Methadone interactions

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)

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)

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)

Alvimopan capsules are contraindicated in patients who have taken therapeutic doses of opioids for more than 7 consecutive days immediately prior to taking alvimopan capsules [see Warnings and Precautions ( 5.3 )]. (Alvimopan label, Contraindications)

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)

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)

Drugs that Prolong QT Avoid use of AGRYLIN in patients taking medications that may prolong QT interval (including, but not limited to, chloroquine, clarithromycin, haloperidol, methadone, moxifloxacin, amiodarone, disopyramide, procainamide, and pimozide) [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] . (Anagrelide label, Drug interactions)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

CONTRAINDICATIONS Diphenoxylate hydrochloride and atropine sulfate is contraindicated in: • Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS ). (Diphenoxylate and atropine label, Contraindications)

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)

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)

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)

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)

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)

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)

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)

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)

Concomitant use of COMPLERA with drugs with a known risk to prolong the QTc interval of the electrocardiogram may increase the risk of Torsade de Pointes. (Emtricitabine, rilpivirine, and tenofovir label, Warnings and precautions)

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)

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)

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)

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)

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)

…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)

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)

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)

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)

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)

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)

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

…Hypericum perforatum ) Lipid modifying agents: Lomitapide, lovastatin, simvastatin Non-nucleoside reverse transcriptase inhibitor: Delavirdine PDE5 inhibitor: Sildenafil (Revatio) (for treatment of pulmonary arterial hypertension) Sedative/hypnotics: Midazolam, triazolam Hypersensitivity to fosamprenavir calcium or amprenavir (e.g., Stevens-Johnson syndrome). (Fosamprenavir label, Contraindications)

(See DOSAGE and ADMINISTRATION. ) Because of the risk of QT prolongation and the potential for torsades de pointes, the use of FOSCAVIR should be avoided in combination with agents known to prolong the QT interval including Class IA (e.g., quinidine or procainamide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents, phenothiazines, tricyclic… (Foscarnet label, Drug interactions)

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

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)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

Opioid Antagonist: naloxegol ↑ naloxegol Avoid use with SUNLENCA; if unavoidable, decrease the dosage of naloxegol and monitor for adverse reactions. (Lenacapavir label, Drug interactions)

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)

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

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)

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)

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)

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)

…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)

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)

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)

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)

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)

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)

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)

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)

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

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

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)

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

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)

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)

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)

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)

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)

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

Risk of Recurrent Respiratory and CNS Depression : A recurrence of respiratory depression is possible, therefore, keep the patient under continued surveillance and administer repeat doses of ZURNAI using a new auto-injector with each dose while awaiting emergency medical assistance. (Nalmefene label, Warnings and precautions)

…concomitantly using strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) because these medications can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)… (Naloxegol label, Contraindications)

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

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

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)

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

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)

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)

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)

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

• Avoid concurrent use of alcohol or other central nervous system (CNS) depressants with RYALTRIS because additional reductions in alertness and additional impairment of CNS performance may occur. (Olopatadine and mometasone label, Warnings and precautions)

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)

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)

Avoid coadministration of oxaliplatin injection with medicinal products with a known potential to prolong the QT interval. (Oxaliplatin label, Drug interactions)

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)

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)

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)

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

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)

Avoid coadministration of VOTRIENT with drugs known to prolong the QT/QTc interval. (Pazopanib label, Drug interactions)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (Vepdegestrant 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)

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)

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)

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)

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)

Paradoxical Effects of Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased… (Methadone label, Drug interactions)

Paradoxical Effects of Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased… (Methadone label, Drug interactions)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

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)

MAO inhibitors, tricyclic antidepressants and drugs that prolong the QTc interval may potentiate effect on the cardiovascular system. (Arformoterol label, Drug interactions)

…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)

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)

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)

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)

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)

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

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)

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)

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

Drugs that Prolong the QT interval QT prolongation has been reported with metronidazole, a component of bismuth subcitrate potassium, metronidazole and tetracycline hydrochloride, particularly when administered with drugs with the potential for prolonging the QT interval. (Bismuth subcitrate, metronidazole, and tetracycline label, Warnings and precautions)

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)

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

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

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

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

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)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Bupivacaine label, Warnings and precautions)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Bupivacaine and epinephrine label, Warnings and precautions)

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)

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)

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)

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

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)

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

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

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)

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)

…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)

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

…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)

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

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

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

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)

MOTOFEN ® may potentiate the action of barbiturates, tranquilizers, narcotics, and alcohol. (Difenoxin and atropine label, Drug interactions)

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)

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)

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)

…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)

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)

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)

…Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased clearance or decreased plasma… (Methadone label, Drug interactions)

…Anti-Retroviral Agents on Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased clearance or decreased plasma… (Methadone label, Drug interactions)

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)

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)

QT Prolongation: Monitor for prolonged QT intervals in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities. (Eribulin label, Warnings and precautions)

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)

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)

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)

…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)

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)

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)

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)

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)

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)

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

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

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

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

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

…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)

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)

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)

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)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (Goserelin label, Warnings and precautions)

