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Methadone in Chronic PainAka: Methadone

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  1. See Also
    1. Methadone for Opioid Dependence
  2. Definition
    1. Schedule II Narcotic used in Chronic Pain
  3. Indications
    1. Cancer Pain
    2. Chronic Pain
    3. Morphine allergy
  4. Mechanism
    1. Mu-Opioid agonist
      1. More potent than morphine on repeat dosing
    2. NMDA receptor antagonist
      1. Decreases risk of developing tolerance
  5. Pharmacokinetics
    1. Bioavailability of oral dosing: 80%
    2. Highly tissue bound (brain, liver, kidneys, muscle)
      1. Release from tissues continues weeks after stopping
    3. Metabolized by liver
    4. Half-life: 22 hours (variable)
    5. No adjustment needed for renal insufficiency
    6. Duration of action
      1. After initial dose: 3 to 6 hours
      2. After repeat dosing: 8 to 12 hours
  6. Dosing: Patient new to Opioids
    1. Initial dose for most patients: 2.5 mg PO q8 hours
    2. Initial dose in frail elderly: 2.5 mg PO once daily
    3. Increase dose as needed every 5-7 days
  7. Dosing: Converting to methadone from other Narcotics
    1. Calculate total morphine equivalent dosing per 24 hours
      1. See Opioid for conversion ratios
      2. Example: Patient uses Oxycontin and Hydrocodone
        1. Oxycontin 80 mg PO every 12 hours
          1. Morphine equivalent: 160 x30/20 = 240 mg/day
        2. Hydrocodone 20 mg PO every 6 hours
          1. Morphine equivalent: 80 x 30/30 = 80 mg/day
        3. Total morphine equivalent: 320 mg/day
    2. Calculate conversion morphine to methadone ratio
      1. Current oral morphine <100 mg/day: 3 to 1 ratio
      2. Current oral morphine <300 mg/day: 5 to 1 ratio
      3. Current oral morphine <600 mg/day: 10 to 1 ratio
      4. Current oral morphine <800 mg/day: 12 to 1 ratio
      5. Current oral morphine <1000 mg/day: 15 to 1 ratio
      6. Current oral morphine >1000 mg/day: 20 to 1 ratio
    3. Calculate daily methadone dose based on ratio
      1. Example: Same patient as above
        1. Methadone equivalent: 320/10 = 32 mg/day
        2. Methadone divided dosing: 10 mg PO q8 hours
    4. Titrate up to effective methadone dose
      1. Provide rescue Analgesics while titrating methadone
      2. Increase methadone gradually to prevent toxicity
      3. Inpatient increases may be made every 1-2 days
      4. Outpatient increases should be made only every 5 days
  8. Drug Interactions
    1. Decreased methadone effect
      1. Opioid agonist-antagonist (Stadol, Nubain, Talwin)
      2. Agents affecting CYP3A4 or CYPD6
        1. Ciprofloxacin
        2. Diazepam
        3. Alcohol intoxication
        4. Fluconazole
    2. Increased methadone effect (via CYP3A4 or CYPD6)
      1. HIV Protease Inhibitors (e.g. Ritonavir, Amprenavir)
      2. Nevirapine
      3. Phenobarbital
      4. Phenytoin
      5. Rifampin
  9. Adverse Effects
    1. Pruritus
    2. Nausea
    3. Constipation
    4. Sedation to confusion
      1. Observe for respiratory depression
    5. Excessive sweating of Flushing
  10. Advantages
    1. By far the least expensive long acting Narcotic agent
      1. One month costs <$10 contrasted with >$100 for others
  11. References
    1. Ayonrinde (2000) Med J Aust 173:536
    2. Indelicato (2002) J Clin Oncol 20:348
    3. Toombs (2005) Am Fam Physician 71:1353

Methadone (C0025605)

Definition (MSH)A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. It also has a depressant action on the cough center and may be given to control intractable cough associated with terminal lung cancer. Methadone is also used as part of the treatment of dependence on opioid drugs, although prolonged use of methadone itself may result in dependence. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3)
Definition (CSP)synthetic narcotic possessing pharmacologic actions similar to those of morphine and heroin and almost equal addiction liability; used as an analgesic and as a narcotic abstinence syndrome suppressant in the treatment of heroin addition.
Definition (NCI)A synthetic opioid with analgesic activity. Methadone mimics the actions of endogenous peptides at CNS opioid receptors, primarily on the mu-receptor and has actions similar to those of morphine and morphine-like agents. The characteristic morphine-like effects include analgesia, euphoria, sedation, respiratory depression, miosis, bradycardia and physical dependence. However, the detoxification symptoms between morphine-like agents and methadone differ in that the onset of methadone's withdrawal symptoms is slower, the course is more prolonged and the symptoms are less severe.
ConceptsOrganic Chemical (T109) , Pharmacologic Substance (T121)
EnglishMethadone, METHADONE PREPARATION
Spanishmetadona
Parent Conceptsdiphenylhaptane derivative opioids (C0682981), Analgesics (C0002771), Narcotics (C0027415), Phenylalkylamine (C0597214), Ketones (C0022634), Opioids (C0242402), Opioid Receptor Agonist (C1883695), Analgesics, Opioid (C0002772), Methadone analog (C0360472), Phenylheptylamine derivative (C1628322), Drugs used to treat addiction (C1629845), Opioid Analgesics, Long-acting (C1579330)
SourcesAOD, CSP, LNC, MEDLINEPLUS, MSH, MTH, NCI, NDFRT, RXNORM, SCTSPA, SNOMEDCT, USPMG, VANDF
Derived from the NIH UMLS (Unified Medical Language System)



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