Chemicals / Complex Chemical Agents/ Chemical:

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

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 

A para-aminobenzoic acid derivative used as an anti-emetic and to normalise gastric and small intestinal motility.

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Names and Formulae

Type A para-aminobenzoic acid derivative. (B263)
Alternative Names --
Chemical Formula --
Chemical Structure --
Molecular Weight --
Related Chemicals --

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Physical Properties / Chemistry

Appearance

Crystalline powder, white and odourless. (B263)

Melting point --
Boiling point --
Density --
Water solubility Approximately one gram in 0.7 mL. (B263)
Other solubility
  • Alcohol: Approximately one gram in 3 mL alcohol. (B263)
Acid/Base
  • pKas of 0.6 and 9.3. (B263)
  • Injectable product: pH 3 - 6.5. (B263)

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Pharmacology & General Information

Pharmacology
  • 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)
Storage / Stability
  • 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)
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Nikki Fox BVSc MRCVS (V.w103)
Referees Debra Bourne MA VetMB PhD MRCVS (V.w5)

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Therapeutic Information

Uses/Indications

Activity Gastrointestinal: Restores normal gastrointestinal motility and facilitates gastric emptying. Gastric contractions are increased in tone and amplitude, the pyloric sphincter is reduced and both duoodenal and jejunal peristalsis are increased; these actions can lead to significant reductions in time to gastric emptying and in intestinal transit time. Increases lower oesophageal sphincter tone and reduces or prevents  gastro-oesophageal reflux (producing a local antiemetic effect). (B263, B373.3.w3)

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

Appropriate Use
  • 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)
Limitations
  • Does not increase motility of the lower small intestine or the large intestine. (B373.3.w3)
Notes --

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Pharmacokinetics and Drug Interactions

Absorption /Bioavailability
  • 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)
Distribution Well distributed; enters the CNS, crosses the placenta. Concentration in milk about twice the concentration in plasma. (B263)
Plasma Protein binding / Storage About 13-22% plasma protein-bound. (B263)
Elimination Route In dogs: 
  • 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)

Elimination half-life / Clearance Rate In dog: half-life about 90 minutes. (B263)
Drug Interactions
  • 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)

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Administration

Formulations available --
Doses / Administration Routes / Frequencies Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:
  • 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

Monitoring parameters Monitor for clinical efficacy and for adverse effects. (B263)

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Withdrawal period / Withholding time

Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products

Contraindications / Precautions Contraindicated in:
  • 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."

Adverse Effects / Side Effects / Warnings --
  • 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)
Operator Warnings --
Overdose / Acute Toxicity High doses are required to reach toxic levels; oral overdose is unlikely to be fatal. (B263)

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)

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Detailed Toxicological Information

Classification --
Acute Toxicity
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data

Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses

Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment

Natural sources --
Human-associated sources

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Effects on the Environment

Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment

Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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