Metoclopramide (with special reference to Lagomorphs, Ferrets and Great Apes)

Crystalline powder, white and odourless. (B263)

• Alcohol: Approximately one gram in 3 mL alcohol. (B263)

• pKas of 0.6 and 9.3. (B263)
• Injectable product: pH 3 - 6.5. (B263)

• Antagonist at both dopamine D₂ and 5HT₃ receptors. It acts in the enteric nervous system and in the chemo-receptor trigger zone. (B373.3.w3)
• Note: Stimulation of upper gastrointestinal motility can be negated by administration of anticholinergic drugs. (B263)

• Store at room temperature in lightproof containers - photosensitive. (B263)
• Store tablets in tight containers. (B263)
• Metoclopramide injection is reported to be stable in solutions of pH 2 - 9 and is reported to be stable in 5% dextrose solution, 0.9% sodium chloride, 5% dextrose - half normal saline, Ringer's solution and lactated Ringer's solution. (B263)

Physical interactions

• Physical compatibility has been reported (for periods of at least 24 hours) for: "aminophylline, ascorbic acid, atropine sulfate, benztropine mesylate, chlorpromazine HCl, cimetidine HCl, clindamycin phosphate, cyclophosphamide, cytarabine, dexamethasone sodium phosphate, dimenhydrinate, diphenhydramine HCl, doxorubicin HCl, droperidol, fentanyl citrate, heparin sodium, hydrocortisone sodium phosphate, hydroxyzine HCl, insulin (regular), lidocaine HCl, magnesium sulfate, mannitol, meperidine HCl, methylprednisolone sodium succinate, morphine sulfate, multivitamin infusion (MVI), pentazocine lactate, potassium acetate/chloride/phosphate, prochlorperazine edisylate, TPN solution (25% dextrose w/4.25% Travasol® w/ or w/o electrolytes), verapamil and vitamin B-complex w/vitamin C." (B263)
• Physical incompatibility has been reported with: "ampicillin sodium, calcium gluconate, cephalothin sodium, chloramphenicol sodium succinate, cisplatin, erythromycin lactobionate, methotrexate sodium, penicillin G potassium, sodium bicarbonate, and tetracycline." (B263)
• Note: Physical compatibility is affected by factors such as concentration, pH, temperature and diluents; specialized references should be consulted for more specific information. (B263)

Associated Techniques

CNS: Central anti-emetic effect and stimulation of prolactin secretion. (B263)

• As an antiemetic, to reduce vomiting in individuals with gastritis (including e.g. uraemic gastritis), or following surgery, or vomiting induced by chemotherapy. (B263, B373.3.w3)
• Treatment of gastric stasis. (B263)
• Treatment of ruminal atony. (B373.3.w3)
• Treatment of abomasal atony and dilatation. (B373.3.w3)
• Treatment of oesophageal reflux. (B373.3.w3)
• Treatment of post-operative ileus. (B373.3.w3)
• To allow small intestine intubation. (B263)

• Does not increase motility of the lower small intestine or the large intestine. (B373.3.w3)

• Oral: well absorbed. Significant first-pass effect in some individuals; in humans it is known this can reduce bioavailability to 30%, but this is highly variable between individuals. Peak plasma levels within two hours of administration.
• Intramuscular: 74 - 96%. (B263)

• Mainly metabolised (to glucuronidated or sulphated conjugated forms) then excreted in urine. 
• About 20-25% excreted unchanged in urine.
• About 5% excreted in faeces.

(B263)

• The gastro-intestinal motility effects of metoclopramide may be negated by anticholinergic compunds such as atropine, and by narcotic analgesics. (B263)
• Absorption of many drugs may be affected by the actions of metoclopramide on the gastrointestinal tract:
  • Reduced absorption may occur with drugs that dissolve, disintegrate or are absorbed in the stomach (e.g. digoxin).
  • Absorption of drugs which are mainly absorbed in the small intestine may be increased.
  • Absorption of food may be accelerated; this may affect the required doses or timing of insulin.

  (B263)

• The CNS effects of metoclopramide may be enhanced by sedatives, tranquillisers and narcotics. (B263)
• The extrapyramidal effects of metoclopramide may be potentiated by phenothiazines such as acepromazine and chlorpromazine, and by butyrephenones such as droperidol and azaperone. (B263)

• 0.2 - 1.0 mg/kg orally, subcutaneously, intramuscularly or intravenously twice daily. (B373.Guide.w41)
• 0.5 mg/kg subcutaneously or orally twice daily. As a motility stimulant. (B600.4.w4)
  • Note: "May not be effective in young rabbits." (B600.4.w4)
• 0.5 mg/kg subcutaneously or orally every 6 - 12 hours. (B603.5.w5)
• 0.5 - 1.0 mg/kg subcutaneously or orally every 6 - 12 hours. (B546)
• 0.2 - 0.5 mg/kg orally or subcutaneously every 2 - 4 hours. (B601.15.w15)
• 0.5 mg/kg orally or subcutaneously every 8 - 24 hours. (B602.41.w41)

Note: Increased efficacy if given as a constant rate intravenous infusion rather than bolus intravenous injections. (B373.3.w3)

Ferrets - Mustela putorius furo - Ferret:

• 0.2 - 1.0 mg/kg orally, subcutaneously or intramuscularly every six to eight hours. (B602.41.w41, B631.21.w21) possibly also intravenously? As an antiemetic. (B631.21.w21)
• 0.5 - 1.0 mg/kg orally twice daily; encourages gastric emptying. (B626.App.w22)
• Note: useful as an anti-emetic in ferrets, but check for GIT foreign body or other causes of gastro-intestinal blockage before administration. (J213.3.w1)

Great Apes

• Adult Pan troglodytes - Chimpanzee: 0.4 mg/kg by slow intravenous injection or intramuscularly or orally, once to three times daily. (W768.Jun2012.w1)

• Individuals with known hypersensitivity to this drug. (B263)
• Individuals with gastrointestinal haemorrhage, obstruction, or perforation. (B263)
  • Do not use if there is a suspicion that a gastro-intestinal foreign body may be present. (B373.3.w3)

Use with caution in individuals with epilepsy/seizures. (B373.3.w3)

Note: "In patients with pheochromocytoma, metoclopramide may induce a hypertensive crisis."

• At normal doses, may cause restlessness, excitement and behavioural disturbances in some individuals. (B373.3.w3)
  • Cats: Frenzied behaviour and disorientation may occur. (B263)
  • Dogs: changes in mentation and behaviour reported. (B263)
  • Horses: with intravenous administration, particularly in adults, sometimes severe CNS effects, with alternating sedation and excitement, and behavioural changes, as well as abdominal pain. (B263)
• Skeletal muscle tremors or rigidity may occur (extrapyramidal side effects). (B373.3.w3)
• Sweating and abdominal cramping may occur. (B373.3.w3)
• Transient incoordination may occur occasionally. (B373.3.w3)
• Constipation sometimes occurs in dogs and cats. (B263)

Warnings:

• Not recommended by the manufacturer for use in early pregnancy. (B373.4.w4)

Signs of overdose might include "sedation, ataxia, agitation, extrapyramidal effects, nausea, vomiting and constipation." (B263)

Treatment:

• Following recent oral overdose, stomach emptying may be beneficial. (B263)
• To control CNS effects, use of anticholinergic drugs which enter the CNS may be useful (e.g. benztropine, diphenhydramine). (B263)

• Mice: Oral LD₅₀ 465 mg/kg. (B263)
• Rats: Oral LD₅₀ 760 mg/kg. (B263)
• Rabbits: Oral LD₅₀ 870 mg/kg. (B263)

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