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MORPHINE SULPHATE 30MG/ML SOLUTION FOR INJECTION

Active substance: MORPHINE SULPHATE

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MORPHINE SULPHATE SOLUTION FOR INJECTION
INFORMATION FOR PATIENTS

a pre-medication before operations.
BEFORE ADMINISTRATION OF THIS MEDICINE
Morphine Sulphate Injection should not be administered if:





Please read this leaflet carefully before this medicine is
administered. It gives an outline of the more important
things you should know. If you want to know more about this
medicine, or you are not sure about anything, ask your doctor or
pharmacist. You should keep this leaflet throughout your course
of treatment.
THE NAME OF YOUR MEDICINE IS MORPHINE SULPHATE
SOLUTION FOR INJECTION
Morphine Sulphate Solution for Injection contains the active
ingredient Morphine Sulphate. The injection is available in
three strengths, 10mg/ml (10mg of active ingredient in 1ml
of solution), 15mg/ml (15mg of active ingredient in 1ml of
solution) and 30mg/ml (30mg of active ingredient in 1ml of
solution).
Other ingredients in your injection are water for injections,
sodium metabisulphite (E223), hydrochloric acid and sodium
hydroxide.
Morphine Sulphate Solution for Injection is a colourless or
almost colourless solution, practically free from particles.
Morphine Sulphate 10mg/ml Solution for Injection is available in
cartons containing 5 × 1ml glass ampoules and 10 × 1ml glass
ampoules.
Morphine Sulphate 15mg/ml Solution for Injection is available in
cartons containing 5 × 1ml glass ampoules and 10 × 1ml glass
ampoules.
Morphine Sulphate 30mg/ml Solution for Injection is available
in cartons containing 5 × 1ml glass ampoules and 10 × 1ml
glass ampoules. It is also available in cartons containing 5 x 2ml
ampoules.
Marketing Authorisation Holder: Wockhardt UK Ltd, Ash
Road North, Wrexham Industrial Estate, Wrexham LL13 9UF,
UK.
Manufacturer: CP Pharmaceuticals Ltd, Ash Road North,
Wrexham, LL13 9UF, UK.
HOW DOES YOUR MEDICINE WORK?
Morphine sulphate belongs to a group of medicines called opioid
analgesics which relieve pain.







You have ever had a reaction or been told that you
are allergic to morphine sulphate or any of the other
ingredients in the injection. Check by reading the list of
ingredients above.
You have severe breathing problems.
You are suffering from acute alcohol poisoning.
You have head injuries or raised intracranial pressure
(increased pressure in the skull).
The patient is in a coma.
You have severe stomach cramps caused by a condition
known as biliary colic.
You are at risk from blocked intestine.
You are suffering from severe diarrhoea caused by an
antibiotic or a poison.
You have been told you have phaeochromocytoma (a
problem with your adrenal gland).

Before this medicine is administered, you should let your doctor
know if :












You are pregnant or breast-feeding or planning to become
pregnant or start breast-feeding.
You suffer from asthma. If your asthma is controlled
you can receive the medicine but it should be used
with care. You should not be given this medicine if you
are having an acute asthma attack.
You suffer from bronchitis, emphysema, cor-pulmonale
(a type of heart failure), severe obesity or a severely
deformed spine.
You have a tendency to abuse drugs or have ever
suffered from drug abuse.
You suffer from bowel disease such as Crohn’s disease
or ulcerative colitis.
You have low blood pressure, are in a state of severe
shock or very run down.
You have an under-active thyroid or adrenal gland.
You have liver or biliary disease or kidney problems.
You suffer from an enlarged prostate or have difficulty
passing water.
You suffer from convulsions (fits).

If the injection makes you feel drowsy, do not drive or operate
machinery.
Taking another medicine when morphine sulphate is
administered can affect how it or the other medicine
works. Make sure that your doctor knows what
other medicines you are taking. Do not take any
other medicines when morphine sulphate is being
administered unless you have told your doctor or
pharmacist and asked their advice. This includes
medicines you may have bought yourself.
Examples of medicines that can affect morphine sulphate are:


WHAT IS MORPHINE SULPHATE FOR?

Monoamine oxidase inhibitors (MAOIs), such as
moclobemide or phenelzine, used in the treatment
of depression.
Tricyclic antidepressants, such as dothiepin, used in
the treatment of depression.

