- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Fertility, pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
Excipients with known effect:5 mg tablet also contains lactose anhydrous 95 mg.10 mg tablet also contains lactose anhydrous 90 mg.15 mg tablet also contains lactose anhydrous 85 mg.30 mg tablet also contains lactose anhydrous 70 mg.60 mg tablet also contains lactose anhydrous 40 mg.30 mg and 60 mg tablets also contain a small amount (<1 mg) sunset yellow (E110).For the full list of excipients see section 6.1.
PosologyMST CONTINUS tablets 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. 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 tablets but in divided doses at 12-hourly intervals.Increasing severity of pain will require an increased dosage of the tablets. 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 tablets 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.
Children: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 tablets are not recommended in the first 24 hours post-operatively or until normal bowel function has returned; thereafter it is suggested that the following dosage schedule be observed at the physician's discretion:(a) MST CONTINUS tablets 20 mg 12 hourly to patients under 70 kg(b) MST CONTINUS tablets 30 mg 12 hourly to patients over 70 kg(c) Elderly - a reduction in dosage may be advisable in the elderly(d) Children - not recommendedSupplemental 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 prolonged release formulation.
Method of administrationRoute of administration: oralMST CONTINUS tablets should be swallowed whole and not broken, chewed or crushed. The administration of broken, chewed or crushed tablets may lead to a rapid release and absorption of a potentially fatal dose of morphine (see section 4.9, Overdose).
|• 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|
|Very Common||Common||Uncommon||Not known|
|Immune system disorders||Allergic reaction||Anaphylactic reaction Anaphylactoid reaction|
|Psychiatric disorders||Confusion Insomnia||Agitation Euphoria Hallucinations Mood altered||Drug dependence Dysphoria Thinking disturbances|
|Nervous system disorders||Dizziness Headache Involuntary muscle contractions Somnolence||Convulsions Hypertonia Myoclonus Paraesthesia Syncope||Hyperalgesia (see section 4.4)|
|Eye disorders||Visual disturbance||Miosis|
|Ear and labyrinth disorders||Vertigo|
|Cardiac disorders||Palpitations||Bradycardia Tachycardia|
|Vascular disorders||Facial flushing Hypotension||Hypertension|
|Respiratory thoracic and mediastinal disorders||Bronchospasm Pulmonary oedema Respiratory depression||Cough decreased|
|Gastrointestinal disorders||Constipation Nausea||Abdominal pain Anorexia Dry mouth Vomiting||Dyspepsia Ileus Taste perversion|
|Hepatobiliary disorders||Increased hepatic enzymes||Biliary pain Exacerbation of pancreatitis|
|Skin and subcutaneous tissue disorders||Hyperhidrosis Rash||Urticaria|
|Renal and urinary disorders||Urinary retention||Ureteric spasm|
|Reproductive system and breast disorders||Amenorrhoea Decreased libido Erectile dysfunction|
|General disorders and administration site conditions||Asthenic conditions Pruritus||Peripheral oedema||Drug tolerance Drug withdrawal syndrome|
Reporting of suspected adverse reactionsReporting 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.
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 antagonists 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 tablets 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.
Pharmacotherapeutic group: natural opium alkaloidATC code: N02A A01Morphine 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 SystemThe 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 centres. Morphine depresses the cough reflex by direct effect on the cough centre 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 haemorrhagic or ischaemic 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 MuscleMorphine 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 SystemMorphine 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 SystemOpioids 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 and testosterone in association with inappropriately low or normal ACTH, LH or FSH levels. Some premenopausal women may have low oestrogen levels. Clinical symptoms may be manifest from these hormonal changes.
Other Pharmacological EffectsIn 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.
Tablet coreLactose Anhydrous Hydroxyethylcellulose Purified WaterCetostearyl AlcoholMagnesium StearatePurified Talc
Film coat5 mg - Opadry Y-1-7000 white containing E171Purified water 10 mg - Opadry 85F270017 tan containing polyvinyl alcohol, macrogol 3350, talc, E171, E172Polyethylene Glycol 400Purified Water15 mg - Opadry 02B21169 (containing E464, E171, macrogol 400, E104, E133, E132, E172)Purified Water30 mg Opadry OY-6708 violet, Purified Water 60 mg Opadry OY-3508 orange, Purified Water 100 mg Opadry OY 8215 grey, Purified Water 200 mg - Opadry 06B21168 (containing E464, E171, E133, E104, macrogol 400)Purified Water
Napp Pharmaceuticals Limited
Cambridge Science Park, Milton Road, Cambridge, Cambridgeshire, CB4 0GW
+44 (0)1223 424 444