Methadone interactions

Methadone (Dolophine, Methadose), an opioid has 296 documented interactions across the FDA labels and fact sheets we index: 182 major, 96 moderate, 15 minor, and 3 where a label reports no significant interaction. Each entry below quotes the sentence behind it. This drug page is a starting point, not a verdict for your situation.

Major interactions (182)

  • AlcoholAlcoholMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • AlprazolambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • AmiodaroneantiarrhythmicMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • Amitriptylinetricyclic antidepressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • AprepitantCYP3A4 inhibitorMajor

    Similarly, discontinuation of concomitant CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers in METHADOSE-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression. (Methadone label, Warnings and precautions)

  • AripiprazoleantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • AsenapineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • AzelastineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Azithromycinmacrolide antibioticMajor

    This risk which can be fatal should be considered in patients with certain cardiovascular disorders including known QT prolongation or history torsades de pointes, those with proarrhythmic conditions, and with other drugs that prolong the QT interval. (Azithromycin label, Warnings and precautions)

  • Baclofenmuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Opioid Antagonist: Naloxegol ↑ naloxegol Avoid use with BIXLENVO; if unavoidable, decrease the dosage of naloxegol and monitor for adverse reactions. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

  • BosentanCYP3A4 inducerMajor

    Similarly, discontinuation of concomitant CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers in METHADOSE-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression. (Methadone label, Warnings and precautions)

  • BrexpiprazoleantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • BrivaracetamanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • BuprenorphineopioidMajor

    Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including METHADOSE. (Methadone label, Warnings and precautions)

  • Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including METHADOSE. (Methadone label, Warnings and precautions)

  • BupropionantidepressantMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • Buspironeserotonergic drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ButorphanolopioidMajor

    Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including METHADOSE. (Methadone label, Warnings and precautions)

  • Cannabidiol (prescription)anticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CarbamazepineanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CariprazineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Carisoprodolmuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CenobamateanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CetirizineantihistamineMajor

    Avoid concurrent use of QUZYTTIR with alcohol or other CNS depressants because additional reduction in alertness and additional impairment of CNS performance may occur. (Cetirizine label, Warnings and precautions)

  • ChlordiazepoxidebenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ChlorpheniramineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ChlorpromazineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CimetidineH2 blockerMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • CiprofloxacinfluoroquinoloneMajor

    Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval. (Ciprofloxacin label, Warnings and precautions)

  • CitalopramSSRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • ClobazambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ClonazepambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Clonidinealpha-adrenergic agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ClozapineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • CodeineopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Cyclobenzaprinemuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Dantrolenemuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Daridorexantsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DarifenacinanticholinergicMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Dexmedetomidinealpha-adrenergic agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Dextromethorphanserotonergic drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • DiazepambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Dihydroergotamineergot alkaloidMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • DimenhydrinateantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DiphenhydramineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Divalproex (valproate)anticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DofetilideantiarrhythmicMajor

    Use with Drugs that Prolong QT Interval and Antiarrhythmic Agents The use of dofetilide in conjunction with other drugs that prolong the QT interval has not been studied and is not recommended. (Dofetilide label, Warnings)

  • Doxepintricyclic antidepressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DoxylamineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DronabinolcannabinoidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • DuloxetineSNRIMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • EletriptantriptanMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • EluxadolineopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • EscitalopramSSRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • EslicarbazepineanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Eszopiclonesedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • EthosuximideanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • EverolimusimmunosuppressantMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • FelbamateanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • FentanylopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • FingolimodimmunosuppressantMajor

    …6-hour observation, or at additional risk for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital long-QT syndrome), or on concurrent therapy with QT prolonging drugs with a known risk of torsades de pointes (e.g., citalopram, chlorpromazine, haloperidol, methadone, erythromycin) should be monitored overnight with continuous ECG in a medical facility. (Fingolimod label, Warnings and precautions)

