Metoclopramide

Registered South African indications:

• Digestive disorders associated with gastric status or hypomotility
• Nausea and vomiting
• Diagnostic radiology
• Duodenal intubation

Contraindications

South African recommendations

• Patients with hypersensitivity to metoclopramide or to any of its excipients
• Patients being treated with phenothiazines
• Patients where stimulation of muscular contractions might adversely affect gastrointestinal conditions, such as in gastrointestinal haemorrhage, obstruction or perforation or immediately after surgery
• Patients with phaechromocytoma as hypertensive crises have been reported
• Metoclopramide should not be given to patients with suspected or confirmed phaeochromocytoma
• Patients with convulsive disorders (epileptic patients, due to risk of increased frequency and severity of seizures)
• Porphyria
• Metoclopramide is not recommended in pregnancy

Recommendations in other jurisdictions

• Hypersensitivity to active substance or any of the excipients
• Gastrointestinal haemorrhage, mechanical obstruction or gastrointestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk
• Confirmed or suspected phaeochromocytoma associated with the risk of severe hypertension episodes
• History of neuroleptic or metoclopramide-induced tardive dyskinesia
• Epilepsy (increased crisis frequency and intensity)
• Parkinson's disease
• Combination with levodopa or dopaminergic agonists
• Known history of methaemoglobinaemia with metoclopramide or NADH cytochrome b5 deficiency
• Use in children less than 1 year of age due to an increased risk of extrapyramidal disorders

Cautions

• Pregnancy (Recommendations in other jurisdictions) 
• 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 (South African recommendations)
• 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
• IV administration (particularly in the elderly, patients with cardiac conduction disturbances (including QT prolongation), uncorrected electrolyte imbalance or bradycardia)
• History of atopy, including asthma or porphyria
• Sick sinus syndrome
• Cardiac conduction disturbances 
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Digestive disorders associated with gastric status or hypomotility
- Management of post-vagotomy syndrome
Nausea and vomiting
- Intolerance to essential medicines possessing emetic properties
- Uraemic conditions
- Malignant disease
- Gastrointestinal disorders
- Post-anaesthetic vomiting
Duodenal intubation
- Useful aid to gastrointestinal intubation procedures

• IV/IM: 10mg, 8-24hrly depending on the severity of the condition

Diagnostic radiology
- In patients where delayed gastric emptying interferes with radiological examination of the stomach and/or small intestine

• IV: 10-20mg, 5-15min before the barium meal
• IM: 10-20 mg, 10-15min before the barium meal

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Metoclopramide should not be diluted for injection since this will upset the isotonicity and stability of the medicine

Paed. forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Severe intractable vomiting of known cause
As an aid to gastrointestinal intubation and diagnostic radiology

Younger than 1 year

• No information available

Between 1-3 years

• IV/IM: 0.5mg, 12hrly (in a tuberculin syringe)

Between 3-5 years

• IV/IM: 1mg, 12hrly (in a tuberculin syringe)

Between 5-14 years

• IV/IM: 2.5 mg, 12hrly (in a tuberculin syringe)

Older than 14 years

• IV/IM: 10mg, 8-24hrly depending on the severity of the condition

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Metoclopramide should not be diluted for injection since this will upset the isotonicity and stability of the medicine

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established
• Animal tests in several mammalian species have shown no teratogenic effects but metoclopramide injection is not recommended during pregnancy

Recommendations in other jurisdictions

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

Breastfeeding

• 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; dose adjustment recommended
  Therapy should be at a reduced dosage

Recommendations in other jurisdictions

• Mild: Caution; no dose adjustment recommended
• Moderate to severe (CrCl 15-60ml/min): Caution; dose adjustment necessary

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; dose adjustment recommended
  Therapy should be at a reduced dosage

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
  Prolonged treatment with metoclopramide injection may cause tardive dyskinesia, potentially irreversible, especially in the elderly

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 weakness
  Prolonged treatment with metoclopramide injection may cause tardive dyskinesia, potentially irreversible, especially in the elderly

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• 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.

Injection (per 2ml) 10mg

• Adcock Metoclopramide (Adcock Ingram)
• Austell Metoclopramide (Austell)
• Clopamon (Pharmacare)
• Maxolon I (Meda) originator
• Pharma-Q Metoclopramide (Pharma Q)