Methadone


Generic Medicine Info
Indications and Dosage
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.

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.
Special Precautions
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.
Adverse Reactions
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.
IM/IV/Parenteral/PO/SC: C
Patient Counseling Information
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

Chemical Structure Image
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.
MIMS Class
Analgesics (Opioid) / Drugs Used in Substance Dependence
ATC Classification
N07BC02 - methadone ; Belongs to the class of drugs used in the management of opioid dependence.
References
Anon. Methadone. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 28/08/2020.

Anon. Methadone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 28/08/2020.

Buckingham R (ed). Methadone Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/08/2020.

Dolophine Tablet (West-Ward Pharmaceuticals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/08/2020.

Joint Formulary Committee. Methadone Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/08/2020.

Methadone Hydrochloride Concentrate (VistaPharm Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/08/2020.

Methadone Hydrochloride Injection, Solution (Mylan Institutional LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/08/2020.

Methadone Hydrochloride Solution (Atlantic Biologicals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/08/2020.

Methadone Hydrochloride Tablet (Cebert Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 28/08/2020.

Methadone Pliva (DCH Auriga (Hong Kong) Ltd). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 01/09/2020.

Physeptone 1 mg/mL Oral Solution Sugar-Free (Martindale Pharmaceuticals Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 28/08/2020.

Physeptone 25 mg/mL Solution for Injection (Macarthys Laboratoris Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 28/08/2020.

Physeptone 5 mg Tablets (Macarthys Laboratoris Ltd). MHRA. https://products.mhra.gov.uk/. Accessed 28/08/2020.

Disclaimer: This information is independently developed by MIMS based on Methadone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 MIMS. All rights reserved. Powered by MIMS.com
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