  • FlibanserinCNS depressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Fluconazoleazole antifungalMajor

    Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole. (Fluconazole label, Contraindications)

  • FluoxetineSSRIMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • FluvoxamineSSRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • FosfomycinantibioticMajor

    Avoid co-administration of CONTEPO with drugs known to prolong the QT interval. (Fosfomycin label, Drug interactions)

  • GabapentinanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • GranisetronQT-prolonging drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Guanfacinealpha-adrenergic agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • HaloperidolantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • HydromorphoneopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • HydroxychloroquineQT-prolonging drugMajor

    Therefore, PLAQUENIL is not recommended in patients taking other drugs that have the potential to prolong the QT interval. (Hydroxychloroquine label, Warnings and precautions)

  • HydroxyzineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • IloperidoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ImatinibCYP3A4 inhibitorMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • IsoniazidantibioticMajor

    Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions ( 5.1 , 5.9 )] . (Methadone label, Drug interactions)

  • Itraconazoleazole antifungalMajor

    Cardiac Dysrhythmias Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using drugs such as, pimozide, methadone, or quinidine concomitantly with oral itraconazole and/or other CYP3A4 inhibitors. (Itraconazole label, Warnings and precautions)

  • Bradycardia may increase the risk of QT prolongation which may lead to severe ventricular arrhythmias, including torsade de pointes, especially in patients with risk factors such as use of QTc prolonging drugs [see Adverse Reactions ( 6.2 )] . (Ivabradine label, Warnings and precautions)

  • KetamineCNS depressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Ketoconazoleazole antifungalMajor

    QT Prolongation and Drug Interactions Leading to QT Prolongation Coadministration of the following drugs with ketoconazole is contraindicated: dofetilide, quinidine, pimozide, lurasidone, cisapride, methadone, disopyramide, dronedarone, ranolazine. (Ketoconazole label, Boxed warning)

  • KetorolacNSAIDMajor

    BOXED WARNING Ketorolac tromethamine tablets, a nonsteroidal anti-inflammatory drug (NSAID), are indicated for the short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level and only as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. (Ketorolac label, Boxed warning)

  • LacosamideanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Lemborexantsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LevetiracetamanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LevocetirizineantihistamineMajor

    Avoid concurrent use of alcohol or other central nervous system depressants with XYZAL. (Levocetirizine label, Warnings and precautions)

  • LevofloxacinfluoroquinoloneMajor

    Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval ( 5.11 , 8.5 ) (Levofloxacin label, Warnings and precautions)

  • Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • LevorphanolopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LinezolidantibioticMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Lithiumserotonergic drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Lofexidinealpha-adrenergic agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LoperamideQT-prolonging drugMajor

    …known to prolong the QT interval, including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmics, antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), or any other drug known to prolong the QT interval (e.g., pentamidine, levomethadyl acetate, methadone). (Loperamide label, Warnings)

  • LorazepambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LumateperoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • LurasidoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • MeclizineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • MeperidineopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Methocarbamolmuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Methylnaltrexoneopioid antagonistMajor

    • Other Opioid Antagonists : Potential for additive effect and increased risk of opioid withdrawal; avoid concomitant use. (Methylnaltrexone label, Drug interactions)

  • Metoclopramidedopamine antagonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • MidazolambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Mirabegronbeta-adrenergic agonistMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • MirtazapineantidepressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • MorphineopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • NalbuphineopioidMajor

    Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including METHADOSE. (Methadone label, Warnings and precautions)

  • Naldemedineopioid antagonistMajor

    Intervention Avoid use of SYMPROIC with another opioid antagonist. (Naldemedine label, Drug interactions)

  • Naloxoneopioid antagonistMajor

    In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated. (Naloxone label, Warnings and precautions)

  • Naltrexoneopioid antagonistMajor

    Naltrexone for extended-release injectable suspension is contraindicated in: Patients receiving opioid analgesics [see Warnings and Precautions ( 5.3 ) ] . (Naltrexone label, Contraindications)

