methadone

Contraindicated in:

Hypersensitivity;
Significant respiratory depression;
Acute or severe bronchial asthma;
Paralytic ileus;
Known alcohol intolerance (some oral solutions);
Concurrent MAO inhibitor therapy.

Use Cautiously in:

Personal or family history of substance use disorder or mental illness (for pain management);
Structural heart disease, concomitant diuretic use, hypokalemia, hypomagnesemia, history of arrhythmia/syncope, or other risk factors for arrhythmias;
Concurrent use of drugs that prolong the QT interval or are CYP3A4 inhibitors;
Head trauma;
Seizure disorders;
↑intracranial pressure;
Severe renal impairment;
Severe hepatic impairment;
Severe pulmonary disease;
Hypothyroidism;
Adrenal insufficiency;
Undiagnosed abdominal pain;
Prostatic hyperplasia or ureteral stricture;
OB: Use during pregnancy only if the potential maternal benefit justifies the potential fetal risk. Prolonged use of methadone during pregnancy can result in neonatal opioid withdrawal syndrome;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Geri: ↑risk of respiratory depression in older adults (dose ↓ suggested).

Adv. Reactions/Side Effects

⬆ ⬇

CV: hypotension, bradycardia, QT interval prolongation, TORSADES DE POINTES

Derm: flushing, sweating

EENT: blurred vision, diplopia, miosis

Endo: adrenal insufficiency

GI: constipation, nausea, vomiting

GU: urinary retention

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, tolerance

Interactions

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Drug-drug:

Use with extreme caution in patients receiving MAO inhibitors (may result in severe, unpredictable reactions; ↓ initial dose of methadone to 25% of usual dose).
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.
Use with extreme caution with CYP3A4 inhibitors, including ketoconazole, itraconazole, erythromycin, clarithromycin, calcium channel blockers, or voriconazole.
Concurrent use with laxatives, diuretics, or mineralocorticoids may ↑ risk of hypomagnesemia or hypokalemia and ↑ risk of arrhythmias.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, MAO inhibitors, TCAs, tramadol, trazodone, mirtazapine, 5-HT3 receptor antagonists, linezolid, methylene blue, and triptans, ↑ risk of serotonin syndrome.
Concurrent use of 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.
Concurrent use with 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.
Administration of agonist/antagonist opioids may precipitate opioid withdrawal in physically dependent patients.
Nalbuphine may ↓ analgesia.
Interferons (alpha) may ↓ metabolism and ↑ effects.
May ↑ blood levels and effects of zidovudine and desipramine.
Concurrent abuse of methadone with benzodiazepines has resulted in death.
Mixed agonist/antagonist analgesics, including nalbuphine or butorphanol, and partial agonist analgesics, including buprenorphine, may ↓ methadone's analgesic effects and/or precipitate opioid withdrawal in physically dependent patients.

Drug-Natural Products:

St. John’s wort↑ metabolism and ↓ blood levels; concurrent use may result in withdrawal.
Kava-kava, valerian, or chamomile can ↑ CNS depression.

Availability

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(Generic available)

Tablets: 1 mg; 5 mg; 10 mg; 25 mg
Tablets for oral suspension: 40 mg (available only to licensed detoxification/maintenance programs)
Oral concentratecherry and unflavored: 10 mg/mL
Oral solution (contains alcohol)citrus: 5 mg/5 mL; 10 mg/5 mL
Solution for injection: 10 mg/mL

Route/Dosage

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Moderate to Severe Pain

PO (Adults and Children ≥50 kg): Usual starting dose for moderate to severe pain in opioid-naive patients: 2.5 mg every 8–12 hr.
PO (Adults and Children <50 kg): 0.1 mg/kg/dose every 4 hr for 2–3 doses, then every 6–8 hr as needed; maximum: 10 mg/dose.
PO IV (Neonates ): Initial 0.05–0.2 mg/kg/dose every 12–24 hr or 0.5 mg/kg/day divided every 8 hr; taper dose by 10–20% per wk over 1–1.5 mo.
IV IM SC (Adults and Children ≥50 kg): 10 mg every 6–8 hr.
IV IM SC (Adults and Children <50 kg): 0.1 mg/kg every 6–8 hr; maximum: 10 mg/dose.

