MAXOLON TABLETS 10MG

SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Maxolon 10mg Tablets

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains Metoclopramide Hydrochloride BP 10mg equivalent to 10mg of
the anhydrous substance.
Excipients with known effect:
Lactose: contains 125.00 mg of lactose per tablet
For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
White uncoated tablets scored and engraved 'Maxolon'.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adult population
Maxolon is indicated in adults for:
- Prevention of delayed chemotherapy induced nausea and vomiting (CINV)
- Prevention of radiotherapy induced nausea and vomiting (RINV).
- Symptomatic treatment of nausea and vomiting, including acute migraine
induced nausea and vomiting. Metoclopramide can be used in combination
with oral analgesics to improve the absorption of analgesics in acute migraine.
Diagnostic procedures:
Radiology,

Duodenal intubation
'Maxolon' speeds up the passage of a barium meal by increasing the rate of
gastric emptying, co-ordinating peristalsis and dilating the duodenal bulb.
'Maxolon' also facilitates duodenal intubation procedures.
Paediatric population

4.2

Maxolon is indicated in children (aged 1-18 years) for:
- Prevention of delayed chemotherapy induced nausea and vomiting (CINV) as
a second line option
Posology and method of administration
Posology:
Adult patients
The recommended single dose is 10 mg, repeated up to three times daily.
The maximum recommended daily dose is 30 mg or 0.5mg/kg body weight.
The maximum recommended treatment duration is 5 days.
Paediatric population:
The safety and efficacy of Maxolon in children below 1 year has not yet been
established (see section 4.3).
Prevention of delayed chemotherapy induced nausea and vomiting (CINV) (paediatric
patients aged 1-18 years)
The recommended dose is 0.1 to 0.15 mg/kg body weight, repeated up to three times
daily by oral route. The maximum dose in 24 hours is 0.5mg/kg body weight.
Dosing table
Age
1-3 years
3-5 years
5-9 years
9-18 years
15-18 years

Body
Weight
10-14 kg
15-19 kg
20-29 kg
30-60 kg
Over 60kg

Dose

Frequency

1 mg
2 mg
2.5 mg
5 mg
10 mg

Up to 3 times daily
Up to 3 times daily
Up to 3 times daily
Up to 3 times daily
Up to 3 times daily

The maximum treatment duration is 5 days for prevention of delayed chemotherapy
induced nausea and vomiting (CINV).
Tablets are not suitable for use in children weighing less than 61 kg. Other
pharmaceutical forms/strengths may be more appropriate for administration to this
population.
A minimal interval of 6 hours between two administrations is to be respected, even in
case of vomiting or rejection of the dose (see section 4.4).
Special population
Elderly

In elderly patients a dose reduction should be considered, based on renal and hepatic
function and overall frailty.
Patients with Renal impairment:
In patients with end stage renal disease (Creatinine clearance ≤ 15 ml/min), the daily
dose should be reduced by 75%.
In patients with moderate to severe renal impairment (Creatinine clearance 15-60
ml/min), the dose should be reduced by 50% (see section 5.2).
Patients with Hepatic impairment:
In patients with severe hepatic impairment, the dose should be reduced by 50% (see
section 5.2).
Other pharmaceutical forms/strengths may be more appropriate for administration to
these populations.
Diagnostic indications:
A single dose of 'Maxolon' may be given 5-10 minutes before the examination,
subject to body weight consideration, (see above).
Method of administration:
For oral use only.

4.3

Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed in section
6.1
- Gastrointestinal haemorrhage, mechanical obstruction or gastro-intestinal
perforation for which the stimulation of gastrointestinal motility constitutes a risk
- Confirmed or suspected pheochromocytoma, due to the risk of severe hypertension
episodes
- History of neuroleptic or metoclopramide-induced tardive dyskinesia
- Epilepsy (increased crises frequency and intensity)
- Parkinson’s disease
- Combination with levodopa or dopaminergic agonists (see section 4.5)
- Known history of methaemoglobinaemia with metoclopramide or of NADH
cytochrome-b5 deficiency.
- Use in children less than 1 year of age due to an increased risk of extrapyramidal
disorders (see section 4.4)
‘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.

