Metoclopramide Hydrochloride 10 Mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Metoclopramide Hydrochloride 10 mg tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains
Metoclopramide Hydrochloride equivalent to 10 mg anhydrous Metoclopramide HydrochlorideExcipients: 101.24 mg lactose monohydrate
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Tablet
White to off-white, round, biconvex tablets with the inscription ‘BD’ on one side and a scoreline on the other side.
The tablet can be divided into equal halves.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Adult population
Nausea and vomiting, whether or not this accompanies chemotherapy.
4.2 Posology and method of administration
For oral use.
Adult population
Nausea and vomiting accompanying chemotherapy: 2-10 mg/kg/day in various doses.
Nausea and vomiting due to causes other than chemotherapy and surgery: 15-40 mg/kg/day in 2-4 doses.
The dose should be reduced in patients with renal dysfunction. A dose reduction of 50% is recommended in patients with creatinine clearance between 10 and 60 ml/min and of 75% in patients with creatinine clearance of less than 10 ml/min. It should be taken into account that metoclopramide is poorly dialysable.
The dose must also be reduced in patients with severely impaired hepatic function. However, the data available are insufficient to make recommendations regarding dose adjustment.
Peadiatric population including adolescents
Use in the paediatric population is not recommended.
4.3 Contraindications
• Hypersensitivity to metoclopramide or to any of the excipients.
• Gastrointestinal bleeding, mechanical obstruction or gastrointestinal perforation where stimulation of gastrointestinal motility constitutes a risk.
• A history of tardive dyskinesia induced by neuroleptics or metoclopramide.
• Confirmed or suspected phaeochromocytoma due to the risk of severe hypertension.
• Combination with levodopa due to mutual antagonism.
• Metoclopramide is contraindicated in children below 1 year.
4.4 Special warnings and precautions for use
Special warnings
Extrapyramidal disorders may occur, particular in children and young adults, and/or when high doses are used (see section 4.8.). The risk of these symptoms occurring increases with an increase in the dose. These undesirable effects disappear after treatment is discontinued. The symptomatic treatment may be required (benzodiazepines or anticholinergic anti Parkinson drugs both for children or adults).
Precautions for use
The time interval (of at least 6 hours in children younger than 15 years) between each dosing of metoclopramide should be looked after. This is also applicable in the case a dose is vomited. This is to prevent from overdosing.
Metoclopramide Hydrochloride tablets are not recommended in patients with epilepsy, as benzamides lower the epileptic stimulus threshold.
Metoclopramide Hydrochloride tTablets should not be used for longer than 3 months because of the risk of developing tardive dyskinesia (see section 4.8).
Dose reduction is recommended in patients with impaired renal or hepatic function (see section 4.2).
The neuroleptic malignant syndrome, which is characterised by hyperthermia, extrapyramidal disturbances, instability of the autonomic nervous system and elevated creatinine phosphokinase levels can occur when using Metoclopramide Hydrochloride tablets. If fever occurs after or during use of Metoclopramide Hydrochloride tablets, neuroleptic malignant syndrome must be considered in the differential diagnosis.
If there is a reasonable probability of neuroleptic syndrome, the use of Metoclopramide Hydrochloride tablets should be discontinued and the patient should be treated without delay.
Methaemoglobinaemia which might be related to an NADH cytochrome b5 reductase deficiency has been reported. In such cases metoclopramide must be stopped immediately and permanently and appropriate measures must be taken, such as an intravenous injection of 1 mg/kg methylene blue.
Metoclopramide Hydrochloride tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not use this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Contraindicated combination
Levodopa and metoclopramide have a mutual antagonism.
Combinations requiring caution
Anticholinergics and morphine derivatives both have mutual antagonism with metoclopramide in respect of intestinal motility.
The sedative effects of agents which depress the central nervous system such as morphine derivatives, hypnotic agents, anxiolytics, sedative H1 antihistamines, some antidepressants, barbiturates, clonidine and related compounds are potentiated by metoclopramide and vice versa.
With neuroleptics, metoclopramide can have an additive effect on extrapyramidal disorders.
The absorption of some medicines may be changed due to an increase in intestinal motility due to metoclopramide.
Metoclopramide lowers the bioavailability of digoxin and possibly of cimetidine, while the bioavailability of ciclosporin is increased. Monitoring of digoxin and/or ciclosporin plasma concentrations is advised.
