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MST CONTINUS SUSPENSION 60MG

Active substance(s): MORPHINE SULPHATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
MST CONTINUS suspension 60 mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains Morphine equivalent to Morphine Sulfate 60 mg.

Excipients with known effect:
Ponceau 4R (E124)
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Prolonged release granules for oral suspension
Pink granules.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
For the prolonged relief of severe and intractable pain.

4.2

Posology and method of administration
Posology
Adults:
A patient presenting with severe pain, uncontrolled by weaker opioids (e.g.
dihydrocodeine) should normally be started on 30 mg 12 hourly. Patients previously
on normal release oral morphine should be given the same total daily dose as MST
CONTINUS suspension but in divided doses at 12-hourly intervals.
Increasing severity of pain will require an increased dosage of the suspension. Higher
doses should be made, where possible in 30-50% increments as required. The correct
dosage for any individual patient is that which is sufficient to control pain with no, or

tolerable, side effects for a full 12 hours. It is recommended that the 200 mg strength
is reserved for patients who have already been titrated to a stable analgesic dose using
lower strengths of morphine or other opioid preparations.
Patients receiving MST CONTINUS suspension in place of parenteral morphine
should be given a sufficiently increased dosage to compensate for any reduction in
analgesic effects associated with oral administration. Usually such increased
requirement is of the order of 100%. In such patients individual dose adjustments are
required.
Paediatric Population:
The use of MST CONTINUS suspension in children has not been extensively
evaluated. For children with severe cancer pain, a starting dose in the range of 0.2 to
0.8 mg morphine per kg bodyweight 12 hourly is recommended. Doses should then
be titrated as for adults.
Post-operative pain
MST CONTINUS suspension is not recommended in the first 24 hours postoperatively or until normal bowel function has returned; thereafter it is suggested that
the following dosage schedule be observed at the physician's discretion:
(a)
(b)
(c)
(d)

MST CONTINUS suspension 20 mg 12 hourly to patients under 70 kg
MST CONTINUS suspension 30 mg 12 hourly to patients over 70 kg
Elderly - a reduction in dosage may be advisable in the elderly
Children - not recommended

Supplemental parenteral morphine may be given if required but with careful
attention to the total dosages of morphine, and bearing in mind the prolonged
effects of morphine in this controlled release formulation.
Method of Administration
The contents of one sachet should be mixed with at least 10 ml water or sprinkled on
to soft food, for example yogurt.

The prolonged release granules must be suspended whole and ingested
immediately, but not be broken, chewed or crushed. The administration of
broken, chewed or crushed morphine granules leads to a rapid release and
absorption of a potentially fatal dose of morphine (see section 4.9, Overdose).
MST CONTINUS suspension should be used at 12-hourly intervals. The
dosage is dependent upon the severity of the pain, the patient's age and
previous history of analgesic requirements.

4.3

Contraindications
Hypersensitivity to the active substance or to any of excipients listed in section 6.1.

Respiratory depression, head injury, paralytic ileus, 'acute abdomen', delayed gastric
emptying, obstructive airways disease, known morphine sensitivity, acute hepatic
disease, concurrent administration of monoamine oxidase inhibitors or within two
weeks of discontinuation of their use.
Children under one year of age.
Pre-operative administration of MST CONTINUS suspension is not recommended.

4.4

Special warnings and precautions for use
As with all narcotics, a reduction in dosage may be advisable in the elderly, in
hypothyroidism and in patients with significantly impaired renal or hepatic function.
Use with caution in patients with impaired respiratory function, severe bronchial
asthma, convulsive disorders, acute alcoholism, delirum tremens, raised intracranial
pressure, hypotension with hypovolaemia, severe cor pulmonale, patients with a
history of substance abuse, diseases of the biliary tract, pancreatitis, inflammatory
bowel disorders, prostatic hypertrophy, adrenocortical insufficiency and opiate
dependent patients.
Should paralytic ileus be suspected or occur during use, MST CONTINUS
suspension should be discontinued immediately.
Morphine may lower the seizure threshold in patients with a history of epilepsy.
The major risk of opioid excess is respiratory depression.
Patients about to undergo additional pain relieving procedures (e.g. surgery, plexus
blockade) should not receive MST CONTINUS suspension for 24 hours prior to the
intervention. If further treatment with MST CONTINUS suspension is indicated,
then the dosage should be adjusted to the new post-operative requirement.
MST CONTINUS suspension should be used with caution post-operatively, and
following abdominal surgery as morphine impairs intestinal motility and should not
be used until the physician is assured of normal bowel function.
MST CONTINUS suspension is not recommended preoperatively or within the first
24 hours postoperatively.
It is not possible to ensure bio-equivalence between different brands of controlled
release morphine products. Therefore, it should be emphasised that patients, once
titrated to an effective dose, should not be changed from MST CONTINUS
preparations to other slow, sustained or controlled release morphine or other potent
narcotic analgesic preparations without retitration and clinical assessment.
The patient may develop tolerance to the drug with chronic use and require
progressively higher doses to maintain pain control. Prolonged use of this product
may lead to physical dependence and a withdrawal syndrome may occur upon abrupt
cessation of therapy. When a patient no longer requires therapy with morphine, it
may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

