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Table 3 Twenty most frequently observed methadone-drug interactions (MDIs) among co-medication subpopulation in the MMTP (128 patients)

From: Survey of methadone-drug interactions among patients of methadone maintenance treatment program in Taiwan

Drugs that interact with methadone Level n (%) Mechanisms of MDI
Tramadol 1 42 (6.0) Concomitant administration of methadone and tramadol may result in withdrawal symptoms; methadone (moderate CYP 2D6 inhibitor) may decrease the metabolism of tramadol
Chlorpromazine 1 22 (3.1) The concomitant use of methadone and chlorpromazine may cause additive CNS and respiratory depression
Levofloxacin 1 16 (2.3) Levofloxacin may increase the QTc prolonging effects of methadone
Prochlorperazine 1 12 (1.7) The concomitant use of methadone and prochlorperazine may cause additive CNS and respiratory depression
Alprazolam 2 99 (14.2) Alprazolam may cause additive CNS depression
Cimetidine 2 84 (12.0) Cimetidine (moderate CYP 3A4 and 2D6 inhibitor) may decrease the metabolism of methadone, raise serum methadone concentrations and consequently increase the toxicity of methadone
Dexamethasone 2 48 (6.9) Dexamethasone (moderate CYP 3A4 and 2B6 inducer) may increase the metabolism of methadone, lower serum methadone concentrations and result in withdrawal symptoms
Estazolam 2 40 (5.7) Estazolam may cause additive CNS depression
Fusidic acid 2 26 (3.7) Fusidic acid may induce CYP enzyme
Pethidine 2 25 (3.6) Interaction probably occurs due to additive opioid effects
Diltiazem 2 23 (3.3) Diltiazem (moderate CYP 3A4 inhibitor) may decrease the metabolism of methadone, raise serum methadone concentrations and consequently increase the toxicity of methadone
Carbamazepine 2 22 (3.1) Carbamazepine (strong CYP 2B6 inducer) may increase the metabolism of methadone, lower serum methadone concentrations and result in withdrawal symptoms
Imipramine 2 22 (3.1) Imipramine (moderate CYP 2D6 inhibitor) may decrease the metabolism of methadone; combination with methadone increases tricyclic antidepressant (TCA) toxicity
Risperidone 2 20 (2.9) Risperidone accelerates methadone metabolism via interfering with absorption or displacing methadone from plasma protein binding sites and results in withdrawal symptoms
Midazolam 2 19 (2.7) Midazolam may cause additive CNS depression
Nifedipine 3 18 (2.6) Methadone possibly increases the effects of nifidepine and increase the toxicity of nifedipine
Morphine 2 13 (1.9) Interaction probably occurs due to additive opioid effects
Paroxetine 2 12 (1.7) Paroxetine (moderate CYP 2B6 and 2D6 inhibitor) may decrease the metabolism of methadone and raise serum methadone concentrations and consequently increase the toxicity of methadone
Erythromycin 2 12 (1.7) Erythromycin (CYP 3A4 inhibitor) may decrease the metabolism of methadone, raise serum methadone concentrations and consequently increase the toxicity of methadone
Dextromethorphan 3 25 (3.6) Methadone may increase the levels/effects of dextromethorphan and increase the toxicity of dextromethorphan
Diazepam 3 15 (2.1) Diazepam may increase the methadone effects and consequently increase the toxicity of methadone