Signs:
The signs of morphine overdosage consist of pin-point pupils, respiratory depression, and hypotension. Circulatory failure and deepening coma may develop in severe cases and death may ensue. Less severe cases may be manifest by nausea, vomiting, tremor, dysphoria, hypothermia, hypotension, confusion and sedation. Rhabdomyolysis progressing to renal failure can also be a consequence of overdosage.
Treatment:
It is vital to maintain and support respiration and circulation. The specific opioid antagonist naloxone should be employed for the reversal of coma and restoration of spontaneous respiration. 400 micrograms of naloxone should be administered intravenously, repeated at 2-3 minute intervals as necessary up to a maximum dose of 10 mg.
36 months
- respiratory depression; obstructive airways disease; excessive bronchial secretions; during a bronchial asthma attack or in heart failure secondary to chronic lung disease
- head injury; raised intra-cranial pressure
- coma
- convulsion disorders
- ulcerative colitis
- presence of a risk of paralytic ileus
- biliary and renal tract spasm
- acute alcoholism
- phaeochromocytoma
- moderate to severe renal impairment (glomerular filtration rate <20ml/min)
- severe or acute liver failure
- patients receiving monoamine oxidase inhibitors or within two weeks of discontinuing such treatment
Use of Morphine sulfate injection during pregnancy or lactation is not recommended.
Morphine sulfate injection is physically incompatible with aciclovir sodium, aminophylline, amobarbital sodium, cefepime hydrochloride, chlorothiazide sodium, floxacillin sodium, furosemide, gallium nitrate, heparin sodium, meperidine hydrochloride, meperidine sodium, methicillin sodium, minocycline hydrochloride, pentobarbital sodium, phenobarbital sodium, phenytoin sodium, sargramostim, sodium bicarbonate, thiopental sodium.
Sodium chloride
Hydrochloric acid
Water for injections
Solution for injection
The side-effects most commonly seen with morphine and other opioids are respiratory depression, nausea, vomiting, constipation, drowsiness and confusion. With long term use these symptoms generally lessen, although constipation frequently persists.
The following adverse events are from published literature and frequencies are not known.
Immune system disorders
Anaphylactic reactions to morphine have been reported rarely.
Endocrine disorders
Long term use of opioid analgesics can cause adrenal insufficiency. Exacerbation of pancreatitis.
Psychiatric disorders
Restlessness, mood changes, hallucinations, delirium, disorientation, excitation, agitation, sleep disturbance.
Nervous system disorders
Headache, vertigo, euphoria, dysphoria, dizziness, taste disturbances, seizures, paraesthesia, raised intracranial pressure.
Eye disorders
Visual disturbances, nystagmus, miosis.
Ear and labyrinth disorders
Vertigo.
Cardiac disorders
Bradycardia, tachycardia, palpitations, syncope.
Vascular disorders
Orthostatic hypotension, hypotension, hypertension, facial flushing, oedema.
Respiratory, thoracic and mediastinal disorders
Bronchospasm (in association with anaphylaxis), inhibition of cough reflex.
Gastrointestinal disorders
Dyspepsia, paralytic ileus, abdominal pain, anorexia.
Hepatobiliary disorders
Biliary spasm.
Skin and subcutaneous tissue disorders
Rashes, urticaria, pruritus.
Musculoskeletal and connective tissue disorders
Muscle fasciculation, myoclonus, rhabdomyolysis, muscle rigidity.
Renal and urinary disorders
Difficult micturition, ureteric spasm, urinary retention.
Reproductive system and breast disorders
Long term use of opioid analgesics can cause hypogonadism in both men and women.
This can lead to amenorrhoea, reduced libido, infertility, depression and erectile dysfunction.
General disorders and administration site conditions
Dry mouth, sweating, hypothermia, malaise, asthenia, pain and irritation at the injection site.
Long Term Use
Long term use of opioid analgesics has been associated with a state of abnormal pain sensitivity (hyperalgesia).
Tolerance and psychological and physical dependence may occur. Decreased potency may be experienced.
High doses may produce respiratory depression and hypotension, with deepening coma. Convulsions may occur particularly in infants.
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.
Non-clinical data based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development reveal no special hazard additional to the known safety profile of morphine in humans.
