PHYSEPTONE

Method of administration Treatment goals and discontinuation Before initiating treatment with Methadone/Physeptone 10mg/ml Solution for injection, 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 Adults Initially 10-20mg per day, increasing by 10-20mg per day, until there are no signs of withdrawal or intoxication.

Treatment must be managed by physicians with suitable experience. The initial dose, safe dosage increments and the establishment of a dose that prevents withdrawal symptoms needs to be individualised. The degree of tolerance or neuroadaptation, any additional consumption of oral methadone or other opiates, the cumulative potential of methadone treatment (as opposed to shorter acting opiates) and the general health of the patient must be taken into account.

Typical doses for heavily addicted users can be fatal to those without such neuroadaptation. The usual dose of injectable methadone, when the addict is stabilised, may need to exceed 100mg daily to prevent symptoms of opiate withdrawal.

The aims of treatment should include reducing criminality and to improve patient’s health and social productivity.

Elderly and debilitated patients:

If repeated doses are required, use with caution due to the long plasma half- life. There may be a greater risk of respiratory depression, with or without any associated renal or hepatic impairment, in this age group.

Paediatric population:

As methadone has not been studied in children it should not be used in children under the age of 16 years.

Hepatic impairment:

In patients with severe liver damage the dose of methadone should be carefully controlled as there is a risk that methadone might precipitate porto-systemic encephalopathy.

Renal Impairment:

The dose may need to be reduced in moderate or severe renal impairment. Method of administration: intramuscular, subcutaneous or intravenous injection. Volumes greater than 2ml given intramuscularly may need to be administered in divided doses at different sites.

Methadone is associated with undesirable effects similar to other opioid analgesics. There are no modern clinical studies available that can be used to determine the frequency of undesirable effects. Therefore, all the undesirable effects listed are classed as “frequency unknown”.

Endocrine Disorders Hyperprolactinaemia. Psychiatric Disorders Confusion, mood change including euphoria and dysphoria, hallucinations, restlessness, sleep disturbances. 4). Nervous System Disorders Drowsiness, dizziness, vertigo. Eye Disorders Dry eyes, visual disturbances such as miosis.

Nystagmus1, strabismus1, visual acuity reduced1. (1Visual effects have been reported in infants and children exposed to methadone during pregnancy- frequency not known). Cardiac Disorders Bradycardia, tachycardia, palpitations, QT prolongation, torsades de pointes.

Vascular Disorders Orthostatic hypotension. 9 overdose), dry nose. Central sleep apnoea syndrome. Hepatobiliary disorders Sphincter of Oddi dysfunction (frequency not known). Gastrointestinal Disorders Nausea, vomiting (particularly at the start of treatment), constipation, biliary spasm, dry mouth.

Acute pancreatitis (frequency not known). Skin & Subcutaneous Tissue Disorders Sweating, facial flushing, rashes (urticaria, pruritus), oedema. Musculoskeletal, Connective Tissue & Bone Disorders Muscle rigidity. Renal & Urinary Disorders Micturition difficulties, urinary retention, ureteric spasm Reproductive System & Breast Disorders Decreased libido, dysmenorrhoea, amenorrhoea, sexual dysfunction Metabolism and nutrition disorders SOC Hypoglycaemia (frequency not known).

General & Administration Site Disorders:

Hypothermia, 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.

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Opioid Use Disorder (abuse and dependence)Methadone is a drug of addiction and is controlled under the Misuse of Drugs Act 1971 (Schedule 2). Methadone has a long half-life and can therefore accumulate. A single dose which will relieve symptoms may, if repeated on a daily basis, lead to accumulation and possible death.

Methadone is an opioid analgesic and is highly addictive in its own right. It has a long half-life and can therefore accumulate. A single dose which will relieve symptoms may, if repeated on a daily basis, lead to accumulation and possible death.

As with other opioids, tolerance, physical, and/or psychological dependence may develop upon repeated administration of methadone. When used for the treatment of pain, repeated use of [product name] can lead to Opioid Use Disorder (OUD).

A higher dose and longer duration of opioid treatment can increase the risk of developing OUD. 2). Before and during treatment the patient should also be informed about the risks and signs of OUD. If these signs occur, patients should be advised to contact their physician.

Abuse or intentional misuse of [product name] may result in overdose and/or death. , major depression, anxiety and personality disorders). , too early requests for refills). This includes the review of concomitant opioids and psycho-active drugs (like benzodiazepines).

For patients with signs and symptoms of OUD, consultation with an addiction specialist should be considered. Tolerance and dependence may occur as with morphine. Methadone can produce drowsiness and reduce consciousness although tolerance to these effects can occur after repeated use.

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 methadone. The decision to maintain a patient on a longterm opioid prescription should be an active decision agreed between the clinician and patient with review at regular intervals (usually at least three-monthly, depending on clinical progress).

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. 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 new-born infants will experience neonatal withdrawal syndrome. Sleep-related breathing disorders Opioids can cause sleep-related breathing disorders including central sleep apnoea (CSA) and sleep-related hypoxemia.

Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the total opioid dosage. Respiratory depression Due to the slow accumulation of methadone in the tissues, respiratory depression may not be fully apparent for a week or two.

Asthma may be exacerbated due to histamine release. Concomitant treatment with other agents with CNS depressant activity is not advised due to the potential for CNS and respiratory depression (see also section

1 • Patients not already receiving methadone (on account of the high methadone concentration). • Patients with respiratory depression and obstructive airways disease. • Use during an acute asthma attack. • Concurrent administration with monoamine oxidase inhibitors, or within 2 weeks of discontinuation of treatment with them.

• Phaeochromocytoma. Opiates may induce the release of endogenous histamine and stimulate catecholamine release. • Risk of paralytic ileus. • Comatose patients.