Metoclopramide

Oral
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.
Renal impairment:

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

Hepatic impairment: Severe: Reduce dose by 50%.

Oral
Nausea and vomiting
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.
Renal impairment:

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

Hepatic impairment: Severe: Reduce dose by 50%.

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 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. Recommended Max treatment duration: 5 days.
Elderly: Dosage reduction may be needed.
Renal impairment:

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

Hepatic impairment: Severe: Reduce dose by 50%.

Oral
Gastro-oesophageal 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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<40	Reduce dose by 50%.

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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<40	Reduce dose by 50%.

Hepatic impairment: Moderate to severe: 5 mg 4 times daily. Max: 20 mg daily.

Oral
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.

Oral
Intubation of the small intestine
Adult: 10 or 20 mg as a single dose given before examination.
Elderly: Initiate at lowest recommended dose.

Intravenous
Nausea and vomiting
Adult: 10 mg up to tid. Max: 30 mg or 0.5mg/kg daily.
Child: 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.
Renal impairment:

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

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.

Intravenous
Prophylaxis of nausea and vomiting associated with radiation therapy
Adult: 10 mg up to tid. Max: 30 mg or 0.5mg/kg daily.
Child: 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.
Renal impairment:

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

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.

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.
Renal impairment:

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

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.

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.
Renal impairment:

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

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.

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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<40	Reduce dose by 50%.

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.

Intravenous
Intubation of the small intestine
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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<40	Reduce dose by 50%.

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.

Intravenous
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.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<40	Reduce dose by 50%.

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.

Special Populations: 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.

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

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, 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. Patient Counselling This drug may cause drowsiness, dizziness and involuntary movements, if affected, do not drive or operate machinery. Monitoring Parameters Monitor blood tests and for signs and symptoms of tardive dyskinesia, neuroleptic malignant syndrome, and extrapyramidal manifestations.

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 administration 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.

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.

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.

Additive sedative effects with alcohol.

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 central nervous system (CNS).
Onset: 30-60 minutes (oral); 1-3 minutes (IV); 10-15 minutes (IM).
Duration: 1-2 hours.
Absorption: Rapidly and almost completely absorbed from the gastrointestinal tract. 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.

Intravenous: Store between 20-25°C. Protect from light. Oral: Store between 20-25°C. Protect from light. Parenteral: Store between 20-25°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.