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Methadose Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Oral concentrate—1000mL
Manufacturer
Generic Availability
YES
Mechanism of Action
Methadone is a mu-agonist with multiple actions involving the CNS and organs composed of smooth muscle. The principal therapeutic uses for methadone are for analgesia and for detoxification or maintenance in opioid addiction. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-aspartate (NMDA) receptor.
Methadose Indications
Indications
Detoxification treatment of opioid addiction (heroin or other morphine-like drugs). Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.
Limitations of Use
Methadone products when used for the treatment of opioid addiction in detoxification or maintenance programs are subject to the conditions for distribution and use required under 21 CFR, Title 42, Sec 8: these products shall be dispensed only by opioid treatment programs (and agencies, practitioners or institutions by formal agreement with the program sponsor) certified by the Substance Abuse and Mental Health Services Administration and approved by the designated state authority.
Methadose Dosage and Administration
Adult
See full labeling. Do not inject. Give orally. Peak respiratory depressant effects typically occur later, and persist longer than peak analgesic effects. ≥18yrs: give under supervision when there are no signs of sedation or intoxication and withdrawal symptoms are present. Induction/initial dosing: 20–30mg as single dose, an additional 5–10mg may be given if withdrawal symptoms not suppressed or if symptoms reappear. Total daily dose on first day of treatment: max 40mg. Adjust dose cautiously. Short-term detoxification: titrate to total daily dose of 40mg in divided doses, continue stabilization for 2–3 days, then gradually decrease dose on a daily basis or at 2-day intervals. Hospitalized patients may tolerate a 20% daily reduction of the total daily dose; ambulatory patients may need a slower schedule. Maintenance treatment: titrate to dose at which opioid withdrawal symptoms are prevented for 24hrs, drug hunger/craving is reduced, euphoric effects are blocked/attenuated, and patient is tolerant to sedative effects; usual range: 80–120mg/day. Medically supervised withdrawal after a period of maintenance treatment: dose reduction should be <10% of maintenance dose, 10–14 day intervals should elapse between dose reductions. Pregnancy: may need dose increase or a decrease in dosing interval.
Children
<18yrs: not established.
Methadose Contraindications
Contraindications
Significant respiratory depression. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment. Known or suspected GI obstruction, including paralytic ileus.
Methadose Boxed Warnings
Boxed Warning
Life-threatening respiratory depression. Risks from concomitant use with benzodiazepines or other CNS depressants. Life-threatening QT prolongation. Accidental ingestion. Misuse, abuse, and diversion of opioids. Interactions with drugs affecting CYP450 isoenzymes. Conditions for distribution and use of methadone products for the treatment of opioid addiction.
Methadose Warnings/Precautions
Warnings/Precautions
Assess the potential need for access to naloxone when initiating and renewing therapy. Consider prescribing naloxone based on risk factors for overdose (eg, history of opioid use disorder, prior opioid overdose, household members or other close contacts at risk for accidental ingestion or overdose). Abuse potential (monitor). Life-threatening respiratory depression; monitor when initiating therapy or following a dose increase. Accidental exposure may cause fatal overdose (esp. in children). Sleep-related breathing disorders (including central sleep apnea (CSA), sleep-related hypoxemia); consider dose reduction if CSA develops. COPD, cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression; monitor and consider non-opioid analgesics. Life-threatening QT prolongation and serious arrhythmia; monitor for cardiac rhythm changes in high-risk patients (eg, cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), history of cardiac conduction abnormalities, and those taking drugs affecting cardiac conduction. Adrenal insufficiency. Monitor for signs of hypotension when initiating or titrating dose. Head injury. Increased intracranial pressure, brain tumors; monitor. Seizure disorders. CNS depression. Impaired consciousness, coma, shock; avoid. Biliary tract disease. Acute pancreatitis. Drug abusers. Renal or hepatic impairment: initiate at lower doses. Reevaluate periodically. Avoid abrupt cessation. Elderly. Cachectic. Debilitated. Pregnancy; potential neonatal opioid withdrawal syndrome during prolonged use. Labor & delivery, nursing mothers: monitor infants.
Methadose Pharmacokinetics
Absorption
Oral bioavailability: 36–100%. Peak plasma concentrations: between 1–7.5 hours.
Distribution
Volume of distribution: 1.0–8.0 L/kg. Predominantly bound to alpha1-acid glycoprotein (85–90%).
Elimination
Renal, fecal. Half-life: 8–59 hours. Plasma clearance: 1.4 and 126 L/h.
Methadose Interactions
Interactions
Increased risk of hypotension, respiratory depression, profound sedation, coma, and death with benzodiazepines or other CNS depressants (eg, non-benzodiazepine sedatives/hypnotics, anxiolytics, general anesthetics, phenothiazines, tranquilizers, muscle relaxants, antipsychotics, alcohol, other opioids); if concomitant use is warranted, strongly consider prescribing naloxone. During or within 14 days of MAOIs: not recommended. Risk of serotonin syndrome with serotonergic drugs (eg, SSRIs, SNRIs, TCAs, triptans, 5-HT3 antagonists, mirtazapine, trazodone, tramadol, cyclobenzaprine, metaxalone, MAOIs, linezolid, IV methylene blue); monitor and discontinue if suspected. Avoid concomitant mixed agonist/antagonist opioids (eg, butorphanol, nalbuphine, pentazocine) or partial agonist (eg, buprenorphine); may reduce effects and/or precipitate withdrawal symptoms. Potentiated by macrolides, azole antifungals, protease inhibitors, fluvoxamine, sertraline, and other CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 inhibitors. Antagonized by rifampin, carbamazepine, phenytoin, St. John's Wort, phenobarbital, abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, tipranivir+ritonavir, and other CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers. Caution with drugs that prolong the QT interval (eg, Class I and III antiarrhythmics, neuroleptics, TCAs, CCBs) and drugs capable of inducing electrolyte disturbances (eg, diuretics, laxatives, mineralcorticoid hormones). May potentiate zidovudine, desipramine. May antagonize diuretics, didanosine, stavudine; monitor. Paralytic ileus may occur with anticholinergics. Diphenhydramine, doxylamine, clomipramine, chlorpromazine, thioridazine, quetiapine, verapamil may cause false (+) methadone drug screens.
Methadose Adverse Reactions
Adverse Reactions
Lightheadedness, dizziness, sedation, nausea, vomiting, sweating; respiratory depression, QT prolongation, serotonin syndrome, adrenal insufficiency, hypotension, GI reactions, seizures, hypoglycemia.
Methadose Clinical Trials
See Literature
Methadose Note
Not Applicable
Methadose Patient Counseling
See Literature
