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.
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.
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.
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.
Administration
May be taken with or without food.
Reconstitution
Dispersible tablet: Dissolve the tablet in approx 120 mL of water, orange juice, or any acidic fruit drink.
Contraindications
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.
This 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.
Overdosage
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.
Drug Interactions
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.
Food Interaction
Increased CNS depressant effect with alcohol. Increased serum plasma concentration with grapefruit. Decreased serum plasma concentration with St John’s Wort.
Action
Description: Methadone is a diphenylheptane derivative opioid agonist that primarily acts on the μ 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). Pharmacokinetics: 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.
Chemical Structure
Methadone Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 4095, Methadone. https://pubchem.ncbi.nlm.nih.gov/compound/Methadone. Accessed Dec. 21, 2020.
Storage
Tab/oral solution: Store between 20-25°C. Oral concentrate/Solution for inj: Store between 20-25°C. Protect from light.
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