Description

Simple

A very strong painkiller medication used to treat severe pain. Also used for the treatment of opioid addiction.

Clinical

An opioid analgesic indicated for management of severe pain that is not responsive to alternative treatments. Also used to aid in detoxification and maintenance treatment of opioid addiction.

Overview

Methadone is a potent synthetic analgesic that works as a full µ-opioid receptor (MOR) agonist and N-methyl-d-aspartate (NMDA) receptor antagonist. As a full MOR agonist, methadone mimics the natural effects of the body's opioids, endorphins, and enkephalins through the release of neurotransmitters involved in pain transmission. It also has a number of unique characteristics that have led to its increased use in the last two decades; in particular, methadone has a lower risk of neuropsychiatric toxicity compared to other opioids (due to a lack of active metabolites), minimal accumulation in renal failure, good bioavailability, low cost, and a long duration of action.[21,22,23,14,19,Read more

Pharmacology

Indication

Methadone is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatment options are inadequate. It's recommended that use is reserved for use in patients for whom alternative treatment options (eg, nonopioid analgesics, opioid combination pr... Read more

Pharmacodynamic

Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis (through binding to receptors in the pupillary muscles), sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and cons... Read more

Mechanism of action

Methadone is a synthetic opioid analgesic with full agonist activity at the µ-opioid receptor. While agonism of the µ-opioid receptor is the primary mechanism of action for the treatment of pain, methadone also acts as an agonist of κ- and σ-opioid receptors within the central and peripheral nervous... Read more

Absorption

Methadone is one of the more lipid-soluble opioids and is well absorbed from the gastrointestinal tract. Following oral administration of methadone, bioavailability ranges from 36-100%, with a marked interindividual variation. It can be detected in blood as soon as 15-45 minutes following administra... Read more

Protein binding

Methadone is highly bound to plasma proteins. While it primarily binds to α1-acid glycoprotein (85-90%), it also binds to albumin and other tissue and plasma proteins including lipoproteins. Methadone is unusual in the opioid class, in that there is extensive binding to tissue proteins and fairly sl... Read more

Volume of distribution

Due to interindividual differences in pharmacokinetics, estimates of methadone's volume of distribution have ranged from 189-470 L[ Read more

Clearance

Due to interindividual differences in pharmacokinetics, estimates of methadone's clearance have ranged from 5.9–13 L/h hours[ Read more

Half life

Due to interindividual differences in pharmacokinetics, estimates of methadone's half-life have ranged from 15–207 hours[ Read more

Route of elimination

The elimination of methadone is mediated by extensive biotransformation, followed by renal and fecal excretion. Unmetabolized methadone and its metabolites are excreted in urine to a variable degree.

Toxicity

In severe overdosage, particularly by the intravenous route, apnea, circulatory collapse, cardiac arrest, and death may occur.

Adverse Effects

Effect Regions Age Groups Incidences Evidence Type
Sweating US
Varying Reports
Reduced libido and/or potency US
Varying Reports
Urinary hesitancy US
Varying Reports
Urinary Retention US
Varying Reports
Reversible thrombocytopenia US
Varying Reports
Skin rashes US
Varying Reports
Urticaria US
Varying Reports
Pruritus US
Varying Reports
Local tissue reactions US
Varying Reports
Amenorhea US
Varying Reports
Antidiuretic effect US
Varying Reports
Visual disturbances US
Varying Reports
Hemorrhagic urticaria US
Varying Reports
Seizures US
Varying Reports
Disorientation US
Varying Reports
Agitation US
Varying Reports
Confusion US
Varying Reports
Insomnia US
Varying Reports
Pulmonary Edema US
Varying Reports
Dysphoria US
Varying Reports
Euphoria US
Varying Reports
Constipation US
Varying Reports
Dry Mouth US
Varying Reports
Anorexia US
Varying Reports
Biliary tract spasm US
Varying Reports
Hypomagnesmia US
Varying Reports
Headache US
Varying Reports
Glossitis US
Varying Reports
Hypokalemia US
Varying Reports
Flushing US
Varying Reports
Cardiomyopathy US
Varying Reports
Hypotension US
Varying Reports
Heart Failure US
Varying Reports
Phlebitis US
Varying Reports
Palpitations US
Varying Reports
Abdmonial pain US
Varying Reports
Syncope US
Varying Reports
Tachycardia US
Varying Reports
Extrasystoles US
Varying Reports
Ventricular Fibrillation US
Varying Reports
Torsade de Pointes US
Varying Reports
ECG abnormalities US
Varying Reports
Ventricular Tachycardia US
Varying Reports
T-wave inversion US
Varying Reports
Prolonged QT Interval US
Varying Reports
Respiratory Depression US
Varying Reports
Severe hypotension US
Varying Reports
Asthenia US
Varying Reports
Edema US
Varying Reports
Weight Gain US
Varying Reports