Morphine Sulphate Solution for Injection is used for the relief of
severe pain and difficulty in breathing due to pulmonary oedema
(waterlogging of the lungs due to heart failure). It is also used as



SUMMARY OF PRODUCT CHARACTERISTICS

tract disorders morphine may exacerbate pain (use in biliary colic
is a contraindication, see 4.3). In patients given morphine after
cholecystectomy, biliary pain has been induced.
Caution is advised when giving morphine to patients with impaired liver
function due to its hepatic metabolism (see 4.2 Posology).
Severe and prolonged respiratory depression has occurred in patients
with renal impairment who have been given morphine (see 4.2
Posology).
Dependence can develop rapidly with regular abuse of opioids but is
less of a problem with therapeutic use. Abrupt withdrawal from persons
physically dependent on them precipitates a withdrawal syndrome, the
severity of which depends on the individual, the drug used, the size and
frequency of the dose and the duration of drug use. Great caution should
be exercised in patients with a known tendency or history of drug abuse.
Dosage should be reduced in elderly and debilitated patients (see 4.2
Posology).
Palliative care - in the control of pain in terminal illness, these conditions
should not necessarily be a deterrent to use.

1


NAME OF THE MEDICINAL PRODUCT
Morphine Sulphate Solution for Injection

2




QUALITATIVE AND QUANTITATIVE COMPOSITION
Morphine Sulphate 10mg/ml
Morphine Sulphate 15mg/ml
Morphine Sulphate 30mg/ml



For full list of excipients, see 6.1.

3


PHARMACEUTICAL FORM
Solution for injection

4
CLINICAL PARTICULARS
4.1
Therapeutic indications
The symptomatic relief of severe pain; relief of dyspnoea of left ventricular
failure and pulmonary oedema; pre-operative use.
4.2
Posology and method of administration
Morphine Sulphate may be given by the subcutaneous, intramuscular
or intravenous route. The subcutaneous route is not suitable for
oedematous patients. The dosage should be based on the severity of
the pain and the response and tolerance of the individual patient. The
epidural or intrathecal routes must not be used as the product contains
a preservative.
Adults:
Subcutaneous or intramuscular injection:
10mg every four hours if necessary (the dose may vary from 5-20mg
depending on the individual patient).
Slow intravenous injection (2mg/minute): Quarter to half of
corresponding intramuscular dose not more than four hourly.
Elderly and debilitated patients: The dose should be reduced because
of the depressant effect on respiration. Caution is required.
Children: Use in children is not recommended.
Hepatic impairment: A reduction in dosage should be considered in
hepatic impairment.
Renal impairment: The dosage should be reduced in moderate to
severe renal impairment.
For concomitant illnesses/conditions where dose reduction may be
appropriate see 4.4 Special Warnings and Precautions for use.
4.3
Contraindications
Acute respiratory depression, known morphine sensitivity, biliary colic
(see also biliary tract disorders 4.4 Special Warnings and Precautions),
acute alcoholism. Conditions in which intracranial pressure is raised,
comatose patients, head injuries, as there is an increased risk of
respiratory depression that may lead to elevation of CSF pressure. The
sedation and pupillary changes produced may interfere with accurate
monitoring of the patient. Morphine is also contraindicated where there
is a risk of paralytic ileus, or in acute diarrhoeal conditions associated
with antibiotic-induced pseudomembranous colitis or diarrhoea caused
by poisoning (until the toxic material has been eliminated).
Phaeochromocytoma (due to the risk of pressor response to histamine
release).
4.4
Special warnings and precautions for use
Morphine should be given in reduced doses or with caution to patients
with asthma or decreased respiratory reserve (including cor pulmonale,
kyphoscoliosis, emphysema, severe obesity). Avoid use during an
acute asthma attack (see 4.3 Contraindications). Opioid analgesics in
general should be given with caution or in reduced doses to patients
with hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy,
urethral stricture, hypotension, shock, inflammatory or obstructive bowel
disorders, or convulsive disorders.
Opioids such as morphine should either be avoided in patients with biliary
disorders or they should be given with an antispasmodic.
Morphine can cause an increase in intrabiliary pressure as a result
of effects on the sphincter of Oddi. Therefore in patients with biliary