Hyperalgesia that will not respond to a further dose of morphine sulfate may very
rarely occur in particular in high doses. A morphine sulfate dose reduction or change
in opioid may be required.
Morphine has an abuse profile similar to other strong agonist opioids. Morphine may
be sought and abused by people with latent or manifest addiction disorders. There is
potential for development of psychological dependence (addiction) to opioid
analgesics, including morphine. The product should be used with particular care in
patients with a history of alcohol and drug abuse.
The contents of the controlled release sachets (granules) must be suspended whole
and drunk immediately after (see section 4.2), but not be broken, crushed or chewed.
The administration of broken, chewed or crushed morphine (granules) leads to a rapid
release and absorption of a potentially fatal dose of morphine (see section 4.9).
Abuse of oral dosage forms by parenteral administration can be expected to result in
serious adverse events, which may be fatal.
Concomitant use of alcohol and MST CONTINUS suspension may increase the
undesirable effects of MST CONTINUS suspension; concomitant use should be
avoided.
The excipient Ponceau 4R may cause allergic reactions.

4.5

Interaction with other medicinal products and other forms of interaction

Morphine potentiates the effects of central nervous system depressants including
tranquillisers, general anaesthetics, phenothiazines, hypnotics, sedatives, muscle relaxants and
antihypertensives. Interactive effects resulting in respiratory depression, hypotension,
profound sedation, or coma may result if these drugs are taken in combination with the usual
doses of morphine.
In a study involving healthy volunteers (N = 12), when a 60 mg controlled-release morphine
capsule was administered 2 hours prior to a 600 mg gabapentin capsule, mean gabapentin
AUC increased by 44% compared to gabapentin administered without morphine. Therefore,
patients should be carefully observed for signs of CNS depression, such as somnolence, and
the dose of gabapentin or morphine should be reduced appropriately.
Alcohol may enhance the pharmacodynamic effects of MST CONTINUS suspension;
concomitant use should be avoided.
Medicinal products that block the action of acetylcholine, for example antihistamines, antiparkinsonians and anti-emetics, may interact with morphine to potentiate anticholinergic
adverse events.
Concurrent administration of antacids may result in a more rapid release of morphine than
otherwise expected; dosing should therefore be separated by a minimum of two hours.
Cimetidine inhibits the metabolism of morphine.
Monoamine oxidase inhibitors are known to interact with narcotic analgesics producing CNS
excitation or depression with hyper- or hypotensive crisis. Morphine should not be co
administered with monoamine oxidase inhibitors or within two weeks of such therapy.

Plasma concentrations of morphine may be reduced by rifampicin.
Although there are no pharmacokinetic data available for concomitant use of ritonavir with
morphine, ritonavir induces the hepatic enzymes responsible for the glucuronidation of
morphine, and may possibly decrease plasma concentrations of morphine.
Mixed agonist/antagonist opioid analgesics (e.g. buprenorphine, nalbuphine, pentazocine)
should not be administered to a patient who has received a course of therapy with a pure
opioid agonist analgesic.

4.6

Fertility, pregnancy and lactation
Pregnancy
MST CONTINUS suspension is not recommended during pregnancy and
labour due to the risk of neonatal respiratory depression.
Breast-feeding
Administration to nursing mothers is not recommended as morphine is excreted in
breast milk. Withdrawal symptoms may be observed in the new born of mothers
undergoing chronic treatment.

4.7

Effects on ability to drive and use machines
Morphine may modify the patient’s reactions to a varying extent depending on the
dosage and susceptibility. If affected, patients should not drive or operate machinery.

