the remainder as sulfate and glucuronide conjugates, or as metabolites); faeces (approx 5%). Terminal elimination half-life: Approx 4-6 hours.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4168, Metoclopramide. https://pubchem.ncbi.nlm.nih.gov/compound/Metoclopramide. Accessed May 31, 2023.

Store below 25°C. Protect from light.

Antiemetics / GIT Regulators, Antiflatulents & Anti-Inflammatories

A03FA01 - metoclopramide ; Belongs to the class of propulsives. Used in the treatment of functional gastrointestinal disorders.

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Maxolon High Dose (Amdipharm UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 25/01/2023.

Metoclopramide 10 mg Tablets (Accord-UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 25/01/2023.

Metoclopramide 5 mg/mL Injection (Baxter Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/04/2023.

Metoclopramide 5 mg/mL Injection (Ennogen Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 22/04/2022.

Metoclopramide Hydrochloride 5 mg Film-coated Tablets (Bristol Laboratories Limited). MHRA. https://products.mhra.gov.uk. Accessed 25/01/2023.

Metoclopramide Hydrochloride 5 mg/5 mL Oral Solution (Rosemont Pharmaceuticals Ltd). MHRA. https://products.mhra.gov.uk. Accessed 22/04/2022.

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