4.4

Special warnings and precautions for use
Precautions:

If vomiting persists the patient should be reassessed to exclude the possibility
of an underlying disorder e.g. cerebral irritation.
Neurological Disorders
Extrapyramidal disorders may occur, particularly in children and young adults,
and/or when high doses are used. These reactions occur usually at the
beginning of the treatment and can occur after a single administration.
Metoclopramide should be discontinued immediately in the event of
extrapyramidal symptoms. These effects are generally completely reversible
after treatment discontinuation, but may require a symptomatic treatment
(benzodiazepines in children and/or anticholinergic anti-Parkinsonian
medicinal products in adults).
The time interval of at least 6 hours specified in the section 4.2 should be
respected between each metoclopramide administration, even in case of
vomiting and rejection of the dose, in order to avoid overdose.
Prolonged treatment with metoclopramide may cause tardive dyskinesia,
potentially irreversible, especially in the elderly. Treatment should not exceed
3 months because of the risk of tardive dyskinesia (see section 4.8). Treatment
must be discontinued if clinical signs of tardive dyskinesia appear.
Neuroleptic malignant syndrome has been reported with metoclopramide in
combination with neuroleptics as well as with metoclopramide monotherapy
(see section 4.8). Metoclopramide should be discontinued immediately in the
event of symptoms of neuroleptic malignant syndrome and appropriate
treatment should be initiated.
Special care should be exercised in patients with underlying neurological
conditions and in patients being treated with other centrally-acting drugs (see
section 4.3)
Symptoms of Parkinson’s disease may also be exacerbated by
metoclopramide.
Methaemoglobinemia
Methemoglobinemia which could be related to NADH cytochrome b5
reductase deficiency has been reported. In such cases, metoclopramide should
be immediately and permanently discontinued and appropriate measures
initiated (such as treatment with methylene blue).
Cardiac Disorders
There have been reports of serious cardiovascular undesirable effects
including cases of circulatory collapse, severe bradycardia, cardiac arrest and
QT prolongation following administration of metoclopramide by injection,
particularly via the intravenous route (see section 4.8).

Special care should be taken when administering metoclopramide, particularly
via the intravenous route to the elderly population, to patients with cardiac
conduction disturbances (including QT prolongation), patients with
uncorrected electrolyte imbalance, bradycardia and those taking other drugs
known to prolong QT interval. Intravenous doses should be administered as a
slow bolus (at least over 3 minutes) in order to reduce the risk of adverse
effects (e.g. hypotension, akathisia).
Renal and Hepatic Impairment
In patients with renal impairment or with severe hepatic impairment, a dose
reduction is recommended (see section 4.2).
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.
Metoclopramide should not be used in the immediate post-operative period (up
to 3-4 days) following pyloroplasty or gut anastomosis, as vigorous
gastrointestinal contractions may adversely affect healing.
Special care should be taken when administering Maxolon intravenously to
patients with “sick sinus syndrome” or other cardiac conduction disturbances.

4.5

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.
Interaction with other medicinal products and other forms of interaction
Contraindicated combination
Levodopa or dopaminergic agonists and metoclopramide have a mutual
antagonism (see section 4.3).
Combination to be avoided
Alcohol potentiates the sedative effect of metoclopramide.
Combination to be taken into account
Due to the prokinetic effect of metoclopramide, the absorption of certain drugs
may be modified.
Anticholinergics and morphine derivatives
Anticholinergics and morphine derivatives may have both a mutual
antagonism with metoclopramide on the digestive tract motility.

