Maxolon 10 mg tablets

SmPC section 2, 4.2, 4.7, 4.8, 5.1, 5.2 and 6.6 has been updated

SmPC section 2, 4.2, 4.7, 4.8, 5.1, 5.2 and 6.6 has been updated

Section 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 5.2 an 10 of the SPC has been updated.

Section 4.1, 4.2, 4.3, 4.4, 4.5, 4.6, 4.7, 4.8, 4.9 5.2 an 10 of the SPC has been updated.

In section 4.1 (Therapeutic Indications) the words ’20 years and over’ have been deleted from the dose given in adults. The paragraph (sub headed ‘Young Adults and Adults’) detailing dosing in young adults and children has also been deleted.

 

In section 4.2 (Posology and method of administration) in Dosage and administration - the sentence beginning ‘It should be noted that total daily dosage of Maxolon, especially for children and young adults’ has been deleted.

 

In section 4.2 in Medical Indications – in the dose for adults the phrase ‘For patients of less than 60kg see below’ has been deleted.

 

In section 4.2 the section with doses in young adults and children has been deleted.

 

In section 4.2 the following statement has been added:

‘Paediatric population including adolescents:

Use in the paediatric population is not recommended.’

 

In section 4.3 (Contraindications)  the following statement has been added:

‘Maxolon’ is contraindicated in neonates.

 

In section 4.4 (Special warnings) the following statement has been added:

‘Extrapyramidal disorders may occur, particularly in children and young adults and/or when high doses are used (see 4.8. undesirable effects).

 

In section 4.8 (Undesirable effects) the following statements (underlined) have been added under the sub headings below:

 

Blood and lymphatic system disorders:

Extremely 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.

 

Nervous system disorders:

The statement ‘Various extrapyramidal reactions to 'Maxolon', usually of the dystonic type, have been reported’ has been replaced with Extrapyramidal 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.). 

 

In section 4.9 (Overdose) the statement has been updated to reflect a warning for extrapyramidal reactions.

 

In section 10 the date has been updated to July 2012

In section 4.1 (Therapeutic Indications) the words ’20 years and over’ have been deleted from the dose given in adults. The paragraph (sub headed ‘Young Adults and Adults’) detailing dosing in young adults and children has also been deleted.

 

In section 4.2 (Posology and method of administration) in Dosage and administration - the sentence beginning ‘It should be noted that total daily dosage of Maxolon, especially for children and young adults’ has been deleted.

 

In section 4.2 in Medical Indications – in the dose for adults the phrase ‘For patients of less than 60kg see below’ has been deleted.

 

In section 4.2 the section with doses in young adults and children has been deleted.

 

In section 4.2 the following statement has been added:

‘Paediatric population including adolescents:

Use in the paediatric population is not recommended.’

 

In section 4.3 (Contraindications)  the following statement has been added:

‘Maxolon’ is contraindicated in neonates.

 

In section 4.4 (Special warnings) the following statement has been added:

‘Extrapyramidal disorders may occur, particularly in children and young adults and/or when high doses are used (see 4.8. undesirable effects).

 

In section 4.8 (Undesirable effects) the following statements (underlined) have been added under the sub headings below:

 

Blood and lymphatic system disorders:

Extremely 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.

 

Nervous system disorders:

The statement ‘Various extrapyramidal reactions to 'Maxolon', usually of the dystonic type, have been reported’ has been replaced with Extrapyramidal 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.). 

 

In section 4.9 (Overdose) the statement has been updated to reflect a warning for extrapyramidal reactions.

 

In section 10 the date has been updated to July 2012

The following changes have been made to the SPC based upon a product licence renewal (01-2009) and PSUR (04-2009) recommendation for update. All changes are noted in bold type under section headings below, which include added text, removed text, and as useful, unchanged text in non-bold to better show changed text.

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains metoclopramide hydrochloride equivalent to 10 mg of the anhydrous substance.

 

            Excipients: Contains Lactose Monohydrate to 125.0mg

 

For a full list of excipients, see section 6.1.

 

3.         PHARMACEUTICAL FORM

 

Tablet

 

White to off-white, round, convex, tablets with a breakline on one side enabling the tablet to be divided into equal halves. The other side is and engraved ‘Maxolon’. on the other.