4.5
Interaction with other medicinal products and other

forms of interaction
Alcohol: enhanced sedative and hypotensive effects.
Anti-arrhythmics: There may be delayed absorption of mexiletine.
Antibacterials: The opioid analgesic papaveretum has been shown
to reduce plasma ciprofloxacin concentration. The manufacturer of
ciprofloxacin advises that premedication with opioid analgesics be
avoided.
Antidepressants, anxiolytics, hypnotics: Severe CNS excitation or
depression (hypertension or hypotension) has been reported with the
concurrent use of pethidine and monoamine oxidase inhibitors (MAOIs)
including selegiline, moclobemide and linezolid. As it is possible that
a similar interaction may occur with other opioid analgesics, morphine
should be used with caution and consideration given to a reduction in
dosage in patients receiving MAOIs.
The sedative effects of morphine (opioid analgesics) are enhanced when
used with depressants of the central nervous system such as hypnotics,
anxiolytics, tricyclic antidepressants and sedating antihistamines.
Antipsychotics: possible enhanced sedative and hypotensive effect.
Antidiarrhoeal and antiperistaltic agents (such as loperamide and kaolin):
concurrent use may increase the risk of severe constipation.
Antimuscarinics: agents such as atropine antagonise morphine-induced
respiratory depression and can partially reverse biliary spasm but are
additive to the gastrointestinal and urinary tract effects. Consequently,
severe constipation and urinary retention may occur during intensive
antimuscarinic-analgesic therapy.
Metoclopramide and domperidone: There may be antagonism of the
gastrointestinal effects of metoclopramide and domperidone.
4.6
Pregnancy and lactation
Morphine sulphate should only be used when benefit is known to
outweigh risk. As with all drugs it is not advisable to administer morphine
during pregnancy.
Morphine crosses the placental barrier. Administration during labour may
cause respiratory depression in the new born infant and gastric stasis
during labour, increasing the risk of inhalation pneumonia. Therefore, it
is not advisable to administer morphine during labour.
Babies born to opioid-dependent mothers may suffer withdrawal
symptoms including CNS hyperirritability, gastrointestinal dysfunction,
respiratory distress and vague autonomic symptoms including yawning,
sneezing, mottling and fever.
While morphine can suppress lactation, the quantity from therapeutic
doses that may reach the neonate via breast milk is probably insufficient
to cause major problems of dependence or adverse effects.
4.7
Effects on ability to drive and use machines
Morphine causes drowsiness so patients should avoid driving or
operating machinery.
Undesirable effects
4.8
The most serious hazard of therapy is respiratory depression (see also
4.9 Overdose).
Morphine Injection contains sodium metabisulphite, which may rarely
cause severe hypersensitivity reactions and bronchospasm.
The commonest side-effects of morphine are nausea, vomiting,
constipation, drowsiness and dizziness. Tolerance generally develops
with long term use, but not to constipation.
Other side effects include the following:
Anaphylaxis: Anaphylactic reactions following intravenous injection have
been reported rarely.











Some medicines used to treat anxiety and insomnia
such as diazepam, nitrazepam and temazepam.
Some antihistamines, used to treat allergies, hayfever
and asthma.
Psychotropic drugs taken for other mental problems
like schizophrenia, such as chlorpromazine and
haloperidol.
Certain antibiotics – ciprofloxacin and linezolid, used
to treat infections.
Selegiline, a drug used in the treatment of Parkinson’s
Disease.
Metoclopramide and domperidone, medicines used to
prevent nausea and vomiting.
Medicines used for diarrhoea (e.g. loperamide,
kaolin).
Antimuscarinics, such as atropine, which are used as
pre-medication before operations and during heart
attacks.
Mexiletine, used to control heart rhythm.

If you have any doubts about whether you should be given this
medicine then talk to your doctor.
ADVICE WHEN MORPHINE SULPHATE
SOLUTION FOR INJECTION IS ADMINISTERED





If morphine sulphate injection is used for too long, you
may become dependent on it and find that it no longer
works as well. You may develop withdrawal symptoms
when you stop having the injections.
You should avoid alcohol while having morphine sulphate
injections.
Morphine sulphate can cause drowsiness so you should
not drive or operate machinery after it is given.

ADMINISTRATION OF THIS MEDICINE
The usual adult dose for relief of pain by subcutaneous
injection (an injection underneath the skin) or intramuscular
injection (an injection into a muscle) is 10mg every four hours,
if necessary. However, this can vary between 5mg and 20mg
depending on your size and response to the drug.
For severe pain your doctor may give you a slow intravenous
injection (an injection given slowly into a vein). The usual
dose is quarter to half of the intramuscular dose.

