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Morphine Sulphate Injection 10mg/Ml

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SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Morphine Sulphate Injection 10mg/ml

2. Qualitative and Quantitative Composition

Morphine Sulphate 10mg/ml.

3. Pharmaceutical Form

Solution for injection containing 10mg/ml Morphine Sulphate in a type I glass 1ml pre-filled syringe.

Clinical Particulars

4.1.    Therap euti c Indi cati ons

For the relief of severe pain.

4.2. Posology and Method of Administration

By intramuscular, subcutaneous or intravenous injection Adults

Initially 10-20mg, dose may be repeated every 4-6 hours. In cases of terminal pain higher doses may be required.

The elderly

Dose of morphine should be reduced in elderly patients and titrated to provide optimal pain relief with minimal side effects. Morphine clearance decreases and half-life increases in older patients.

Children

Not recommended for children under 6 years

For children 6-12 years (after risk/benefit assessment), 5-10 mg by subcutaneous or intramuscular routes only.

4.3. Contra-indications

Respiratory depression, acute alcoholism, head injuries, increased intracranial pressure, bronchial asthma, heart failure secondary to lung disease. Monoamine oxidase inhibitors (MAOIs) or if MAOI’s have been withdrawn within the previous 2 weeks.

4.4. Special Warnings and Precautions for Use

Repeated use can cause tolerance and dependence. A reduction of dose is advisable in the elderly, in cases of hypothyroidism, renal disease and chronic hepatic disease.

4.5. Interactions with other Medicaments and other forms of Interaction

Morphine may potentiate the action of hypnotics and anxiolytics.

4.6. Pregnancy and Lactation

Morphine Sulphate should not be used during pregnancy or lactation as it crosses the placenta and is secreted in breast milk and can cause respiratory depression in the neonate.

4.7. Effects on Ability to Drive and Use Machines

May cause drowsiness; patients should not drive or operate machinery.

4.8. Undesirable Effects

Nausea, vomiting, drowsiness, confusion, dry mouth, sweating, facial flushing, respiratory depression, bradycardia, palpitations and hypotension.

4.9. Overdose

Symptoms and signs: Pin point pupils, respiratory depression, hypotension. Circulatory    failure and coma may occur in

more severe cases.

Treatment:    Treat with intravenous Naloxone. Maintain fluid and

electrolyte levels    and provide assisted respiration if

necessary.

Pharmacological Properties

5.1. Pharmacodynamic Properties

Morphine is a phenanthrene derivative and the principal alkaloid of opium and is an opioid analgesic. Morphine acts as an agonist at □ opioid receptors and, to a lesser extent, □ receptors and mainly acts on the central nervous system and smooth muscle. Although morphine is predominantly a central nervous system depressant (on, for example, the thalamus, sensory cortex, respiratory and cough centres) it has some central stimulant actions which result in nausea and vomiting and miosis. Morphine generally increases smooth muscle tone, especially the sphincters of the gastrointestinal and biliary tracts.

5.2. Pharmacokinetic Properties

The majority of a dose of morphine is conjugated with glucoronic acid in the liver and gut to produce morphine-3-glucoronide and morphine-6-glucoronide, the latter of which is considered the active metabolite. Morphine-3-glucuronide, however, is thought to antagonise the effect of morphine-6-glucoronide. Morphine is distributed throughout the body, but is mainly found in the kidneys, liver, lungs and spleen. Morphine also crosses the placenta and follows a similar distribution pattern in neonates. The mean elimination halflife for morphine is 3 hours. Morphine is bound to plasma proteins only to the extent of 25 - 35%, therefore factors that change the extent of protein binding will only have a minor effect. Approximately 60% of morphine is excreted in urine after 24 hours of administration, of which a small proportion is free morphine (higher in alkaline urine) and about 60 - 70% is conjugated. Up to 10% of the dose may eventually be excreted as conjugates through bile and faeces. Morphine is also excreted in trace amounts in sweat and at levels generally less than 1% of any dose in breast milk.

5.3.


Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Pharmaceutical Particulars

6.1. List of Excipients

Sodium Chloride Sodium Metabisulphite Water for Injections Sulphuric acid Nitrogen

6.2. Incompatibilities

Morphine salts are sensitive to changes in pH and morphine is liable to precipitate 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, are listed below.

Acyclovir sodium: precipitate noted two hours after admixture with morphine sulphate solution.

Chlorpromazine hydroMetabisulphite injection: precipitation was considered to be due to chlorocresol present in the morphine sulphate injection.

Fluorouracil: Immediate precipitate formed after admixture of fluorouracil (1-16mg/ml) with morphine sulphate (1mg/ml) in dextrose 5% or sodium chloride 0.9%.

Frusemide: precipitate noted one hour after admixture with morphine sulphate solution.

Heparin sodium: incompatibility has been reported from straightforward additive studies. More recent studies indicate that morphine sulphate and heparin sodium were only incompatible at morphine sulphate concentrations greater than 5mg per ml and that this incompatibility could be prevented by using 0.1% sodium Metabisulphite solution as the admixture diluent rather than water.

Pethidine hydrochloride: incompatibility has been noted following admixture with morphine sulphate.

Prochlorperazine edisylate: immediate precipitation was attributed to phenol in the morphine sulphate injection formulation.

Promethazine hydrochloride: cloudiness was reported to develop when 2.5mg of promethazine hydrochloride was drawn into a syringe containing morphine sulphate 8mg. Others have noted no incompatibility.

Tetracyclines: colour change from pale yellow to light green occurred when solutions of minocycline hydroMetabisulphite or tetracycline hydroMetabisulphite were mixed with morphine sulphate in 5% glucose injection.

Oral formulations: there was no evidence of incompatibility in an oral morphine mixture containing methyl and propyl hydroxybenzoates as preservatives.

6.3.    Shelf Life

18 months

6.4.    Special Precautions for Storage

Do not store above 25 °C.

Store in the original container

6.5.    Nature and Contents of Container

Morphine Sulphate 10mg/ml in a 1ml pre-filled syringe (Type 1 clear glass with rubber stopper (type PH 701/50/C black) and tip cap rubber W 1883).

6.6.    Instruction for Use/Handling

Use once, then immediately and safely discard any remaining solution.

Administrative Data

7. Marketing Authorisation Holder

Aurum Pharmaceuticals LTD Bampton Road

Harold Hill Romford Essex RM3 8UG United Kingdom

8. Marketing Authorisation Number

12064/0084

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

04/02/2009

10 DATE OF REVISION OF THE TEXT

04/02/2009