Symptoms
In cases of overdosage, acute dystonic/extrapyramidal reactions have occurred. Very rarely AV block has been observed.
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.
3 years
- Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal perforation for which the stimulation of gastrointestinal motility constitutes a risk
- Confirmed or suspected pheochromocytoma, due to the risk of severe hypertension episodes
- History of neuroleptic or metoclopramide-induced tardive dyskinesia
- Epilepsy (increased crises frequency and intensity)
- Parkinson's disease
- Combination with levodopa or dopaminergic agonists
- 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
Not applicable
Sodium chloride
Water for injections
Adverse reactions listed by System Organ Class. Frequencies are defined using the following convention: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10000, <1/1000), very rare (<1/10000), not known (cannot be estimated from the available data).
| System Organ Class | Frequency | Adverse Reactions |
| 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; dyspnoea | |
| Endocrine disorders* | ||
| Uncommon | Amenorrhoea, Hyperprolactinaemia | |
| Rare | Galactorrhoea | |
| Not known | Gyneacomastia | |
| 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, 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 phaechromocytoma , 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, hallucination.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard.
No additional data available.
Pharmacotherapeutic group: Agents stimulating gastro-intestinal motility
ATC Code: A03FA01
This medicine is indicated for the treatment of nausea and vomiting associated with intolerance to cytotoxic drugs. It is specially formulated to ensure compatibility in solution with cisplatin.
This medicine exerts a three-fold anti-emetic action: by inhibiting central dopamine receptors this medicine raises the threshold of the chemoreceptor trigger zone, and reduces the reaction of the adjacent vomiting centre to centrally-acting emetics. This medicine decreases the sensitivity of the visceral afferent nerves to the vomiting centre, reducing the effect of locally-acting emetics and irritant substances. In the upper gastro-intestinal tract this medicine promotes normal gastric emptying and it may thus abolish gastric stasis which is part of the vomiting reflex.
This medicine is not intended for use in the wider range of indications for which this medicine at standard dose is indicated.
Absorption
Based on current literature, a metoclopramide concentration range of about 0.85µg/ml would appear desirable for the control of cytotoxic drug induced emesis. Such plasma concentrations may be achieved by the administration of a loading dose of 2-4 mg/kg infused over 15-30 minutes prior to cytotoxic drug therapy followed by a maintenance continuous infusion of 3-5 mg/kg over 8-12 hours.
Biotransformation
Metoclopramide is metabolised in the liver and the predominant route of elimination of metoclopramide and its metabolites is via the kidney.
Renal impairment
The clearance of metoclopramide is reduced by up to 70% in patients with severe renal impairment, while the plasma elimination half-life is increased (approximately 10 hours for a creatinine clearance of 10-50 mL/minute and 15 hours for a creatinine clearance <10 mL/minute).
Hepatic impairment
In patients with cirrhosis of the liver, accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance.
15/09/2016
Amdipharm UK Limited
Capital House, 85 King William Street,
London EC4N 7BL, UK
If ampoules are removed from their carton, they should be stored away from light. If inadvertent exposure occurs, ampoules showing discolouration must be discarded.
Clear glass 20ml ampoules (Ph. Eur. Type I neutral glass) packed in boxes of 10.
PL 20072/0052
Pregnancy
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 newborn cannot be excluded. Metoclopramide should be avoided at the end of pregnancy. If metoclopramide is used, neonatal monitoring should be undertaken.
Breast-feeding
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.
Neurological Disorders
Extrapyramidal disorders may occur, particularly in children and young adults, and/or when high doses are used.
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.
Special care should be exercised in patients with underlying neurological conditions and in patients being treated with other centrally-acting drugs
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.
Intravenous doses should be administered as a slow bolus (at least over 3 minutes) in order to reduce the risk of adverse effects (e.g. hypotension, akathisia).
Renal and Hepatic Impairment
In patients with renal impairment or with severe hepatic impairment, a dose reduction is recommended.
Risk-benefit should be carefully considered in patients with significant hepatic or renal impairment (loss of conjugation and increased risk of extrapyramidal effects) or with Parkinson's disease (symptoms may be exacerbated).
Precautions:
If vomiting persists the patient should be reassessed to exclude the possibility of an underlying disorder e.g. cerebral irritation.
Care should be exercised in patients being treated with other centrally acting drugs.
This medicine should be used with care in combination with other serotonergic drugs including SSRIs.
Patients receiving this drug for the disorders associated with delayed gastric emptying should be reviewed at an early stage for response to treatment.
Metoclopramide may cause elevation of serum prolactin levels.
Care should be exercised when using this medicine in patients with a history of atopy (including asthma) or porphyria.
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.
Protect from light.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
16 June 1995
Contraindicated combination
Levodopa or dopaminergic agonists and metoclopramide have a mutual antagonism. Metoclopramide should be used with care in association with other drugs acting at central dopamine receptors such as bromocriptine and pergolide.
Combination to be avoided
Alcohol potentiates the sedative effect of metoclopramide.
Combination to be taken into account
Due to the prokinetic effect of metoclopramide, the absorption of certain drugs may be modified.
Anticholinergics, morphine derivatives and other opioid analgesics
Anticholinergics and morphine derivatives may have both a mutual antagonism with metoclopramide on the digestive tract motility.
The absorption of aspirin and paracetamol may be modified by the effect of metoclopramide on gastric motility.
Concomitant use of anticholinergic drugs may inhibit the favourable effects on gastrointestinal motility.
Since extrapyramidal reactions may occur with this medicine, Phenothiazines and Tetrabenazine, care should be exercised in the event of co-administration of these drugs.
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 of extrapyramidal disorders.
Monoamine oxidase inhibitors
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.
Serotonergic drugs
The use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of serotonin syndrome.
Digoxin
Metoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasma concentration 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 is uncertain.
Mivacurium and suxamethonium
Metoclopramide injection may prolong the duration of neuromuscular block (through inhibition of plasma cholinesterase).
Strong CYP2D6 inhibitors
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.
Antiprotozoals
This medicine may reduce plasma concentrations of atovaquone.