Other side-effects include itching, wheals or skin rashes,
difficulty in passing water, passing less water than usual,
stomach pains, dry mouth, sweating, flushing of the face,
giddiness, slow or rapid pulse, palpitations, low blood pressure
(you may feel faint, especially on standing), mental clouding
or confusion, headache, mood swings, imagining things
(hallucinations), small pupils (in the eye), blurred vision, double
vision or other changes in vision.
Long term use may lead to reduced sexual drive or impotence.
Occasionally the skin where the medicine has been injected
may become irritated or hardened.
Very rarely, intravenous injection (injection into a vein) may
cause a severe allergic reaction.
If you have to be given this injection for a long time, you may
need higher doses and it is possible that you could become
dependent on it and have withdrawal symptoms if it is stopped
suddenly.
If you are given morphine during pregnancy, there is a risk that
the new-born baby may become dependent on it and suffer
from withdrawal symptoms following delivery. If you are given
morphine during labour, there is a risk that you could be sick
and have breathing difficulties, or the baby could have difficulty
starting breathing.
If you experience any other side effects or feel that the medicine
is affecting you badly, tell your doctor or pharmacist.
SAFE KEEPING FOR THIS MEDICINE





This medicine should not be given to you if the expiry date
on the label has passed or if the injection shows signs of
“going off” such as discoloration.
Do not store this injection above 25oC.
Keep this injection in the package or container in which it
was supplied in order to protect from light.
Morphine Sulphate Injection must be kept in a secure
place where children cannot get at it.

DATE OF LAST REVISION

September 2007
101088/3

In general, doses will be reduced if you are elderly or debilitated
or have kidney or liver problems. You may also be given a
reduced dose if you suffer from any of the conditions listed above
in the Section headed “Before this medicine is administered, you
should let your doctor know if:”
Your doctor will decide the dose that is best for you. If you
do not understand what you are being given, or think you are
being given too much morphine, talk to your doctor or nurse.
ARE THERE ANY SIDE-EFFECTS?
Like many medicines Morphine Sulphate Solution for Injection
may cause side-effects in some patients, particularly when
it is first given. The most serious problem is with breathing
which may become shallower. Morphine Injection contains
sodium metabisulphite, which may rarely cause severe
hypersensitivity reactions and bronchospasm. The most
common side-effects that some other patients have had with
Morphine Sulphate Solution for Injection include feeling sick,
being sick, constipation, drowsiness and dizziness.

Cardiovascular: facial flushing bradycardia, palpitations, tachycardia,
orthostatic hypotension.
Central Nervous System: mental clouding, confusion (with large doses),
hallucinations, headache, vertigo, mood changes including dysphoria
and euphoria.
Gastrointestinal: dry mouth, biliary spasm.
Disorders of the eye: blurred or double vision or other changes in vision,
miosis.
Sexual dysfunction: long term use may lead to a reversible decrease in
libido or potency.
Skin: pruritus, urticaria, rash, sweating. Contact dermatitis has been
reported and pain and irritation may occur on injection.
Urinary: difficulty with micturition, ureteric spasm, urinary retention,
antidiuretic effect. Tolerance develops to the effects of opioids on the
bladder.
The euphoric activity of morphine has led to its abuse and physical and
psychological dependence may occur (see also 4.4 Special Warnings
and Precautions).
4.9
Overdose
Toxic doses vary considerably with the individual, and regular users may
tolerate large doses.
The triad of respiratory depression, coma and constricted pupils is
considered indicative of opioid overdosage with dilatation of the pupils
occurring as hypoxia develops. Death may occur from respiratory failure
Other opioid overdose symptoms include hypothermia, confusion, severe
dizziness, severe drowsiness, hypotension, bradycardia, circulatory failure
pulmonary oedema, severe nervousness or restlessness, hallucinations,
convulsions (especially in infants and children). Rhabdomyolysis,
progressing to renal failure, has been reported in overdosage.
Treatment: The medical management of overdose involves prompt
administration of the specific opioid antagonist naloxone if coma or
bradypnoea are present using one of the recommended dosage
regimens. Both respiratory and cardiovascular support should be given
where necessary.
5
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Morphine is obtained from opium, which acts mainly on the CNS and
smooth muscle.
Morphine is a potent analgesic with competitive agonist actions at the
µ-receptor, which is thought to mediate many of its other actions of
µ-receptor,
respiratory depression, euphoria, inhibition of gut motility and physical
dependence. It is possible that analgesia, euphoria and dependence
may be due to the effects of morphine on a µ-1 receptor subtype,
while respiratory depression and inhibition of gut motility may be due
to actions on a µ-2 receptor subtype. Morphine is also a competitive
agonist at theκ-receptor that mediates spinal analgesia, miosis and
sedation. Morphine has no significant actions at the other two major
opioid receptors, theδ- and theσ-receptors.
Morphine directly suppresses cough by an effect on the cough centre in
the medulla. Morphine also produces nausea and vomiting by directly
stimulating the chemoreceptor trigger zone in the area postrema of the
medulla. Morphine provokes the release of histamine.
5.2
Pharmacokinetic properties
Absorption: Variably absorbed after oral administration; rapidly absorbed
after subcutaneous or intramuscular administration.
Blood concentration: After an oral dose of 10mg as the sulphate, peak
serum concentrations of free morphine of about 10ng/ml are attained in
15 to 60 minutes.
After an intramuscular dose of 10mg, peak serum concentrations of 70 to
80ng/ml are attained in 10 to 20 minutes.
After an intravenous dose of 10mg, serum concentrations of about 60ng/
ml are obtained in 15 minutes falling to 30ng/ml after 30 minutes and to
10ng/ml after three hours.
Subcutaneous doses give similar concentrations to intramuscular doses
at 15 minutes but remain slightly higher during the following three hours;
serum concentrations measured soon after administration correlate
closely with the ages of the subjects studied and are increased in the
elderly.
Half-life: Serum half-life in the period ten minutes to six hours following
intravenous administration-two to three hours; serum half-life in the
period six hours onwards-10 to 44 hours.
Distribution: Widely distributed throughout the body, mainly in the
kidneys, liver, lungs and spleen; lower concentrations appear in the brain
and muscles. Morphine crosses the placenta and traces are secreted in
sweat and milk.
Protein binding-about 35% bound to albumin and to immunoglobulins at