  • Naltrexone and bupropionopioid antagonistMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • …voclosporin • Microsomal triglyceride transfer protein inhibitor: lomitapide • Migraine medications: eletriptan, ubrogepant • Mineralocorticoid receptor antagonists: finerenone • Non-opioid analgesic (selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial… (Nirmatrelvir and ritonavir label, Contraindications)

  • Nortriptylinetricyclic antidepressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • OlanzapineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • OliceridineopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • OlopatadineantihistamineMajor

    Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal spray ( 5.2 ). (Olopatadine label, Warnings and precautions)

  • OndansetronQT-prolonging drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • OxcarbazepineanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • OxycodoneopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • OxymorphoneopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PaliperidoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ParoxetineSSRIMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • Withdrawal Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist, including METHADOSE. (Methadone label, Warnings and precautions)

  • PerampanelanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PhenelzineMAO inhibitorMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • PhenobarbitalbarbiturateMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Phentermine and topiramateCNS stimulantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PhenytoinanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PimavanserinantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PitolisantQT-prolonging drugMajor

    The use of WAKIX should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong the QT interval [see Drug Interactions ( 7.1 )]. (Pitolisant label, Warnings and precautions)

  • Pramipexoledopamine agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PregabalinanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PrimidoneanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ProchlorperazineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PromethazineantihistamineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • PropafenoneantiarrhythmicMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • PropofolCNS depressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Prucaloprideserotonergic drugMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • QuetiapineantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Ramelteonsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • RanolazineQT-prolonging drugMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • RasagilineMAO inhibitorMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • RifampinantibioticMajor

    Similarly, discontinuation of concomitant CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers in METHADOSE-treated patients may increase methadone plasma concentrations resulting in fatal respiratory depression. (Methadone label, Warnings and precautions)

  • RisperidoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • RitonavirantiretroviralMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • RizatriptantriptanMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Ropiniroledopamine agonistMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • RufinamideanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ScopolamineanticholinergicMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • SelegilineMAO inhibitorMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • SertralineSSRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Sodium oxybateCNS depressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • SolriamfetolCNS stimulantMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • St. John's wortHerbal and supplementMajor

    St. John's wort can weaken these medicines by speeding up their breakdown, which can mean organ rejection, clots, or loss of effect. (NCCIH, St. John's Wort)

  • SumatriptantriptanMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Suvorexantsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TapentadolopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Tasimelteonsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TemazepambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TerbinafineantifungalMajor

    Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The concomitant use of METHADOSE with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. (Methadone label, Boxed warning)

  • TetrabenazineVMAT2 inhibitorMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TiagabineanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Tizanidinemuscle relaxantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TopiramateanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TramadolopioidMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TranylcypromineMAO inhibitorMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • TrazodoneantidepressantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • TriazolambenzodiazepineMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • Valproic acidanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • VenlafaxineSNRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • VigabatrinanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • VilazodoneSSRIMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • VortioxetineantidepressantMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Zaleplonsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ZiprasidoneantipsychoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ZolmitriptantriptanMajor

    Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration. (Methadone label, Warnings and precautions)

  • Zolpidemsedative-hypnoticMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

  • ZonisamideanticonvulsantMajor

    Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (Methadone label, Boxed warning)

Moderate interactions (96)

  • Acetazolamidecarbonic anhydrase inhibitorModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • AclidiniumanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Allopurinolxanthine oxidase inhibitorModerate

    Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants. (Allopurinol label, Warnings and precautions)

  • AmantadineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Amiloridepotassium-sparing diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Amlodipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Amlodipine and benazeprildihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • ArmodafinilCNS stimulantModerate

    …agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

  • BeclomethasonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • BenztropineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • BetamethasonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Bisoprolol and hydrochlorothiazidebeta blockerModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Brimonidinealpha-adrenergic agonistModerate

