Blood and lymphatic system disordersExtremely rarely 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. If this occurs the drug should be withdrawn. Methaemoglobinaemia may be treated using methylene blue.
Immune system disordersVery rarely hypersensitivity, including anaphylactic/anaphylactoid reactions, have been reported (including symptoms such as tongue swelling/oedema).
Endocrine disordersRaised serum prolactin levels have been observed during metoclopramide therapy: this may result in galactorrhoea, irregular periods and gynaecomastia.
Psychiatric disordersRarely, restlessness, confusion, agitation and anxiety have been reported in patients receiving metoclopramide therapy. Depression has been reported extremely rarely.
Nervous system disordersExtrapyramidal symptoms: 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.). 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 disordersVisual disturbances have been reported.
Cardiac disordersVery rare reports of abnormalities of cardiac conduction (bradycardia, asystole, heart block, sinus arrest and cardiac arrest) have been reported following intravenous administration.
Vascular disordersAcute hypertension may occur in patients with phaeochromocytoma (see section 4.3 Contraindications). Hypotension has also been reported.
Respiratory , thoracic and mediastinal disordersDyspnoea may occur.
Skin and subcutaneous tissue disordersA small number of skin reactions such as rashes, urticaria, pruritus and angioedema have also been reported.
General disorders and administration site conditionsOedema