Morphine sulfate
- Drugs List
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
24 hour modified release capsules containing morphine sulfate 30mg
24 hour modified release capsules containing morphine sulfate 60mg
24 hour modified release capsules containing morphine sulfate 90mg
24 hour modified release capsules containing morphine sulfate 120mg
24 hour modified release capsules containing morphine sulfate 150mg
24 hour modified release capsules containing morphine sulfate 200mg
Drugs List
Dosage
The dosage is dependent upon the severity of the pain, the patient's age and previous history of analgesic requirements.
Patients presenting with severe, uncontrolled pain, who are not currently receiving opioids, should, if possible, have their dose requirements calculated through the use of immediate release morphine before converting to 24 hour modified release preparations.
Adults
Patients presenting with pain, who are currently receiving weaker opioids should commence therapy at the following dosages:
Patients weighing over 70kg
60mg once daily
Patients weighing less than 70kg
30mg once daily
Increasing severity of pain will require increased doses. Higher doses should be made, where appropriate, in 30-50% increments as required.
The correct dosage for any individual patient is that which controls the pain with no or tolerable side effects for a full 24hours.
Elderly
Children
Children 1 year and above
For severe and intractable pain in cancer a starting dose in the range of 0.4-1.6mg/kg daily is recommended. Doses should be titrated in the normal way as for adults.
The use of morphine 24 hour modified release preparations in infants under 1 year has not been fully evaluated.
Patients with Renal Impairment
Use with caution in patients with renal impairment; it may be advisable to use a reduced dose. There may be an increased or prolonged effect in patients with renal impairment, and an increased cerebral sensitivity.
The Renal Dose Handbook mentions that some units avoid slow release oral preparations as any side effects may be prolonged. If used, it suggests the following dose adjustments:
20-50ml/min GFR - 75% of normal dose
10-20ml/min GFR - use small doses, e.g. 2.5-5mg and extended dosing intervals. Titrate according to response.
<10ml/min GFR - use small doses, e.g. 1.25-2.5mg and extended dosing intervals. Titrate according to response.
Patients with Hepatic Impairment
Contraindicated in patients with acute hepatic disease.
Use with caution in patients with hepatic impairment; it may be advisable to use a reduced dose. Use of morphine sulfate in liver disease may precipitate coma.
Additional Dosage Information
Patients receiving modified release morphine in place of parenteral morphine should be given a sufficiently increased dose to compensate for any reduction in analgesic effects associated with oral administration. Usually this increase is in the region of 100%.
It should be emphasised that patients, once titrated to an effective dose of a certain opioid drug, should not be changed to other slow, sustained or controlled release morphine or other narcotic analgesic preparations without retitration and clinical assessment, otherwise a continuing analgesic action cannot be assured.
Administration
For oral administration
The capsules should be swallowed whole or opened and the contents sprinkled on to soft cold food. The capsules and contents should not be crushed or chewed as this leads to a rapid release and absorption of a potentially fatal dose of morphine.
Contraindications
Respiratory depression
Obstructive pulmonary disease
Paralytic ileus
Risk of paralytic ileus
Infants under 1 year
Acute hepatic disorder
Within 2 weeks of discontinuing MAOIs
Raised intracranial pressure
Acute abdomen
Head trauma
Delayed gastric emptying
Acute asthma
Phaeochromocytoma
Coma
Pre-operative use
24 hours post-operatively
Pregnancy (see Pregnancy )
Cardiac failure secondary to pulmonary disorder
Precautions and Warnings
Reduced respiratory reserve
Asthma
Elderly (see Dosage - Elderly )
Debilitation - reduce dose
Cardiac arrhythmias
Acute alcohol intoxication
Delirium tremens
Hypothyroidism - reduce dose
Renal impairment (see Dosage - Renal impairment )
Hepatic impairment (see Dosage - Hepatic impairment )
Hypotension with hypovolaemia
History of substance abuse
Prostatic hypertrophy
Adrenocortical insufficiency - reduce dose
Biliary tract disorder
Pancreatitis
Obstructive or inflammatory bowel disease
Myasthenia gravis
Shock
Opioid dependent patients
Breastfeeding (see Lactation )
Convulsive disorders - may lower the seizure threshold
Morphine should be discontinued at least 24 hours before cordotomy or other pain relieving procedures.
Morphine should be used with caution post-operatively, in particular following abdominal surgery as morphine impairs intestinal motility. If paralytic ileus is suspected, or occurs, morphine should be discontinued immediately.
It is not possible to ensure bioequivalence between different brands of controlled release morphine products. Therefore, once titrated to an effective dose, patients should not be switched to other slow, sustained or controlled release morphine without retitration and clinical assessment.
Morphine may cause sedation, and so patients should be advised not to drive or operate machinery if they experience drowsiness.
The major risk of opioid excess is respiratory depression.
Due to the effects of morphine, it has the potential for abuse. Tolerance and dependence may occur. Use with particular care in patients with a history of alcohol and drug abuse.
