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METOCLOPRAMIDE 5MG/ML SOLUTION FOR INFUSION

Active substance(s): METOCLOPRAMIDE HYDROCHLORIDE / METOCLOPRAMIDE HYDROCHLORIDE / METOCLOPRAMIDE HYDROCHLORIDE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Maxolon High Dose
Metoclopramide 5mg/ml Solution for Infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 20ml ampoule contains Metoclopramide Hydrochloride BP equivalent to
100mg of the anhydrous substance.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Clear colourless solution for intravenous infusion.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Adult population
Metoclopramide is indicated in adults for:
- Prevention of post-operative nausea and vomiting (PONV)
- Symptomatic treatment of nausea and vomiting, including acute migraine
induced nausea and vomiting
- Prevention of radiotherapy induced nausea and vomiting (RINV).
Paediatric population

4.2

metoclopramide is indicated in children (aged 1-18 years) for:
- Prevention of delayed chemotherapy induced nausea and vomiting (CINV)
as a second line option
- Treatment of established post-operative nausea and vomiting (PONV) as a
second line option
Posology and method of administration

Posology
All indications (adult population)
For prevention of PONV a single dose of 10mg is recommended.
For the symptomatic treatment of nausea and vomiting, including acute
migraine induced nausea and vomiting and for the prevention of radiotherapy
induced nausea and vomiting (RINV): 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 injectable treatment duration should be as short as possible and transfer to
oral treatment should be made as soon as possible.
Continuous infusion (recommended method):
This medicine is given by IV infusion as a loading dose followed by a
continuous infusion to maintain a metoclopramide serum concentration of 0.85
μg - 1.0μg/ml. The loading dose should be given before starting cytotoxic
chemotherapy.

Loading dose

Maintenance dose

Maxolon 'High
Dose'
(Metoclopramide
Infusion)
2-4 mg/kg body
weight
3-5 mg/kg body
weight

Volume
Of
Diluent
50-100
ml
500 ml

IV
Infusi
on
Time
15-20
minut
es
8-12
hours

Total dosage in any 24 hour period should not normally exceed 10 mg/kg body
weight.
Where cisplatin is to be used the loading dose of this medicine should be at
least 3 mg/kg body weight and the maintenance dose at least 4 mg/kg body
weight.
Intermittent Infusion (alternative regimen)
This medicine can be given by intermittent IV infusion suitably diluted. The
initial dose should be given before starting cytotoxic chemotherapy.
Maxolon 'High Dose'
(Metoclopramide
Infusion)

Volume
Of
Diluent

IV
Infusion
Time

Initial dose

Up to 2 mg/kg body
weight

at least
50 ml

Repeat doses at
2 hourly
intervals

Up to 2 mg/kg body
weight

at least
50 ml

at least
15
minutes
at least
15
minutes

Total dosage in any 24 hour period should not normally exceed 10 mg/kg body
weight.
Special population
Elderly
In elderly patients a dose reduction should be considered, based on renal and
hepatic function and overall frailty.
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 1560 ml/min), the dose should be reduced by 50% (see section 5.2).
Hepatic impairment:
In patients with severe hepatic impairment, the dose should be reduced by
50% (see section 5.2).
Compatibility with cytotoxic agents:
This medicine is compatible with a number of cytotoxic drugs; however it
should not be mixed in solution with therapeutic agents other than those stated.
This medicine is compatible with cisplatin, cyclophosphamide and
doxorubicin hydrochloride and is stable over the concentration ranges listed
below for 24 hours at room temperature when protected from light.
40-200 ml cisplatin (1 mg/ml) per 100 mg/20 ml of this medicine in 1 litre of
sodium chloride 0.9%.
Up to 40 mg doxorubicin hydrochloride (powder) per 100 mg/20 ml of this
medicine.
Up to 4 g cyclophosphamide (1 g/50 ml) per 100 mg/20 ml of this medicine.
Compatibility with morphine/diamorphine:
This medicine is compatible with morphine hydrochloride and diamorphine
hydrochloride and is stable over the concentration ranges listed below for 48
hours at room temperature under normal fluorescent lighting.
Up to 100 mg of morphine hydrochloride per 100 mg/20 ml of this medicine.
Up to 50 mg of diamorphine hydrochloride per 100 mg/20 ml of this medicine.
This medicine 100 mg/20 ml also remains stable for 48 hours at room
temperature with 100 mg of morphine hydrochloride, or 50 mg diamorphine
hydrochloride, when diluted 1 in 10 with sodium chloride 0.9%.
Stability in intravenous fluids:
Ideally intravenous solutions should be prepared at the time of infusion.

