Dopamine D2-receptor antagonist / gastrointestinal prokinetic-antiemetic

Metoclopramide

Dosage form
Tablet
Available strengths
5 mg/mL
Drug class
Dopamine D2-receptor antagonist / gastrointestinal prokinetic-antiemetic
Common brand
Generic products

Clinical overview. Metoclopramide is an injectable dopamine D2-receptor antagonist used to speed stomach emptying in patients with delayed gastric emptying, to prevent nausea and vomiting from cisplatin-based chemotherapy, to aid small bowel intubation, and to prevent vomiting after surgery. It works by increasing the strength and speed of stomach and intestinal contractions. Its most notable risks are movement disorders such as tardive dyskinesia and acute dystonic reactions, particularly with higher doses, prolonged use, or use in children and young adults.

Indication

Common therapeutic uses

  • Metoclopramide injection is used as an adjunct in managing delayed gastric emptying associated with subacute or chronic gastritis or following gastric surgery such as vagotomy or pyloroplasty.
  • It is used to prevent nausea and vomiting caused by cancer chemotherapy regimens that include cisplatin.
  • It is used as an adjunct to help guide a feeding tube through the small bowel.
  • It is used to prevent vomiting after surgery.

Pregnancy

Risk assessment and monitoring considerations

  • The safe use of metoclopramide in pregnancy has not been established, so it should not be used in pregnant women unless the expected benefits outweigh the potential risks to the fetus.

Breastfeeding

Infant exposure considerations

  • Metoclopramide passes into breast milk and can affect a nursing infant.
  • Discuss the best feeding approach with a healthcare professional before using metoclopramide while breastfeeding.

Geriatrics

Dosing and tolerability considerations

  • Elderly patients, particularly elderly women, are at increased risk of developing tardive dyskinesia with metoclopramide use.
  • Older adults often have reduced kidney function, so a lower starting dose and careful monitoring are appropriate.

Pediatrics

Use in children and adolescents

  • Metoclopramide is contraindicated in children under 1 year of age.
  • It should not be used in children over 1 year of age unless the anticipated benefits clearly outweigh the risks.
  • Extrapyramidal symptoms can occur in children even at recommended doses; the pediatric daily dose should not exceed 0.5 mg/kg.

Dosage & Administration

Practical dosing and administration

  • For delayed gastric emptying, the usual adult dose is 10 mg (2 mL) given intramuscularly or by slow intravenous injection, 2 to 3 times daily as needed.
  • For prevention of cisplatin-induced vomiting, adults are given 1 mg/kg by intravenous infusion for cisplatin doses up to 100 mg/m2, or 2 mg/kg for higher cisplatin doses, infused over 15 minutes and repeated every 2 hours for two doses, then every 3 hours for three more doses.
  • For prevention of postoperative vomiting, adults are given 10 mg intramuscularly near the end of surgery, increased to 20 mg in high-risk patients, and may be repeated every 4 to 6 hours.
  • For small bowel intubation, adults are given 10 mg by slow intravenous injection, and children are given a single dose of 100 mcg/kg intravenously, slowly.
  • Except for cisplatin-induced vomiting prophylaxis, the total daily dose should not exceed 0.5 mg/kg of body weight.
  • In patients with a creatinine clearance below 40 mL/min, therapy should be started at about half the usual dose and adjusted based on response and safety.
  • Metoclopramide undergoes minimal liver metabolism, and its use has been described as safe in patients with advanced liver disease whose kidney function is normal.

Overdose

Recognizing and responding to overdose

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

  • The most frequent effects of metoclopramide overdose are extrapyramidal reactions, involuntary movements such as muscle spasms, tremor, or restlessness.
  • These reactions can usually be controlled with antiparkinson agents or antihistamine/anticholinergic drugs such as diphenhydramine.
  • Management otherwise relies on close observation and supportive care; hemodialysis removes little metoclopramide and is not considered an effective way to remove the drug after overdose.
  • In premature and full-term newborns, repeated dosing well above the recommended amount has caused methemoglobinemia, which can be reversed with intravenous methylene blue.

Common side effects

Frequently reported tolerability concerns

  • Drowsiness may occur.
  • Fatigue may occur.
  • A general feeling of low energy (lassitude) may occur.
  • Headache may occur.
  • Dizziness may occur.
  • Insomnia may occur.
  • Bowel disturbances such as diarrhea may occur.
  • Menstrual irregularities or unexpected breast milk production (galactorrhea) may occur.

Serious side effects

Findings that may require urgent assessment

Serious side effects require immediate discussion with the prescriber or emergency care.

