Metoclopramide

Registered South African indications:

• As an adjunct to the X-ray examination of the stomach and duodenum
• Post-operative hypotonia (postvagotomy syndrome)
• Anti-emetic for the prevention and treatment of irradiation sickness
• Post-operative vomiting
• Drug-induced nausea and vomiting

Contraindications

South African recommendations

• Metoclopramide should not be used where gastrointestinal conditions might be adversely affected as in intestinal obstruction or immediately after surgery
• Patients with phaeochromocytoma or convulsive disorders

Recommendations in other jurisdictions

• Hypersensitivity to metoclopramide hydrochloride or any of the excipients
• Patients hypersensitive to procaine and procainamide may show cross-sensitivity
• Metoclopramide should not be used during the first three to four days following operations such as pyloroplasty or gut anastomosis as vigorous muscular contractions may not help healing
• Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk
• Confirmed or suspected pheochromocytoma, due to the risk of severe hypertension episodes
• History of neuroleptic or metoclopramide-induced tardive dyskinesia
• Epilepsy (increased crises frequency and intensity)
• Parkinson's disease
• Combination with levodopa or dopaminergic agonists
• Known history of methaemoglobinaemia with metoclopramide, or of NADH cytochrome-b5 deficiency
• Use in children less than 1 year of age due to an increased risk of extrapyramidal disorders

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment (South African recommendations)
  Moderate to severe renal impairment, and end-stage renal disease (Recommendations in other jurisdictions)
• Hepatic impairment (South African recommendations)
• Severe hepatic impairment (Recommendations in other jurisdictions)
• Elderly
• Children
• Young adults
• High dose therapy
• Prolonged therapy
• Treatment duration >3 months
• Administration at intervals of <6 hours between doses
• Underlying neurological disorders
• Hypertension
• Patients that have undergone gastrointestinal anastomosis or closure
• Parkinson's disease
• History of atopy, including asthma or porphyria
• Galactose intolerance
• Total lactase deficiency
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab, syr

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages
Post-operative hypotonia (postvagotomy syndrome)
Anti-emetic for the prevention and treatment of irradiation sickness
Post-operative vomiting
Drug-induced nausea and vomiting

• Oral (tab, syr): 10mg, 8hrly

As an adjunct to the X-ray examination of the stomach and duodenum
- Diagnostic radiology and duodenal intubation

• Oral (tab, syr): 20mg, as a single dose before barium meal

---

Prolonged treatment (greater than 12 weeks) with metoclopramide should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risks to the patient of developing tardive dyskinesia

Paed. forms avail. in SA and covered in this monograph: tab, syr

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages
Post-operative hypotonia (postvagotomy syndrome)
Anti-emetic for the prevention and treatment of irradiation sickness
Post-operative vomiting
Drug-induced nausea and vomiting

Younger than 3 years

• No information available

Between 3-5 years

• Oral (syr): 2mg, 8-12hrly

Between 5-14 years

• Oral (syr): 2.5-5mg, 8hrly

Older than 14 years

• See adult dosage

---

Prolonged treatment (greater than 12 weeks) with metoclopramide should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risks to the patient of developing tardive dyskinesia

Pregnancy

South African recommendations

• Caution; positive evidence of risk in animal studies
• The use of metoclopramide throughout the duration of pregnancy is considered unsafe, as teratogenicity has been demonstrated in animal studies

Recommendations in other jurisdictions

• Caution
• A large amount of data on pregnant women (more than 1000 exposed outcomes) indicates no malformative toxicity nor foetotoxicity. Metoclopramide can be used during pregnancy if clinically needed. Due to pharmacological properties (as other neuroleptics), in case of metoclopramide administration at the end of pregnancy, extrapyramidal syndrome in newborn cannot be excluded
• Metoclopramide should be avoided at the end of pregnancy. If metoclopramide is used, neonatal monitoring should be undertaken

Breastfeeding

South African recommendations

• Caution; no information available

Recommendations in other jurisdictions

• Caution; not recommended
• Metoclopramide is excreted in breast milk at low levels. Adverse reactions in the breastfed baby cannot be excluded. Therefore metoclopramide is not recommended during breastfeeding. Discontinuation of metoclopramide in breastfeeding women should be considered

