Morphine sulfate oral 12 hour modified release
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Modified release oral formulations of morphine sulfate.
Drugs List
Therapeutic Indications
Uses
Prolonged relief of severe and intractable pain
Treatment of post-operative pain
Dosage
Dose requirements depend on the severity of pain, patient age and previous history of analgesic requirements. Treatment should aim to provide sufficient pain relief with no, or tolerable, side effects for a 12 hour period. During titration, breakthrough pain should be managed with immediate release morphine.
Adults
Switching from immediate release morphine preparations
Treatment may be initiated with an immediate release morphine preparation which, once titrated to an effective dose, can be switched to a modified release preparation.
When switching from an oral immediate release preparation, the total daily dose of morphine should be divided into two doses, given at 12 hour intervals. When switching from a parenteral immediate release preparation, higher doses may be required as oral modified release preparations may be associated with a reduction in analgesic effects. Doses should be guided by individual patient response.
Severe pain
Opioid naive:
Initially, 10mg to 20mg every 12 hours. Adjusted according to individual patient requirements.
Switching from weaker opioids:
Initially, 30mg every 12 hours. Adjusted according to individual patient requirements.
Post-operative pain
Treatment should not be initiated until at least 24 hours after the procedure.
Supplemental parenteral morphine may be given if required, however the prolonged effects of the modified release morphine preparations must be considered.
Patients under 70kg: 20mg every 12 hours.
Patients over 70kg: 30mg every 12 hours.
Children
Severe pain in cancer.
Initially, 200micrograms/kg to 800micrograms/kg every 12 hours.
Doses should be titrated according to individual patient response, aiming for a dose that provides adequate pain relief with no, or tolerable, side effects for a 12 hour period.
Patients with Renal Impairment
Use of modified release preparations may cause prolonged adverse effects.
In severe renal impairment, dose reductions required may not be practical to administer using modified release preparations. In such cases, conversion to an immediate release morphine preparation or an alternative analgesic suitable for use in renal impairment may be required.
The Renal Drug Handbook suggests the following dose adjustments:
GFR 20 to 50ml/minute:
75% of normal dose.
GFR 10 to 20ml/minute:
Use small doses and extend dosing intervals. Titrate according to response.
An initial dose of 2.5mg to 5mg is suggested, as such it may be more practical to switch to an immediate release preparation or explore alternative analgesic options.
GFR below 10ml/minute:
Use small doses and extended dosing intervals. Titrate according to response.
An initial dose of 1.25mg to 2.5mg is suggested, as such it may be more practical to switch to an immediate release preparation or explore alternative analgesic options.
Additional Dosage Information
Bioequivalence between different brands of modified release morphine preparations cannot be ensured. As such, patients should not be changed to other slow, sustained or controlled release morphine preparations. Where this cannot be avoided, dosage requirements must be reviewed and closely monitored.
Contraindications
24 hours post-operatively
Acute abdomen
Acute alcohol intoxication
Children under 1 year
Pre-operative administration
Risk of paralytic ileus
Within 2 weeks of discontinuing MAOIs
Acute asthma
Acute hepatic disorder
Acute respiratory depression
Breastfeeding
Cardiac failure secondary to pulmonary disorder
Delayed gastric emptying
Head trauma
Labour
Obstructive pulmonary disease
Paralytic ileus
Phaeochromocytoma
Pregnancy
Raised intracranial pressure
Severe hepatic impairment
Precautions and Warnings
Children under 18 years
Constipation
Elderly
Impaired consciousness
Adrenal insufficiency
Asthma
Benign prostatic hyperplasia
Biliary tract disorder
Delirium tremens
Drug misuse
Excessive bronchial secretions
Galactosaemia
Gastrointestinal obstruction
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hereditary fructose intolerance
History of alcohol abuse
History of drug misuse
History of opioid abuse
Hypotension
Hypothyroidism
Hypovolaemia
Inflammatory bowel disease
Lactose intolerance
Myasthenia gravis
Opioid dependence
Pancreatitis
Renal impairment
Respiratory impairment
Seizures
Sickle cell disease
Sleep apnoea
Ulcerative colitis
Urethral stricture
Before administration after abdominal surgery ensure normal bowel function
Reduce dose in hypothyroidism
Reduce dose in patients with hepatic impairment
Reduce dose in patients with renal impairment
Advise patient ability to drive or operate machinery may be impaired
