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 In the treatment of opioid drug addiction.

Initially 10 - 20mg/day, increasing by 10 - 20mg/day until there is no sign of withdrawal or intoxication. The dose is adjusted according to the degree of dependence, with the aim of gradual reduction. Providing a dosage schedule is difficult as it is largely subjective based on the addict’s reported drug use and a clinical assessment of their dependence.

A cautious approach is usually adopted starting at a low dose and following with incremental increases as judged appropriate bearing in mind the general health of the patient. 5 below). The usual dose of injectable methadone, when the addict is stabilised, may need to exceed 100mg daily to prevent symptoms of opiate withdrawal.

In the treatment of moderate to severe pain Usually 5 - 10mg every 6 - 8 hours although doses should be adjusted according to response. In prolonged use it should not be administered more than twice daily. Elderly and debilitated patients In the case of the elderly or ill patients, repeated doses should be given with extreme 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 until further data becomes available 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.

Method of administration Sterile solution for subcutaneous or intramuscular injection. If repeated doses are required the intramuscular route should be used. The intramuscular route is preferred when repeated administration is required.

Volumes greater than 2ml (20mg) may need to be given 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), dry nose. Central sleep apnoea syndrome.

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 Hepatobiliary disorders: Sphincter of Oddi dysfunction (frequency not known) Metabolism and nutrition disorders SOC: Hypoglycaemia.

Reproductive System & Breast Disorders:

Decreased libido, dysmenorrhoea, amenorrhoea, sexual dysfunction 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

In the case of elderly or ill patients, repeated doses should only be given with extreme caution. Methadone is a drug of addiction and is controlled under the Misuse of Drugs Act 1971 (Schedule 2). 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. Opioid Use Disorder (abuse and dependence) 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 long-term 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 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.