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Metoclopramide, 10 mg/ 2 ml solution for injection

Drug formAmpoules for injection

ATC categoryGastroenterology. Hepatology

ATC subcategoryAgents affecting GI motility

Brand nameMetoclopramide

Generic nameMetoclopramide

Composition

Each 1 ml Metoclopramide, solution for injection, contains:

active ingredient: Metoclopramide hydrochloride – 5.27 mg;

excipients: sodium chloride,sodium metabisulfite,benzyl alcohol,water for injection.

Pharmacological group and ATC code
Antiemetic agent. ATC code A03FA01.
Chemical name and CAS number
4-Amino-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide. 364-62-5.
Pharmacology

Metoclopramide as a dopamine antagonist stimulates gastric motility and gastric emptying and speeds small intestinal transit time by increasing gastric peristalsis and increasing the resting tone of the gastro oesophageal sphincter.

Pharmacokinetics
Metoclopramide is metabolised in the liver and the predominant route of elimination of metoclopramide and its metabolites is via the kidney.

Uses
Paediatric population including adolescents:
Metoclopramide is indicated for the treatment of postoperative nausea and vomiting for children from 1 year of age.
For other indications, the use in the paediatric population is not recommended.

Adult population:

1) The use of metoclopramide in young adult patients (16 to 19 years) should be restricted to the following: severe intractable vomiting of known cause, vomiting associated with radiotherapy and intolerance to cytotoxic drugs, as an aid to gastro-intestinal intubation, as part of the pre-medication before surgical procedures.

2) As a dopamine antagonist, motility stimulant to gastric emptying and small intestinal transit time by increasing gastric peristalsis and increasing the resting tone of the gastro-oesophageal sphincter.

3) Relief of symptoms associated with oesophageal reflux.

4) Treatment of non-specific or cytotoxic induced nausea and vomiting.

5) Relief of symptoms associated with migraine such as nausea and vomiting by speeding up gastric emptying. This also improves the absorption of concurrently administered analgesics such as paracetamol.

6) In diagnostic procedures, speeding transit time of radiopaque materials by increasing gastric emptying.

7) To facilitate intubation of the small intestine in patients in whom the tube (e.g. endoscope, biopsy tube) does not pass through the pylorus with conventional manoeuvres.

The 50 mg in 10 ml and 100 mg in 20 ml strength is deliberately formulated to provide for high dose therapy to counteract nausea and vomiting associated with cytotoxic therapy.

The 50 mg in 10 ml and 100 mg in 20 ml are not intended to be used for the broad indications outlined in the application for Metoclopramide 10 mg in 2 ml as reactions associated with metoclopramide are more likely with these higher doses.

Dosage and administration
Paediatric population:

For the treatment of postoperative nausea and vomiting, metoclopramide should be administered after the termination of the surgical procedure.

The recommended dose in children aged 1-15 yrs old is 0.15 mg/kg b.w. given as a slow injection (at least 3 minutes).

The maximum dose in 24 hours is 0.5 mg/kg b.w. If additional doses are needed, these should be separated by at least 6 hours.

Metoclopramide should not be used in children younger than 1 year as there are insufficient data regarding efficacy and safety of the product in this patient population.

Adult population:

Metoclopramide 5 mg/ml Injection 10 mg in 2ml should be given by intramuscular injection or by slow intravenous injection (over 2 minutes).
The potential for side effects such as dystonia is increased if the dosage exceeds that recommended below.
Each 2 ml of Metoclopramide 5 mg/ml Injection contains 10 mg of anhydrous substance.

For treatment and relief of symptoms numbering 1 – 5 :
Adult patients (20 years and over):

60 kg and above – 10 mg three times daily;
below 60 kg – 5 mg three times daily.

Young adult patients (16 to 19 years):
Caution should be exercised when treating young adults. Dosage schedules should be calculated according to body weight and commenced at the lower dosage where stated.

Above 60 kg – As above;
30 – 59 kg – 5 mg three times daily.
Doses should not exceed 0.5 mg per kg body weight as a total daily dose.

For diagnostic procedures numbers 6 and 7 :
A single IV dose may be given 10 minutes before the investigation.

Above 60 kg – 10 mg;
30 – 59 kg – 5 mg.