Central nervous system depressants (morphine derivatives, anxiolytics,
sedative H1 antihistamines,sedative antidepressants, barbiturates, clonidine
and related)
Sedative effects of Central Nervous System depressants and metoclopramide
are potentiated.
Neuroleptics
Metoclopramide may have an additive effect with other neuroleptics on the
occurrence of extrapyramidal disorders.
Serotonergic drugs
The use of metoclopramide with serotonergic drugs such as SSRIs may
increase the risk of serotonin syndrome.
Digoxin
Metoclopramide may decrease digoxin bioavailability. Careful monitoring of
digoxin plasma concentration is required.
Cyclosporine
Metoclopramide increases cyclosporine bioavailability (Cmax by 46% and
exposure by 22%). Careful monitoring of cyclosporine plasma concentration is
required. The clinical consequence is uncertain.
Mivacurium and suxamethonium
Metoclopramide injection may prolong the duration of neuromuscular block
(through inhibition of plasma cholinesterase).
Strong CYP2D6 inhibitors
Metoclopramide exposure levels are increased when co-administered with
strong CYP2D6 inhibitors such as fluoxetine and paroxetine. Although the
clinical significance is uncertain, patients should be monitored for adverse
reactions.
‘Maxolon’ may reduce plasma concentrations of atovaquone.

4.6

Fertility, pregnancy and lactation
Pregnancy
A large amount of data on pregnant women (more than 1000 exposed
outcomes) indicates no malformative toxicity nor foetotoxicity.
Metoclopramide can be used during pregnancy if clinically needed. Due to
pharmacological properties (as other neuroleptics), in case of metoclopramide
administration at the end of pregnancy, extrapyramidal syndrome in newborn
cannot be excluded.
Metoclopramide should be avoided at the end of pregnancy. If
metoclopramide is used, neonatal
monitoring should be undertaken.
Breastfeeding

Deleted:

¶

Metoclopramide is excreted in breast milk at low level. Adverse reactions in
the breast-fed baby cannot be excluded. Therefore metoclopramide is not
recommended during breastfeeding. Discontinuation of metoclopramide in
breastfeeding women should be considered.
4.7

Effects on ability to drive and use machines
Maxolon has moderate influence on the ability to drive and use machines.
Metoclopramide may cause drowsiness, dizziness, dyskinesia and dystonias
which could affect the vision and also interfere with the ability to drive and
operate machinery.

4.8

Undesirable effects
Adverse reactions listed by System Organ Class. Frequencies are defined
using the following convention: very common (>1/10), common (>1/100 to
<1/10), uncommon (>1/1000 to<1/100), rare (>1/10000 to<1/1000), very rare
(<1/10000), not known (cannot be estimated from the available data).

Frequency
System
Organ
Class
Blood and lymphatic system disorders
Not known

Cardiac disorders
Uncommon
Not known

Endocrine disorders*
Uncommon
Rare
Not known
Gastrointestinal disorders

Adverse reactions

Methaemoglobinaemia, which could
be related to NADH cytochrome b5
reductase deficiency, particularly in
neonates (see section 4.4);
Sulfhaemoglobinaemia, mainly with
concomitant administration of high
doses of sulphur-releasing medicinal
products
Bradycardia, particularly with
intravenous formulation
Cardiac arrest, occurring shortly after
injectable use, and which can be
subsequent to bradycardia (see
section 4.4);
Atrioventricular block, Sinus arrest
particularly with intravenous
formulation;
Electrocardiogram QT prolonged;
Torsade de Pointes;
Amenorrhoea, Hyperprolactinaemia,
Galactorrhoea
Gynaecomastia

Common
Diarrhoea
General disorders and administration site conditions
Common
Asthenia
Immune system disorders
Uncommon
Hypersensitivity
Not known
Anaphylactic reaction (including
anaphylactic shock particularly with
intravenous formulation
Nervous system disorders
Very common
Common