However, this medicine has been shown to be stable for at least 48 hours at
room temperature in the following solutions when administered in a PVC
R
infusion bag (e.g. Viaflex Travenol).
Sodium chloride intravenous infusion B.P. (0.9% w/v)
Glucose intravenous infusion B.P. (5% w/v)
Sodium chloride and glucose intravenous infusion B.P. (sodium chloride
0.18% w/v; glucose 4% w/v)
Compound sodium lactate intravenous infusion B.P. (Ringer-lactate solution;
Hartmann’s solution)
Note: preparation must be under appropriate aseptic conditions if the above
extended storage periods are required. The high dose ampoule presentation is
not suitable for multidose use.
Paediatric population:
All indications (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 intravenous route. The maximum dose in 24 hours is 0.5 mg/kg
body weight.
Dosing table
Age

Dose

Frequency

1-3 years

Body
Weight
10-14 kg

1 mg

3-5years

15-19 kg

2 mg

5-9 years

20-29 kg

2.5 mg

9-15
years
15-18
years

30-60 kg

5 mg

Over 60kg

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 48 hours for treatment of established postoperative nausea and vomiting (PONV).
The maximum treatment duration is 5 days for prevention of delayed
chemotherapy induced nausea and vomiting (CINV).
For the treatment of postoperative nausea and vomiting, metoclopramide
should be administered after the termination of the surgical procedure.
The recommended dose is 0.15 mg/kg body weight given as a slow injection
(at least 3 minutes).
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).

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 see section 4.3.
Method of administration
This medicine is administered by IV infusion, suitably diluted. The
recommended method of administration is by continuous infusion which
allows steady serum levels of metoclopramide to be maintained.

4.3

Contraindications










4.4

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)
Special warnings and precautions for use
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).
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.

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
metoclopramide.

disease

may

also

be

exacerbated

by

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).

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).
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.
This medicine should be used with care in combination with other serotonergic
drugs including SSRIs.
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.

4.5

Care should be exercised when using this medicine in patients with a history
of atopy (including asthma) or porphyria.
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). Metoclopramide should be used with care in
association with other drugs acting at central dopamine receptors such as
bromocriptine and pergolide.
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, morphine derivatives and other opioid analgesics
Anticholinergics and morphine derivatives may have both a mutual
antagonism with metoclopramide on the digestive tract motility.
The absorption of aspirin and paracetamol may be modified by the effect of
metoclopramide on gastric motility.
Concomitant use of anticholinergic drugs may inhibit the favourable effects on
gastrointestinal motility.
Since extrapyramidal reactions may occur with this medicine, Phenothiazines
and Tetrabenazine, care should be exercised in the event of co-administration
of these drugs.
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.
Monoamine oxidase inhibitors
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.
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.
Antiprotozoals
This medicine 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.
Breast-feeding
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
Metoclopramide 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,
<1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare
(<1/10000), not known (cannot be estimated from the available data).
System Organ Frequency
Class
Blood and lymphatic system disorders
Not known

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

Cardiac disorders
Uncommon

Not known

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; dyspnoea
Endocrine disorders*
Uncommon

Amenorrhoea,
Hyperprolactinaemia
Galactorrhoea
Gyneacomastia

Rare
Not known
Gastrointestinal disorders
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

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

Uncommon

Dystonia, Dyskinesia, Depressed
level of consciousness

Rare

Convulsion especially in epileptic
patients

Not known

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)

Psychiatric disorders
Common
Uncommon

Depression
Hallucination

Rare
Vascular disorder
Common
Not known

Confusional State
Hypotension, particularly with
intravenous formulation
Shock, syncope after injectable
use, Acute hypertension in
patients with phaechromocytoma
(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, 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 via the Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard.

4.9

Overdose
Symptoms
In cases of overdosage, acute dystonic/extrapyramidal reactions have
occurred. Very rarely AV block has been observed.
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
Pharmacotherapeutic group: Agents stimulating gastro-intestinal motility
ATC Code: A03FA01
This medicine is indicated for the treatment of nausea and vomiting associated
with intolerance to cytotoxic drugs. It is specially formulated to ensure
compatibility in solution with cisplatin.
This medicine exerts a three-fold anti-emetic action: by inhibiting central
dopamine receptors this medicine raises the threshold of the chemoreceptor
trigger zone, and reduces the reaction of the adjacent vomiting centre to
centrally-acting emetics. This medicine decreases the sensitivity of the
visceral afferent nerves to the vomiting centre, reducing the effect of locallyacting emetics and irritant substances. In the upper gastro-intestinal tract this
medicine promotes normal gastric emptying and it may thus abolish gastric
stasis which is part of the vomiting reflex.

5.2

This medicine is not intended for use in the wider range of indications for
which this medicine at standard dose is indicated.
Pharmacokinetic properties
Absorption
Based on current literature, a metoclopramide concentration range of about
0.85µg/ml would appear desirable for the control of cytotoxic drug induced
emesis. Such plasma concentrations may be achieved by the administration of
a loading dose of 2-4 mg/kg infused over 15-30 minutes prior to cytotoxic
drug therapy followed by a maintenance continuous infusion of 3-5 mg/kg
over 8-12 hours.
Biotransformation
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

5.3

In patients with cirrhosis of the liver, accumulation of metoclopramide has
been observed, associated with a 50% reduction in plasma clearance.
Preclinical safety data
No additional data available.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium chloride
Water for injections

6.2

Incompatibilities
Not applicable

6.3

Shelf life
3 years

6.4

Special precautions for storage
If ampoules are removed from their carton, they should be stored away from light. If
inadvertent exposure occurs, ampoules showing discolouration must be discarded.

6.5

Nature and contents of container
Clear glass 20ml ampoules (Ph. Eur. Type I neutral glass) packed in boxes of 10.

6.6

Special precautions for disposal

Protect from light.
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 20072/0052

9

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

10

DATE OF REVISION OF THE TEXT
15/09/2016

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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