Methadone

Oral
Severe pain
Adult: For pain management that is opioid responsive and requires daily, continuous and long-term treatment: 2.5-10 mg 6-8 hourly.
Renal impairment: Dosage adjustment may be needed.
Hepatic impairment: Dosage adjustment may be needed. Severe: Contraindicated.
Reconstitution: Dispersible tablet: Dissolve the tablet in approx 120 mL of water, orange juice, or any acidic fruit drink.

Oral
Opioid dependence
Adult: Initially, 10-40 mg daily, may increase in increments of 5-10 mg to a max weekly increase of 30 mg. Dosage must be individualised and adjusted to keep withdrawal symptoms at a tolerable level.
Renal impairment: Dosage adjustment may be needed.
Hepatic impairment: Dosage adjustment may be needed. Severe: Contraindicated.
Reconstitution: Dispersible tablet: Dissolve the tablet in approx 120 mL of water, orange juice, or any acidic fruit drink.

Parenteral
Severe pain
Adult: For pain management that is opioid responsive and requires daily, continuous and long-term treatment: 2.5-10 mg 6-8 hourly via IM/SC/IV inj.
Renal impairment: Dosage adjustment may be needed.
Hepatic impairment: Dosage adjustment may be needed. Severe: Contraindicated.
Reconstitution: Dispersible tablet: Dissolve the tablet in approx 120 mL of water, orange juice, or any acidic fruit drink.

Parenteral
Opioid dependence
Adult: Initially, 10-40 mg daily, may increase in increments of 5-10 mg to a max weekly increase of 30 mg. Doses are given via IM/SC/IV inj. Dosage must be individualised and adjusted to keep withdrawal symptoms at a tolerable level.
Renal impairment: Dosage adjustment may be needed.
Hepatic impairment: Dosage adjustment may be needed. Severe: Contraindicated.
Reconstitution: Dispersible tablet: Dissolve the tablet in approx 120 mL of water, orange juice, or any acidic fruit drink.

May be taken with or without food.

Severe respiratory depression, bronchial asthma (in the absence of resuscitative equipment or with unmonitored settings), hypercabia, known or suspected gastrointestinal obstruction, paralytic ileus, ulcerative colitis, biliary or renal tract spasm, increased intracranial pressure, head injury, acute alcoholism, severe hepatic impairment; patient under coma. Concurrent use of or within 14 days of discontinuing MAOIs.

Patient with CV disease (e.g. acute MI, cardiac hypertrophy), hypovolaemia, COPD, adrenocortical insufficiency (e.g. Addison's disease), seizures, delirium tremens, mental health disorders (e.g. depression, anxiety disorders, posttraumatic stress disorder), psychosis, prostatic hyperplasia, thyroid dysfunction, electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia). Elderly, debilitated, and obese patients. Renal and hepatic impairment. Pregnancy and lactation. Avoid abrupt withdrawal. Patient CounsellingThis drug may cause drowsiness, if affected, do not drive or operate machinery. Monitoring Parameters Screen patient for any physical or psychological dependence before treatment. Obtain baseline ECG and monitor for QTC prolongation. Routinely check blood pressure, CNS status, respiratory status, and degree of sedation. Assess for signs of misuse, abuse, or addiction, respiratory depression, and serotonin syndrome.

Significant: QT prolongation, serious arrhythmias (e.g. torsade de pointes), severe hypotension, serotonin syndrome, constipation, secondary hypogonadism leading to mood disorders and osteoporosis (long term use), severe elevation of intracranial pressure, seizures, sleep related disorders (e.g. central sleep apnoea [CSA], hypoxaemia), Oddi constriction. Ear and labyrinth disorders: Vertigo. Eye disorders: Blurred vision, miosis. Gastrointestinal disorders: Nausea, vomiting, dry mouth. General disorders and administration site conditions: Fatigue, injection site pain, erythema, and swelling. Investigations: Increased weight. Metabolism and nutrition disorders: Fluid retention. Nervous system disorders: Sedation, dizziness, drowsiness, light-headedness, confusion. Psychiatric disorders: Euphoria, hallucinations. Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria, diaphoresis.
Potentially Fatal: Respiratory depression.

Symptoms: Respiratory depression, somnolence progressing to stupor or coma, pin-point pupils, skeletal muscle flaccidity, cold and clammy skin, bradycardia, hypotension, mydriasis with hypoxia; pulmonary oedema, apnoea, circulatory collapse, cardiac arrest, death. Management: Supportive treatment. For patients with clinically significant respiratory depression, administer IV opioid antagonists (e.g. naloxone). Acidify the urine to increase excretion. Perform ECG monitoring; check for respiratory function.

Increased serum concentrations with CYP3A4 inhibitors (e.g. clarithromycin, erythromycin, delavirdine, fluconazole, itraconazole, ketoconazole, fluoxetine, fluvoxamine). Decreased serum concentrations with CYP3A4 inducers (e.g. barbiturates, carbamazepine, phenytoin, nevirapine, rifampicin, efavirenz, amprenavir, spironolactone, dexamethasone). Increased risk of QT prolongation with antiarrhythmics (e.g. sotalol, amiodarone), antipsychotics (e.g. thioridazine, haloperidol, sertindole, phenotiazines), antidepressants (e.g. paroxetine, sertraline). Increased risk of serotonin syndrome with SSRIs, SNRIs and TCAs.
Potentially Fatal: Increased risk of CNS depression with MAOIs.

Increased CNS depressant effect with alcohol. Increased serum plasma concentration with grapefruit. Decreased serum plasma concentration with St John's wort.

Methadone is a diphenylheptane derivative opioid agonist that primarily acts on the mc receptor. It inhibits the ascending pain pathways, alters the perception of and response to pain, and causes a generalized CNS depression.
Onset: 0.5-1 hour (oral); 10-20 minutes (parenteral).
Duration: 4-8 hours (as single oral dose); 22-48 hours (as maintenance oral dose).
Absorption: Readily absorbed from the gastrointestinal tract. Bioavailability: 36-100% (oral). Time to peak plasma concentration: 1-7.5 hours
Distribution: Widely distributed in the body tissues, crosses placenta, and enters breast milk. Volume of distribution: 1-8 L/kg. Plasma protein binding: 60-90% mainly to α₁-acid glycoprotein.
Metabolism: Metabolised in the liver via N-demethylation by CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6 into its inactive metabolites.
Excretion: Via urine (<10% as unchanged drug) and faeces. Terminal elimination half-life: 8-59 hours.

Oral: Tab/oral solution: Store between 20-25°C. Oral concentrate/Solution for inj: Store between 20-25°C. Protect from light Parenteral: Tab/oral solution: Store between 20-25°C. Oral concentrate/Solution for inj: Store between 20-25°C. Protect from light

Analgesics (Opioid) / Antidotes, Detoxifying Agents & Drugs Used in Substance Dependence

N07BC02 - methadone ; Belongs to the class of drugs used in the management of opioid dependence.