  • Tardive dyskinesia, a movement disorder involving involuntary movements of the tongue, face, mouth, or jaw, can develop, particularly with treatment beyond 12 weeks, and may be irreversible in some cases.
  • Acute dystonic reactions, including involuntary limb movements, facial grimacing, abnormal neck posturing, or spasms of the tongue or jaw, can occur, usually within the first 24 to 48 hours of treatment.
  • Parkinsonian-like symptoms, including tremor, rigidity, and mask-like facial expression, can develop, usually within the first 6 months of treatment.
  • Neuroleptic malignant syndrome, a rare but potentially fatal reaction involving high fever, muscle rigidity, altered consciousness, and irregular heartbeat, has been reported.
  • Mental depression, including suicidal thoughts, has occurred in patients with and without a prior history of depression.
  • Methemoglobinemia has been reported in neonates and infants given metoclopramide overdoses.
  • In patients with pheochromocytoma, intravenous metoclopramide may trigger a hypertensive crisis.
  • Seek urgent medical attention for involuntary movements, muscle stiffness, high fever with a fast or irregular heartbeat, or thoughts of self-harm.

Use with caution

Situations requiring closer assessment

  • Use with caution in patients with epilepsy, since seizure frequency and severity may increase.
  • Use with caution in patients taking other drugs that can cause extrapyramidal reactions, since effects may be additive.
  • Use with caution in patients with pheochromocytoma, given the risk of a hypertensive crisis with intravenous use.
  • Use with caution in patients with impaired kidney or liver function, and adjust the dose accordingly.
  • Use with caution in patients with a personal history of depression.
  • Use with caution in patients with a history of breast cancer, since metoclopramide raises prolactin levels and some breast cancers are prolactin-dependent.
  • Use with caution in elderly patients, especially elderly women, given the increased risk of tardive dyskinesia.
  • Avoid prolonged treatment beyond 12 weeks unless the therapeutic benefit is judged to outweigh the risk of tardive dyskinesia.

Contraindications

Situations where therapy may be inappropriate

  • Contraindicated in patients with gastrointestinal hemorrhage.
  • Contraindicated in patients with gastrointestinal perforation or mechanical obstruction.
  • Contraindicated in patients with epilepsy or those receiving other drugs likely to cause extrapyramidal reactions.
  • Contraindicated in children under 1 year of age.
  • Contraindicated in patients with known hypersensitivity or intolerance to metoclopramide.

Drug interactions

Clinically relevant combinations

  • Anticholinergic drugs antagonize the effects of metoclopramide on gastrointestinal motility.
  • Metoclopramide reduces the absorption of digoxin from the stomach.
  • Metoclopramide accelerates the absorption of acetaminophen, ethanol, levodopa, and tetracyclines from the small bowel.
  • Concomitant use with neuroleptic or ganglion-blocking drugs is not recommended, since their effects may be potentiated.
  • Sedatives, narcotics, anxiolytics, and hypnotics can have their sedative effects potentiated by metoclopramide.
  • Caution is required with monoamine oxidase inhibitors, since animal studies showed increased toxicity when combined with intravenous metoclopramide.
  • In patients with pheochromocytoma, intravenous metoclopramide can provoke a hypertensive crisis; phentolamine may be given by slow intravenous injection to control this effect.

Food interactions

Meal-related administration

  • No specific food interactions have been established, though metoclopramide's effect of speeding gastric emptying can alter the absorption timing of other oral medications taken around the same time.

Time of administration

Practical scheduling

  • The timing of injections depends on the indication being treated, such as before or after surgery, before chemotherapy, or as needed for delayed gastric emptying, rather than a fixed time of day.
  • For cisplatin-induced vomiting prevention, doses are timed relative to the chemotherapy infusion, starting before treatment and continuing on a set schedule afterward.

Storage

Product handling

  • Store between 15°C and 30°C, and protect from light.
  • Diluted intravenous solutions are stable for up to 48 hours at room temperature; discard any unused portion.

Patient take-away

Key counselling points for a quick closing summary

  • Metoclopramide injection is used to speed stomach emptying, prevent chemotherapy-related vomiting, assist with small bowel tube placement, and prevent vomiting after surgery.
  • The most common effects are drowsiness, fatigue, headache, and dizziness.
  • Seek urgent medical attention for involuntary muscle movements, severe muscle stiffness, high fever with a fast heartbeat, or thoughts of self-harm.
  • Tell your healthcare professional if you are pregnant, breastfeeding, have epilepsy, or have a history of depression or breast cancer before starting treatment.

References

Source material and product information

  1. Health Canada Product Monograph — Metoclopramide

For professional reference. Confirm patient-specific decisions against the current approved product monograph and applicable clinical guidance.

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