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MORPHINE SULPHATE INJECTION BP MINIJET 1MG/ML

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Morphine Sulphate Injection BP MinijetTM
Morphine Sulphate Injection BP Rapiject®

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Morphine Sulphate 1mg/ml
For excipients, see 6.1.

3

PHARMACEUTICAL FORM
Sterile aqueous solution for intravenous, intramuscular or subcutaneous
injection.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For intravenous, intramuscular or subcutaneous injection.
For the relief of moderate to severe pain such as in myocardial infarction,
severe injuries, neoplastic disease, surgery, renal colic, terminal disease and
other conditions where non-narcotic analgesia has failed.
Morphine is effective in the control of post-operative pain and anxiety.
Morphine may be used for its sedative effect in the management of the severe
dyspnoea in terminal lung cancer or other terminal respiratory disease.
Morphine should be used as a sedative or hypnotic generally only when pain
relief and sedation are required. It is used in pre-anaesthetic medication for
surgery, where it reduces anxiety and also the amount of anaesthetic required.
For open-heart surgery, especially in high risk patients with cardiac disease,
morphine may be used to produce anaesthesia.

4.2

Posology and method of administration
The dose and dosing regimen should be tailored to the individual patient’s
needs.
Adults and children over 12 years:
Intramuscular or subcutaneous administration
5 - 20mg every 4 hours as necessary, dependent upon the patient’s response
and cause of pain.
For the relief of pain and as pre-anaesthetic, the usual dose is 10mg every 4
hours depending on the severity of the condition and the patient’s response.

The usual individual dose range is 5 - 15mg. The usual daily dose range is 12 120mg.
Intravenous administration
Acute pain:
2 - 15mg by slow intravenous injection.
or
Loading dose as above, followed by 2.5 - 5mg every hour by infusion. If using
Patient Controlled Analgesia (PCA), bolus doses of 1 - 2mg may be given
with a lock out of 5 - 20 minutes. A commonly applied dose limit used in PCA
is 30mg in 4 hours, although some patients may require higher doses.
or
Frequent small doses (e.g. 1 - 3mg every 5 minutes) reaching a maximum
cumulative dose of 2 - 3mg/kg. (This is the preferred regimen for patients with
myocardial infarction.)
Chronic pain:
Loading doses of 15mg or more. Maintenance doses for infusion are in the
range 0.8 - 80mg/hour, although higher maintenance doses of 150 200mg/hour may be required.
Similar doses have been given by subcutaneous infusion
Open heart surgery:
Large doses (0.5 - 3mg/kg) may be administered intravenously by slow
continuous infusion as the sole anaesthetic agent.
Elderly:
Morphine should be administered with caution in the elderly and a reduced
starting dose titrated to provide optimal pain relief.
Children under 12 years:
Intramuscular or subcutaneous administration:
Up to 1 month: 150mcg/kg every 4 hours
1-12 months:
200mcg/kg every 4 hours
1-5 years:
2.5 - 5mg every 4 hours
6-12 years:
5 - 10mg every 4 hours
Slow intravenous infusion:
Up to 6 months:
up to 10mcg/kg/hour with respiratory support. Bolus
injection to be avoided.
6 months - 12 years: 10-30mcg/kg/hour. A loading dose of 100 - 200mcg/kg
may be given initially with bolus top-up doses of 50 100mcg/kg every 4 hours.
Subcutaneous infusion:
6 months - 12 years: 30 - 60mcg/kg/hour. For the relief of pain in terminal
disease.

4.3

Contraindications
Morphine is contraindicated in patients with obstructive airways disease;
respiratory depression; known morphine sensitivity; sensitivity to any of the
other ingredients; head injuries; coma; convulsive disorders and raised
intracranial pressure; biliary colic; acute alcoholism; cerebral oedema;
concurrent treatment with monoamine oxidase inhibitors or within two weeks
of their discontinuation of treatment with them; phaeochromocytoma, those at
risk of paralytic ileus and in patients with acute diarrhoea caused by poisoning
or invasive pathogens.

