Methadone

Methadone is contraindicated in patients with known long QT syndrome or significant QTc prolongation. ECG monitoring at baseline and after dose changes is required for all patients.

Concurrent use of methadone with other QT-prolonging medications requires ECG monitoring, electrolyte correction, and risk-benefit assessment. Dose reduction or alternative opioid selection should be considered.

Methadone is contraindicated in patients with severe respiratory insufficiency, including advanced COPD with respiratory failure, severe asthma, and conditions causing significant baseline hypoxia or hypercapnia.

Concurrent use of methadone with monoamine oxidase inhibitors is contraindicated due to risk of lethal serotonin syndrome. A washout period is required when switching between these drug classes.

Patients with hepatic impairment require reduced doses, extended dosing intervals, and monitoring for accumulation. The long half-life (up to 130 hours) means accumulation may take days to manifest.

Patients with known CYP2B6 poor metabolizer status require dose reduction, enhanced cardiac monitoring (ECG), and careful titration. Pharmacogenomic testing should be considered in non-responders or those with unexpected toxicity.

Pregnancy is a relative contraindication in non-OUD contexts. For pregnant women with opioid use disorder, methadone maintenance is recommended by clinical guidelines, with neonatal monitoring to at least day of life 5 for withdrawal signs.

Concurrent benzodiazepine use is the most common co-factor in methadone fatalities. If the combination is clinically necessary, dose reduction of both agents and respiratory monitoring are essential.