This medicine can impair cognitive function and can affect a patient’s ability to
drive safely. This class of medicine is in the list of drugs included in regulations
under 5a of the Road Traffic Act 1988. When prescribing this medicine, patients
should be told:
 The medicine is likely to affect your ability to drive.
 Do not drive until you know how the medicine affects you.
 It is an offence to drive while you have this medicine in your body over a
specified limit unless you have a defence (called the ‘statutory defence’).
 This defence applies when:

The medicine has been prescribed to treat a medical or dental problem;
and

You have taken it according to the instructions given by the prescriber
and in the information provided with the medicine.
 Please note that it is still an offence to drive if you are unfit because of the
medicine (i.e. your ability to drive is being affected).”
Details regarding a new driving offence concerning driving after drugs have
been taken in the UK may be found here: https://www.gov.uk/drug-driving-law

4.8

Undesirable effects
In normal doses, the commonest side effects of morphine are nausea, vomiting,
constipation and drowsiness. With chronic therapy, nausea and vomiting are unusual
with MST CONTINUS suspension but should they occur the suspension could be
readily combined with an anti-emetic if required. Constipation may be treated with
appropriate laxatives.
The following frequencies are the basis for assessing undesirable effects:
Very common (≥ 1/10)
Common (≥ 1/100 to < 1/10)
Uncommon (≥ 1/1,000 to <1/100)
Rare (≥ 1/10,000 to < 1/1,000)
Very rare (<1/10,000)
Not known (cannot be estimated from the available data)

Very
Common

Common

Immune
system
disorders

Uncommon

Not known

Allergic
reaction

Anaphylactic
reaction
Anaphylactoid
reaction
Drug
dependence
Dysphoria
Thinking
disturbances
Hyperalgesia
(see section
4.4)

Psychiatric
disorders

Confusion
Insomnia

Agitation
Euphoria
Hallucinations
Mood altered

Nervous
system
disorders

Dizziness
Headache
Involuntary
muscle
contractions
Somnolence

Convulsions
Hypertonia
Myoclonus
Paraesthesia
Syncope

Eye disorders
Ear and
labyrinth
disorders
Cardiac
disorders
Vascular
disorders

Visual
disturbance
Vertigo

Miosis

Palpitations

Bradycardia
Tachycardia
Hypertension

Facial
flushing
Hypotension

Very
Common

Common

Respiratory
thoracic and
mediastinal
disorders
Gastrointestinal Constipation Abdominal
disorders
Nausea
pain
Anorexia
Dry mouth
Vomiting
Hepatobiliary
disorders
Skin and
subcutaneous
tissue disorders
Renal and
urinary
disorders
Reproductive
system and
breast disorders

General
disorders and
administration
site conditions

Uncommon

Bronchospasm Cough
Pulmonary
decreased
oedema
Respiratory
depression
Dyspepsia
Ileus
Taste
perversion

Increased
hepatic
enzymes
Hyperhidrosis Urticaria
Rash
Urinary
retention

Asthenic
conditions
Pruritus

Not known

Peripheral
oedema

Biliary pain
Exacerbation
of pancreatitis

Ureteric
spasm
Amenorrhoea
Decreased
libido
Erectile
dysfunction
Drug
tolerance
Drug
withdrawal
syndrome

The effects of morphine have led to its abuse and dependence may develop with
regular, inappropriate use. This is not a major concern in the treatment of patients
with severe pain.

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
Signs of morphine toxicity and overdose are drowsiness, pin-point pupils, skeletal
muscle flaccidity, bradycardia, respiratory depression, hypotension, somnolence and
central nervous system depression which can progress to stupor or coma. Circulatory
failure and deepening coma may occur in more severe cases. Overdose can result in

death. Rhabdomyolosis progressing to renal failure has been reported in opioid
overdose.
Crushing and taking contents of a controlled release dosage form leads to the release
of the morphine in an immediate fashion; this might result in a fatal overdose.
Treatment of morphine overdose
Primary attention should be given to the establishment of a patent airway and
institution of assisted or controlled ventilation.
Oral activated charcoal (50g for adults, 1 g/kg for children) may be considered if a
substantial amount has been ingested within one hour, provided the airway can be
protected.
The pure opioid agonists are specific antidotes against the effects of opioid overdose.
Other supportive measures should be employed as needed.
In the case of massive overdose, administer naloxone 0.8 mg intravenously. Repeat
at 2-3 minute intervals as necessary, or by an infusion of 2 mg in 500 ml of normal
saline or 5% dextrose (0.004 mg/ml).
The infusion should be run at a rate related to the previous bolus doses administered
and should be in accordance with the patient's response. However, because the
duration of action of naloxone is relatively short, the patient must be carefully
monitored until spontaneous respiration is reliably re-established. MST CONTINUS
suspension will continue to release and add to the morphine load for up to 12 hours
after administration and the management of morphine overdose should be modified
accordingly.
For less severe overdose, administer naloxone 0.2 mg intravenously followed by
increments of 0.1 mg every 2 minutes if required.
Naloxone should not be administered in the absence of clinically significant
respiratory or circulatory depression secondary to morphine overdose.
Naloxone should be administered cautiously to persons who are known, or suspected,
to be physically dependent on morphine. In such cases, an abrupt or complete
reversal of opioid effects may precipitate an acute withdrawal syndrome.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: natural opium alkaloid