4.4

Special warnings and precautions for use
Morphine is a potent medicine but with considerable potential for harmful
effect, including addiction. It should be used only if other drugs with fewer
hazards are inadequate, and with the recognition that it may possibly mask
significant manifestations of disease which should be identified for proper
diagnosis and treatment. It should be used with special caution in patients with
a history of drug abuse. Dependence may occur after 1 - 2 weeks of treatment.
Morphine should be given with caution where there is a reduced respiratory
reserve e.g. in conditions including but not restricted to the following:
emphysema, asthma, chronic cor pulmonale, kyphoscoliosis, excessive obesity
and sleep apnoea. Opiates should also be used cautiously in patients with
cardiac arrhythmias, myasthenia gravis or inflammatory or obstructive bowel
disorders.
Morphine should be administered with caution or in reduced doses to patients
with hypotension, hypothyroidism, adrenocortical insufficiency, impaired
kidney or liver function, prostatic hypertrophy, urethral stricture or shock.
Morphine should be given with great care to infants, especially neonates.
Dosage should be reduced in elderly and debilitated patients.
Disappearance of opioid analgesic effects, particularly when associated with
an unexplained increase in pain, may indicate the development of tolerance or
opioid-induced hyperalgesia. An unexplained increase in abdominal pain
associated with disturbed intestinal motility, symptoms of constipation,
bloating, abdominal distension and increased gastroesophageal reflux during
treatment with morphine sulphate, may indicate the development of opioidinduced bowel dysfunction or narcotic bowel syndrome. In such situations
consider the use of alternative analgesics and a morphine detoxification.

4.5

Interaction with other medicinal products and other forms of interaction
Monoamine oxidase inhibitors markedly potentiate the action of morphine;
morphine should not be administered to patients receiving monoamine oxidase
inhibitors (see section 4.3).
The sedative effects of morphine may be potentiated and prolonged by central
nervous system depressants such as alcohol, anaesthetics, analgesics,
antihistamines, barbiturates, narcotics, phenothiazines, sedatives, anxiolytics,
hypnotics and tricyclic antidepressants.

Chlorpromazine and some other phenothiazines appear to enhance the sedative
action but diminish the analgesic effect of morphine. The use of tricyclic
antidepressants, aspirin and other NSAIDs may increase the extent of pain
relief of morphine. They also increase the risks of adverse effects.
Anticholinergic agents such as atropine antagonise morphine-induced
respiratory depression and can partially reverse biliary spasm but are additive
to the gastro-intestinal and urinary tract effects. Consequently, severe
constipation and urinary retention may occur during intensive anticholinergicanalgesic therapy.
Morphine Sulphate should not be used for pre-medication when ciprofloxacin
is given for surgical prophylaxis as serum levels of ciprofloxacin are reduced
and adequate cover may not be obtained during surgery.

4.6

Fertility, pregnancy and lactation
There is inadequate evidence of safety in human pregnancy. Morphine is
known to cross the placenta and it may cause respiratory depression by this
route. It is not advised to administer morphine during pregnancy or during
labour. It may reduce uterine contractions, cause respiratory depression in the
foetus and neonate, and may have significant effects on the foetal heart rate.
The amount of morphine secreted in breast milk after a single-dose
administration seems to be compatible with breast feeding and insufficient to
cause major problems or dependence. However long-term treatment with
morphine in high doses may cause significant plasma concentration. That is
why caution is advised on the use of morphine in breast-feeding patient and
the benefit must outweigh the risk to the infant. If breast feeding is continued,
the infant should be observed for possible adverse effects.

4.7

Effects on ability to drive and use machines
Morphine may cause drowsiness. Patients receiving morphine should not drive
or operate machinery.

4.8

Undesirable effects

Morphine may cause the following adverse events:
Nervous system disorders:
allodynia, coma, convulsion, drowsiness, headache, increased intracranial pressure,
myoclonus, opioid-induced hyperalgesia (or hyperaesthesia), vertigo
Psychiatric disorders:
confusional state, decreased libido, hallucinations, mood swings, physical and psychological
dependence, restlessness
Eye disorders:
blurred vision, miosis, nystagmus
Respiratory, thoracic and mediastinal disorders:

bronchospasm, pulmonary oedema, which can lead to death, respiratory depression,
respiratory failure, which also can lead to death
Cardiac disorders:
bradycardia, circulatory failure, palpitations, tachycardia
Vascular disorders:
hypotension, orthostatic hypotension
Gastrointestinal disorders:
dry mouth, constipation, intestinal functional disorder, paralytic ileus, narcotic bowel
syndrome, nausea, vomiting
Hepatobiliary disorders:
biliary spasm, hepatic enzyme increase, spasm of the sphincter of Oddi,
Reproductive system and breast disorders:
erectile dysfunction
Renal and urinary disorders:
renal failure, urethral spasm, urinary retention
Immune system disorders:
anaphylactic reaction, hypersensitivity
Musculoskeletal and connective tissue disorders:
muscle rigidity, rhabdomyolysis
Skin and subcutaneous tissue disorders:
angioedema, contact dermatitis, pruritus, rash, urticaria
General disorders and administration site conditions:
drug tolerance, fatigue, facial flushing, hyperhidrosis, hypothermia, injection site pain,
injection site irritation, withdrawal syndrome
Babies born to opioid-dependent mothers also risk to present withdrawal syndrome.
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 at: www.mhra.gov.uk/yellowcard