…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)

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

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)

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

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)

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)

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)

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)

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)

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)

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)

Zidovudine Experimental evidence demonstrated that methadone increased the AUC of zidovudine which could result in toxic effects. (Methadone label, Drug interactions)

TYKERB may prolong the QT interval in some patients. (Lapatinib label, Warnings and precautions)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (Leuprolide label, Warnings and precautions)

…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)

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)

Possible early warning signs of central nervous system (CNS) toxicity are restlessness, anxiety, incoherent speech, lightheadedness, metallic taste, tinnitus, dizziness, blurred vision, tremors, twitching, CNS depression, or drowsiness. (Lidocaine and epinephrine label, Warnings and precautions)

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)

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)

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)

…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)

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)

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)

Other Drugs that Prolong the QTc Interval Coadministration of other drugs known to alter cardiac conduction (e.g., anti-arrhythmic or beta-adrenergic blocking agents, calcium channel blockers, antihistamines or H 1 -blocking agents, tricyclic antidepressants and phenothiazines) might also contribute to a prolongation of the QTc interval. (Mefloquine label, Drug interactions)

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)

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

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)

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)

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)

Concurrent use of metyrosine with alcohol or other CNS depressants can increase their sedative effects. (Metyrosine label, Drug interactions)

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)

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)

There is little or no experience with high exposure, concomitant dosing with other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval. [See Warnings & Precautions ( 5.6 )] To minimize risk, the lowest effective dose should always be used. (Mifepristone label, Warnings and precautions)

…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)

…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)

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

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)

…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)

…Methadone Concurrent use of certain protease inhibitors with CYP3A4 inhibitory activity, alone and in combination, such as abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, and tipranvir+ritonavir, has resulted in increased clearance or decreased plasma levels of methadone. (Methadone label, Drug interactions)

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)

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)

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)

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)

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)

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)

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)

Drugs that Prolong QT: Use with caution in patients who are at significant risk of developing QTc prolongation. (Pasireotide label, Drug interactions)

Anti-Arrhythmic Drugs, QT Prolonging Drugs, Drugs that may Decrease Heart Rate PONVORY has not been studied in patients taking QT prolonging drugs. (Ponesimod label, Drug interactions)

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)

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

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

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

QT Interval Prolonging Drugs The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between Primaquine phosphate Tablets and other drugs that effect cardiac conduction is unknown. (Primaquine label, Drug interactions)

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)

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)

…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)

…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)

However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. (Rilpivirine label, Drug interactions)

QT Interval Prolongation The overall analysis of ECG data in pediatric patients indicates that the concomitant use of Rocuronium Bromide Injection with general anesthetic agents can prolong the QTc interval [see Clinical Studies ( 14.3 )]. (Rocuronium label, Warnings and precautions)

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)

Monitor electrolytes and electrocardiograms in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. (Sorafenib label, Warnings and precautions)

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)

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)

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)

Drugs that Prolong QT Interval SUTENT is associated with QTc interval prolongation [see Warnings and Precautions (5.3) , Clinical Pharmacology (12.2) ] . (Sunitinib label, Drug interactions)

…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)

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)

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)

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

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

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)

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)

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)

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

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)

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)

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)

The recent use of other drugs that cause CNS depression or EPS symptoms may also increase the risk; consider reducing the dosage or discontinuing the drug. (Trimethobenzamide label, Warnings and precautions)

Effect on QT/QTc Interval: Androgen deprivation therapy may prolong the QT interval. (Triptorelin label, Warnings and precautions)

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)

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)

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)

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)

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)

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)

Zidovudine Experimental evidence demonstrated that methadone increased the AUC of zidovudine which could result in toxic effects. (Methadone label, Drug interactions)

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)

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

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)

Antihistamines Amphetamines may counteract the sedative effect of antihistamines. (Dextroamphetamine label, Drug interactions)

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

In Postanesthetic Use Doxapram is neither an antagonist to muscle relaxant drugs nor a specific narcotic antagonist. (Doxapram label, Warnings)

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

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)

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

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)

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

Patients with Grade 1 and 2 TFR may also be treated with corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or narcotic analgesics for management of TFR symptoms. (Lenalidomide label, Warnings and precautions)

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)

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)

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

…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)

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

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

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)

…clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: dolutegravir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, and methadone [see Clinical Pharmacology (12.3) ]. (Doravirine label, Drug interactions)

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)

…sofosbuvir is used with the following drugs [see Clinical Pharmacology (12.3) ]: abacavir, atazanavir/ritonavir, cyclosporine, darunavir/ritonavir, dolutegravir, efavirenz, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, emtricitabine, lamivudine, methadone, midazolam, oral contraceptives, pravastatin, raltegravir, rilpivirine, tacrolimus, or verapamil. (Ledipasvir and sofosbuvir label, Drug interactions)

…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)

Drugs without Clinically Significant Interactions with ISENTRESS In drug interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: hormonal contraceptives, methadone, lamivudine, tenofovir, etravirine, darunavir/ritonavir, or boceprevir. (Raltegravir label, Drug interactions)

…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)