WESTADONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WESTADONE (WESTADONE).
Mu-opioid receptor agonist; also acts as an NMDA receptor antagonist and inhibits serotonin and norepinephrine reuptake.
| Metabolism | Primarily hepatic via CYP3A4, CYP2B6, CYP2D6, and CYP2C19; also undergoes N-demethylation. Metabolites are inactive. |
| Excretion | Primarily renal (40-50% as unchanged methadone and its metabolites, 15-20% as metadone-N-oxide), biliary/fecal (5-10%). |
| Half-life | Terminal elimination half-life: 15-60 hours (mean ~24 hours). Clinical context: Prolonged half-life supports once-daily dosing in opioid maintenance; accumulation occurs with repeated dosing due to long half-life. |
| Protein binding | 85-90% bound primarily to alpha-1-acid glycoprotein (AAG) and albumin. |
| Volume of Distribution | Vd: 3-5 L/kg. Clinical meaning: Extensive tissue distribution, with accumulation in liver, lungs, kidneys, and brain; reflects high lipophilicity and slow redistribution. |
| Bioavailability | Oral: 70-80% (range 40-100%); Rectal: approximately 70%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Subcutaneous/Intramuscular: 10-20 minutes; Intravenous: <5 minutes. |
| Duration of Action | Oral: 4-8 hours (acute analgesia); maintenance therapy: 24-36 hours (due to accumulation and tolerance). Note: Duration for analgesia is shorter than for suppression of opioid withdrawal. |
Oral: 2.5-10 mg every 4-6 hours as needed for pain; maximum 40 mg per day.
| Dosage form | TABLET, EFFERVESCENT |
| Renal impairment | GFR 30-59 mL/min: administer 50% of usual dose; GFR <30 mL/min: administer 25% of usual dose; hemodialysis: administer 25% of usual dose after dialysis. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use or reduce by 75%. |
| Pediatric use | For patients >2 years: 0.1-0.2 mg/kg/dose every 4-6 hours as needed; maximum 2.5 mg/dose for <50 kg, 10 mg/dose for ≥50 kg. |
| Geriatric use | Start at lowest effective dose (2.5 mg every 6-8 hours) and titrate slowly due to increased risk of sedation and falls; maximum 20 mg per day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WESTADONE (WESTADONE).
| Breastfeeding | M/P ratio 0.8–1.0 (theoretical). Methadone appears in breast milk at low concentrations (milk:plasma ~0.8). AAP rating: compatible. Benefits of breastfeeding outweigh risks in stable mothers. Monitor infant for sedation, respiratory depression, feeding difficulties, and weight gain. Avoid if maternal illicit drug use. |
| Teratogenic Risk | Pregnancy category C. First trimester: May cause neural tube defects, oral clefts, cardiac malformations (cohort studies show small absolute risk increase). Second/third trimester: Risk of fetal growth restriction, preterm birth, neonatal opioid withdrawal syndrome (NOWS); chronic exposure may reduce head circumference. Opioid antagonists may precipitate withdrawal if given. |
■ FDA Black Box Warning
Risk of respiratory depression, which may be fatal; risk of opioid addiction, abuse, and misuse; life-threatening respiratory depression and death in children due to accidental ingestion; risk of neonatal opioid withdrawal syndrome with prolonged use during pregnancy; risk of QT interval prolongation and serious arrhythmias (e.g., torsades de pointes).
| Serious Effects |
Hypersensitivity to methadone or any component of the formulation; significant respiratory depression; acute or severe bronchial asthma in an unmonitored setting or without resuscitative equipment; known or suspected gastrointestinal obstruction, including paralytic ileus; concurrent use of monoamine oxidase inhibitors (MAOIs) or within 14 days of such therapy.
| Precautions | Life-threatening respiratory depression; addiction, abuse, and misuse; QT interval prolongation; neonatal opioid withdrawal syndrome; interactions with CNS depressants; use in patients with head injuries, increased intracranial pressure, or impaired consciousness; use in elderly, cachectic, or debilitated patients; use in patients with hepatic or renal impairment; risk of serotonin syndrome with concomitant serotonergic drugs; severe hypotension; adrenal insufficiency; misuse by crushing, chewing, or injecting. |
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| Fetal Monitoring | Maternal: liver function tests, ECG (QTc prolongation risk), urine toxicology screens, fetal kick counts. Fetal: serial ultrasound for growth and anatomy, nonstress tests or biophysical profiles from 32 weeks, umbilical artery Doppler if growth restriction suspected. Neonatal: monitor for NAS using Finnegan score for at least 72 hours. |
| Fertility Effects | Methadone may cause menstrual irregularities, anovulation, and reduced libido due to hyperprolactinemia and hypothalamic-pituitary axis suppression. Effects are reversible upon dose reduction or cessation. In men, may decrease testosterone levels and spermatogenesis. |