MXL

Posology MXL prolonged-release capsules should be used at 24-hourly intervals. The dosage is dependent upon the severity of the pain, the patient’s age and previous history of analgesic requirements. Adults and elderly Patients presenting with severe uncontrolled pain, who are not currently receiving opioids, should have their dose requirements calculated through the use of immediate release morphine, where possible, before conversion to MXL prolonged-release capsules.

Patients presenting in pain, who are currently receiving weaker opioids should be started on: a) 60 mg MXL prolonged-release capsules once-daily if they weigh over 70 kg. b) 30 mg MXL prolonged-release capsules once-daily if they weigh under 70 kg, are frail or elderly.

Increasing severity of pain will require an increased dosage of MXL prolonged-release capsules using 30 mg, 60 mg, 90 mg, 120 mg, 150 mg or 200 mg alone or in combination to achieve pain relief. Higher doses should be made, where appropriate in 30% - 50% increments as required.

The correct dosage for any individual patient is that which controls the pain with no or tolerable side effects for a full 24 hours. Patients receiving MXL prolonged-release capsules in place of parenteral morphine should be given a sufficiently increased dosage to compensate for any reduction in analgesic effects associated with oral administration.

Usually such increased requirement is of the order of 100%. In such patients, individual dose adjustments are required. Children aged 1 year and above The use of MXL prolonged-release capsules in children has not been extensively evaluated.

6 mg morphine per kg bodyweight daily is recommended. Doses should be titrated in the normal way as for adults. Method of administration Route of administration: oral The capsules may be swallowed whole or opened and the contents sprinkled on to soft cold food.

The capsule and contents should not be crushed or chewed. MXL prolonged-release capsules should be used at 24h-hourly interval. The dosage is dependent upon the severity of the pain, the patient’s age and previous history of analgesic requirements.

Treatment goals and discontinuation Before initiating treatment with MXL prolonged-release capsules, a treatment strategy including treatment duration and treatment goals, and a plan for end of the treatment, should be agreed together with the patient, in accordance with pain management guidelines.

During treatment, there should be frequent contact between the physician and the patient to evaluate the need for continued treatment, consider discontinuation and to adjust dosages if needed. When a patient no longer requires therapy with MXL prolonged-release capsules, it may be advisable to taper the dose gradually to prevent symptoms of withdrawal.

4). Duration of treatment MXL prolonged-release capsules should not be used longer than necessary. Discontinuation of therapy An abstinence syndrome may be precipitated if opioid administration is suddenly discontinued. Therefore, the dose should be gradually reduced prior to discontinuation.

In normal doses, the commonest side effects of morphine are nausea, vomiting, constipation and drowsiness. With chronic therapy, nausea and vomiting are unusual with MXL prolonged-release capsules but should they occur the capsules can be readily combined with an anti-emetic if required.

Constipation may be treated with appropriate laxatives.

The following frequencies are the basis for assessing undesirable effects:

Very common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100), Rare (≥ 1/10,000 to < 1/1,000), Very rare (< 1/10,000), Not known (cannot be estimated from the available data). 4) Eye disorders Visual impairment Miosis Ear and labyrinth disorders Vertigo Cardiac disorders Palpitations Bradycardia Tachycardia Vascular disorders Facial flushing Hypotension Hypertension Respiratory thoracic and mediastinal disorders Bronchospasm Pulmonary oedema Respiratory depression Cough decreased Central sleep apnoea syndrome Gastrointestinal disorders Constipation Nausea Abdominal pain Anorexia Dry mouth Vomiting Dyspepsia Ileus Taste perversion Pancreatitis Hepatobiliary disorders Increased hepatic enzymes Biliary pain Exacerbation of pancreatitis Sphincter of Oddi dysfunction Skin and subcutaneous tissue disorders Rash Urticaria Acute generalised exanthematous pustulosis (AGEP) Renal and urinary disorders Urinary retention Ureteric spasm Very Common Common Uncommon Not known Reproductive system and breast disorders Amenorrhoea Decreased libido Erectile dysfunction General disorders and administration site conditions Asthenia Fatigue Malaise Pruritus Peripheral oedema Drug tolerance Drug withdrawal (abstinence) syndrome Drug withdrawal (abstinence) syndrome neonatal The effects of morphine have led to its abuse and dependence may develop with regular, inappropriate use.

This is not a major concern in the treatment of patients with severe pain. Drug dependence and withdrawal (abstinence) syndrome Repeated use of MXL prolonged-release capsules can lead to drug dependence, even at therapeutic doses. 4).

5) • Tolerance, physical dependence and withdrawal (see below) • Opioid Use Disorder • Psychological dependence [addiction], abuse profile and history of substance and/or alcohol abuse (see below) • Acute alcoholism • Delirium tremens • Intracranial lesions or increased intracranial pressure, reduced level of consciousness of uncertain origin • Hypotension with hypovolaemia • Hypothyroidism • Adrenocortical insufficiency • Convulsive disorders • Biliary tract disorders • Pancreatitis • Prostatic hypertrophy • Inflammatory bowel disorders • Severely impaired renal function • Severely impaired hepatic function • Constipation As with all narcotics, a reduction in dosage may be advisable in the elderly.

MXL prolonged-release capsules should not be used where there is a possibility of paralytic ileus occurring. Should paralytic ileus be suspected or occur during use, MXL prolonged-release capsules should be discontinued immediately.

Respiratory depression The primary risk of opioid excess is respiratory depression. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use may increase the risk of CSA in a dose-dependent fashion. 8). In patients who present with CSA, consider decreasing the total opioid dosage. Severe cutaneous adverse reactions (SCARs) Acute generalized exanthematous pustulosis (AGEP), which can be life-threatening or fatal, has been reported in association with morphine treatment.

Most of these reactions occurred within the first 10 days of treatment. Patients should be informed about the signs and symptoms of AGEP and advised to seek medical care if they experience such symptoms. If signs and symptoms suggestive of these skin reactions appear, morphine should be withdrawn and an alternative treatment considered.

Risk from concomitant use of sedative medicines such as benzodiazepines or related drugs: Concomitant use of morphine and sedative medicines such as benzodiazepine or related drugs may result in sedation, respiratory depression, coma and death.

1. • Severe chronic obstructive pulmonary disease • Severe bronchial asthma • Severe respiratory depression with hypoxia and/or hypercapnia • paralytic ileus • Acute abdomen • Head injury • Delayed gastric emptying • Known morphine sensitivity • Acute hepatic disease • Concurrent administration of monoamine oxidase inhibitors (MAOIs) or within two weeks of discontinuation of their use.

Not recommended during pregnancy or for pre-operative use or for the first 24 hours post- operatively. Children under one year of age.