Morphine Sulphate Injection BP 10mg in1ml, 15mg in 1ml or 30mg in 1ml.

Morphine Sulphate Injection BP 10mg, 15mg or 30mg in 1ml.

Sterile aqueous solution for parenteral administration to human beings.

Morphine is used for the symptomatic relief of severe pain; relief of dyspnoea of left ventricular failure and pulmonary oedema; pre-operative use.

The injection may be given by the intravenous, intramuscular or subcutaneous route.

Adults: The dosage should be based on the severity of the pain and the response and tolerance of the patient. The usual adult subcutaneous or intramuscular dose is 10mg every 4 hours if necessary, but may range from 5mg to 20mg.

The usual adult intravenous dose is 2.5mg to 15mg not more than 4 hourly, where necessary, but dosage and dosing interval must be titrated against the patient's response and adjustments made until analgesia is achieved.

Elderly: Because of the depressant effect on respiration, caution is necessary when giving morphine to the elderly and reduced doses may be required.

Children: Use in children is not recommended.

Respiratory depression, obstructive airways disease, concurrent treatment with monoamine oxidase inhibitors or within two weeks of their discontinuation of treatment with them.

Known morphine sensitivity, or sensitivity to any of the ingredients. Cerebral oedema, head injuries, coma, convulsive disorders and raised intracranial pressure, biliary colic and acute alcoholism.

Administration of morphine is contra-indicated in patients with phaeochromocytoma or those at risk of paralytic ileus.

Morphine should be administered with care to patients with hypotension, asthma, hypothyroidism, decreased respiratory reserve, hepatic and renal impairment, adrenocortical insufficiency, prostatic hypertrophy, shock, inflammatory or obstructive bowel disease or myasthenia gravis, and to patients with a history of drug abuse.

Concurrent administration of other CNS depressants, including hypnotics and anxiolytics, may potentiate the sedative effects.

Morphine should not be administered to patients receiving monoamine oxidase inhibitors (see section 4.3).

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

Morphine sulphate should not be used for premedication when ciprofloxacin is given for surgical prophylaxis as serum levels of ciprofloxacin are reduced and adequate cover may not be obtained during surgery.

Pregnancy: Since morphine rapidly crosses the placental barrier, it is not advised to administer morphine during labour because of the risk of respiratory depression in the new born infant.

As with all drugs it is not advisable to administer morphine during pregnancy.

Lactation: Only small amounts of morphine are secreted in breast milk and the quantity that may reach the neonate via breast milk is probably insufficient to cause major problems of dependence or adverse effects. However, caution is advised on the use of morphine in breast-feeding patient and the benefit must outweigh the risk to the infant. If breast feeding is continued, the infant should be observed for possible adverse effects.

Morphine may cause drowsiness. If this occurs the patient should not be allowed to drive or operate machinery.

Morphine may cause nausea, vomiting, constipation, drowsiness, confusion, dry mouth, sweating, facial flushing, vertigo, bradycardia, palpitations, tachycardia, orthostatic hypotension, hypothermia, restlessness, hallucinations, headache, changes of mood and miosis, muscle rigidity with high doses, decreased libido or potency. Micturition may be difficult and there may be ureteric or biliary spasm. There is also an antidiuretic effect. These effects are more likely to occur in ambulant patients.

Raised intracranial pressure occurs in some patients. Morphine has been reported to increase liver enzymes as a result of spasm of the sphincter of Oddi.

Allergic reactions including urticaria, pruritus, rash, contact dermatitis, bronchospasm, angioedema and anaphylactic reactions may occasionally occur. Pain and irritation may occur on injection.

Larger doses of morphine may produce respiratory depression and hypotension with circulatory failure and deepening coma. Death may occur from respiratory failure. Morphine may produce physical and psychological dependence.

Symptoms of serious overdose include respiratory depression and hypotension with circulatory failure, deepening coma, hypothermia, convulsions especially in infants and children and rhabdomyolosis progressing to renal failure.

Treatment with specific antidote Naloxone is used to rapidly counteract the severe respiratory depression and coma produced by excessive doses of morphine.