Chronic use may cause tolerance, requiring progressively higher doses to maintain pain control. Prolonged use may lead to physical dependence, and withdrawal syndrome upon abrupt cessation. Abrupt withdrawal should therefore be avoided after long term treatment, in favour of a gradual tapering of the dose.
The capsules must be not be broken, chewed, dissolved or crushed, as this leads to a rapid release and absorption of a potentially fatal dose of morphine.
Morphine may potentiate the effects of alcohol; patients should be advised to avoid alcohol during treatment.
Pregnancy and Lactation
Pregnancy
The use of morphine preparations is not recommended by the manufacturer for use during pregnancy and labour. Teratogenic effects have been observed in animal studies, but there are currently no reports linking use at therapeutic doses with major congenital defects, and there is not thought to be any increased incidence of birth defects in humans. Use for prolonged periods of time or at term should be avoided due to increased risk of neonatal respiratory depression and withdrawal following maternal use, 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. There is a possibility of long-term or late-developing behavioural abnormalities, but the link is unclear at the time of writing.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Recommended for use in pregnancy? - No.
Known human teratogen? - Unknown.
Animal data - Teratogenic effects observed in some studies.
Crosses placenta? - Yes, rapidly.
Other information - Not recommended due to risk of effects on neonate, but may be used if compellingly indicated.
Lactation
Morphine preparations are not recommended by the manufacturer for nursing mothers, due to the fact that morphine is excreted in breast milk. However, no toxic symptoms were observed in an infant exposed to up to 12% of the maternal dose, and the levels are not thought to be clinically relevant. Morphine is considered an opiate analgesic of choice during breastfeeding due to its relatively poor oral bioavailability of 26%. The infant should be monitored for drowsiness, adequate weight gain and developmental milestones, particularly younger, exclusively breastfed infants. Medical advice should be sought immediately if the infant suffers from increased sleepiness, has difficulty breastfeeding, breathing difficulties or limpness. Particular care should be taken with children with a tendency for apnoea, due to the risk of respiratory depression, and infants should be monitored for somnolence and respiratory problems in the case of repeated doses. Opiate analgesics should only be used for short periods of time during breastfeeding; consider limiting the mother's parenteral morphine dosage by supplementing analgesia with a non-narcotic analgesic. The long-term effects on neurobehaviour and development are unknown at the time of writing, but warrant further study.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Drug excreted in breast milk? - Yes, in amounts unlikely to be harmful to the infant.
Considered suitable or recommended by manufacturer? - No.
UK Drugs in Lactation Advisory Service Classification - May be administered to breastfeeding mothers.
Drug substance licensed in infants? - Yes, in infants over one year.
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
Counselling
Morphine may cause sedation, and so patients should be advised not to drive or operate machinery if they experience drowsiness.
Advise patients to avoid alcohol during treatment
Side Effects
Allergic reaction
Anaphylactic reaction
Anaphylactoid reaction
Confusion
Insomnia
Thinking disturbances
Agitation
Drug dependence
Dysphoria
Euphoria
Hallucinations
Mood changes
Headache
Involuntary muscle contractions
Myoclonus
Somnolence
Convulsions
Hypertonia
Paraesthesia
Syncope
Vertigo
Miosis
Visual disturbances
Bradycardia
Palpitations
Hypertension
Tachycardia
Facial flushing
Hypotension
Bronchospasm
Cough decreased
Pulmonary oedema
Respiratory depression
Abdominal pain
Anorexia
Constipation
Dry mouth
Dyspepsia
Nausea
Vomiting
Gastrointestinal disorders
Ileus
Taste perversion
Pancreatitis
Biliary colic
Increases in hepatic enzymes
Hyperhidrosis
Rash
Urticaria
Ureteric spasm
Urinary retention
Amenorrhea
Reduced libido
Erectile dysfunction
Asthenia
Pruritus
Drug tolerance
Drug withdrawal syndrome
Malaise
Peripheral oedema
Delirium
Infertility
Depression
Micturition difficulties
Hypothermia
Excitation
Disorientation
Dizziness
Drowsiness
Sleep disturbances
Seizures
Rhabdomyolysis
Restlessness
Sexual dysfunction
Raised intracranial pressure
Postural hypotension
Nystagmus
Muscle rigidity
Muscle fasciculation
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 ).
Shelf Life and Storage
Do not store above 25 degrees C
Reference Sources
Summary of Product Characteristics: MXL capsules. Napp Pharmaceuticals Ltd. Revised July 2012
British National Formulary, 63rd Edition (2012) Pharmaceutical Press, London.
BNF for Children (2012-2013) Pharmaceutical Press, London.
Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.
US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed). Record 370 - Morphine
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last revised: 5 February 2008
Last accessed: 19 April 2011
UK Drugs in Lactation Advisory Service.
Available at: https://www.ukmicentral.nhs.uk/drugpreg/qrg_p1.asp
Last accessed: 19 April 2011
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: 6 January 2015
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