Uncommon
Rare
Not known

Psychiatric disorders
Common
Uncommon
Rare
Vascular disorder
Common:
Not known

Somnolence
Extrapyramidal disorders
(particularly in children and young
adults and/or when the recommended
dose is exceeded, even following
administration of a single dose of the
drug) (see section 4.4), Parkinsonism,
Akathisia
Dystonia, Dyskinesia, Depressed
level of consciousness
Convulsion especially in epileptic
patients
Tardive dyskinesia which may be
persistent, during or after prolonged
treatment, particularly in elderly
patients (see section 4.4), Neuroleptic
malignant syndrome (see section 4.4)
Depression
Hallucination
Confusional state
Hypotension, particularly with
intravenous formulation
Shock, syncope after injectable use,
Acute hypertension in patients with
phaeochromocytoma (see section 4.3)
Transient increase in blood pressure

* Endocrine disorders during prolonged treatment in relation with
hyperprolactinaemia (amenorrhoea, galactorrhoea, gynaecomastia).
The following reactions, sometimes associated, occur more frequently when
high doses are used:
- Extrapyramidal symptoms: acute dystonia and dyskinesia, parkinsonian
syndrome, akathisia, even following administration of a single dose of the
medicinal product, particularly in children and young adults (see section 4.4).
- Drowsiness, decreased level of consciousness, confusion and hallucination.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal
product is important. It allows continued monitoring of the benefit/ risk
balance of the medicinal product. Healthcare professionals are asked to report
any suspected adverse reactions viaYellow Card Scheme Website: www.mhra.gov.uk/yellowcard

4.9

Overdose
Symptoms
Extrapyramidal disorders, drowsiness, decreased level of consciousness,
confusion, hallucination, and cardio-respiratory arrest may occur.
Management
In case of extrapyramidal symptoms related or not to overdose, the treatment
is only symptomatic (benzodiazepines in children and/or anticholinergic antiparkinsonian medicinal products in adults).

A symptomatic treatment and a continuous monitoring of the cardiovascular and
respiratory functions should be carried out according to clinical status.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: A03FA01 (Drugs For Functional Gastrointestinal Disorders- Propulsives)
Mechanism of action
The action of metoclopramide is closely associated with parasympathetic nervous
control of the upper gastro-intestinal tract where it has the effect of encouraging
normal peristaltic action. 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
Metoclopramide is metabolised in the liver and the predominant route of
elimination of metoclopramide and its metabolites is via the kidney.
Renal impairment
The clearance of metoclopramide is reduced by up to 70% in patients with
severe renal impairment, while the plasma elimination half-life is increased
(approximately 10 hours for a creatinine clearance of 10-50 mL/minute and 15
hours for a creatinine clearance <10 mL/minute).
Hepatic impairment

Deleted:

¶

In patients with cirrhosis of the liver, accumulation of metoclopramide has
been observed, associated with a 50% reduction in plasma clearance.

5.3

Preclinical safety data
No additional data available.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Maize starch (dried)
Colloidal silicon dioxide
Magnesium stearate
Pregelatinised maize starch
Lactose.

6.2

Incompatibilities
Not applicable.

6.3

Shelf life
Sixty months.

6.4

Special precautions for storage
Do not store above 30°C

6.5

Nature and contents of container
Standard aluminium containers of 3, 6, 9, 12, 100 or 500 tablets.
Plastic reclosable containers packed into carton of 42, 84, 100 or 500 tablets.

Amber glass bottles of 100 or 500 tablets.
PVC blister (300 microns) of 20, 21, 42 or 84 tablets backed with aluminium foil (20
microns). The underside of the foils is coated with vinyl based laquer.
PVC (200 microns) / PVDC (60gsm) blister of 20, 21, 42 or 84 tablets.
Standard aluminium canister for 12 tablets packed with one ampoule of Maxolon
injection as a home visit pack.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements for disposal.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Amdipharm UK Limited
Capital House, 85 King William Street,
London EC4N 7BL, UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 20072/0048

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
16 June 1995

10

DATE OF REVISION OF THE TEXT
15/09/2016