METH-a-done
High Alert
Absorption: 50% absorbed following oral administration. IV administration results in complete bioavailability.
Distribution: Widely distributed to tissues.
Protein Binding: 85–90%.
Half-Life: 15–25 hr (↑ with chronic use).
(analgesic effect)
| ROUTE | ONSET | PEAK | DURATION |
|---|---|---|---|
| PO | 30–60 min | 90–120 min | 4–12 hr |
| IM, IV, SUBQ | 10–20 min | 60–120 min | 8–12 hr |
Contraindicated in:
Use Cautiously in:
Structural heart disease, concurrent diuretic use, hypokalemia, hypomagnesemia, history of arrhythmia/syncope, or other risk factors for arrhythmias
;CV: hypotension, bradycardia,
QT interval prolongation
, TORSADES DE POINTESDerm: flushing, sweating
EENT: blurred vision, diplopia, miosis
Endo: adrenal insufficiency
GI: constipation, nausea, vomiting
Neuro: confusion, sedation, dizziness, dysphoria, euphoria, floating feeling, hallucinations, headache, unusual dreams
Resp: RESPIRATORY DEPRESSION (INCLUDING CENTRAL SLEEP APNEA AND SLEEP-RELATED HYPOXEMIA)
Misc: allodynia, opioid-induced hyperalgesia,
physical dependence
,psychological dependence
, toleranceDrug-drug:
Use with extreme caution with any drug known to potentially prolong QT interval, including class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers
.CYP3A4 inhibitors, CYP2C9 inhibitors, CYP2C19 inhibitors, or CYP2D6 inhibitors, including ritonavir, ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, diltiazem, verapamil, nelfinavir, fosamprenavir, and fluvoxamine, ↑ levels and risk of opioid toxicity; careful monitoring during initiation, dose changes, or discontinuation of the inhibitor is recommended.
CYP3A4 inducers, CYP2C9 inducers, or CYP2C19 inducers, including barbiturates, carbamazepine, efavirenz, corticosteroids, modafinil, nevirapine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, or rifampin, may ↓ levels and analgesia; if inducers are discontinued or dosage ↓, patients should be monitored for signs of opioid toxicity and necessary dose adjustments should be made.
Use with benzodiazepines or other CNS depressants, including other opioids, nonbenzodiazepine sedative/hypnotics, anxiolytics, general anesthetics, muscle relaxants, antipsychotics, and alcohol, may cause profound sedation, respiratory depression, coma, and death; reserve concurrent use for when alternative treatment options are inadequate.
Drug-Natural Products:
Moderate to Severe Pain
Opioid Detoxification
Assess BP, HR, and respiratory rate before and periodically during administration. If respiratory rate <10/min, assess level of sedation. Dose may need to be ↓ by 25–50%. Initial drowsiness will ↓ with continued use. Monitor for respiratory depression, especially during initiation or following dose ↑; serious, life-threatening, or fatal respiratory depression may occur. May cause sleep-related breathing disorders (central sleep apnea, sleep-related hypoxemia).
Prolonged use may lead to physical and psychological dependence and tolerance, which should not prevent patient from receiving adequate analgesia. Patients who receive methadone for pain rarely develop psychological dependence. Progressively higher doses may be required to relieve pain with long-term therapy.
Assess for history of structural heart disease, arrhythmia, and syncope. Obtain a pretreatment ECG to measure QTc interval and follow-up ECG within 30 days and annually. Additional ECGs recommended if dose >100 mg/day or if patients have unexplained syncope or seizures. If QTc interval >450 msec but <500 msec, discuss potential risks and benefits with patients and monitor more frequently. If the QTc interval >500 msec, consider discontinuing or ↓ dose; eliminating contributing factors (drugs that promote hypokalemia) or using an alternative therapy.
Assess risk for opioid addiction, abuse, or misuse prior to administration. Abuse or misuse by crushing, chewing, snorting, or injecting dissolved product will result in uncontrolled delivery of methadone and can result in overdose and death.
Lab Test Considerations:
Toxicity and Overdose:
When used for the treatment of opioid addiction in detoxification or maintenance programs, methadone is dispensed only by opioid treatment programs certified by the Substance Abuse and Mental Health Services Administration approved by the designated state authority.
Discuss availability of naloxone for emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing therapy, especially if patient has household members (including children) or other close contacts at risk for accidental exposure or overdose. Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concurrent use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. However, the presence of risk factors for overdose should not prevent the proper management of pain in any patient.
IV Administration:
Inform patient of the potential for arrhythmias and emphasize the importance of regular ECGs.