Morphine is a narcotic analgesic obtained from opium, which acts mainly on the central nervous system and smooth muscle.

Absorption:Variably absorbed after oral administration; rapidly absorbed after subcutaneous or intramuscular administration.

Blood concentration: After an oral dose of 10mg as the sulphate, peak serum concentrations of free morphine of about 10ng/ml are attained in 15 to 60 minutes; after an intramuscular dose of 10mg, peak serum concentrations of 70 to 80ng/ml are attained in 10 to 20 minutes; after an intravenous dose of 10mg, serum concentrations of about 60ng/ml are obtained in 15 minutes falling to 30ng/ml after 30 minutes and to 10ng/ml after 3 hours; subcutaneous doses give similar concentrations to intramuscular doses at 15 minutes but remain slightly higher during the following 3 hours; serum concentrations measured soon after administration correlate closely with the ages of the subjects studied and are increased in the aged.

Half life: Serum half life in the period 10 minutes to 6 hours following intravenous administration, 2 to 3 hours; serum half life in the period 6 hours onwards, 10 to 44 hours.

Distribution: Widely distributed throughout the body, mainly in the kidneys, liver, lungs and spleen; lower concentrations appear in the brain and muscles; morphine crosses the placenta and traces are secreted in sweat and milk; protein binding, about 35% bound to albumin and to immunoglobulins at concentrations within the therapeutic range.

Metabolic reactions: Mainly glucuronic acid conjugation to form morphine-3 and

6-glucuronides, with sulphate conjugation. N-demethylation, 0-methylation and N-oxide glucuronide formation occurs in the intestinal mucosa and liver; N-demethylation occurs to a greater extent after oral than parenteral administration; the 0-methylation pathway to form codeine has been challenged and codeine and norcodeine metabolites in urine may be formed from codeine impurities in the morphine sample studied.

Excretion: After an oral dose, about 60% is excreted in the urine in 24 hours, with about 3% excreted as free morphine in 48 hours; after parenteral dose, about 90% is excreted in 24 hours, with about 10% as free morphine, 65 to 70% as conjugated morphine, 1% as normorphine and 3% as normorphine glucuronide; after administration of large doses to addicts about 0.1% of a dose is excreted as norcodeine; urinary excretion of morphine appears to be pH dependent to some extent: as the urine becomes more acid more free morphine is excreted and as the urine becomes more alkaline more of the glucuronide conjugate is excreted; up to 10% of a dose may be excreted in the bile.

None available

Sodium metabisulphite

Sodium hydroxide (as in solution)

Sulphuric acid (as in solution)

Water for injection

Morphine salts may be precipitated in alkaline solution.

3 years

Store below 25°C and protect from light.

Ceramically printed, ring snap ampoule manufactured from white neutral glass type 1, conforming to European Pharmacopoeia test for hydrolytic resistance containing morphine sulphate injection 10mg in 1ml, packed in cartons of 5 or 10 ampoules; 15mg in 1ml packed in cartons of 5 or 10 ampoules or 30mg in 1ml packed in cartons of 5 or 10 ampoules and 60mg in 2ml, packed in cartons of 5 ampoules.

Ring snap ampoule manufactured from white neutral glass type 1 conforming to European Pharmacopoeia test for hydrolytic resistance to which will be attached an adhesive vinyl label after filling containing morphine sulphate injection 10mg in 1ml, packed in cartons of 5 or 10 ampoules; 15mg in 1ml packed in cartons of 5 or 10 ampoules or 300mg in 10ml, packed in cartons of 1 ampoule.

None

UCB Pharma Limited

208 Bath Road

Slough

Berkshire

SL1 3WE

UK

10mg/ml: PL 00039/5681R

15mg/ml PL 00039/5682R

30mg/ml: PL 00039/5684R

10mg/ml: 17 May 1982 / 15 September 1997

15mg/ml: 17 May 1982 / 20 August 1997

30mg/ml: 14 May 1982 / 20 August 1997

June 2005