| To update section 4.3 (Contraindications), 4.4 (Special warnings), 4.5
(Indications) and 4.8 (Undesirable effects) of the SPC and consequently the PIL, following the review of documentation performed during preparation of the
PSUR submitted in August 2008 as noted below in bold text. The SPC is also harmonised with the Irish SPC.
4.3 Contraindications
‘Maxolon’ should not be used in patients with phaeochromocytoma as it may induce an acute hypertensive response.
‘Maxolon’ should not be used in patients suffering from epilepsy, since the frequency and severity of seizures may be increased.
‘Maxolon’ should not be used during the first three to four days following operations such as pyloroplasty or gut anastomosis as vigorous muscular contractions may not help healing.
‘Maxolon’ should not be administered to patients with gastrointestinal obstruction, perforation or haemorrhage.
‘Maxolon’ is contraindicated in patients who have previously shown hypersensitivity to metoclopramide or any of its components.
4.4 Special warnings and special precautions for use
Precautions:
If vomiting persists the patient should be reassessed to exclude the possibility of an underlying disorder e.g. cerebral irritation.
Care should be exercised in patients being treated with other centrally acting drugs.
Risk-benefit should be carefully considered in patients with significant hepatic or renal impairment (loss of conjugation and increased risk of extrapyramidal effects) or with Parkinson’s disease (symptoms may be exacerbated).
The neuroleptic malignant syndrome has been reported with metoclopramide in combination with neuroleptics as well as with metoclopramide monotherapy (see adverse reactions).
Maxolon should be used with care in combination with other serotonergic drugs including SSRIs.
Since extrapyramidal symptoms may occur with both metoclopramide and neuroleptics such as the phenothiazines, particular care should be exercised in the event of these drugs being prescribed concurrently.
Patients receiving this drug for the disorders associated with delayed gastric emptying should be reviewed at an early stage for response to treatment.
Metoclopramide may cause elevation of serum prolactin levels.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency of glucose-galactose malabsorption should not take this medicine.
Care should be exercised when using Maxolon in patients with a history of atopy (including asthma) or porphyria.
Special care should be taken when administering Maxolon intravenously to patients with “sick sinus syndrome” or other cardiac conduction disturbances.
There have been very rare reports of abnormalities of cardiac conduction with intravenous metoclopramide. Maxolon should be used with care with other drugs affecting cardiac conduction.
4.5 Interaction with other medicaments and other forms of interaction
The action of 'Maxolon' on the gastrointestinal tract is antagonised by anticholinergics and opioid analgesics. The absorption of any concurrently administered oral medication may be modified by the effect of 'Maxolon' on gastric motility. Drugs known to be affected in this way include aspirin and paracetamol.
‘Maxolon’ should be used with care in association with other drugs acting at central dopamine receptors, such as levodopa, bromocriptine and pergolide.
Concomitant use of anticholinergic drugs may inhibit the favourable effects on gastrointestinal motility.
Since metoclopramide influences gastrointestinal motility and absorption, the dosage of other drugs used concomitantly may possibly need adjustment.
’Maxolon’ may potentiate the effects of alcohol.
Concomitant use of ‘Maxolon’ with ciclosporin or suxamethonium may increase plasma levels of either ciclosporin or suxamethonium.
Since extrapyramidal reactions may occur with ‘Maxolon’, Phenothiazines and Tetrabenazine, care should be exercised in the event of co-administration of these drugs.
The effects of certain other drugs with potential central stimulant effects, e.g. monoamine oxidase inhibitors and sympathomimetics, may be modified when prescribed with metoclopramide and their dosage may need to be adjusted accordingly.
The use of Maxolon with serotonergic drugs may increase the risk of serotonin syndrome.
‘Maxolon’ may reduce plasma concentrations of atovaquone.
4.8 Undesirable effects
Blood and lymphatic system disorders
Extremely rarely cases of red cell disorders such as methaemoglobinaemia and sulphaemoglobinaemia have been reported, particularly at high doses of metoclopramide. If this occurs the drug should be withdrawn. Methaemoglobinaemia may be treated using methylene blue.
Immune system disorders
Very rarely hypersensitivity, including anaphylactic/anaphylactoid reactions, have been reported (including symptoms such as tongue swelling/oedema).
Endocrine disorders
Raised serum prolactin levels have been observed during metoclopramide therapy: this may result in galactorrhoea, irregular periods and gynaecomastia.
Psychiatric disorders
Rarely, restlessness, confusion, agitation and anxiety have been reported in patients receiving metoclopramide therapy. Depression has been reported extremely rarely.
Nervous system disorders
Various extrapyramidal reactions to 'Maxolon', usually of the dystonic type, have been reported. The incidence of dystonic reactions, particularly in children and young adults, is increased if daily dosages higher than 0.5mg per kg body weight are administered. Dystonic reactions include: spasm of the facial muscles, trismus, rhythmic protrusion of the tongue, a bulbar type of speech, spasm of extra-ocular muscles including oculogyric crises, unnatural positioning of the head and shoulders and opisthotonos. There may be a generalised increase in muscle tone. The majority of reactions occur within 36 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-Parkinsonian drug, or a benzodiazepine may be used.
Tardive dyskinesia, which may be persistent, has been reported as a side effect in elderly patients undergoing long-term therapy with metoclopramide. Prolonged therapy in such patients should be carefully reviewed. The likelihood of the occurrence of this serious effect is increased when neuroleptic agents are used concurrently.
Very rare occurrences of the 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, dizziness and tremor may occur.
Eye disorders
Visual disturbances have been reported.
Cardiac disorders
Very rare reports of abnormalities of cardiac conduction (bradycardia, asystole, heart block, sinus arrest and cardiac arrest) have been reported following intravenous administration.
Vascular disorders
Acute hypertension may occur in patients with phaeochromocytoma (see section 4.3 Contraindications). Hypotension has also been reported.
Respiratory, thoracic and mediastinal disorders
Dyspnoea may occur.
Gastrointestinal disorders
Diarrhoea
Skin and subcutaneous tissue disorders
A small number of skin reactions such as rashes, urticaria, pruritus and angioedema have also been reported.
General disorders and administration site conditions
Oedema
10. DATE OF (PARTIAL) REVISION OF THE TEXT
January 2011
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