    Use with CNS depressants may result in an additive or potentiating effect. (Brimonidine label, Drug interactions)

  • BudesonidecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Budesonide and formoterolcorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Bumetanideloop diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Chlorthalidonethiazide diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Clarithromycinmacrolide antibioticModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • ClobetasolcorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Clopidogrelantiplatelet agentModerate

    Opioids: Decreased exposure to clopidogrel. (Clopidogrel label, Drug interactions)

  • Clotrimazoleazole antifungalModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • CyclopentolateanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Deferasiroxiron supplementModerate

    …agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

  • DesmopressinModerate

    …Hyponatremia Concomitant administration of DESMODA with other drugs that may increase the risk of water intoxication with hyponatremia, (e.g., tricyclic antidepressants, selective serotonin re-uptake inhibitors, chlorpromazine, opiate analgesics, thiazide diuretics, NSAIDs, lamotrigine, sulfonylureas, particularly chlorpropamide, oxybutynin and carbamazepine). (Desmopressin label, Drug interactions)

  • DesonidecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • DeutetrabenazineVMAT2 inhibitorModerate

    Alcohol or other sedating drugs: May have additive sedation and somnolence ( 7.5 ) (Deutetrabenazine label, Drug interactions)

  • DexamethasonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • DicyclomineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Digoxindigitalis glycosideModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Diltiazemcalcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • DolutegravirantiretroviralModerate

    …interaction trial results, the following drugs can be coadministered with dolutegravir without a dose adjustment: atazanavir/ritonavir, darunavir/ritonavir, elbasvir/grazoprevir, methadone, midazolam, omeprazole, oral contraceptives containing norgestimate and ethinyl estradiol, prednisone, rifabutin, rilpivirine, sofosbuvir/velpatasvir, and tenofovir [see Clinical… (Dolutegravir label, Drug interactions)

  • DronedaroneantiarrhythmicModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Econazoleazole antifungalModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • Eplerenonealdosterone antagonistModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Erythromycinmacrolide antibioticModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • Esmololbeta blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Ethacrynic acidloop diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Felodipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • FesoterodineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Fidaxomicinmacrolide antibioticModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • FlecainideantiarrhythmicModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • FludrocortisonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • FluocinonidecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • FluticasonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Fluticasone and salmeterolcorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Formoterolbeta-adrenergic agonistModerate

    …Antidepressants, QTc Prolonging Drugs Formoterol, as with other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval because the effect of adrenergic agonists on the cardiovascular system may be potentiated by these agents. (Formoterol label, Drug interactions)

  • Furosemideloop diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • GlycopyrrolateanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • GriseofulvinantifungalModerate

    …agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

  • HalobetasolcorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Hydrochlorothiazidethiazide diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • HydrocortisonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • HyoscyamineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Indapamidethiazide diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • IpratropiumanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Isradipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Levothyroxinethyroid hormoneModerate

    …Drugs That May Alter T 4 and Triiodothyronine (T 3 ) Serum Transport Without Effecting Free Thyroxine (FT 4 ) Concentration (Euthyroidism) Drug or Drug Class Effect Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin/Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may increase serum thyroxine-binding globulin (TBG) concentration. (Levothyroxine label, Drug interactions)

  • Lidocainelocal anestheticModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Lidocaine and prilocainelocal anestheticModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Liothyroninethyroid hormoneModerate

    Table 2: Drugs That May Alter Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism) Drug or Drug Class Effect Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin/Methadone 5-Fluorouracil Mitotane Tamoxifen These drugs may increase serum thyroxine-binding globulin (TBG) concentration. (Liothyronine label, Drug interactions)

  • Lisinopril and hydrochlorothiazideACE inhibitorModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Losartan and hydrochlorothiazideangiotensin II receptor blocker (ARB)Moderate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • LubiprostoneModerate

