Dosing and uses of Methadose, Dolophine (methadone)
Adult dosage forms and 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
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
Pediatric dosage forms and 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
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
Geriatric dosage forms and strengths
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
Methadose, Dolophine (methadone) adverse (side) 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
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
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 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
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
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug excreted in breast milk; use caution
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.
Pharmacology of Methadose, Dolophine (methadone)
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
