Morphine Sulphate 10mg/ml Solution for Injection

Morphine Sulphate 10mg/ml

For full list of excipients, see 6.1.

Solution for injection

The symptomatic relief of severe pain; relief of dyspnoea of left ventricular failure and pulmonary oedema; pre-operative use.

Morphine Sulphate may be given by the subcutaneous, intramuscular or intravenous route. The subcutaneous route is not suitable for oedematous patients. The dosage should be based on the severity of the pain and the response and tolerance of the individual patient. The epidural or intrathecal routes must not be used as the product contains a preservative.

Adults:

Subcutaneous or intramuscular injection:

10mg every four hours if necessary (the dose may vary from 5-20mg depending on the individual patient).

Slow intravenous injection (2mg/minute):

Quarter to half of corresponding intramuscular dose not more than four hourly.

Elderly and debilitated patients: The dose should be reduced because of the depressant effect on respiration. Caution is required.

Children: Use in children is not recommended.

Hepatic impairment:

A reduction in dosage should be considered in hepatic impairment.

Renal impairment:

The dosage should be reduced in moderate to severe renal impairment.

For concomitant illnesses/conditions where dose reduction may be appropriate see 4.4 Special Warnings and Precautions for Use.

Acute respiratory depression, known morphine sensitivity, biliary colic (see also biliary tract disorders 4.4 Special Warnings and Precautions), acute alcoholism. Conditions in which intracranial pressure is raised, comatose patients, head injuries, as there is an increased risk of respiratory depression that may lead to elevation of CSF pressure. The sedation and pupillary changes produced may interfere with accurate monitoring of the patient. Morphine is also contraindicated where there is a risk of paralytic ileus, or in acute diarrhoeal conditions associated with antibiotic-induced pseudomembranous colitis or diarrhoea caused by poisoning (until the toxic material has been eliminated).

Phaeochromocytoma (due to the risk of pressor response to histamine release).

Morphine should be given in reduced doses or with caution to patients with asthma or decreased respiratory reserve (including cor pulmonale, kyphoscoliosis, emphysema, severe obesity). Avoid use during an acute asthma attack (see 4.3 Contraindications). Opioid analgesics in general should be given with caution or in reduced doses to patients with hypothyroidism, adrenocortical insufficiency, prostatic hypertrophy, urethral stricture,hypotension, shock, inflammatory or obstructive bowel disorders, or convulsive disorders.

Opioids such as morphine should either be avoided in patients with biliary disorders or they should be given with an antispasmodic.

Morphine can cause an increase in intrabiliary pressure as a result of effects on the sphincter of Oddi. Therefore in patients with biliary tract disorders morphine may exacerbate pain (use in biliary colic is a contraindication, see 4.3). In patients given morphine after cholecystectomy, biliary pain has been induced.

Caution is advised when giving morphine to patients with impaired liver function due to its hepatic metabolism (see 4.2 Posology).

Severe and prolonged respiratory depression has occurred in patients with renal impairment who have been given morphine (see 4.2 Posology).

Dependence can develop rapidly with regular abuse of opioids but is less of a problem with therapeutic use. Abrupt withdrawal from persons physically dependent on them precipitates a withdrawal syndrome, the severity of which depends on the individual, the drug used, the size and frequency of the dose and the duration of drug use. Great caution should be exercised in patients with a known tendency or history of drug abuse.

Dosage should be reduced in elderly and debilitated patients (see 4.2 Posology).

Palliative care - in the control of pain in terminal illness, these conditions should not necessarily be a deterrent to use.

Alcohol: enhanced sedative and hypotensive effects.

Anti-arrhythmics: There may be delayed absorption of mexiletine.

Antibacterials: The opioid analgesic papaveretum has been shown to reduce plasma ciprofloxacin concentration. The manufacturer of ciprofloxacin advises that premedication with opioid analgesics be avoided.

Antidepressants, anxiolytics, hypnotics: Severe CNS excitation or depression (hypertension or hypotension) has been reported with the concurrent use of pethidine and monoamine oxidase inhibitors (MAOIs) including selegiline, moclobemide and linezolid. As it is possible that a similar interaction may occur with other opioid analgesics, morphine should be used with caution and consideration given to a reduction in dosage in patients receiving MAOIs.

The sedative effects of morphine (opioid analgesics) are enhanced when used with depressants of the central nervous system such as hypnotics, anxiolytics, tricyclic antidepressants and sedating antihistamines.

Antipsychotics: possible enhanced sedative and hypotensive effect.

Antidiarrhoeal and antiperistaltic agents (such as loperamide and kaolin): concurrent use may increase the risk of severe constipation.

Antimuscarinics: agents such as atropine antagonise morphine-induced respiratory depression and can partially reverse biliary spasm but are additive to the gastrointestinal and urinary tract effects. Consequently, severe constipation and urinary retention may occur during intensive antimuscarinic-analgesic therapy.