Elderly patients dosage: As for adults. The recommended doses for adults should not be exceeded in the elderly. In particular during long term therapy in the elderly, dosage should be regularly reviewed.

Metoclopramide should be used with caution and in reduced dosage during prolonged therapy in patients with clinically significant degrees of renal or hepatic impairment. Metoclopramide is metabolised in the liver and the predominant route of elimination of metoclopramide and its metabolites is via the kidney.

Adverse effects

Blood and lymphatic system disorders

– Very rare cases of red cell disorders such as methaemoglobinaemia (which could be related to NADH cytochrome b5 reductase deficiency particularly in neonates) and sulphaemoglobinaemia have been reported, particularly at high doses of metoclopramide, and may be more severe in patients with G6PD deficiency. Metoclopramide should be withdrawn and appropriate treatment instituted.

Immune system disorders

– Very rarely, hypersensitivity, including anaphylaxis, bronchospasm and cutaneous reactions, has been reported (see also Skin and subcutaneous tissue disorders)

Endocrine disorders

– Raised prolactin levels, resulting in galactorrhoea, irregular menstrual periods and gynaecomastia may occur during metoclopramide therapy.

Psychiatric disorders

– Rare cases of confusion, restlessness, anxiety and depression have been reported.

Nervous system disorders

– Metoclopramide may cause extrapyramidal reactions such as acute dystonia and dyskinesia, parkinsonian syndrome, akathisia, even following administration of a single dose of the drug, particularly in children and young adults (see Section 4.4.). These reactions may occur following single or low dose regimes, but are more likely if the dose of metoclopramide is above 500 micrograms per kg body weight. Dystonic reactions include: spasm of the facial muscles, trismus, rhythmic protrusion of the tongue, a bulbar type of speech, spasm of the extra-ocular muscles including oculogyric crises, unnatural positioning of the head and shoulders and opisthotonos. Extrapyramidal reactions generally occur within 24 – 48 hours of starting treatment, and the effects usually disappear within 24 hours of withdrawal of the drug.
Should treatment of a dystonic reaction be required, an anticholinergic anti-Parkinson drug, or a benzodiazepine may be used.

– Chronic tardive dyskinesia, which may be irreversible, has developed in patients receiving long term therapy with metoclopramide. This occurs most commonly in geriatric patients (particularly women) and usually develops following discontinuation of the drug. It is manifested by orobuccolingual dyskinetic movements. Patients on prolonged therapy should be regularly reviewed. Very rare occurrences of neuroleptic malignant syndrome have been reported. This syndrome is potentially fatal and comprises hyperpyrexia, altered consciousness, muscle rigidity, autonomic instability and elevated levels of creatine phosphokinase (CPK) and must be treated urgently (recognised treatments include dantrolene and bromocriptine). Metoclopramide should be stopped immediately if this syndrome occurs.

– Drowsiness, fatigue and dizziness may occur (rare).

Cardiac disorders

– Very rare reports of abnormalities of cardiac conduction (bradycardia, asystole, heart block) have been reported following intravenous administration.

Vascular disorders

– Transient hypotension followed by compensatory tachycardia may occur.

– Hypertensive crises have occurred in patients with phaeochromocytomas given metoclopramide.

Gastrointestinal disorders

– Diarrhoea

Skin and subcutaneous tissue disorders

– Skin reactions such as rash, pruritus, angioedema and urticaria.

General and Administration Site Disorders

– Very rare reports of injection site inflammation and local phlebitis have been received.

Contraindications
Metoclopramide is contraindicated in neonates.

Hypersensitivity to metoclopramide or any of the ingredients.

Metoclopramide should not be used where gastro intestinal conditions might be adversely affected, as in intestinal obstruction, perforation or haemorrhage or immediately after surgery.

Other underlying causes of vomiting such as cerebral irritation should be excluded as use of metoclopramide may mask such symptoms.

Metoclopramide should be avoided in patients with phaeochromocytoma as concurrent administration may precipitate hypertensive crises.

Metoclopramide should not be used during breast feeding .

Overdosage

Symptoms of metoclopramide overdose are generally self-limiting and usually subside within 24 hours. Haemodialysis or peritoneal dialysis is unlikely to enhance the elimination of metoclopramide.