concentrations within the therapeutic range.
Metabolic reactions: Mainly glucuronic acid conjugation to form
morphine-3 and 6-glucuronides. N-demethylation, O-methylation and
N-oxide glucuronide formation occurs in the intestinal mucosa and
liver; N-demethylation occurs to a greater extent after oral than parental
administration; the O-methylation pathway to form codeine has been
challenged and codeine and norcodeine metabolites in urine may be
formed from codeine impurities in the morphine sample studied.
Excretion: After an oral dose, about 60% is excreted in the urine in 24
hours, with about 3% excreted as free morphine in 48 hours.
After a parental dose, about 90% is excreted in 24 hours, with about
10% as free morphine, 65 to 70% as conjugated morphine, 1% as
normorphine and 3% as normorphine glucuronide.
After administration of large doses to addicts about 0.1% of a dose is
excreted as norcodeine.
Urinary excretion of morphine appears to be pH dependent to some
extent; as the urine becomes more acidic more free morphine is excreted
and as the urine becomes more alkaline more of the glucuronide
conjugate is excreted.
Up to 10% of a dose may be excreted in the bile.
5.3
Preclinical safety data
There are no pre-clinical data of relevance to the prescriber, which are
additional to those included in other sections.
6
6.1





PHARMACEUTICAL PARTICULARS
List of excipients
Water for injections
Sodium metabisulphite
Sodium hydroxide
Hydrochloric acid

6.2
Incompatibilities
Morphine salts are sensitive to changes in pH and morphine is liable to
be precipitated out of solution in an alkaline environment. Compounds
incompatible with morphine salts include aminophylline and sodium
salts of barbiturates and phenytoin. Other incompatibilities (sometimes
attributed to particular formulations) have included aciclovir sodium,
doxorubicin, fluorouracil, frusemide, heparin sodium, pethidine
hydrochloride, promethazine hydrochloride and tetracyclines. Specialised
references should be consulted for specific compatibility information.
6.3


Shelf life
36 months

6.4
Special precautions for storage
Do not store above 25ºC. Keep container in the outer carton.
6.5



Nature and contents of container
5 x 1ml Type I glass ampoules
10 x 1ml Type I glass ampoules

6.6


Special precautions for disposal
None

7



MARKETING AUTHORISATION HOLDER
Wockhardt UK Ltd, Ash Road North,
Wrexham, LL13 9UF, UK

8




MARKETING AUTHORISATION NUMBER(S)
Morphine Sulphate 10mg/ml Injection – PL 29831/0146
Morphine Sulphate 15mg/ml Injection – PL 29831/0145
Morphine Sulphate 30mg/ml Injection – PL 29831/0147

9





DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
Morphine Sulphate 10mg/ml Injection – 08/05/2007
Morphine Sulphate 15mg/ml Injection – 21/04/2007
Morphine Sulphate 30mg/ml Injection – 16/04/2007

10


DATE OF REVISION OF THE TEXT
September 2007

101088/3

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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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