Morphine sulfate injection is indicated for the relief of moderate to severe pain. Morphine sulfate injection is used especially in pain associated with cancer, myocardial infarction and surgery. Morphine also helps to relieve the anxiety and insomnia which may be associated with severe pain.
Pharmacotherapeutic group: Opioids, natural opium alkaloids, ATC code: N02AA01
Morphine acts as a competitive agonist at opiate receptors in the CNS, particularly mu and to a lesser extent kappa receptors. Activity at the mu-1 subtype receptor is thought to mediate analgesia, euphoria and dependence whilst activity at the mu-2 receptor is thought to be responsible for respiratory depression and inhibition of gut motility. Action at the kappa receptor may mediate spinal analgesia. The analgesic action of morphine is effective at several spinal and supraspinal sites.
Absorption
Onset of action is rapid following parenteral administration of morphine with peak analgesic effect occurring within 20 minutes via the intravenous route.
Distribution
Morphine is widely distributed in the body, with an apparent volume of distribution of 2-3 lkg-1. Due to its relatively hydrophilic nature, morphine does not readily cross the blood-brain barrier although it is detectable in the cerebrospinal fluid.
Biotransformation
Morphine is extensively metabolised by the liver. Renal glucuronidation also takes place. The major metabolite, quantitatively, is morphine-3-glucuronide although morphine-6-glucuronide is significant in terms of potency. The metabolites are excreted mainly via the renal route.
26/01/2017
Morphine Sulfate 1 mg per ml solution for injection
hameln pharmaceuticals ltd
Gloucester
UK
Do not store above 25°C. Keep the ampoules in the outer carton in order to protect from light.
10 ml colourless glass ampoules (type I) in packs of 10 ampoules.
PL 01502/0098
Pregnancy
There are no adequate data from the use of morphine in pregnant women. Studies in animals have shown reproductive toxicity. Morphine sulfate injection is not, therefore, recommended for use in pregnancy.
Breast-feeding
Morphine has been shown to suppress lactation, although morphine is secreted in breast milk and may cause respiratory depression in the infant. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from morphine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility
- Preclinical safety data).- Undesirable effects).Each 10 ml ampoule contains 10 mg morphine sulfate pentahydrate
Excipient with known effect:
As with other narcotics, a dose reduction may be appropriate in elderly patients, in patients with hypothyroidism, renal and chronic hepatic disease.
Morphine sulfate injection should be used with caution in debilitated patients and those with adrenocortical insufficiency; hypopituitarism; prostatic hypertrophy; shock; diabetes mellitus; diseases of the biliary tract; myasthenia gravis; cardiac arrhythmias; excessive obesity; hypotension and severe cardiac failure.- Interaction with other medicinal products and other forms of interaction).
Drug dependence and tolerance
Morphine can produce drug dependence and therefore has the potential for being abused or misused. Upon repeated administration of morphine, psychological and physical dependence may occur and tolerance may develop, particularly in individuals with a history of alcohol or drug abuse and dependence. However, when doses of morphine are carefully titrated against pain, clinically significant respiratory depression, addiction, rapid tolerance and euphoria rarely develop. With regular administration of morphine at doses optimised for the individual patient drug dependence does not develop, and psychological dependence does not occur. A certain degree of physical dependence is possible, however. If patients no longer require morphine for relief of pain, doses should be gradually reduced in order to prevent withdrawal symptoms. Clinically significant tolerance to morphine is unusual in cancer patients with severe pain.
Morphine sulfate injection contains 0.15 mmol (or 3.54 mg) sodium per millilitre solution. By application of large volumes of the solution (e.g. more than 6.5 ml corresponding to more than 1 mmol sodium) this has to be taken into consideration by patients on a controlled sodium diet.
Morphine has major influence on the ability to drive and use machines. It may modify the patient's reactions to a varying extent depending on the dosage and individual susceptibility. Ambulatory patients should be warned not to use machines.
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 under the influence of this medicine
- However, you would not be committing an offence (called 'statutory defence') if:
o The medicine has been prescribed to treat a medical or dental problem and
o You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
o It was not affecting your ability to drive safely
Posology
Adults and children over 12 years:
Morphine sulfate injection is formulated for use by the intravenous route in Patient Controlled Analgesia (PCA) systems. PCA, which permits adjustment of dosage according to the patient's individual needs, must only be carried out in departments and by staff who are trained and have experience of the system. Patient selection for the use of PCA must ensure that the patient is capable of understanding and following the instructions of the medical/nursing staff. The specific department or unit protocols must be covered to ensure aseptic transfer of the contents of the vial to the PCA system.
