METHADOSE

Treatment goals and discontinuation Before initiating treatment with methadone, a treatment strategy including treatment duration and treatment goals 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. 4). 4).

Posology Dosage Recommendations:

Adults: Initially 10-20mg per day, increasing by 10-20mg per day until there are no signs of withdrawal or intoxication. The usual dose is 40-60mg per day. The dose is adjusted according to the degree of dependence with the aim of gradual reduction.

Elderly:

In the case of elderly or ill patients repeated doses should only be given with extreme caution.

Children:

Not recommended for children. Method of Administration For oral administration only. This product is intended to be used with a diluent.

The adverse effects of methadone are generally the same as with other opioids, most commonly nausea and vomiting, which are observed in approximately 20% of the patients who undergo methadone out-patient treatment, where the medicinal control is often unsatisfactory.

The most serious adverse effect of methadone is respiratory depression, which may emerge during the stabilisation phase. Apnoea, shock and cardiac arrest have occurred. Adverse reactions listed below are classified according to frequency and system organ class.

These reactions are more frequently observed in non- opioid-tolerant individuals. Frequency groupings are defined according to the following convention: 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).

System organ class (MedDRA) Frequency Adverse event Blood and lymphatic system disorders Not known Reversible thrombocytopenia has been reported in opioid- dependent patients with chronic hepatitis. 4) Common SedationNervous system disorders Uncommon Headache, syncope Common Blurred vision, miosis, dry eyes Eye disorders Not known Nystagmus, Strabismus, visual acuity reduced* Ear and labyrinth disorders Common Vertigo Cardiac disorders Rare Bradycardia, palpitations, cases of prolonged QT interval and torsade de pointes have been reported, especially with high doses of methadone.

Vascular disorders Uncommon Facial flush, hypotension Uncommon Pulmonary oedema, exacerbation of asthma, dry nose, respiratory depression particularly with large doses, Respiratory, thoracic and mediastinal disorders Not known Central sleep apnoea syndrome Very common Nausea, vomiting Common Constipation Gastrointestinal disorders Uncommon Xerostomia, glossitis Hepatobiliary disorders Uncommon Bile duct dyskinesia Common Transient rash, sweatingSkin and subcutaneous tissue disorders Uncommon Pruritis, urticaria, other rash and in very uncommon cases bleeding urticaria Endocrine disorders Not known Raised prolactin levels with long-term administration Hypoadrenalism, Hypogonadism Renal and urinary disorders Uncommon Urinary retention, anti- diuretic effect Reproductive system and breast disorders Uncommon Reduced potency, galactorrhoea, dysmenorrhoea and amenorrhoea Common Fatigue, drowsinessGeneral disorders and administration site conditions Uncommon Oedema of the lower extremities, asthenia, oedema, hypothermia, drug withdrawal syndrome Investigations Common Weight increase *Visual effects have been reported in infants and children exposed to methadone during pregnancy.

Tolerance and dependence of the morphine type may occur, though it is said that methadone has a greater respiratory depressive effect and a lesser sedative effect than an equianalgesic dose of morphine. Toxic doses are highly variable, regular usage giving tolerance.

Pulmonary oedema is a frequent corollary of overdosage whilst the dose-related histamine-releasing property of methadone may account for at least some of the urticaria and pruritis associated with methadone administration. Methadone may lead to an increase in intracranial pressure.

Adverse effects occurring more rarely in patients being treated for opioid addiction are as follows: (a) A number of heroin patients have been reported to die within a few days of starting a methadone maintenance programme. Evidence of chronic persistent hepatitis was detected in ten heroin patients, who died within 2-6 days of starting methadone treatment.

The mean prescribed dose at the time of death was about 60mg. It has been suggested that these sudden deaths may have arisen as a result of accumulation of methadone over several days resulting in death from complications such as cardiac arrhythmias or cardiovascular collapse as methadone, like dextropropoxyphene, has membrane stabilising activity and can block nerve conduction.

In view of the possibility of reduced clearance and raised plasma levels it is recommended that liver function tests and urine tests be carried out prior to maintenance and that lower starting doses of methadone be used. (b) Evidence of hypoadrenalism has been found in chronic methadone patients.

Findings consistent with both deficient ACTH production and subsequent secondary hypoadrenalism and methadone induced primary adrenal cortical hypofunction have been reported. (c) Choreic movements involving the upper limbs, torso and speech mechanisms have been reported in a 25-year-old man receiving methadone hydrochloride maintenance therapy (45-60 mg/day) for 2 years.

• Respiratory depression, obstructive airway disease. Use during an acute asthma attack is not recommended. 5). 5). • Patients dependent on non-opioid drugs. • Use during labour is not recommended, the prolonged duration of action increases the risk of neonatal depression.

• Methadone is not suitable for children (serious risk of toxicity). 1. 8: papillary response affected) or head injury. • Phaeochromocytoma. • Risk of paralytic ileus (including drug induced gastrointestinal hypotonia).