i) Diamorphine Hydrochloride BP for Injection 10mg.

ii) Diamorf 10mg

iii) 'Diagesil' precedes Diamorphine Hydrochloride BP for Injection 10mg when marketed by APS Berk

Diamorphine Hydrochloride BP 10mg.

A freeze dried powder, which when in aqueous solution is suitable for parenteral administration.

For the relief of severe pain such as that associated with cancer, acute myocardial infarction and in the treatment of acute pulmonary oedema.

By intramuscular, subcutaneous or intravenous injection, the latter 2 routes using either bolus injection or infusion.

It is important that dosage be suited to the individual patient, taking into account the properties of the drug, the nature of the pain, the total condition of the patient and previous or concurrent medication.

Adults:

Cancer: Use of diamorphine or other narcotic analgesics although very important, should be only one part of the comprehensive approach to total pain control, which ideally should include non-drug measures and psycho-social support. Diamorphine may be used parenterally when oral administration of narcotic analgesics is no longer possible because of the dosage required, impaired absorption, intestinal disorders, nausea and vomiting or difficulty in swallowing.

An initial dosage of 5 to 10mg every 4 hours may be suitable, but higher doses are reported in the literature (Dover SB, BMJ 1987, 294, 553-555). The initial dosage will usually depend on the doses and drugs given previously.

Persistent pain is controlled by titrating the dose against the degree of pain, until the smallest dose required to remove the pain is reached. This dose is maintained and the patient's condition continually re-assessed, the dose being increased or decreased as necessary. The therapeutic objective must be to control the pain by regular administration of the correct dose when this is determined, and continuous infusion may be preferred to intermittent therapy.

Acute myocardial infarction: A dose of 5mg may be given by slow intravenous injection (1mg per minute), followed by 2.5 to 5mg if necessary.

Acute pulmonary oedema: A dose of 2.5 to 5mg may be given by slow intravenous injection (1mg per minute).

Equivalent Doses of Morphine Sulphate by mouth (as oral solution or standard tablets or as modified-release tablets) or of Diamorphine Hydrochloride by Intramuscular Injection or by Subcutaneous Infusion:

These equivalences are approximate only and may need to be adjusted according to response:

Children:

Diamorphine has been used in the treatment of terminally ill children. Diamorphine has been administered in reduced doses to children with neoplastic disease when it becomes difficult to give treatment orally. The starting dose should be selected according to age, size, symptoms and previous analgesic requirements and administered 4 hourly; the dose being titrated according to the degree of pain. If treatment continues for more than 24 hours it may be appropriate to use a syringe driver (Burne R, Hunt A, Palliative Medicine 1987, 1, 27-30)

Elderly:

Mainly because of its respiratory depressant effect caution should be exercised when giving the drug to the elderly and a reduced dose should be used.

Respiratory depression, obstructive airways disease. Concurrent administration of monoamine oxidase inhibitors or within two weeks of discontinuation of treatment with them. Biliary Colic. Phaeochromocytoma.

Tolerance and physical dependence on the drug is likely to develop in most patients after a few weeks of treatment, but this does not prevent reduction of dosage or discontinuation when considered necessary, and drug abuse is not normally a problem in patients with severe pain. Caution should be exercised, however, in using the drug in patients with a known tendency to, or history of, drug abuse. Care should be exercised in treating the elderly, debilitated patients, and those with hepatic or renal impairment. It is recommended that a lower than normal initial dose is given to these patients. Administration to patients with head injuries or raised intracranial pressure increases the risk of respiratory depression and further elevation of CSF pressure. The sedation and pupillary changes produced may interfere with accurate monitoring of the patient. The drug can cause hypotension in patients who already have conditions or drug therapy that interfere with the ability to maintain normal blood pressure. Careful consideration should be given before treating patients with myxoedema or hypothyroidism, adrenocortical insufficiency, toxic psychoses, CNS depression, prostatic hypertrophy or urethral stricture, kyphoscoliosis, acute alcoholism and delirium tremens, severe inflammatory bowel disease and severe diarrhoea.

Concurrent administration of other CNS sedative/hypnotic drugs may have an addictive effect necessitating their dosage reduction. Administration of drugs having anti-muscarinic activity (atrophine and synthetic anti-cholinergics) may increase the risk of severe constipation and/or urinary retention.

There is no evidence of safety in human pregnancy, therefore, as with all drugs it is not advisable to administer diamorphine during pregnancy. Use during labour is not advisable due to the risk of respiratory depression in the new-born.

There is limited information on diamorphine levels in breast milk and it is, therefore, not advisable for patients on high doses of diamorphine to breast-feed.

May impair ability to drive and use machinery.

The most serious hazards of therapy are respiratory depression and arrest, although circulatory depression, shock and cardiac arrest can occur. The most common side-effects are:- sedation, nausea and vomiting, constipation and sweating. Other side-effects include tachycardia, postural hypotension, palpitations, faintness and syncope, euphoria, dysphoria, weakness, insomnia, dizziness, confusional symptoms and occasionally hallucinations; dry mouth, anorexia, cramps, taste alterations; urinary retention, reduced libido or potency; pruritus, urticaria and other skin rashes.

The symptoms of serious overdosage are respiratory depression, stupor or coma, muscle flaccidity, cold clammy skin, constricted pupils and occasionally bradycardia and hypotension. The specific antidote naloxone is indicated if coma or bradypnoea are present. A dose of 0.4 to 2mg may be given by s.c., i.m. or i.v. injection repeated at intervals of 2-3 minutes up to a maximum of 10mg if respiratory function does not improve. The dosage for children is 10 micrograms per kilogram body weight. Alternatively, naloxone may be given by continuous i.v. infusion; 2mg diluted in 500ml intravenous solution, at a rate adjusted to the patient's response.

Diamorphine is a narcotic analgesic obtained from opium which acts mainly on the central nervous system and smooth muscle. It can provoke the release of endogenous histamine and thereby induce catecholamine release.

Absorption:

Rapidly and completely absorbed after oral administration or by injection, absorption from the gastro-intestinal tract may be erratic.

Blood concentration:

In cases of fatal overdose, the total morphine concentrations of 100 to 900ng/ml have been detected.

Half life

Range 1.7 - 5.3 minutes, mean 3 minutes, active metabolites 2-3 hours.

Distribution:

The diamorphine metabolites, morphine and 6-monoacetylmorphine, rapidly cross the blood brain barrier. Morphine crosses the placenta and is secreted in the milk.

Metabolic reactions:

Rapidly hydrolysed to 6-monoacetylmorphine which is further hydrolysed to morphine. Normorphine is also formed, all metabolites may be conjugated with glucuronic acid, morphine may be conjugated at positions 3 or 6.

Excretion:

Up to 80% of a dose is recovered in the urine in 24 hours, after oral or parenteral administration, most of the dose is recovered as morphine-3-glucuronide with about 5 to 7% as free morphine, 1% as 6-monoacetylmorphine, 0.1% as unchanged drug and trace amounts of the other metabolites.

None available.

None detectable

Diamorphine is incompatible with mineral acids and alkalis.

24 months

Store below 25ºC. Protect from light.

Five 2ml type 1 neutral glass ampoules contained in a printed tamper evident cardboard carton.

Reconstitute in 1ml of water for injections. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.

Novartis Vaccines and Diagnostics Limited

Gaskill Road

Speke

Liverpool

L24 9GR

United Kingdom

PL 18532/0005

1 February 2001

August 2006