Opioid Detoxification

PO (Adults and Children ≥50 kg): 15–40 mg once daily or amount needed to prevent withdrawal. Dose may be ↓ every 1–2 days; maintenance dose is determined on an individual basis.
PO (Adults and Children <50 kg): 0.05–0.1 mg/kg/dose every 6 hr; ↑ by 0.05 mg/kg/dose until withdrawal symptoms controlled; after 1–2 days, lengthen dosing interval to every 12–24 hr; taper by ↓ dose by 0.05 mg/kg/day.
IV IM SC (Adults and Children ≥50 kg): 15–40 mg once daily or amount needed to prevent withdrawal. Dose may be ↓ every 1–2 days; maintenance dose is determined on an individual basis.

US Brand Names

⬆ ⬇

~~Dolophine,~~ Methadose

Action

⬆ ⬇

Binds to opiate receptors in the CNS.
Alters the perception of and response to painful stimuli while producing generalized CNS depression.

Therapeutic effects:

Decrease in severity of pain.
Suppression of withdrawal symptoms during detoxification and maintenance from heroin and other opioids.

Classifications

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Therapeutic Classification: opioid analgesics

Pharmacologic Classification: opioid agonists

Pharmacokinetics

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Absorption: 50% absorbed following oral administration. IV administration results in complete bioavailability.

Distribution: Widely distributed to tissues.

Protein Binding: 85–90%.

Metabolism/Excretion: Mostly metabolized by the liver; some metabolites are active and may accumulate with chronic administration. Primarily excreted in the urine (<10% as unchanged drug).

Half-Life: 15–25 hr (↑ with chronic use).

Contr. Subst. Schedule

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Canadian Brand Names

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Time/Action Profile

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(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

Patient/Family Teaching

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Explain purpose and side effects of methadone to patient. Instruct them to take medication as directed and when to ask for pain medication. Advise patient to read Patient Informationbefore starting and with each Rx refill in case of changes.
REMS: Instruct patient to take methadone exactly as directed. If dose is less effective after a few wk, do not dose without consulting health care professional. Discuss safe use, risks, and proper storage and disposal of opioid analgesics with patients and caregivers with each Rx. The Patient Counseling Guide is available at www.fda.gov/OpioidAnalgesicREMSPCG.
Advise patient that methadone is a drug with known abuse potential. Protect it from theft, and never give to anyone other than the individual for whom it was prescribed. Store out of sight and reach of children, and in a location not accessible by others.
Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose. Inform patients and caregivers about various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (Rx, direct from pharmacist, or state programs). OTC naloxone nasal spray is available at pharmacies nationwide for overdose or accidental ingestion.
Medication may cause drowsiness or dizziness. Advise patient to call for assistance when ambulating and to avoid driving or other activities that require alertness until response to the medication is known.
Inform patient of the potential for arrhythmias and emphasize the importance of regular ECGs.
Advise patient to notify health care professional if pain control is not adequate or if side effects occur.
Caution patient to notify health care professional if signs of overdose (difficult or shallow breathing; extreme tiredness or sleepiness; blurred vision; inability to think, talk, or walk normally; and feelings of faintness, dizziness, or confusion) occur. Methadone has a prolonged action, causing ↑ risk of overdose.
Advise patient to change positions slowly to minimize orthostatic hypotension.
Advise patient to tell health care professional what medications they are taking and to avoid taking new Rx, OTC, vitamins, or herbal products without consulting health care professional. Caution patient to avoid concurrent use of alcohol or other CNS depressants, including other opioids, with this medication.
Encourage patient to turn, cough, and breathe deeply every 2 hr to prevent atelectasis.
Emphasize the importance of aggressive prevention of constipation with the use of methadone.
Rep: Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of potential for neonatal opioid withdrawal syndrome with prolonged use during pregnancy. Monitor neonate for signs and symptoms of withdrawal (irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, failure to gain weight); usually occur the first days after birth. Monitor infants exposed to methadone through breast milk for excess sedation and respiratory depression. Chronic use may ↓ fertility in females and males. During pregnancy, a woman’s methadone dose may need to be ↑ or the dosing interval ↓ due to ↑ clearance.

section name header

Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Contr. Subst. Schedule ⬆ ⬇

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆

Indications

Contraind./Precautions