DIAMORPHINE HYDROCHLORIDE Powder for reconstitution for injection Ref.[9783] Active ingredients: Diamorphine

Morphine-like opioids should either be avoided in patients with biliary tract disorders or they should be given with an antispasmodic (use in biliary colic is a contraindication see 4.3 Contraindications).

Diamorphine should be given in reduced doses or with caution to patients with asthma or decreased respiratory reserve (including kyphoscoliosis, emphysema, severe obesity, cor pulmonale). Avoid use during an acute asthma attack (see 4.3 Contraindications).

Use with caution or in reduced doses in patients with toxic psychosis, CNS depression, myxoedema, prostatic hypertrophy or urethral stricture, severe inflammatory or obstructive bowel disorders, hypotension, shock, convulsive disorders, adrenal insufficiency or debilitated patients.

Care should be exercised in treating the elderly, children or debilitated patients and those with hepatic or renal impairment (see 4.2 Posology for dosage recommendations).

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

Drug dependence, tolerance and potential for abuse

For all patients, prolonged use of this product may lead to drug dependence (addiction), even at therapeutic doses. The risks are increased in individuals with current or past history of substance misuse disorder (including alcohol misuse) or mental health disorder (e.g., major depression).

Additional support and monitoring may be necessary when prescribing for patients at risk of opioid misuse.

A comprehensive patient history should be taken to document concomitant medications, including over-the-counter medicines and medicines obtained on-line, and past and present medical and psychiatric conditions.

Patients may find that treatment is less effective with chronic use and express a need to increase the dose to obtain the same level of pain control as initially experienced. Patients may also supplement their treatment with additional pain relievers. These could be signs that the patient is developing tolerance. The risks of developing tolerance should be explained to the patient.

Overuse or misuse may result in overdose and/or death. It is important that patients only use medicines that are prescribed for them at the dose they have been prescribed and do not give this medicine to anyone else.

Patients should be closely monitored for signs of misuse, abuse, or addiction.

The clinical need for analgesic treatment should be reviewed regularly.

Drug withdrawal syndrome

Prior to starting treatment with any opioids, a discussion should be held with patients to put in place a withdrawal strategy for ending treatment with diamorphine.

Drug withdrawal syndrome may occur upon abrupt cessation of therapy or dose reduction. When a patient no longer requires therapy, it is advisable to taper the dose gradually to minimise symptoms of withdrawal. Tapering from a high dose may take weeks to months.

The opioid drug withdrawal syndrome is characterised by some or all of the following: restlessness, lacrimation, rhinorrhoea, yawning, perspiration, chills, myalgia, mydriasis and palpitations. Other symptoms may also develop including irritability, agitation, anxiety, hyperkinesia, tremor, weakness, insomnia, anorexia, abdominal cramps, nausea, vomiting, diarrhoea, increased blood pressure, increased respiratory rate or heart rate.

If women take this drug during pregnancy, there is a risk that their newborn infants will experience neonatal withdrawal syndrome.

Hyperalgesia

Hyperalgesia may be diagnosed if the patient on long-term opioid therapy presents with increased pain. This might be qualitatively and anatomically distinct from pain related to disease progression or to breakthrough pain resulting from development of opioid tolerance. Pain associated with hyperalgesia tends to be more diffuse than the pre-existing pain and less defined in quality. Symptoms of hyperalgesia may resolve with a reduction of opioid dose.

Alcohol: Alcohol may enhance the sedative and hypotensive effects of diamorphine.

Anti-arrhythmics: Diamorphine may delay the absorption of mexiletine.

Antidepressants, anxiolytics, hypnotics: Severe CNS excitation or depression (hypertension or hypotension) has been reported with the concomitant use of monoamine oxidase inhibitors (MAOIs) and pethidine. It is therefore possible that a similar interaction may occur with other opioid analgesics – avoid concomitant use and for two weeks after stopping MAOIs.

The depressant effects of diamorphine may be exaggerated and prolonged by tricyclic antidepressants, anxiolytics and hypnotics.

Antivirals: Plasma concentration of opioid analgesics (except methadone) is possibly increased by ritinovir.

Opioids potentiate the effects of CNS depressants including tricyclic antidepressants, anxiolytics and hypnotics.

Antipsychotics: enhanced sedative and hypotensive effect.

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

Antimuscarinics: The risk of severe constipation and/or urinary retention is increased by administration of antimuscarinic drugs (e.g. atropine).

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

Cimetidine inhibits metabolism of opioid analgesics.

Pregnancy

Regular use during pregnancy may cause drug dependence in the foetus, leading to withdrawal symptoms in the neonate.

If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

Administration during labour may depress respiration in the neonate and an antidote for the child should be readily available.

Breast-feeding

Administration to nursing women is not recommended as diamorphine may be secreted in breast milk and may cause respiratory depression in the infant.

Diamorphine causes drowsiness and mental clouding. If affected patients should not drive or 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:
  • The medicine has been prescribed to treat a medical or dental problem and
  • You have taken it according to the instructions given by the prescriber and in the information provided with the medicine and
  • It was not affecting your ability to drive safely.

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

The most common side effects are sedation, nausea and vomiting, constipation and sweating. 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: orthostatic hypotension, facial flushing, palpitations, tachycardia, bradycardia.

Central Nervous System: dizziness, vertigo, mental clouding, confusion (with large doses), hallucinations, headache, 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: rash, pruritus, urticaria.

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

Psychiatric disorders: drug dependence (see section 4.4).

General disorders and administration site conditions: drug withdrawal syndrome.

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 or search for MHRA Yellow Card in the Google Play or Apple App store.

Physical incompatibility has been reported with mineral acids and alkalis and with chlorocresol. Mixtures of diamorphine with cyclizine, haloperidol or dexamethasone may result in precipitation. Mixtures of diamorphine and metoclopramide may become discoloured and should be discarded. Specialised references should be consulted for specific compatibility information.