 

 

4.1       Therapeutic indications

 

Adults 20 years and over:

                                                                                                                                                      

1)      Disorders of the gastrointestinal tract associated with delayed gastric emptying e.g. reflux oesophagitis, hiatus hernia, post-vagotomy syndrome.

 

2)      Nausea and vomiting associated with gastrointestinal disorders, administration of some cytotoxic drugs, congestive heart failure and radiotherapy.

 

3)      Diagnostic procedures e.g. barium studies and duodenal intubations.

 

4)      To counteract gastric stasis associated with attacks of migraine and assist absorption of orally administered analgesics for that condition.

 

Young adults and children:

 

The use of Maxolon in patients under 20 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 gastrointestinal intubation and as part of the pre-medication before surgical procedures.

         

4.3       Contraindications

 

‘Maxolon’ should not be used in patients with phaeochromocytoma as it may induce an acute hypertensive response.

Use in patients with phaeochromocytoma, as an acute hypertensive response may be induced.

 

‘Maxolon’ should not be used Use 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.

Use in presence of gastrointestinal haemorrhage, mechanical obstruction or perforation.

 

Use in patients with a previous history of hypersensitivity to metoclopramide or excipients.

 

4.4       Special warnings and special precautions for use

 

Special care should be taken when administering 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.

 

This productMaxolon 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 metoclopramide and phenothiazines and tetrabenazine, care should be exercised when both are used concurrently.

 

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.

 

4.6       Pregnancy and lactation

 

Animal tests in several mammalian species and clinical experience have not indicated a teratogenic effect.  Nevertheless ‘Maxolon’ should only be used when there are compelling reasons and is not advised during the first trimester.

 

During lactation metoclopramide is found in breast milk, therefore it should not be used during lactation.

                                                                                                                                         This product should not be used in pregnancy and lactation unless considered absolutely essential by the physician.

 

Metoclopramide is excreted in breast milk and should not be given to nursing mothers.

 

4.7       Effects on ability to drive and use machines

 

‘Maxolon’ may cause drowsiness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery.

None, but see 4.8.

 

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

Use of this drug may increase extrapyramidal side effects, including facial spasm, trismus, rhythmic protrusion of the tongue, a bulbar type of speech, spasm of extra ocular muscles including oculogyric crises, unnatural positioning of head and shoulders.

 

Very rarely hypersensitivity, including anaphylaxis, has been reported.

 

Rarely diarrhoea, drowsiness, restlessness, confusion and anxiety have been reported in patients receiving metoclopramide therapy.  Depression has been reported extremely rarely. 

 

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 CPK and must be treated urgently (recognised treatments include dantrolene and bromocriptine).  Metoclopramide should be stopped immediately if this syndrome occurs.

 

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.

 

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.

                                                                                                                                         Anaphylactic reactions, angioedema, urticaria and rash have been reported very rarely.

 

Acute hypertension may occur in patients with phaeochromocytoma (see section 4.3 Contraindications).

 

5.1       Pharmacodynamic properties

 

The action of metoclopramide is closely associated with parasympathetic nervous control of the upper gastrointestinal tract, where it has the effect of encouraging normal peristaltic action. Metoclopramide is a benzamide derivative which acts peripherally to enhance cholinergic action at muscarinic synapses and in the central nervous system to antagonise dopamine. This provides for a fundamental approach to the control of those conditions where disturbed gastrointestinal motility is a common underlying factor.

 

5.2       Pharmacokinetic properties

                                                                                                                                         Absorption from the gut gastrointestinal tract is rapid. The drug undergoes significant first-pass hepatic metabolism.  It is excreted in the urine as unchanged drug and metabolites in both free and conjugated form.  The drug is also excreted in breast milk.

 

10.       DATE OF REVISION OF THE TEXT

 

            April 2009

The following changes have been made to the SPC based upon a product licence renewal (01-2009) and PSUR (04-2009) recommendation for update. All changes are noted in bold type under section headings below, which include added text, removed text, and as useful, unchanged text in non-bold to better show changed text.

 

2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains metoclopramide hydrochloride equivalent to 10 mg of the anhydrous substance.

