Summary of Product Characteristics Updated 15-Sep-2016 | hameln pharmaceuticals ltd
Paediatric population:Metoclopramide 5 mg/ml Injection is indicated in children (1 18 years) for: • Prevention of delayed chemotherapy induced nausea and vomiting (CINV) as a second line option • Treatment of established post-operative nausea and vomiting (PONV) as a second line option For other indications, the use in the paediatric population is not recommended.
Adult population:Metoclopramide 5 mg/ml Injection is indicated in adults for: • Prevention of post-operative nausea and vomiting (PONV) • Symptomatic treatment of nausea and vomiting, including acute migraine induced nausea and vomiting • Prevention of radiotherapy induced nausea and vomiting (RINV)
All indications (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 intravenous route. The maximum dose in 24 hours is 0.5 mg/kg body weight.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).
|1-3 years||10-14kg||1 mg||Up to 3 times daily|
|3-5 years||15-19 kg||2 mg||Up to 3 times daily|
|5-9 years||20-29 kg||2.5 mg||Up to 3 times daily|
|9-18 years||30-60 kg||5 mg||Up to 3 times daily|
|15-18 years||Over 60 kg||10 mg||Up to 3 times daily|
ElderlyIn elderly patients a dose reduction should be considered, based on renal and hepatic function and overall frailty.
Renal impairmentIn 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 impairmentIn 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 the 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.
MethaemoglobinaemiaMethaemoglobinaemia 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).
Contraindicated combinationLevodopa or dopaminergic agonists and metoclopramide have a mutual antagonism (see section 4.3).
Combination to be avoidedAlcohol potentiates the sedative effect of metoclopramide.
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 both have 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.
CyclosporineMetoclopramide 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 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.
PregnancyA 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 the 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 a 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); Atrioventricular block, Sinus arrest particularly with intravenous formulation; Electrocardiogram QT prolonged; Torsade de Pointes;|
|General disorders and administration site conditions|
|Not Known||Injection site inflammation and local phlebitis|
|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, 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 (see section 4.4), Neuroleptic malignant syndrome (see section 4.4)|
|Common:||Hypotension, particularly with intravenous formulation|
|Not known||Shock, syncope after injectable use. Acute hypertension in patients with phaeochromocytoma (see section 4.3). Transient increase in blood pressure|
|Not known||Skin reactions such as rash, pruritus, angioedema and urticaria|
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.
SymptomsExtrapyramidal disorders, drowsiness, a 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.
Nexus, Gloucester Business Park, Gloucester, GL3 4AG
+44 (0)1452 621 661
+44 (0)1452 632 732