Advise patient not to drive until they know how the medicine affects them
Advise patient this medicine is subject to driving restrictions
May reduce seizure threshold
Not all available brands are licensed for all age groups
Not all presentations are licensed for all indications
Some formulations contain cetostearyl alcohol
Some formulations contain lactose
Some formulations contain Ponceau 4R (E124)-may cause allergic reactions
Some formulations contain sucrose
Some formulations contain sunset yellow (E110); may cause allergic reaction
Other modified-release formulations may not be bioequivalent
May cause adrenal suppression
Monitor at regular intervals as withdrawal symptoms & dependence may occur
Monitor patient for signs and symptoms of respiratory depression
Monitor patients with a history of alcoholism and drug abuse
Neonate exposed in utero: Monitor for neonatal withdrawal syndrome
Potential for drug abuse
Tolerance and dependence may occur
Consider dose reduction if sleep-related breathing disorders occur
Increased risk of central sleep apnoea and sleep-related hypoxemia
Neonate exposed in labour: Risk of respiratory depression
Potential for withdrawal symptoms
Prolonged use at high doses may result in hyperalgesia
Prolonged use may lead to adrenal insufficiency or hypogonadism
Avoid abrupt withdrawal
Discontinue treatment 24 hours prior to surgery
Discontinue if paralytic ileus is suspected
Discontinue if paralytic ileus occurs
Consider dose reduction or alternative opioid in cases of hyperalgesia
Do not change to other modified release analgesic without dose re-titration
Reduce dose in elderly
Advise patient that the effects of alcohol may be potentiated
Advise patient to avoid alcohol during treatment
Advise that effects are potentiated by CNS depressants (including alcohol)
Hyperalgesia, which will not respond to further dose increases, has been reported rarely in patients receiving high doses for prolonged periods. For patients with chronic non-malignant pain, use the lowest effective dose and consider intermittent use. If no response to a good trial of morphine is seen with these patients, treatment should be discontinued in preference to further dose increases. If hyperalgesia occurs, reduce the dose or consider switching to an alternative opioid or other analgesic.
May influence hypothalamus pituitary adrenal or gonadal axes, clinical symptoms may manifest from hormonal changes such as inappropriately low or normal ACTH, LH or FSH levels. May result in adrenal insufficiency or hypogonadism.
Pregnancy and Lactation
Pregnancy
Modified release morphine sulfate is contraindicated during pregnancy.
Manufacturers do not recommend using modified release morphine sulfate during pregnancy and labour.
Teratogenic effects have been observed in animal studies. At the time of writing, there is no published information linking use at therapeutic doses with major congenital defects in humans. Use for prolonged periods or at term is associated with an increased risk of neonatal respiratory depression and withdrawal syndrome, particularly if used during labour. Use in the third trimester and during labour should therefore be avoided.
Maternal addiction can also increase the risk of neonatal withdrawal syndrome. Effects on the neonate include tremors, irritability, diarrhoea, vomiting and seizures. Long-term or late-developing behavioural abnormalities may also occur, but the link is currently unclear. Where continued use of morphine cannot be avoided, discontinuation should be via a gradual reduction in dose to minimise any neonatal withdrawal effects.
Lactation
Modified release morphine sulfate is contraindicated during breastfeeding.
Manufacturers do not recommend using modified release morphine sulfate during breastfeeding.
Morphine is excreted in breast milk (LactMed, 2021). Repeated administration in neonates may lead to accumulation due to immature drug metabolism. Effects on exposed infants are unclear but potentially include central nervous system depression and respiratory depression. At the time of writing, long term effects on neurobehaviour and development are unknown. As such morphine should only be used where non-opioid analgesics are insufficient to manage pain. Use should be restricted to short periods. Particular care should be exercised in neonates and those with a tendency for apnoea.
Exposed infants should be monitored for drowsiness, adequate weight gain and developmental milestones. Medical advice should be sought immediately if the infant suffers from increased sleepiness, has difficulty breastfeeding, breathing difficulties or limpness. Infants exposed to morphine over longer periods through long term breastfeeding exposure and/or additional exposure in utero should be monitored for signs of withdrawal if morphine or breastfeeding is stopped abruptly.