    Methadone Diphenylheptane opioids (e.g., methadone) have been shown in nonclinical studies to dose-dependently reduce the activation of ClC-2 by lubiprostone in the gastrointestinal tract. (Lubiprostone label, Drug interactions)

  • MethylprednisolonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Metolazonethiazide diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • MetronidazoleantibioticModerate

    Drugs that Prolong the QT Interval QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. (Metronidazole label, Drug interactions)

  • Miconazoleazole antifungalModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • ModafinilCNS stimulantModerate

    …agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6, CYP2C19, or CYP2C9 inducers can decrease the plasma concentration… (Methadone label, Drug interactions)

  • MometasonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • MoxifloxacinfluoroquinoloneModerate

    Pharmacokinetic studies between moxifloxacin and other drugs that prolong the QT interval such as cisapride, erythromycin, antipsychotics, and tricyclic antidepressants have not been performed. (Moxifloxacin label, Warnings and precautions)

  • Nicardipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Nifedipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Nisoldipinedihydropyridine calcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • OxybutyninanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Posaconazoleazole antifungalModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

  • Prasugrelantiplatelet agentModerate

    Opioids: Decreased exposure to prasugrel. (Prasugrel label, Drug interactions)

  • PrednisolonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • PrednisonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • SolifenacinanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Sotalolbeta blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Spironolactonealdosterone antagonistModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Spironolactone and hydrochlorothiazidealdosterone antagonistModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • TheophyllinemethylxanthineModerate

    25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (Theophylline label, Drug interactions)

  • Ticagrelorantiplatelet agentModerate

    Opioids: Decreased exposure to ticagrelor. (Ticagrelor label, Drug interactions)

  • TiotropiumanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • TolterodineanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Torsemideloop diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • TriamcinolonecorticosteroidModerate

    If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. (Methadone label, Warnings and precautions)

  • Triamterenepotassium-sparing diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Triamterene and hydrochlorothiazidepotassium-sparing diureticModerate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • TrihexyphenidylanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • TrospiumanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Umeclidinium and vilanterolanticholinergicModerate

    Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. (Methadone label, Drug interactions)

  • Valsartan and hydrochlorothiazideangiotensin II receptor blocker (ARB)Moderate

    Closely monitor patients with risk factors for development of prolonged QT interval (e.g., cardiac hypertrophy, concomitant diuretic use, hypokalemia, hypomagnesemia), a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction. (Methadone label, Warnings and precautions)

  • Verapamilcalcium channel blockerModerate

    Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

  • Voriconazoleazole antifungalModerate

    Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir), fluconazole, fluvoxamine, some selective serotonin reuptake inhibitors (SSRIs) (e.g., sertraline, fluvoxamine) Inducers of CYP3A4, CYP2B6, CYP2C19, or CYP2C9 Clinical Impact: The concomitant use of methadone and CYP3A4, CYP2B6,… (Methadone label, Drug interactions)

Minor mentions (15)

  • Atomoxetinenorepinephrine reuptake inhibitorMinor

    Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone),… (Methadone label, Warnings and precautions)

  • BisacodyllaxativeMinor

    Drugs capable of inducing electrolyte disturbances: Diuretics, laxatives, and, in rare cases, mineralocortocoid hormones. (Methadone label, Drug interactions)

  • CyclosporineimmunosuppressantMinor

    Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. (Methadone label, Drug interactions)

  • DocusatelaxativeMinor

    Drugs capable of inducing electrolyte disturbances: Diuretics, laxatives, and, in rare cases, mineralocortocoid hormones. (Methadone label, Drug interactions)

  • Epoetin alfaMinor

    The “gasping syndrome” is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. (Epoetin alfa label, Warnings and precautions)

  • InfliximabimmunosuppressantMinor

    In RA, concomitant medications besides MTX were nonsteroidal anti-inflammatory agents (NSAIDs), folic acid, corticosteroids and/or narcotics. (Infliximab label, Drug interactions)