Mivacurium and suxamethonium: metoclopramide injection can prolong the duration of a neuromuscular blockade (by inhibition of plasma cholinesterase).
Combination to be avoided
Alcohol potentiates the sedative effect of metoclopramide.
4.6 Fertility, pregnancy and lactation
Pregnancy
A large quantity of data on the use of metoclopramide during human pregnancy does not point at a higher risk of congenital defects or adverse effects on the health of the unborn child. So far, animal experiments do not point at reproduction toxicity. The use of metoclopramide during pregnancy can be considered.
Breastfeeding
Metoclopramide is secreted into the milk of the mother. Effects on the newborn fed with mother milk cannot be excluded. It should be decided whether breastfeeding should be discontinued or the treatment with Metoclopramide should be discontinued or not started at all. For this the advantage of breastfeeding for the child should be weighed against the advantage for the mother to be treated.”
4.7 Effects on ability to drive and use machines
Drowsiness can occur after administration of Metoclopramide Hydrochloride tablets. This can be potentiated by agents which depress the central nervous system and alcohol.
Caution is advised in activities requiring concentration, such as driving and using machines.
4.8 Undesirable effects
Side effects can occur with the following frequencies: very common (>1/10), common (>1/100, <1/10), uncommon (> 1/1,000, <1/100), rare (>1/10,000, <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Blood and lymphatic system disorders
Not known:
• Methaemoglobinaemia which could be related to an NADH cytochrome b5 reductase deficiency, in particular in neonates (see section 4.4).
• Sulfhaemoglobinaemia, primarily with concomitant administration of high doses of drugs which release sulfur.
Endocrine disorders
Not known:
• Endocrine disorders during long-term treatment in conjunction with hyperprolactinaemia (amenorrhoea, galactorrhoea, gynaecomastia).
Psychiatric disorders
Not known:
• Confusion, hallucination.
• Depression.
Central nervous system disorders
Common:
• Drowsiness Uncommon:
• Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian syndrome, akathisia even after administration of a single dose of the drug particularly in children and young adults (see section 4.4).
Not known:
• Reduced level of consciousness.
• Tardive dyskinesia during or after long-term treatment, especially in elderly patients (see section 4.4)
• Convulsions.
• Neuroleptic malignant syndrome.
Cardiac disorders
Not known:
• Hypotension, especially when administered intravenously
• Bradycardia and heart block, in particular when administered intravenously.
Gastrointestinal disorders
Uncommon:
• Diarrhoea
General disorders and administration site conditions
Common:
• Asthenia.
Not known:
Allergic reactions including anaphylaxis.
4.9 Overdose
Extrapyramidal symptoms and drowsiness, reduced level of consciousness, confusion, hallucinations can occur. The treatment of extrapyramidal symptoms is only symptomatic (benzodiazepines or anticholinergic anti Parkinson drugs both for children or adults).
5 PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: preparations to combat nausea/vomiting.
ATC code: A03F A01
5.1 Pharmacodynamic properties
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.
5.2 Pharmacokinetic properties
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
Clearance of metoclopramide is significantly reduced in renal failure, while the plasma elimination half-life is increased (10 hours with a creatinine clearance of 1050 ml/min and 15 hours with a creatinine clearance of <10 ml/min).
In patients with cirrhosis of the liver, an accumulation of metoclopramide accompanied by a 50% reduction in plasma clearance has been observed.
5.3 Preclinical safety data
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.
6.1 List of excipients
The tablet contains the following excipients:
Lactose monohydrate.
Pre-gelatinised starch.
Maize starch.
Anhydrous colloidal silica.
Magnesium stearate.
6.2 Incompatibilities
No particulars.
6.3 Shelf life
The shelf life is 2 years in PVC/PVdC/aluminium blister strips.
6.4 Special precautions for storage
Store below 30 °C.
6.5 Nature and contents of container
Metoclopramide Hydrochloride tablets are packaged in PVC/PVdC/aluminium blister strips. The carton contains 20, 24, 28, 30, 60, 500 tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Accord Healthcare Limited,
Sage House, 319 Pinner Road, North Harrow, Middlesex HA1 4HF,
United Kingdom
MARKETING AUTHORISATION NUMBER(S)
8
PL 20075/0331
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
01/03/2012
10 DATE OF REVISION OF THE TEXT
17/04/2013