methadone (Rx)

Brand and Other Names:Methadose, Dolophine
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injectable solution: Schedule II

  • 10mg/mL

tablet: Schedule II

  • 5mg
  • 10mg

dispersible tablet: Schedule II

  • 40mg

oral solution: Schedule II

  • 5mg/5mL
  • 10mg/5mL

oral concentrate solution: Schedule II

  • 10mg/mL
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Chronic Severe Pain

Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Opioid-naive patients: 2.5 mg PO q8-12hr; titrate slowly with dose increases no more frequent than every 3-5 days

Opioid-tolerant patients

  • Discontinue all other around-the-clock opioids
  • Substantial interpatient variability, see prescribing information for guidance

Opioid-tolerant definition

  • Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
  • Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid

Limitations of use

  • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
  • Not indicated for acute pain or as a PRN analgesic

Detoxification

20-30 mg PO once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

Dosing Modifications

Renal impairment (CrCl <10mL/min): 50-75% of normal dose

Hepatic impairment: Not recommended in severe liver disease:

Dosing Considerations

Conversion from PO to parenteral: Parenteral-to-PO ratio, 1:2 (5 mg parenteral = 10 mg PO)

To convert to methadone from another opioid, use available conversion factors to obtain estimated dose

Do not abruptly discontinue methadone in a physically dependent patient

Dosage Forms & Strengths

injected solution: Schedule II

  • 10mg/mL

tablet: Schedule II

  • 5mg
  • 10mg
  • 40mg

dispersible tablet: Schedule II

  • 40mg

oral solution: Schedule II

  • 5mg/5mL
  • 10mg/5mL
more...

Pain (Off-label)

0.7 mg/kg/day PO/SC/IV/IM divided q6hr PRN; not to exceed 10 mg/dose  

Opiate Withdrawal (Off-label)

Neonates: 0.05-0.2 mg/kg PO q12-24hr; reduce dose by 10-20% per week over 4-6 weeks; adjust tapering on signs and symptoms of withdrawal

Pain

2.5 mg PO/IM q8-12hr; titrate slowly with dose increases no more frequent than every 3-5 days

Detoxification

20-30 mg PO once daily or minimum dosage necessary to suppress withdrawal; may be titrated to 40 mg/day in divided doses and continued for 2-3 days, then decreased 20% daily as tolerated

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Interactions

Interaction Checker

and methadone

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            Adverse Effects

            Frequency Not Defined

            Agitation

            Angina pectoris

            Anticholinergic effects (dry mouth, palpitation, tachycardia)

            Bradycardia

            Cardiac arrest

            Coma

            Constipation

            Dizziness

            Dysphoria

            Euphoria

            Faintness

            Mental clouding or depression

            Myocardial infarction

            Nausea

            Pruritus, urticaria

            Nervousness

            QT-interval prolongation

            Respiratory arrest

            Respiratory/circulatory depression

            Restlessness

            Sedation

            Seizures

            Severe cardiac arrhythmias

            Shock

            ST-segment elevation

            Sweating, flushing, warmness of face/neck/upper thorax

            Syncope

            Urinary retention, oliguria

            Ventricular tachycardia

            Visual disturbances

            Vomiting

            Weakness

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            Warnings

            Black Box Warnings

            Detoxification and maintenance of dependence

            • For detoxification and maintenance of opioid dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration

            Addiction, abuse, and misuse

            • Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
            • Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions

            Life-threatening respiratory depression

            • Serious, life-threatening, or fatal respiratory depression may occur
            • Monitor for respiratory depression, especially during initiation or following a dose increase
            • Instruct patients to swallow tablet/capsule whole; crushing, chewing, snorting, injecting or dissolving can cause rapid release and absorption of a potentially fatal dose
            • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death

            Accidental exposure

            • Accidental of even 1 dose, especially by children, can result in a fatal overdose

            Neonatal opioid withdrawal syndrome

            • Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
            • Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
            • Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
            • If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available

            Contraindications

            Hypersensitivity to methadone or formulation components; acute abdominal condition, toxin-mediated diarrhea, pseudomembranous colitis, respiratory depression; concurrent use of selegiline, known or suspected gastrointestinal obstruction, including paralytic ileus, asthma (acute), significant respiratory impairment

            Acute pain or postoperative pain; pain that is mild or not expected to persist

            Cautions

            Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black Box Warnings)

            Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black Box Warnings)

            Serious, life-threatening, or fatal respiratory depression reported (see Black Box Warnings)

            Accidental exposure reported, including fatalities (see Black Box Warnings)

            Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)

            Interactions with CNS depressants (eg, alcohol, sedatives, anxiolytics, hypnotics, neuroleptics, other opioids) can cause additive effects and increase risk for respiratory depression, profound sedation, and hypotension; deaths reported due to methadone abuse in conjunction with benzodiazepines

            Monitor for hypotension during dose initiation and titration

            In patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock

            Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients

            Risk of QT interval prolongation at high doses

            Use caution in cardiac arrhythmias, drug abuse or dependence, emotional lability, gallbladder disease, head injury, prostatic hyperplasia,/urethral stricture, hepatic impairment, thyroid dysfunction, increased intracranial pressure, prostatic hypertrophy, adrenal insufficiency, history of depression or suicidal tendencies, renal function impairment, seizures with epilepsy, urethral stricture, patients who are morbidly obese, urinary tract surgery

            May cause CNS depression; use caution in performing tasks, which require mental alertness

            Not recommended to treat abdominal conditions; may obscure diagnosis or clinical course of patients with acute abdominal conditions

            Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist; mixed agonists/antagonist and partial agonist analgesics may reduce analgesic effect and/or may precipitate withdrawal symptoms; when discontinuing therapy, gradually taper dosage; do not abruptly discontinue therapy

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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies in pregnant women; untreated opioid addiction is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death; in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use; neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged use of opioids during pregnancy

            Pregnant women in methadone maintenance programs may have reduced incidence of obstetric and fetal complications and neonatal morbidity and mortality when compared to women using illicit drugs; untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes and risk of continued or relapsing illicit opioid use; these risks should be considered in women receiving maintenance treatment of opioid addiction; for women treated with pain severe enough to require daily, around-the-clock, long-term opioid treatment, therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus

            Infertility

            • Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible; reproductive function in human males may be decreased by methadone treatment; reductions in ejaculate volume and seminal vesicle and prostate secretions have been reported in methadone-treated individuals; in addition, reductions in serum testosterone levels and sperm motility, and abnormalities in sperm morphology have been reported

            Lactation

            Methadone present in low levels in human milk; did not show adverse reactions in breastfed infants; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for methadone and any potential adverse effects on the breastfed child from drug or from underlying maternal condition; advise breastfeeding women taking methadone to monitor the infant for increased drowsiness and breathing difficulties

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Narcotic agonist-analgesic of opiate receptors; inhibits ascending pain pathways, thus altering perception and response to pain; produces analgesia, respiratory depression, and sedation

            Absorption

            Bioavailability: 36-100%

            Onset: PO, 0.5-1 hr; parenteral, 10-20 min

            Duration: 4-8 hr; repeated administration, 22-48 hr; overdosage, 36-48 hr

            Peak plasma time: 1-7.5 hr

            Distribution

            Protein bound: 85-90%

            Vd: 1-8 L/kg

            Metabolism

            Metabolized in liver via N-demethylation

            Elimination

            Half-life: 8-59 hr

            Excretion: Urine

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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