This information is intended for use by health professionals
Each 5ml of oral solution contains metoclopramide hydrochloride monohydrate, equivalent to 5mg metoclopramide hydrochloride.
Excipient(s) with known effect:
Methyl parahydroxybenzoate (E218) – 5mg/5ml
Propyl parahydroxybenzoate (E216) – 1mg/5ml
Sorbitol solution (non-crystallising) (E420) – 0.25ml/5ml
Propylene glycol (E1520) – 0.25ml/5ml
For the full list of excipients, see section 6.1.
Adult populationMetoclopramide 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 populationMetoclopramide is indicated in children (aged 1-18 years) for:- Prevention of delayed chemotherapy induced nausea and vomiting (CINV) as a second line option.
Method of Administration.For oral use.Suitable for administration via nasogastric (NG) or percutaneous endoscopic gastrostomy (PEG) tubes. For further instructions see section 6.6.
All indications (adult patients)The recommended single dose is 10 mg, repeated up to three times daily.The maximum recommended daily dose is 30 mg or 0.5 mg/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.
|1-3 years||10-14 kg||1 mg (1ml)||Up to 3 times daily|
|3-5 years||15-19 kg||2 mg (2ml)||Up to 3 times daily|
|5-9 years||20-29 kg||2.5 mg (2.5ml)||Up to 3 times daily|
|9-18 years||30-60 kg||5 mg (5ml)||Up to 3 times daily|
|15-18 years||Over 60 kg||10 mg (10ml)||Up to 3 times daily|
Method of administration:A minimal interval of 6 hours between two administrations is to be respected, even in case of vomiting or rejection of the dose (see section 4.4).
ElderlyIn elderly patients a dose reduction should be considered, based on renal and hepatic function and overall frailty.
Renal impairment:In patients with end stage renal disease (Creatinine clearance ≤ 15 ml/min), the daily dose should be reduced by 75%. In patients with moderate to severe renal impairment (Creatinine clearance 15-60 ml/min), the dose should be reduced by 50% (see section 5.2).
Hepatic impairment:In patients with severe hepatic impairment, the dose should be reduced by 50% (see section 5.2).
Paediatric populationMetoclopramide is contraindicated in children aged less than 1 year (see section 4.3).
Neurological DisordersExtrapyramidal 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 completely reversible after treatment discontinuation, but may require a symptomatic treatment (benzodiazepines in children and/or anticholinergic anti-Parkinsonian medicinal products in adults).The time interval of at least 6 hours specified in section 4.2 should be respected between each metoclopramide administration, even in case of vomiting and rejection of the dose, in order to avoid overdose.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 (see section 4.8). 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 (see section 4.8). 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 (see section 4.3).Symptoms of Parkinson's disease may also be exacerbated by metoclopramide.
MethaemoglobinemiaMethaemoglobinemia 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 DisordersThere 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 (see section 4.8). 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 ImpairmentIn patients with renal impairment or with severe hepatic impairment, a dose reduction is recommended (see section 4.2).
• Methyl and propyl parahydroxybenzoates are contained in this product which may cause allergic reactions (possibly delayed).
• Sorbitol. This medicine contains 227.3mg sorbitol (E420) in each 5ml.
The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.
Patients with hereditary fructose intolerance (HFI) should not take/be given this medicinal product.
• Propylene glycol. This medicine contains 259mg propylene glycol (E1520) in each 5ml.
Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce adverse effects in children less than 5 years old.
While propylene glycol has not been shown to cause reproductive or development toxicity in animals or humans, it may reach the foetus and was found in milk. As a consequence, administration of propylene glycol to pregnant or lactating patients should be considered on a case by case basis.
Medical monitoring is required in patients with impaired renal or hepatic functions because various adverse events attributed to propylene glycol have been reported such as renal dysfunction (acute tubular necrosis), acute renal failure and liver dysfunction.
Contraindicated combinationLevodopa or dopaminergic agonists (including apomorphine, bromocriptine and pergolide) and metoclopramide have a mutual antagonism (see section 4.3).
Combination to be avoidedAlcohol potentiates the sedative effect of metoclopramide; concurrent use may also accelerate gastric emptying of alcohol and thus may promote the rate and extent of absorption from the small intestine.
Combination to be taken into accountDue to the prokinetic effect of metoclopramide, the absorption of certain drugs may be modified.
Anticholinergics and morphine derivativesAnticholinergics and morphine derivatives may have both a mutual antagonism with metoclopramide 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.