Renal Impairment

South African recommendations

• Caution; no dose adjustment recommended

Recommendations in other jurisdictions

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; dose adjustment recommended

CrCl (ml/min)	Dose
15-60	Reduce dose by 50%
≤15 (end stage renal disease)	Reduce dose by 75%

Hepatic Impairment

South African recommendations

• Caution; no dose adjustment recommended

Recommendations in other jurisdictions

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; dose adjustment recommended
  The dose should be reduced by 50% 
  In patients with cirrhosis of the liver accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance

Elderly

South African recommendations

• Caution; no dose adjustment recommended

Recommendations in other jurisdictions

• Caution; dose adjustment recommended
  In elderly patients a dose reduction should be considered, based on renal and hepatic function and overall frailty

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

•  Permitted - No warnings

Central Nervous System Disorders

• Asthenia
• Somnolence
• Extrapyramidal disorders
• Parkinsonism
• Akathisia
• Dystonia
  - Visual disturbances
  - Oculogyric crisis
• Depressed level of consciousness
• Seizures
• Tardive dyskinesia
• Neuroleptic malignant syndrome
• Depression
• Hallucination
• Confusional state

Cardiovascular Disorders

• Bradycardia
• Cardiac arrest
• Atrioventricular block
• Sinus arrest
• QT prolongation
• Torsade de Pointes
• Hypotension
• Shock
• Syncope
• Acute hypertension (patients with phaeochromocytoma)
• Transient increase in blood pressure

Gastrointestinal Disorders

• Diarrhoea

Endocrine and Metabolic Disorders

• Amenorrhoea
• Hyperprolactinaemia
• Galactorrhoea
• Gynaecomastia

Immune, Blood and Lymphatic System Disorders

• Methaemoglobinaemia
• Sulfhaemoglobinaemia
• Hypersensitivity
• Anaphylactic reactions

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritus
• Angioedema
• Urticaria
• Injection site inflammation
• Local phlebitis

• Levodopa
• Dopaminergic agonists
• QT prolonging agents
• Anticholinergics
• Morphine derivatives
• Central nervous system depressants
• Anxiolytics
• Sedative H1 antihistamines
• Sedative antidepressants
• Barbiturates
• Clonidine
• Neuroleptics
• Serotonergic agents
• Selective serotonin re-uptake inhibitors
• Digoxin
• Cyclosporine
• Mivacurium
• Suxamethonium
• Strong CYP2D6 inhibitors
• Fluoxetine
• Paroxetine
• Monoamine oxidase inhibitors
• Sympathomimetics
• Aspirin
• Paracetamol
• Atovaquone
• Alcohol

None routine. Specific cases may require

• Renal function
• Hepatic function
• ECG

Persistence of symptoms

• If vomiting persists the patient should be reassessed to exclude the possibility of an underlying disorder, such as cerebral
  irritation

Metoclopramide, a dopamine-receptor antagonist, antagonises dopaminergic D2 receptors in the chemoreceptor trigger zone and in the vomiting centre of the medulla, which is affected in apomorphine-induced vomiting. Metoclopramide also antagonises the serotoninergic 5HT3 receptors with an agonist effect on the 5HT4 receptors which are affected in chemotherapy-induced vomiting.

In addition to the central action, metoclopramide has a stimulant effect on gastrointestinal motility via a peripheral mechanism of action. There is an antidopaminergic effect and potentiation of the effect of acetylcholine. This causes accelerated emptying of the stomach and there is an increase in the pressure exerted by the lower oesophageal sphincter. Metoclopramide has no effect on gastric secretions.

Tablet 10mg

• Adco-Contromet (Adcock Ingram)
• Betaclopramide (Be-Tabs)
• Bio Metoclopramide (Biotech)
• Clomax (Medicine Dev)
• Clopamon (Pharmacare)
• Maxolon t (Meda) originator
• Merck-Metoclopramide (Mylan)
• Setin (Alliance)
• Metoclopramide 10 Oethmaan (Oethmaan Biosims)

Syrup (per 5ml) 5mg

• Adco-Contromet (Adcock Ingram)
• Clopamon (Pharmacare)
• Maxolon s (Meda) originator