Metoclopramide

The effects of certain other drugs with potential central stimulant effects, e.g. monoamine oxidase inhibitors and sympathomimetics, may be modified when prescribed with metoclopramide and their dosage may need to be adjusted accordingly.

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.

The use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of serotonin syndrome.

Alcohol potentiates the sedative effect of metoclopramide.

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

In patients with moderate to severe renal impairment (creatinine clearance 15-60ml/min), the dose should be reduced by 50%.

In patients with end stage renal disease (GFR ≤15 ml/min), the daily dose should be reduced by 75%.

In patients with severe hepatic impairment, the dose should be reduced by 50%.

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

Metoclopramide may have an additive effect with other neuroleptics on the occurrence of extrapyramidal disorders.

Metoclopramide may reduce plasma concentrations of atovaquone.

Metoclopramide increases cyclosporine bioavailability (C_max by 46% and exposure by 22%). Careful monitoring of cyclosporine plasma concentration is required. The clinical consequence is uncertain.

Metoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasma concentration is required.

Metoclopramide injection may prolong the duration of neuromuscular block (through inhibition of plasma cholinesterase).

Extrapyramidal disorders may occur, particularly 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 completelyreversible after treatment discontinuation, but may require a symptomatic treatment (benzodiazepines in children and/or anticholinergic anti-Parkinsonian medicinal products in adults).

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.

A large amount of data on pregnant women (more than 1000 exposed outcomes) indicates no malformative toxicity nor foetotoxicity. Metoclopramide can be used during pregnancy if clinically needed. Due to pharmacological properties (as other neuroleptics), in case of metoclopramide administration at the end of pregnancy, extrapyramidal syndrome in new born cannot be excluded.

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

Metoclopramide is excreted in breast milk at low level. Adverse reactions in the breast-fed baby cannot be excluded. Therefore metoclopramide is not recommended during breastfeeding. Discontinuation of metoclopramide in breastfeeding women should be considered.

Metoclopramide has moderate influence on the ability to drive and use machines. Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery.

Adverse reactions listed by System Organ Class. Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to<1/100), rare (≥1/10000 to<1/1000), very rare (<1/10000), not known (cannot be estimated from the available data).

Blood and lymphatic system disorders

Not known: Methaemoglobinaemia, which could be related to NADH cytochrome b5 reductase deficiency, particularly in neonates; Sulfhaemoglobinaemia, mainly with concomitant administration of high doses of sulphur-releasing medicinal products

Cardiac disorders

Uncommon: Bradycardia, particularly with intravenous formulation

Not known: Cardiac arrest, occurring shortly after injectable use, and which can be subsequent to bradycardia; Atrioventricular block, Sinus arrest particularly with intravenous formulation; Electrocardiogram QT prolonged; Torsade de Pointes;

Endocrine disorders*

Uncommon: Amenorrhoea, Hyperprolactinaemia,

Rare: Galactorrhoea

Not known: Gynaecomastia

Gastrointestinal disorders

Common: Diarrhoea

General disorders and administration site conditions

Common: Asthenia

Immune system disorders

Uncommon: Hypersensitivity

Not known: Anaphylactic reaction (including anaphylactic shock particularly with intravenous formulation

Nervous system disorders

Very common: Somnolence

Common: Extrapyramidal disorders (particularly in children and young adults and/or when the recommended dose is exceeded, even following administration of a single dose of the drug), Parkinsonism, Akathisia

Uncommon: Dystonia including oculogyric crisis, Dyskinesia, Depressed level of consciousness

Rare: Convulsion especially in epileptic patients

Not known: Tardive dyskinesia which may be persistent, during or after prolonged treatment, particularly in elderly patients, Neuroleptic malignant syndrome

Psychiatric disorders

Common: Depression

Uncommon: Hallucination

Rare: Confusional state

Vascular disorder

Common: Hypotension, particularly with intravenous formulation

Not known: Shock, syncope after injectable use, Acute hypertension in patients with phaeochromocytoma, Transient increase in blood pressure

* Endocrine disorders during prolonged treatment in relation with hyperprolactinaemia (amenorrhoea, galactorrhoea, gynaecomastia).

The following reactions, sometimes associated, occur more frequently when high doses are used:

• Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian syndrome, akathisia, even following administration of a single dose of the medicinal product, particularly in children and young adults.
• Drowsiness, decreased level of consciousness, confusion and hallucination.