NeurolepticsMetoclopramide may have an additive effect with other neuroleptics on the occurrence of extrapyramidal disorders.
Serotonergic drugsThe use of metoclopramide with serotonergic drugs such as SSRIs may increase the risk of serotonin syndrome.
DigoxinMetoclopramide may decrease digoxin bioavailability. Careful monitoring of digoxin plasma concentration is required.
CiclosporinMetoclopramide increases ciclosporin bioavailability (Cmax by 46% and exposure by 22%). Careful monitoring of ciclosporin plasma concentration is required. The clinical consequence is uncertain.Mivacurium and suxamethoniumMetoclopramide injection may prolong the duration of neuromuscular block (through inhibition of plasma cholinesterase).
Strong CYP2D6 inhibitorsMetoclopramide 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.Extrapyramidal reaction causing drugs (such as phenothiazines and tetrabenazine) Concurrent use with metoclopramide may increase the frequency and severity of extrapyramidal side effects. Care should be exercised in the event of co-administration of these drugs.
MexiletineConcurrent use with metoclopramide may accelerate absorption of mexiletine.
Diagnostic interferenceWith Gonadorelin test, concurrent use with metoclopramide may blunt the response to gonaderelin by increasing serum prolactin concentrations. Concurrent metoclopramide therapy may increase aldosterone and serum prolactin levels.
Aspirin and paracetamolThe absorption of any concurrently administered oral drug may be modified by the effect of metoclopramide on gastric motility. Drugs known to be affected in this way include aspirin and paracetamol.
AtovaquoneMetoclopramide may reduce plasma concentrations of atovaquone.
PregnancyA large amount of data on pregnant women (more than 1000 exposed outcomes) indicates neither malformative toxicity nor foetotoxicity. Metoclopramide can be used during pregnancy if clinically needed. Due to pharmacological properties (as with 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.
BreastfeedingMetoclopramide 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.
|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 (see section 4.4); Sulfhaemoglobinaemia, mainly with concomitant administration of high doses of sulfur-releasing medicinal products|
|Uncommon||Bradycardia, particularly with intravenous formulation|
|Not known||Cardiac arrest, occurring shortly after injectable use, and which can be subsequent to bradycardia (see section 4.4); Asystole; Atrioventricular block; Sinus arrest particularly with intravenous formulation; Electrocardiogram QT prolonged; Torsade de Pointes|
|Rare||Constipation; Nausea; Unusual dryness of mouth|
|General disorders and administration site conditions|
|Rare||Oedema (including face oedema)|
|Immune system disorders|
|Not known||Anaphylactic reaction (including anaphylactic shock particularly with intravenous formulation)|
|Nervous system disorders|
|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) (see section 4.4); Parkinsonism; Akathisia|
|Uncommon||Dystonia (including visual disturbances and oculogyric crisis); Dyskinesia; Depressed level of consciousness|
|Rare||Convulsion especially in epileptic patients; Dizziness ; Headache|
|Not known||Tardive dyskinesia which may be persistent, during or after prolonged treatment, particularly in elderly patients (see section 4.4); Neuroleptic malignant syndrome (see section 4.4)|
|Rare||Confusional state; Trouble sleeping; Unusual irritability|
|Respiratory, thoracic and mediastinal disorders|
|Not known||Dyspnoea may occur|
|Skin and subcutaneous tissue disorders|
|Rare||Skin rash; A small number of skin reactions such as urticaria and pruritus|
|Common:||Hypotension; particularly with intravenous formulation|
|Not known||Shock, Syncope after injectable use, Acute hypertension in patients with phaeochromocytoma (see section 4.3)|
Reporting of suspected adverse reactionsReporting 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 at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
SymptomsExtrapyramidal Disorder (muscle spasms, especially of jaw, neck, back, shuffling walk, tic like (jerky) movements of head and face, trembling and shaking of hands), drowsiness, decreased level of consciousness, confusion, hallucination and cardio-respiratory arrest may occur.
ManagementIn 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.
Renal impairmentThe 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 impairmentIn patients with cirrhosis of the liver, accumulation of metoclopramide has been observed, associated with a 50% reduction in plasma clearance.
|Bottle:||Amber Type III glass bottle|
|Closures:||HDPE, EPE wadded, tamper evident, child resistant|
|Syringe:||Polypropylene body and purple HDPE plunger with a capacity of 10ml, graduated at each 1ml and intermediate marks every 0.5ml|
|Bottle adaptor:||Low density polyethylene|
26th August 2020