Effects on Ability to Drive and Operate Machinery
This class of medicine is in the list of drugs included in regulations under 5a of the Road Traffic Act 1988 (England and Wales). This medicine may be subject to police testing and has specified maximum blood levels for driving. When prescribing this medicine: Advise patient the medicine can affect cognitive function and is likely to affect ability to drive. Advise patient not to drive until they know how the medicine affects them. It is an offence to drive while under the influence of this medicine. However, a patient is not committing an offence (called 'statutory defence') if: 1.The medicine has been prescribed to treat a medical or dental problem and 2.The medicine has been taken according to the instructions given by the prescriber and/or in the information provided with the medicine and 3.The medicine was not affecting the ability to drive safely. For further guidance see https://www.gov.uk
Side Effects
Abdominal pain
Abnormal thoughts
Agitation
Allergic reaction
Amenorrhoea
Anaphylactic reaction
Anaphylactoid reaction
Anorexia
Anti-diuretic effect
Asthenia
Asthma
Biliary pain
Biliary spasm
Bradycardia
Bronchospasm
Chills
Colic
Confusion
Constipation
Cough suppression
Decrease in blood pressure
Delirium
Dependence
Depression
Difficulty in micturition
Disorientation
Dizziness
Drowsiness
Dry mouth
Dyspepsia
Dysphoria
Dysuria
Erectile dysfunction
Euphoria
Excitement
Facial flushing
Fasciculation
Fatigue
Gastrointestinal disorder
Hallucinations
Headache
Hyperalgesia
Hyperhidrosis
Hypertension
Hypertonia
Hypotension
Hypothermia
Ileus
Impaired vision
Increases in hepatic enzymes
Infertility
Insomnia
Involuntary muscle contractions
Malaise
Miosis
Mood changes
Muscle rigidity
Myoclonus
Nausea
Nystagmus
Orthostatic hypotension
Palpitations
Pancreatitis
Paraesthesia
Paralytic ileus
Peripheral oedema
Pruritus
Pulmonary oedema
Raised intracranial pressure
Rash
Reduced libido
Reduction of male potency
Respiratory depression
Restlessness
Rhabdomyolysis
Sedation
Seizures
Sleep apnoea
Sleep disturbances
Somnolence
Sweating
Syncope
Tachycardia
Taste disturbances
Tolerance
Ureteric spasm
Urinary retention
Urticaria
Vertigo
Visual disturbances
Vomiting
Withdrawal symptoms
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: January 2018
Reference Sources
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Medications and Mothers' Milk, 16th Edition (2014) Hale, T and Rowe, H. Hale Publishing, Plano, Texas.
The Renal Drug Handbook. 4th edition. (2014) ed. Ashley, C and Dunleavy, A. Radcliffe Publishing Ltd, London.
Gov.uk. Government departments. Department for Transport. Publications. Drug driving and medicine: advice for healthcare professionals. Drug driving: Guidance for healthcare professionals on drug driving. Available at: https://www.gov.uk Last accessed: 10 January 2018
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 24 May 2018
Summary of Product Characteristics: Morphgesic SR 100mg tablets. Concordia International. Revised May 2015.
Summary of Product Characteristics: Morphgesic SR 60mg tablets. Concordia International. Revised May 2015.
Summary of Product Characteristics: Morphgesic SR 30mg tablets. Concordia International. Revised May 2015.
Summary of Product Characteristics: Morphgesic SR 10mg tablets. Concordia International. Revised May 2015.
Summary of Product Characteristics: MST Continus 20mg suspension. Napp Pharmaceuticals. Revised February 2018.
Summary of Product Characteristics: MST Continus 30mg suspension. Napp Pharmaceuticals. Revised February 2018.
Summary of Product Characteristics: MST Continus 60mg suspensions. Napp Pharmaceuticals. Revised February 2018.
Summary of Product Characteristics: MST Continus 100mg suspension. Napp Pharmaceuticals. Revised February 2018.
Summary of Product Characteristics: MST Continus 200mg suspension. Napp Pharmaceuticals. Revised February 2018.
Summary of Product Characteristics: MST Continus 5mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 10mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 15mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 30mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 60mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 100mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: MST Continus 200mg tablets. Napp Pharmaceuticals. Revised November 2020.
Summary of Product Characteristics: Zomorph capsules. Ethypharm UK Ltd. Revised August 2016.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://www.ncbi.nlm.nih.gov/books/NBK501922/
Morphine
Last revised: 15 February 2021
Last accessed: 15 March 2021
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