Contraindications

  • Regions: Canada
  • Patient Conditions:
      • Name: Status Asthmaticus
      • Drugbank Id: DBCOND0001831
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute Pain Management
      • Drugbank Id: DBCOND0056394
      • Modification Of:
        • Base:
          • Name: Pain Management
          • Drugbank Id: DBCOND0037199
        • Severity:
          • Includes:
            • acute
  • Regions: Canada
  • Patient Conditions:
      • Name: Opioid naive
      • Drugbank Id: DBCOND0098668
  • Regions: Canada
  • Patient Conditions:
      • Name: Labor and Delivery
      • Drugbank Id: DBCOND0067235
  • Regions: Canada
  • Patient Conditions:
      • Name: Pregnancy
      • Drugbank Id: DBCOND0018394
  • Regions: Canada
  • Patient Conditions:
      • Name: CNS depression
      • Drugbank Id: DBCOND0094584
  • Regions: Canada
  • Patient Conditions:
      • Name: Cor Pulmonale
      • Drugbank Id: DBCOND0042897
  • Regions: Canada
  • Patient Conditions:
      • Name: Clostridium Difficile Infection-associated Diarrhea and Colitis
      • Drugbank Id: DBCOND0120879
  • Regions: Canada
  • With Categories Coadmin:
      • Name: Monoamine Oxidase Inhibitors
      • Drugbank Id: DBCAT001004
      • Mesh Id: D008996
  • Regions: Canada
  • Patient Conditions:
      • Name: Convulsive disorders
      • Drugbank Id: DBCOND0107830
  • Regions: Canada
  • Patient Conditions:
      • Name: Delirium Tremens (DTs)
      • Drugbank Id: DBCOND0107126
  • Regions: Canada
  • Patient Conditions:
      • Name: Acute alcoholism
      • Drugbank Id: DBCOND0107892
      • Modification Of:
        • Base:
          • Name: Alcoholism
          • Drugbank Id: DBCOND0006017
        • Severity:
          • Includes:
            • acute
  • Regions: Canada
  • Patient Conditions:
      • Name: Suspected surgical abdomen
      • Drugbank Id: DBCOND0107886
  • Regions: US
  • Patient Conditions:
      • Name: Bowel Obstruction
      • Drugbank Id: DBCOND0031840
  • Regions: US
  • Patient Conditions:
      • Name: Acute or severe bronchial asthma
      • Drugbank Id: DBCOND0107797
  • Regions: US
  • Patient Conditions:
      • Name: Paralytic Ileus
      • Drugbank Id: DBCOND0047064
  • Route:
    • Subcutaneous
    • Intramuscular
    • Intravenous
    • Oral
  • Dose Form:
    • Injection
  • Regions: US
  • Patient Conditions:
      • Name: Hypercarbia
      • Drugbank Id: DBCOND0063116
  • Route:
    • Subcutaneous
    • Intramuscular
    • Intravenous
    • Oral
  • Dose Form:
    • Injection
  • Regions: US
  • Patient Conditions:
      • Name: Respiratory Depression
      • Drugbank Id: DBCOND0034868

Food Interactions

Avoid alcohol.

Take with or without food. Food does not significantly affect absorption.