4.9

Overdose
Symptoms: respiratory depression, pin-point pupils and coma. In addition,
shock, reduced body temperature and hypotension may occur. In mild
overdose, symptoms include nausea and vomiting, tremor, miosis, dysphoria,
hypothermia, hypotension, confusion and sedation. In cases of severe
poisoning, hypotension with circulatory failure, rhabdomyolosis progressing
to renal failure, respiratory collapse and death may occur.

Treatment: the patient must be given respiratory support and the specific
antagonist, naloxone, should be administered at a dose of 0.4 - 2.0mg
intravenously. This dose should be repeated at 2 - 3 minute intervals if
improvement is not achieved, up to a total of 10mg. Fluid and electrolyte
levels should be maintained.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
ATC Code: N02A A01
Morphine is the principle alkaloid of opium and is a potent analgesic. It exerts
its primary effects on the central nervous system and smooth muscle.
Pharmacological effects include analgesia, drowsiness, alteration in mood,
reduction in body temperature, dose-related respiratory depression,
interference with adrenocortical response to stress (at high doses) and a
reduction in peripheral resistance with little or no effect on cardiac index and
miosis. Morphine, as other opioids, acts as an agonist interacting with
stereospecific and saturable binding sites/receptors in the brain, spinal cord
and other tissues.
Morphine acts on the cough centre to suppress coughing and also directly
stimulates the chemoreceptor trigger zone in the medulla to produce nausea
and vomiting. Morphine provokes the release of histamine.

5.2

Pharmacokinetic properties
After subcutaneous or intramuscular injection, morphine is readily absorbed
into the blood. Peak analgesia occurs 50 - 90 minutes after SC injection, 30 60 minutes after IM and 20 minutes after IV infusion. The effect persists for
up to 4 - 5 hours.
Most of the morphine dose is conjugated with glucoronide in the liver (first
pass effect), resulting in morphine-3-glucoronide (inactive) and morphine-6glucuronide (active). Other active metabolites are formed in small amounts.
About 35% of the dose is protein bound. Morphine can cross the placenta and
blood-brain barrier and its metabolites have been detected in the cerebrospinal
fluid. Morphine is distributed throughout the body, mainly into skeletal
muscle, kidneys, liver, intestinal tract, lungs and spleen.
The mean plasma elimination half-life for morphine is 1.5 - 2.0 hours and for
the 3-glucuronide ranges from 2.5 - 7.0 hours.
Approximately 90% of a parenteral dose of morphine appears in the urine
within 24 hours, primarily as the product of glucuronide conjugation with only
a small amount as the unchanged drug. 7 - 10% is excreted in the bile and
eliminated in the faeces.

5.3

Preclinical safety data
Not applicable, since morphine sulphate has been used in clinical practice for
many years and its effects on man are well known.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Disodium edetate
Sulphuric acid (1M; pH adjustment)
Water for Injection

6.2

Incompatibilities
Morphine salts may be precipitated in alkaline solution. Compatibility should
be checked before admixture with other drugs.

6.3

Shelf life
24 months

6.4

Special precautions for storage
Do not store above 25ºC. Protect from light.

6.5

Nature and contents of container
The solution is contained in a Type I USP glass vial with a rubber closure
which meets all the relevant USP specifications for elastomeric closures.
The following volumes are available:
Morphine Sulphate Injection 1mg/ml: 2ml (MinijetTM)
10ml (MinijetTM)
50ml (Rapiject®)

6.6

Special precautions for disposal
The 2ml and 10ml containers are designed for use with the IMS MinijetTM
injector.
The 50ml container is designed for use with a syringe driver.

7

MARKETING AUTHORISATION HOLDER
International Medication Systems (UK) Ltd
208 Bath Road
Slough
Berkshire
SL1 3WE

8

MARKETING AUTHORISATION NUMBER(S)
PL 03265/0037

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
14/03/1978

10

DATE OF REVISION OF THE TEXT
14/08/2015

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