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.
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.
- Hypersensitivity to the active substance or any of the excipients listed in 6.1.
- 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 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
- 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 Plasil-induced tardive dyskinesia
- Epilepsy (increased crises frequency and intensity)
- Parkinson's disease
- Combination with levodopa or dopaminergic agonists
- Known history of methaemoglobinaemia with Plasil or of NADH cytochrome-b5 deficiency.
- Use in children less than 1 year of age due to an increased risk of extrapyramidal disorders
No particulars.
None known.
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).
| Systeme 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; | |
| 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 | 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 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, 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 at: www.mhra.gov.uk/yellowcard.
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 sulfur-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, 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, 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 abnormalities have been found in animal studies to indicate a safety risk in humans. This is based on data from pharmacological studies relating to safety, and data on toxicity following repeated administration, genotoxicity, carcinogenicity and reproductive toxicity.
Not applicable.
Metoclopramide is a substituted benzamide. It is used among other things because of its anti-emetic 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.
Plasil hydrochloride is an anti-emetic and an accelerator of gastric emptying.
Following oral administration the relative bioavailability compared with intravenous administration is 60 to 100%. Peak plasma concentrations are reached within 0.5 to 2 hours.
The distribution volume is 2-3 l/kg; 13-22% is bound to plasma proteins. Metoclopramide is excreted primarily in the urine, both in unchanged form and in sulfate or glucuronide conjugate form. The principal metabolite is an N-4 sulphur conjugate.
The plasma elimination half-life is 5 to 6 hours, irrespective of the route of administration.
Special patient populations
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.
Renal impairment
The clearance of Plasil 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 Plasil has been observed, associated with a 50% reduction in plasma clearance.
Special warnings
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.
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 dministration 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.
Plasile tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicine.
Neurological Disorders
Extrapyramidal disorders may occur, particularly in children and young adults, and/or when high doses are used.
Prolonged treatment with Plasil 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 Plasil in combination with neuroleptics as well as with Plasil monotherapy. Plasil 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 Plasil.
Methaemoglobinemia
Methemoglobinemia which could be related to NADH cytochrome b5 reductase deficiency has been reported. In such cases, Plasil 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 Plasil by injection, particularly via the intravenous route.
Special care should be taken when administering Plasil, 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.
Contains lactose:
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery.
Plasil may cause drowsiness, dizziness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery.
No special requirements.
Not applicable.
Administrative data
