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BackMethadone Data - Uses, Dosage, Drug class, Brand name, Warnings, etc
| Pharmacology | Methadone is a phenylheptylamine opioid agonist, qualitatively similar to morphine but structurally distinct from opium alkaloid derivatives. The analgesic activity of (R)-methadone is 8–50 times that of (S)-methadone, with 10-fold higher opioid receptor affinity. It is lipophilic with extensive tissue distribution, sustaining plasma concentrations during long-term treatment via a peripheral reservoir. Methadone lacks cross-tolerance with other opioids, requiring lower-than-expected doses in opioid-tolerant patients. Unlike other opioids, it has no active or toxic metabolites causing CNS toxicity (e.g., myoclonus, seizures). It is used for analgesia maintenance and detoxification, with a slower-onset, longer-duration abstinence syndrome compared to morphine. |
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| Administration and Adult Dosage |
- PO, IV, or SC for pain: 5–80 mg/day in 1–3 divided doses; escalate dosage slowly (~2%/day) - PO for maintenance and detoxification: Minimum effective dose ~60 mg/day to reduce illicit heroin use; optimal range 80–120 mg/day. Taper gradually over 4–12 months if discontinuing - Conversion from another opioid: Decrease prior opioid by one-third over 24 hr, replace with methadone (1 mg oral methadone = 10 mg oral morphine). On day 2, reduce prior opioid by another one-third; on day 3, discontinue remaining prior opioid. Maintain on every 8 hr schedule with ~10% of daily methadone dose for breakthrough pain |
| Special Populations - Pediatric Dosage |
- IV for pain: 0.1 mg/kg every 6–8 hr - PO for pain: 0.2 mg/kg every 6–8 hr |
| Special Populations - Geriatric Dosage | Same as adult dosage. |
| Dosage Forms |
- Tablet: 5, 10 mg - Dispersible Tablet: 40 mg - Solution: 1, 2, 10 mg/mL - Injection: 10 mg/mL - Powder: 50, 100, 500, 1000 g |
| Patient Instructions |
- Take as directed; do not exceed recommended dosage - Increase dosage cautiously with clinician guidance - May cause drowsiness; avoid driving or operating machinery until effects are known - Avoid alcohol and other CNS depressants - Report severe constipation, difficulty breathing, or confusion to your physician |
| Missed Doses |
- If taken on a regular schedule, take a missed dose as soon as remembered - If near the time for the next dose, take that dose only; do not double the dose or take extra |
| Pharmacokinetics - Onset and Duration |
- Analgesia: • SC onset: 10–20 min; peak 4 hr • PO onset: 30–60 min • Duration (single dose): 4–12 hr (PO/SC/IV); 8–48 hr with multiple doses |
| Pharmacokinetics - Serum Levels |
- Best rehabilitation in methadone maintenance: >211 µg/L (682 nmol/L) - No good correlation between serum levels and analgesia |
| Pharmacokinetics - Fate |
- Bioavailability: 92 ± 21% PO - Protein Binding: 89% - Distribution: Vd = 3.8 ± 0.6 L/kg; greater for (R)-methadone - Clearance: Cl = 0.084 ± 0.03 L/hr/kg; greater for (R)-methadone - Metabolism: Hepatic via N-demethylation to inactive metabolites; may increase with long-term therapy, reducing serum levels by 15–25% - Excretion: 24 ± 10% unchanged in urine, increased by urine acidification; also excreted in bile |
| Pharmacokinetics - t¹⁄₂ |
- Elimination half-life: 35 ± 12 hr - (R)-methadone: 37.5 hr - (S)-methadone: 28.6 hr |
| Adverse Reactions & Side Effects |
- Sedation, dizziness, nausea, vomiting, constipation, respiratory depression - Increased toxicity risk with inappropriate dosage increases due to long half-life and lack of cross-tolerance |
| Contraindications | - Hypersensitivity to methadone or other opioids |
| Precautions & Warnings |
- Use with caution in patients with respiratory disease, head injury, increased intracranial pressure, or hepatic impairment - Switching to methadone from another opioid is complex; should be done by experienced clinicians in an inpatient setting over 3–6 days - Risk of respiratory depression requires close monitoring |
| Drug Interactions |
- CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) decrease methadone levels, potentially causing withdrawal - Enzyme inhibitors (e.g., diazepam, erythromycin, fluvoxamine, ritonavir) increase methadone levels and effects - CNS depressants (e.g., alcohol, benzodiazepines) increase sedation and respiratory depression risk |
| Parameters to Monitor |
- For analgesia: Monitor vital signs and pain ratings routinely - For maintenance: Monitor for withdrawal signs (lacrimation, rhinorrhea, diaphoresis, yawning, restlessness, insomnia, dilated pupils, piloerection) |
| Class and Drug Brand Name |
- Class: Opioids - Brand Names: Dolophine, Various |
| Notes |
- For narcotic addiction treatment, methadone may only be dispensed by approved pharmacies for detoxification or maintenance - Maintenance therapy (>3 weeks) restricted to approved methadone programs, except for hospitalized addicts with other medical conditions - Methadone’s long half-life and lack of toxic metabolites make it suitable for analgesia maintenance and detoxification |
References
Hand of Clinical Drug Data