METO (Metoclopramide Tablets BP 10mg)

Pharmacotherapeutic group: preparations to combat nausea/vomiting. ATC code: A03F A01

Metoclopramide is a substituted benzamide. It is used among other things because of its antiemetic properties. The anti-emetic effect is the result of two mechanisms of action involving the central nervous system:

antagonism of the dopaminergic D2 receptors in the chemoreceptor trigger zone and in the vomiting centre of the medulla which is affected in apomorphine-induced vomiting;
antagonism of the serotoninergic 5HT3 receptors and 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.

Therapeutic indications

Adult population

Metoclopramide is indicated in adults for:

Prevention of delayed chemotherapy induced nausea and vomiting (CINV)
Prevention of radiotherapy induced nausea and vomiting (RINV).
Symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting.

Metoclopramide can be used in combination with oral analgesics to improve the absorption of analgesics in acute migraine.

Paediatric population

Metoclopramide is indicated in children (aged 1-18 years) for Prevention of delayed chemotherapy induced nausea and vomiting (CINV) as a second line option.

Posology and method of administration Posology

Adult population: The recommended single dose is 10 mg, repeated up to three times daily.

The maximum recommended daily dose is 30 mg or 0.5mg/kg body weight. The maximum recommended treatment duration is 5 days.

Prevention of delayed chemotherapy induced nausea and vomiting (CINV) (paediatric patients aged 1-18 years): The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to three times daily by oral route. The maximum dose in 24 hours is 0.5 mg/kg body weight.

Contraindications

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

Special warnings and precautions for use

Neurological Disorders: Extrapyramidal disorders may occur, particular in children and young adults, and/or when high doses are used.

These reactions occur usually at the beginning of the treatment and can occur after a single administration. Metoclopramide should be discontinued immediately in the event of extrapyramidal symptoms. These effects are generally completely reversible after treatment discontinuation, but may require a symptomatic treatment (benzodiazepines in children and/or anticholinergic anti- Parkinsonian medicinal products in adults).

Prolonged treatment with Metoclopramide may cause tardive dyskinesia, potentially irreversible, especially in the elderly. Treatment should not exceed 3 months because of the risk of tardive dyskinesia. Treatment must be discontinued if clinical signs of tardive dyskinesia appear.

Neuroleptic malignant syndrome has been reported with Metoclopramide in combination with neuroleptics as well as with Metoclopramide monotherapy. Metoclopramide should be discontinued immediately in the event of symptoms of neuroleptic malignant syndrome and appropriate treatment should be initiated.

Symptoms of Parkinson’s disease may also be exacerbated by Metoclopramide.

Methaemoglobinemia: Methemoglobinemia which could be related to NADH cytochrome b5 reductase deficiency has been reported. In such cases, Metoclopramide should be immediately and permanently discontinued and appropriate measures initiated (such as treatment with methylene blue).

Cardiac Disorders: There have been reports of serious cardiovascular undesirable effects including cases of circulatory collapse, severe bradycardia, cardiac arrest and QT prolongation following administration of Metoclopramide by injection, particularly via the intravenous route.

Special care should be taken when administering Metoclopramide, particularly via the intravenous route to the elderly population, to patients with cardiac conduction disturbances (including QT prolongation), patients with uncorrected electrolyte imbalance, bradycardia and those taking other drugs known to prolong QT interval.

Renal and Hepatic Impairment: In patients with renal impairment or with severe hepatic impairment, a dose reduction is recommended.

Metoclopramide Hydrochloride tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicine.

Interaction with other medicinal products and other forms of interaction

Concomitant use not recommended

Contraindicated combination: Levodopa or dopaminergic agonists and Metoclopramide have a mutual antagonism.

Combination to be avoided

Alcohol potentiates the sedative effect of Metoclopramide.

Combination to be taken into account

Anticholinergics and morphine derivatives: Anticholinergics and morphine derivatives may have both a mutual antagonism withMetoclopramide on the digestive tract motility.

Central nervous system depressants (morphine derivatives, anxiolytics, sedative H1 antihistamines, sedative antidepressants, barbiturates, clonidine and related): Sedative effects of Central Nervous System depressants and Metoclopramide are potentiated.

Neuroleptics: Metoclopramide may have an additive effect with other neuroleptics on the occurrence ofextrapyramidal disorders.

Serotonergic drugs: The use of Metoclopramide with serotonergic drugs such as SSRIs may increase the risk ofserotonin syndrome.

Digoxin: Metoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasmaconcentration is required.

Cyclosporine: Metoclopramide increases cyclosporine bioavailability (Cmax by 46% and exposure by 22%).Careful monitoring of cyclosporine plasma concentration is required. The clinical consequence isuncertain.

Mivacurium and suxamethonium: Metoclopramide injection may prolong the duration of neuromuscular block (through inhibitionof plasma cholinesterase).

Strong CYP2D6 inhibitors: Metoclopramide exposure levels are increased when co-administered with strong CYP2D6inhibitors such as fluoxetine and paroxetine. Although the clinical significance is uncertain,patients should be monitored for adverse reactions.

Pregnancy, lactation and fertility

Pregnancy: A large amount of data on pregnant women (more than 1000 exposed outcomes) indicates nomalformative toxicity nor foetotoxicity. Metoclopramide can be used during pregnancy if clinicallyneeded. Due to pharmacological properties (as other neuroleptics), in case of Metoclopramideadministration at the end of pregnancy, extrapyramidal syndrome in newborn cannot be excluded.

Metoclopramide should be avoided at the end of pregnancy. If Metoclopramide is used, neonatal monitoring should be undertaken.

Breastfeeding: Metoclopramide is excreted in breast milk at low level. Adverse reactions in the breast-fed babycannot be excluded. Therefore Metoclopramide is not recommended during breastfeeding.

Discontinuation of Metoclopramide in breastfeeding women should be considered.

Effects on ability to drive and use machines

Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonias which could affect thevision and also interfere with the ability to drive and operate machinery.

Overdose

Symptoms: Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, and cardio-respiratory arrest may occur.

Management: In case of extrapyramidal symptoms related or not to overdose, the treatment is only symptomatic (benzodiazepines in children and/or anticholinergic anti-parkinsonian medicinal products in adults).

A symptomatic treatment and a continuous monitoring of the cardiovascular and respiratory functions should be carried out according to clinical status.

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METO (Metoclopramide Tablets BP 10mg)

METO (Metoclopramide Tablets BP 10mg)

Therapeutic indications