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Drug Information
Pharmacokinetics
| Indication
& Dosage | Action
| Interacations |
Precautions |
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Pharmacokinetics
Metoclopramide is
rapidly and almost completely absorbed from the gastrointestinal tract
following a dose by mouth, although conditions such as vomiting or
impaired gastric motility may reduce absorption. Peak plasma
concentrations of metoclopramide occur about 1 to 2 hours after an oral
dose. However, it undergoes hepatic first-pass metabolism, which varies
considerably between subjects, and hence the absolute bioavailability
and the plasma concentrations are subject to wide interindividual
variation. On average, the bioavailability of oral metoclopramide is
about 75%, but it appears to vary between about 30 and 100%.
Attempts to overcome the problems of oral administration by rectal or
intranasal administration have demonstrated that bioavailability is
equally variable by these routes, although it may be somewhat better if
given intramuscularly.
Metoclopramide is widely distributed in the body, with an apparent
volume of distribution of about 3.5 litres per kg. It readily crosses
the blood-brain barrier into the CNS. It also freely crosses the
placenta, and has been reported to attain concentrations in fetal plasma
about 60 to 70% of those in maternal plasma. Concentrations higher than
those in maternal plasma may be reached in the breast milk of lactating
mothers, particularly in the early puerperium, although concentrations
decrease somewhat in the late puerperium.
Elimination of metoclopramide is biphasic, with a terminal elimination
half-life of about 4 to 6 hours, although this may be prolonged in renal
impairment, with consequent elevation of plasma concentrations. It is
excreted in the urine, about 85% of a dose being eliminated in 72 hours,
20 to 30% as unchanged metoclopramide and the remainder as sulphate or
glucuronide conjugates, or as metabolites. About 5% of a dose is
excreted in faeces viat
he bile.
TOP
Oral; IM/IV
NAUSEA, VOMITING DUE TO VARIOUS CAUSES EXCEPT IN MOTION SICKNESS; DELAYED GASTRIC EMPTYING; DIABETIC GASTROPARESIS: Adult: 10mg 2-4 times/day. Young Adults 15-20 yrs: 5-10mg 2-4 times/day. 5-8 yrs: 2.5mg 2-4 times/day. 3-4 yrs: 2mg 2-4 times/day. 1-2 yr: 1mg 2-4 times/day. under 1yr: img b.i.d. Maximum daily oral dose: 0.5mg/kg.
OESOPHAGEAL REFLUX: 10-15mg q.i.d. 30 min befor each meal and at bedtime.
CANCER CHEMOTHERAPY (NAUSEA, VOMITING): 2-4mg/kg as IV drip over 15-30min. Maintenace dose: 3-5mg/kg given over 8 hrs. Max: 10mg/kg/day.
NOTE: Renal impairment: Creatinine clearance under 40ml/min, the starting dose is reduced by 50%
TOP.
Metoclopramide blocks central and peripheral dopamine receptors. The latter activity results in stimulation of plain muscle in the stomach and upper GI tract. This results in rapid gastric emptying and faster intestinal trasnsit. Lower oesophageal sphincter pressure is increased and this prevents oesophageal reflux. Central dopamine inhibition abolishes nauses and vomiting. Prolactin levels are increased and extrapyramidal side effects may be seen.
Caution should be observed when using metoclopramide in patients taking other drugs that can also cause extrapyramidal reactions, such as the phenothiazines. Increased toxicity may occur if metoclopramide is used in patients receiving lithium, and caution is advisable with other centrally active drugs including antidepressants, antiepileptics, and sympathomimetics. Antimuscarinics and opioid analgesics antagonise the gastrointestinal effects of metoclopramide.
The absorption of other drugs may be affected by metoclopramide; it may either diminish absorption from the stomach (as with digoxin) or enhance absorption from the small intestine (for example, with aspirin or paracetamol). It inhibits serum cholinesterase and may prolong suxamethonium-induced neuromuscular blockade.
Metoclopramide may also increase prolactin blood-concentrations and therefore interfere with drugs which have a hypoprolactinaemic effect such as bromocriptine. It has been suggested that it should not be given to patients receiving monoamine oxidase inhibitors (MAOIs).
Drowsiness, facial spasm, trismus, oculogyric crisis seen commonly in children and young adults. Tardive dyskinesia in elderly on prolonged use, gynaecomastia, galactorrhoea, diarrhoea and restlessness.
Precaution: IV injection ot be administered slowly to avoid restlessness and anxiety.
Pregnancy: Safety not established.
Breast Feeding: Use with Caution.
Man: May be givenin reduced dose.
