Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Methadone
Drug ID BADD_D01405
Description 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.[F4685,F4688,F4691,A185885,A185900,A185903] Due to its unique mechanism of action, methadone is particularly useful for the management of hard to treat pain syndromes such as neuropathic pain and cancer pain requiring higher and more frequent doses of shorter-acting opioids.[A185888,A185891,A185897] Compared with [morphine], the gold standard reference opioid, methadone also acts as an agonist of κ- and σ-opioid receptors, as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, and as an inhibitor of serotonin and norepinephrine uptake.[A497,A5344] Specifically by inhibiting the NMDA receptor, methadone dampens a major excitatory pain pathway within the central nervous system.[A185876] Compared to other opioids, methadone's effects on NMDA inhibition may explain it's improved analgesic efficacy and reduced opioid tolerance.[A185891,A185894] Methadone shares similar effects and risks of other opioids such as [morphine], [hydromorphone], [oxycodone], and [fentanyl]. However, it also has a unique pharmacokinetic profile. Compared with short-acting and even extended-release formulations of [morphine], methadone displays a comparatively longer duration of action and half-life. These effects make methadone a good option for the treatment of severe pain and addiction as fewer doses are needed to maintain analgesia and prevent opioid withdrawal symptoms. However, methadone also has an unpredictable half-life with interindividual variability, which leads to an unpredictable risk of respiratory depression and overdose when initiating or titrating therapy.[A183995] Overall, methadone's pharmacological actions result in analgesia, suppression of opioid withdrawal symptoms, sedation, miosis, sweating, hypotension, bradycardia, nausea and vomiting (via binding within the chemoreceptor trigger zone), and constipation. At higher doses, methadone use can result in respiratory depression, overdose, and death.[F4685,F4688,F4691] Treatment of opioid addiction with methadone, [buprenorphine], or slow-release oral [morphine] (SROM) is termed Opioid Agonist Treatment (OAT) or Opioid Substitution Therapy (OST). The intention of substitution of illicit opioids with the long-acting opioids used in OAT is to prevent withdrawal symptoms for 24-36 hours following dosing to ultimately reduce cravings and drug-seeking behaviours. Use of OAT is also intended to lead to social stabilization by reducing crime rates, incarceration, use of illicit opioids such as [heroin] or [fentanyl], and ultimately marginalization.[A185882] Illegally purchased opioids present many other harms in addition to overdose as they can be injected and may be laced with other substances that increase the risk of harm or overdose. Provision of OAT is often combined with education about harm reduction including use of clean needles and injection supplies in an effort to reduce the risks associated with injection drug use such as contraction of HIV and Hepatitis C and other complications including skin infections, abscesses, or endocarditis.
Indications and Usage 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 products) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.[F4688] Methadone is also indicated for detoxification treatment of opioid addiction (heroin or other morphine-like drugs), and for maintenance substitution treatment for opioid dependence in adults in conjunction with appropriate social and medical services.[F4685,F4691]
Marketing Status approved
ATC Code N07BC02
DrugBank ID DB00333
KEGG ID D08195
MeSH ID D008691
PubChem ID 4095
TTD Drug ID D09OJQ
NDC Product Code 66689-836
UNII UC6VBE7V1Z
Synonyms Methadone | Biodone | Dolophine | Metadol | Metasedin | Symoron | Methadone Hydrochloride | Hydrochloride, Methadone | Methadose | Methex | Phenadone | Physeptone | Phymet | Pinadone | Amidone | Methaddict
Chemical Information
Molecular Formula C21H27NO
CAS Registry Number 76-99-3
SMILES CCC(=O)C(CC(C)N(C)C)(C1=CC=CC=C1)C2=CC=CC=C2
Chemical Structure
ADRs Induced by Drug
*The priority for ADR severity classification is based on FAERS assessment, followed by the most severe level in CTCAE rating. If neither is available, it will be displayed as 'Not available'.
**The 'Not Available' level is hidden by default and can be restored by clicking on the legend twice..
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Abdominal distension07.01.04.001--
Abdominal pain07.01.05.002--
Abdominal pain upper07.01.05.003--
Acute psychosis19.03.01.0010.000265%Not Available
Acute pulmonary oedema22.01.03.005; 02.05.02.0040.001326%Not Available
Acute respiratory distress syndrome24.03.02.034; 10.02.01.067; 22.01.03.0010.001458%
Acute respiratory failure22.02.06.001; 14.01.04.0040.001326%Not Available
Adrenal insufficiency14.11.01.004; 05.01.02.0010.000928%
Aggression19.05.01.0010.001724%Not Available
Agitation19.06.02.001; 17.02.05.0120.005224%
Agitation neonatal18.04.04.002; 17.02.05.0280.000663%Not Available
Altered state of consciousness19.07.01.003; 17.02.04.0010.001458%Not Available
Amenorrhoea21.01.02.001; 05.05.01.002--
Anaphylactic shock24.06.02.004; 10.01.07.002--Not Available
Anoxia22.02.02.0090.000265%Not Available
Anxiety19.06.02.002--
Apnoea22.02.01.0010.002121%
Arachnoiditis17.06.01.001; 12.02.04.0020.000265%
Arrhythmia02.03.02.0010.001724%Not Available
Asphyxia22.02.02.001; 12.01.08.0110.001193%Not Available
Aspiration22.02.07.0070.000928%
Asthenia08.01.01.001--Not Available
Ataxia17.02.02.001; 08.01.02.0040.001326%
Blindness transient06.02.10.006; 17.17.01.0040.000398%Not Available
Blood testosterone decreased13.10.05.004--Not Available
Body temperature decreased13.15.01.010--Not Available
Body temperature increased13.15.01.001--Not Available
Bradycardia02.03.02.0020.003182%Not Available
Bradykinesia17.01.02.0040.000265%Not Available
Bradypnoea22.02.01.0020.002917%Not Available
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