Treatment of metoclopramide overdosage, generally involves symptomatic and supportive care. There is no specific antidote for metoclopramide; however, agents with central anticholinergic activity (e.g. diphenhydramine, benztropine) may be useful in extrapyramidal reactions (benzodiazepines in children). The patient should be treated with gastric lavage.

Precautions

Extrapyramidal disorders may occur, particularly in children and young adults and/or when high doses are used

Respect the time interval (at least 6 hours) specified for children in the dosage section between each metoclopramide administration, even in case of vomiting, in order to avoid overdose.

Metoclopramide should be used in caution in patients with hepatic and renal impairment and in the elderly, young adults and children. Special care should be taken in cases of severe renal and hepatic insufficiency Metoclopramide should be used with caution in patients with hypertension, since there is limited evidence that the drug may increase circulating catecholamines in such patients. The frequency and severity of seizures may be increased by metoclopramide, in patients with a history of seizure disorders. Metoclopramide should only be given with great caution in patients receiving drugs that are likely to cause extrapyramidal reactions (e.g. phenothiazines, butyrophenones), since the frequency and severity of these reactions may be increased by metoclopramide especially in children / young adults.

The neuroleptic malignant syndrome has been reported with metoclopramide in combination with neuroleptics as well as with metoclopramide monotherapy.

Metoclopramide should be used with care in combination with other serotonergic drugs including SSRIs.

Metoclopramide may mask symptoms underlying conditions such as cerebral irritation and pregnancy.

Care should be exercised when using metoclopramide in patients with a history of atopy (including asthma) or porphyria.

Care should be exercised in epileptic patients and patients being treated with other centrally acting drugs.

Because metoclopramide can stimulate gastro-intestinal mobility, the drug theoretically could produce increased pressure on the suture lines following gastro-intestinal anastomosis or closure.

Effects on ability to drive and use machines
– Metoclopramide may cause side effects including drowsiness, dyskinesia, dystonias and visual disturbances which could interfere with the ability to drive or operate machinery.

Pregnancy and breastfeeding

Pregnancy

There is no adequate clinical experience with carvedilol in pregnant women.

Animal studies are insufficient with respect to effects on pregnancy, embryonal/foetal development, parturition and postnatal development. The potential risk for humans is unknown.Carvedilol should not be used during pregnancy unless the potential benefit outweighs the potential risk.Beta blockers reduce placental perfusion, which may result in intrauterine foetal death, and immature and premature deliveries. In addition, adverse effects (especially hypoglycaemia and bradycardia) may occur in the foetus and neonate. There may be an increased risk of cardiac and pulmonary complications in the neonate in the postnatal period. Animal studies have not shown substantive evidence of teratogenicity with carvedilol

Lactation

Animal studies demonstrated that carvedilol or its metabolites are excreted in breast milk. It is not known whether carvedilol is excreted in breast milk. Breast feeding is therefore not recommended during administration of carvedilol.

Drug interactions

Metoclopramide may affect the absorption of other drugs, either by diminishing absorption from the stomach or by enhancing the absorption from the small intestine (e.g. the effects of paracetamol and aspirin are enhanced). The effects of CNS depressants may be enhanced.

Metoclopramide may increase the absorption of ciclosporin and raise its blood levels.

The action of metoclopramide on the gastro-intestinal tract is antagonised by anticholinergics and opioid analgesics.

Since metoclopramide may cause extrapyramidal reactions, care should be taken when using in combination with other drugs with similar effects (e.g. phenothiazines, butyrophenones, tetrabenazine). The effects of anti-Parkinson agents such as levodopa, amantadine, pergolide and ropinirole may be reduced.

Metoclopramide may antagonise the hypoprolactinaemic effect of prolactin, and medications such as bromocriptine and cabergoline.

The use of metoclopramide with serotonergic drugs may increase the risk of serotonin syndrome.

Metoclopramide may reduce plasma concentrations of atovaquone.

Metoclopramide enhances the neuromuscular blocking effects of suxamethonium.

Identification

Clear colorless solution.

Presentation

5 ampoules with 2 ml sterile solution in PVC- container. 2 containers with leaflet inserted in cardboard box.

Expiry date

3 years. Do not use after the expiration date.

Prescription status

To be dispensed without prescription.

Storage conditions

Store at a room temperature, in a dry place, out of the reach of children. Protect from light.