ATC code: N02A A01
Morphine acts as an agonist at opiate receptors in the CNS particularly mu and
to a lesser extent kappa receptors. mu receptors are thought to mediate
supraspinal analgesia, respiratory depression and euphoria and kappa
receptors, spinal analgesia, miosis and sedation.
Central Nervous System
The principal actions of therapeutic value of morphine are analgesia and
sedation (i.e., sleepiness and anxiolysis).
Morphine produces respiratory depression by direct action on brain stem
respiratory centers.
Morphine depresses the cough reflex by direct effect on the cough center in
the medulla. Antitussive effects may occur with doses lower than those
usually required for analgesia.
Morphine causes miosis, even in total darkness. Pinpoint pupils are a sign of
narcotic overdose but are not pathognomonic (e.g., pontine lesions of
hemorrhagic or ischemic origin may produce similar findings). Marked
mydriasis rather than miosis may be seen with hypoxia in the setting of
morphine overdose.
Gastrointestinal Tract and Other Smooth Muscle
Morphine causes a reduction in motility associated with an increase in smooth
muscle tone in the antrum of the stomach and duodenum. Digestion of food in
the small intestine is delayed and propulsive contractions are decreased.
Propulsive peristaltic waves in the colon are decreased, while tone is increased
to the point of spasm resulting in constipation.
Morphine generally increases smooth muscle tone, especially the sphincters of
the gastrointestinal and biliary tracts. Morphine may produce spasm of the
sphincter of Oddi, thus raising intrabiliary pressure.
Cardiovascular System
Morphine may produce release of histamine with or without associated
peripheral vasodilation. Manifestations of histamine release and/or peripheral
vasodilation may include pruritus, flushing, red eyes, sweating, and/or
orthostatic hypotension.
Endocrine System

Opioids may influence the hypothalamic-pituitary-adrenal or -gonadal axes.
Some changes that can be seen include an increase in serum prolactin, and
decreases in plasma cortisol, oestrogen and testosterone in association with
inappropriately low or normal ACTH, LH or FSH levels. Clinical symptoms
may be manifest from these hormonal changes.
Other Pharmacologic Effects
In vitro and animal studies indicate various effects of natural opioids, such as
morphine, on components of the immune system; the clinical significance of
these findings is unknown.

5.2

Pharmacokinetic Properties
Morphine is bound to a cationic exchange resin and drug release is effected
when morphine is displaced by ions in the gastrointestinal tract. Morphine is
well absorbed and adequate plasma morphine levels are achieved following
the recommended dosage regimen. However, first pass metabolism occurs in
the liver.
In a single dose study in healthy volunteers, the systemic availability of
morphine from MST CONTINUS suspension 30 mg was equivalent to that
from an immediate release solution 30 mg (mean 91%, 95% CI 81-102%) and
from MST CONTINUS tablet 30 mg (mean 101%, 95% CI 93-109%). The
suspension provided a retarded plasma profile which was comparable to that
of the MST CONTINUS tablet.

5.3

Pre-clinical Safety Data
There are no pre-clinical data of relevance to the prescriber which are
additional to that already included in other sections of the SPC.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of Excipients
Dowex 50WX8 100-200 mesh cationic exchange resin
Xylitol
Xanthan gum
Raspberry flavour
Ponceau 4R (E124)

6.2

Incompatibilities

Not Applicable
6.3

Shelf-Life
2 years.

6.4

Special Precautions for Storage
Do not store above 25°C.

6.5

Nature and contents of container
Pack type: surlyn lined, laminated aluminium foil sachets coated with polyethylene
and clay coated Kraft paper.
Pack size: Boxboard cartons of 10, 20, 30, 60 sachets or medical sample packs of up
to 14 sachets.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling
The contents of the sachet should be added to water or sprinkled onto soft
food, e.g. yoghurt (see 4.2 Posology and Method of Administration).

7.

MARKETING AUTHORISATION HOLDER
Napp Pharmaceuticals Limited
Cambridge Science Park
Milton Road
CAMBRIDGE
CB4 0GW
United Kingdom

8.

MARKETING AUTHORISATION NUMBER(S)
PL 16950/0032

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
19/11/2006

10

DATE OF REVISION OF THE TEXT
18/07/2016

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Source: Medicines and Healthcare Products Regulatory Agency

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