Metoclopramide and domperidone: There may be antagonism of the gastrointestinal effects of metoclopramide and domperidone.

Morphine sulphate should only be used when benefit is known to outweigh risk. As with all drugs it is not advisable to administer morphine during pregnancy.

Morphine crosses the placental barrier. Administration during labour may cause respiratory depression in the new born infant and gastric stasis during labour, increasing the risk of inhalation pneumonia. Therefore, it is not advisable to administer morphine during labour.

Babies born to opioid-dependent mothers may suffer withdrawal symptoms including CNS hyperirritability, gastrointestinal dysfunction, respiratory distress and vague autonomic symptoms including yawning, sneezing, mottling and fever.

While morphine can suppress lactation, the quantity from therapeutic doses that may reach the neonate via breast milk is probably insufficient to cause major problems of dependence or adverse effects.

Morphine causes drowsiness so patients should avoid driving or operating machinery.

The most serious hazard of therapy is respiratory depression (see also 4.9 Overdose).

The commonest side-effects of morphine are nausea, vomiting, constipation, drowsiness and dizziness. Tolerance generally develops with long term use, but not to constipation.

Other side effects include the following:

Anaphylaxis: Anaphylactic reactions following intravenous injection have been reported rarely.

Cardiovascular: facial flushing bradycardia, palpitations, tachycardia, orthostatic hypotension.

Central Nervous System: mental clouding, confusion (with large doses), hallucinations, headache, vertigo, mood changes including dysphoria and euphoria.

Gastrointestinal: dry mouth, biliary spasm.

Disorders of the eye: blurred or double vision or other changes in vision, miosis.

Sexual dysfunction: long term use may lead to a reversible decrease in libido or potency.

Skin: pruritus, urticaria, rash, sweating.Contact dermatitis has been reported and pain and irritation may occur on injection.

Urinary: difficulty with micturition, ureteric spasm, urinary retention, antidiuretic effect. Tolerance develops to the effects of opioids on the bladder.

The euphoric activity of morphine has led to its abuse and physical and psychological dependence may occur (see also 4.4 Special Warnings and Precautions for use).

Toxic doses vary considerably with the individual, and regular users may tolerate large doses.

The triad of respiratory depression, coma and constricted pupils is considered indicative of opioid overdosage with dilatation of the pupils occurring as hypoxia develops. Death may occur from respiratory failure

Other opioid overdose symptoms include hypothermia, confusion, severe dizziness, severe drowsiness, hypotension, bradycardia, circulatory failure pulmonary oedema, severe nervousness or restlessness, hallucinations, convulsions (especially in infants and children). Rhabdomyolysis, progressing to renal failure, has been reported in overdosage.

Treatment: The medical management of overdose involves prompt administration of the specific opioid antagonist naloxone if coma or bradypnoea are present using one of the recommended dosage regimens. Both respiratory and cardiovascular support should be given where necessary.

Morphine is obtained from opium, which acts mainly on the CNS and smooth muscle.

Morphine is a potent analgesic with competitive agonist actions at the μ-receptor, which is thought to mediate many of its other actions of respiratory depression, euphoria, inhibition of gut motility and physical dependence. It is possible that analgesia, euphoria and dependence may be due to the effects of morphine on a μ-1 receptor subtype, while respiratory depression and inhibition of gut motility may be due to actions on a μ-2 receptor subtype. Morphine is also a competitive agonist at the κ-receptor that mediates spinal analgesia, miosis and sedation. Morphine has no significant actions at the other two major opioid receptors, the δ- and the σ-receptors.

Morphine directly suppresses cough by an effect on the cough centre in the medulla. Morphine also produces nausea and vomiting by directly stimulating the chemoreceptor trigger zone in the area postrema of the medulla. Morphine provokes the release of histamine.

There are no pre-clinical data of relevance to the prescriber, which are additional to those included in other sections.

Water for injections

Sodium metabisulphite

Sodium hydroxide

Hydrochloric acid

Morphine salts are sensitive to changes in pH and morphine is liable to be precipitated out of solution in an alkaline environment. Compounds incompatible with morphine salts include aminophylline and sodium salts of barbiturates and phenytoin. Other incompatibilities (sometimes attributed to particular formulations) have included aciclovir sodium, doxorubicin, fluorouracil,frusemide, heparin sodium, pethidine hydrochloride, promethazine hydrochloride and tetracyclines. Specialised references should be consulted for specific compatibility information.

36 months

Do not store above 25°C. Keep container in the outer carton.

5 × 1ml glass ampoules

10 × 1ml glass ampoules

None

Wockhardt UK Ltd

Ash Road North

Wrexham LL13 9UF

United Kingdom

PL 29831/0146

8th May 2007

17 March 2010