 

            Excipients: Contains Lactose Monohydrate to 125.0mg

 

For a full list of excipients, see section 6.1.

 

3.         PHARMACEUTICAL FORM

 

Tablet

 

White to off-white, round, convex, tablets with a breakline on one side enabling the tablet to be divided into equal halves. The other side is and engraved ‘Maxolon’. on the other.

 

 

4.1       Therapeutic indications

 

Adults 20 years and over:

                                                                                                                                                      

1)      Disorders of the gastrointestinal tract associated with delayed gastric emptying e.g. reflux oesophagitis, hiatus hernia, post-vagotomy syndrome.

 

2)      Nausea and vomiting associated with gastrointestinal disorders, administration of some cytotoxic drugs, congestive heart failure and radiotherapy.

 

3)      Diagnostic procedures e.g. barium studies and duodenal intubations.

 

4)      To counteract gastric stasis associated with attacks of migraine and assist absorption of orally administered analgesics for that condition.

 

Young adults and children:

 

The use of Maxolon in patients under 20 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 gastrointestinal intubation and as part of the pre-medication before surgical procedures.

         

4.3       Contraindications

 

‘Maxolon’ should not be used in patients with phaeochromocytoma as it may induce an acute hypertensive response.

Use in patients with phaeochromocytoma, as an acute hypertensive response may be induced.

 

‘Maxolon’ should not be used Use 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.

Use in presence of gastrointestinal haemorrhage, mechanical obstruction or perforation.

 

Use in patients with a previous history of hypersensitivity to metoclopramide or excipients.

 

4.4       Special warnings and special precautions for use

 

Special care should be taken when administering 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.

 

This productMaxolon 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 metoclopramide and phenothiazines and tetrabenazine, care should be exercised when both are used concurrently.

 

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.

 

4.6       Pregnancy and lactation

 

Animal tests in several mammalian species and clinical experience have not indicated a teratogenic effect.  Nevertheless ‘Maxolon’ should only be used when there are compelling reasons and is not advised during the first trimester.

 

During lactation metoclopramide is found in breast milk, therefore it should not be used during lactation.

                                                                                                                                         This product should not be used in pregnancy and lactation unless considered absolutely essential by the physician.

 

Metoclopramide is excreted in breast milk and should not be given to nursing mothers.

 

4.7       Effects on ability to drive and use machines

 

‘Maxolon’ may cause drowsiness, dyskinesia and dystonias which could affect the vision and also interfere with the ability to drive and operate machinery.

None, but see 4.8.

 

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

Use of this drug may increase extrapyramidal side effects, including facial spasm, trismus, rhythmic protrusion of the tongue, a bulbar type of speech, spasm of extra ocular muscles including oculogyric crises, unnatural positioning of head and shoulders.

 

Very rarely hypersensitivity, including anaphylaxis, has been reported.

 

Rarely diarrhoea, drowsiness, restlessness, confusion and anxiety have been reported in patients receiving metoclopramide therapy.  Depression has been reported extremely rarely. 

 

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 CPK and must be treated urgently (recognised treatments include dantrolene and bromocriptine).  Metoclopramide should be stopped immediately if this syndrome occurs.

 

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.

 

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.

                                                                                                                                         Anaphylactic reactions, angioedema, urticaria and rash have been reported very rarely.

 

Acute hypertension may occur in patients with phaeochromocytoma (see section 4.3 Contraindications).

 

5.1       Pharmacodynamic properties

 

The action of metoclopramide is closely associated with parasympathetic nervous control of the upper gastrointestinal tract, where it has the effect of encouraging normal peristaltic action. Metoclopramide is a benzamide derivative which acts peripherally to enhance cholinergic action at muscarinic synapses and in the central nervous system to antagonise dopamine. This provides for a fundamental approach to the control of those conditions where disturbed gastrointestinal motility is a common underlying factor.

 

5.2       Pharmacokinetic properties

                                                                                                                                         Absorption from the gut gastrointestinal tract is rapid. The drug undergoes significant first-pass hepatic metabolism.  It is excreted in the urine as unchanged drug and metabolites in both free and conjugated form.  The drug is also excreted in breast milk.

 

10.       DATE OF REVISION OF THE TEXT

 

            April 2009