  • IvacaftorCYP3A4 inhibitorMinor

    Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. (Methadone label, Drug interactions)

  • LactuloselaxativeMinor

    Drugs capable of inducing electrolyte disturbances: Diuretics, laxatives, and, in rare cases, mineralocortocoid hormones. (Methadone label, Drug interactions)

  • OfloxacinfluoroquinoloneMinor

    Interaction With Laboratory or Diagnostic Testing Some quinolones, including ofloxacin, may produce false-positive urine screening results for opiates using commercially available immunoassay kits. (Ofloxacin label, Precautions)

  • PalbociclibCYP3A4 inhibitorMinor

    Inhibitors of CYP3A4, CYP2B6, CYP2C19, CYP2C9, or CYP2D6 Clinical Impact: Methadone undergoes hepatic N-demethylation by several cytochrome P450 (CYP) isoforms, including CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6. (Methadone label, Drug interactions)

  • Polyethylene glycol 3350laxativeMinor

    Drugs capable of inducing electrolyte disturbances: Diuretics, laxatives, and, in rare cases, mineralocortocoid hormones. (Methadone label, Drug interactions)

  • Prazosinalpha blockerMinor

    …to date with the following: (1) cardiac glycosides– digitalis and digoxin; (2) hypoglycemics–insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; (3) tranquilizers and sedatives–chlordiazepoxide, diazepam, and phenobarbital; (4) antigout–allopurinol, colchicine, and probenecid; (5) antiarrhythmics–procainamide, propranolol (see WARNINGS however),… (Prazosin label, Drug interactions)

  • Pyridostigminecholinesterase inhibitorMinor

    Narcotics: Exacerbation of bradycardia possible. (Pyridostigmine label, Drug interactions)

  • Senna (sennosides)laxativeMinor

    Drugs capable of inducing electrolyte disturbances: Diuretics, laxatives, and, in rare cases, mineralocortocoid hormones. (Methadone label, Drug interactions)

  • Viloxazinenorepinephrine reuptake inhibitorMinor

    Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone),… (Methadone label, Warnings and precautions)

No significant interaction reported (3)

  • Emtricitabine and tenofovirantiretroviralNo interaction

    No clinically significant drug interactions have been either observed or are expected when DESCOVY is combined with the following drugs: buprenorphine, itraconazole, ketoconazole, lorazepam, methadone, midazolam, naloxone, norbuprenorphine, norgestimate/ethinyl estradiol, and sertraline. (Emtricitabine and tenofovir label, Drug interactions)

  • Montelukastleukotriene receptor antagonistNo interaction

    …adjustment is needed when SINGULAIR is co-administered with theophylline, prednisone, prednisolone, oral contraceptives, fexofenadine, digoxin, warfarin, gemfibrozil, itraconazole, thyroid hormones, sedative hypnotics, non-steroidal anti-inflammatory agents, benzodiazepines, decongestants, and Cytochrome P450 (CYP) enzyme inducers [see Clinical Pharmacology (12.3) ]. (Montelukast label, Drug interactions)

  • Sofosbuvir and velpatasvirantiviralNo interaction

    …drug interactions have been observed with the following drugs [see Clinical Pharmacology (12.3) ]: VOSEVI: cobicistat, darunavir, elvitegravir, emtricitabine, ethinyl estradiol/norgestimate, gemfibrozil, rilpivirine, ritonavir, tenofovir alafenamide, voriconazole Sofosbuvir/velpatasvir: dolutegravir, ketoconazole, raltegravir Sofosbuvir: methadone, tacrolimus (Sofosbuvir and velpatasvir label, Drug interactions)

Check Methadone against everything you take. Add your full list; every pair is checked at once.

Open in the checker

Not medical advice. Severity reflects the label's wording, not your circumstances. A "major" flag can be routine under supervision and a "minor" one can matter at high doses. Ask a pharmacist.