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Methadone in Chronic Pain
Aka: Methadone in Chronic Pain, Methadone
- See Also
- Methadone for Opioid Dependence
- Definition
- Schedule II Narcotic used in Chronic Pain
- Indications
- Cancer Pain
- Chronic Pain
- Morphine allergy
- Precautions
- QT Prolongation risk and respiratory depression (especially with conversion from other Narcotic)
- FDA black box warnings
- Methadone accounts for only 2% of Opioid prescriptions
- Yet Methadone is responsible for 30% of Opioid prescription related deaths
- Prescribe Naloxone Auto-Injector
- Methadone has significant Drug Interactions (see below)
- Methadone has a very long half-life with significant variability between patients
- Respiratory depression may be significantly delayed from time of dosing
- Start at low dose, and increase by no more than 5 mg/day each week
- Closely monitor, esp. in the first 2 weeks on Methadone, or with dosage increase
- Caution patients to be aware of symptoms
- Sedation that precedes pain relief suggests a dose too high (taper down)
- Patients should not take extra doses for incomplete relief
- Avoid Methadone with Alcohol or Benzodiazepines
- Mechanism
- Mu-Opioid agonist
- More potent than Morphine on repeat dosing
- NMDA receptor antagonist
- Decreases risk of developing tolerance
- Pharmacokinetics
- Bioavailability of oral dosing: 80%
- Highly tissue bound (brain, liver, Kidneys, muscle)
- Release from tissues continues weeks after stopping
- Metabolized by liver
- Half-life: 22 hours (variable)
- No adjustment needed for Renal Insufficiency
- Duration of action
- After initial dose: 3 to 6 hours
- After repeat dosing: 8 to 12 hours
- Dosing: Patient new to Opioids
- Initial dose for most patients: 2.5 mg orally every 8 hours
- Initial dose in frail elderly: 2.5 mg orally once daily
- Increase dose as needed every 7 days
- Increase by no more than 5 mg/day each week
- Dosing: Converting to Methadone from other Narcotics
- Calculate total Morphine Equivalent dosing per 24 hours
- See Opioid for conversion ratios
- Example: Patient uses Oxycontin and Hydrocodone
- Oxycontin 80 mg PO every 12 hours
- Morphine Equivalent: 160 x30/20 = 240 mg/day
- Hydrocodone 20 mg PO every 6 hours
- Morphine Equivalent: 80 x 30/30 = 80 mg/day
- Total Morphine Equivalent: 320 mg/day
- Calculate conversion Morphine to Methadone ratio
- Current oral Morphine <100 mg/day: 3 to 1 ratio
- Current oral Morphine <300 mg/day: 5 to 1 ratio
- Current oral Morphine <600 mg/day: 10 to 1 ratio
- Current oral Morphine <800 mg/day: 12 to 1 ratio
- Current oral Morphine <1000 mg/day: 15 to 1 ratio
- Current oral Morphine >1000 mg/day: 20 to 1 ratio
- Calculate daily Methadone dose based on ratio
- Example: Same patient as above
- Methadone equivalent: 320/10 = 32 mg/day
- Methadone divided dosing: 10 mg PO q8 hours
- Titrate up to effective Methadone dose
- Provide rescue Analgesics while titrating Methadone
- Increase Methadone gradually to prevent toxicity
- Inpatient increases may be made every 1-2 days
- Outpatient increases should be made only every 5 days
-
Drug Interactions
- Avoid with medications that prolong QT Interval
- See Prolonged QT Interval due to Medication
- Avoid with CNS Depressants
- Avoid with Alcohol, Benzodiazepines
- Decreased Methadone effect
- Opioid agonist-antagonist (Stadol, Nubain, Talwin)
- Agents affecting CYP3A4 or CYPD6
- Ciprofloxacin
- Diazepam
- Alcohol Intoxication
- Fluconazole
- Increased Methadone effect (via CYP3A4 or CYPD6)
- HIV Protease Inhibitors (e.g. Ritonavir, Amprenavir)
- Nevirapine
- Phenobarbital
- Phenytoin
- Rifampin
- Adverse Effects
- Pruritus
- Nausea
- Constipation
- Sedation to confusion
- Observe for respiratory depression
- Excessive sweating of Flushing
- Advantages
- By far the least expensive long acting Narcotic agent
- One month costs <$10 contrasted with >$100 for others
- References
- Ayonrinde (2000) Med J Aust 173:536-40 [PubMed]
- Indelicato (2002) J Clin Oncol 20:348-52 [PubMed]
- Toombs (2005) Am Fam Physician 71:1353-8 [PubMed]