There is a considerable variation in analgesic requirements among patients and therefore individualised treatment strategies are required. Dosage should be based on the severity of the pain and the response and opiate tolerance of the patient.
Loading dose
Loading doses of typically between 1 mg and 10 mg (maximum 15 mg) of morphine sulfate may be given by intravenous infusion over four or five minutes. The loading dose used will depend upon the patient's diagnosis and condition.
PCA demand dose
An initial demand dose of 1 mg Morphine sulfate injection with a lockout period of 5 to 10 minutes is recommended. Dosages may vary depending on the loading dose, the tolerance and condition of the patient, and whether a background infusion of morphine is being given.
The patient should be specifically monitored for pain, sedation and respiratory rate during the first few hours of treatment to ensure that the dosage regimen is suitable.
The duration of treatment should be kept to a minimum, although dependence and tolerance are not generally a problem when morphine is used legitimately in patients with opioid-sensitive pain.
Use in children:
Not recommended for children under 12 years.
Use in the elderly:
Morphine doses need to be reduced in elderly patients.
Method of administration
For intravenous injection.
The product should not be diluted before use.
The medicinal product is to be visually inspected prior to use. Only clear solutions practically free from particles should be used.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
28/10/2015
Drug dependence and tolerance
Morphine can produce drug dependence and therefore has the potential for being abused or misused. Upon repeated administration of morphine, psychological and physical dependence may occur and tolerance may develop, particularly in individuals with a history of alcohol or drug abuse and dependence. However, when doses of morphine are carefully titrated against pain, clinically significant respiratory depression, addiction, rapid tolerance and euphoria rarely develop. With regular administration of morphine at doses optimised for the individual patient drug dependence does not develop, and psychological dependence does not occur. A certain degree of physical dependence is possible, however. If patients no longer require morphine for relief of pain, doses should be gradually reduced in order to prevent withdrawal symptoms. Clinically significant tolerance to morphine is unusual in cancer patients with severe pain.
Morphine sulfate injection contains 0.15 mmol (or 3.54 mg) sodium per millilitre solution. By application of large volumes of the solution (e.g. more than 6.5 ml corresponding to more than 1 mmol sodium) this has to be taken into consideration by patients on a controlled sodium diet.
4.5 Interaction with other medicinal products and other forms of interactionMonoamine oxidase inhibitors (MAOIs):
Concomitant or recent use of monoamine oxidase inhibitors with morphine is contraindicated since interactions have been reported, resulting in CNS excitation or depression with hyper- or hypotensive crises.
Hyperpyrexia and CNS toxicity may result from an opiate selegiline combination. Such combinations should, therefore, be used with extreme caution.
CNS depressants
The CNS depressant effects of morphine are increased by the co-administration of CNS depressants including alcohol, anaesthetics, muscle relaxants, hypnotics, sedatives, tricyclics, neuroleptics and phenothiazines as well as other opioid analgesics.
The analgesic effects of opioids tend to be enhanced by the concomitant administration of dexamphetamine, hydroxyzine and some phenothiazines (although the latter may also cause respiratory depression).
Diuretics:
Morphine may reduce the efficacy of diuretics by inducing the release of the antidiuretic hormone.
Anticholinergics:
The combination of morphine with anticholinergics may enhance the constipatory effect and urinary retention.
Antihistamines:
Cimetidine and ranitidine appear to interfere with the metabolism of morphine.
Disulfiram:
The metabolism and excretion of morphine may be inhibited by disulfiram.
Prokinetics:
Increased morphine levels may result from the co-administration of cisapride.
Metoclopramide and domperidone may antagonise morphine's gastrointestinal effects and metoclopramide enhances it sedative effect.
Antibiotics:
Ciprofloxacin concentration may be reduced.
Anti-arrhythmics:
Mexiletine absorption may be delayed by co-administered opiate. Co-administration of morphine with esmolol results in a slight increase in the esmolol levels, but the clinical implications of this increase are not considered very significant.
Enzyme modulating agents:
Animal data suggest that propranolol may increase the toxicity of opioids. Ritonavir can induce the formation of metabolising enzymes made in the liver and can cause increased metabolism of morphine which can reduce the clinical efficacy of the analgesic.
