Eslicarbazepine interactions

CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during YONSA treatment. (Abiraterone label, Drug interactions)

• CYP3A Inducers: Avoid co-administration with strong CYP3A inducers. (Acalabrutinib label, Drug interactions)

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Acetaminophen and codeine label, Boxed warning)

Combining alcohol with sedating medicines (opioids, benzodiazepines, sleep medicines, muscle relaxants) can cause dangerous drowsiness, slowed breathing, and overdose. (NIAAA, Harmful Interactions: Mixing Alcohol with Medicines)

CYP3A4 Inducers : Avoid coadministration of VIJOICE with a strong CYP3A4 inducer. (Alpelisib label, Drug interactions)

• Effects on Driving and Operating Machinery: Patients receiving • alprazolam XR should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs. (Alprazolam label, Warnings and precautions)

• Simultaneous use of combined P-gp and strong CYP3A4 inducers reduces blood levels of apixaban: Avoid concomitant use. (Apixaban label, Drug interactions)

Drug Interactions : Use with strong cytochrome P450 enzyme inducers (e.g., rifampin, phenobarbital, carbamazepine, phenytoin) is not recommended because loss of efficacy may occur ( 5.5 , 7.1 ) (Apremilast label, Warnings and precautions)

CYP3A4 Inducers : Avoid concomitant use for greater than 14 days ( 7.1 ) (Aripiprazole label, Drug interactions)

• when coadministered with drugs that are strong inducers of CYP3A due to the potential for loss of therapeutic effect and development of resistance. (Atazanavir label, Contraindications)

• Avoid concurrent use of alcohol or other central nervous system (CNS) depressants with azelastine hydrochloride and fluticasone propionate nasal spray because further decreased alertness and impairment of CNS performance may occur. (Azelastine and fluticasone label, Warnings and precautions)

…AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL EXPOSURE; NEONATAL OPIOD WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH ALCOHOL, BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Belladonna and opium suppositories expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Belladonna and opium label, Boxed warning)

Concomitant administration of BIXLENVO is contraindicated with: dofetilide due to the potential for increased dofetilide plasma concentrations and associated serious and/or life-threatening events. strong CYP3A inducers due to decreased plasma concentrations of BIC and LEN, which may result in the loss of therapeutic effect and development of resistance to BIXLENVO. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Contraindications)

Strong CYP3A4 Inducers: Avoid concomitant use. (Bortezomib label, Drug interactions)

• Strong CYP3A Inducers: Avoid concomitant use with BOSULIF. (Bosutinib label, Drug interactions)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Buprenorphine label, Boxed warning)

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.3)] . (Bupropion label, Contraindications)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Butalbital, acetaminophen, caffeine, and codeine label, Boxed warning)

Concomitant use of opioids or a barbiturate with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Butalbital, aspirin, caffeine, and codeine label, Boxed warning)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Butorphanol label, Boxed warning)

…diphosphate glucuronosyltransferase (UGT)1A1 enzyme induction, which may result in loss of virologic response [see Drug Interactions ( 7.2 , 7.3 ), Clinical Pharmacology ( 12.3 )] : o Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin o Antimycobacterials: Rifampin, rifapentine Prior to initiation of VOCABRIA, note that use of CABENUVA (cabotegravir… (Cabotegravir label, Contraindications)

Avoid chronic co-administration of strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. (Cabozantinib label, Drug interactions)

Serious and sometimes fatal dermatologic reactions, including TEN and SJS, have also been reported in patients using oxcarbazepine or carbamazepine which are chemically related to APTIOM. (Eslicarbazepine label, Warnings and precautions)

Avoid concurrent use of Carbinoxamine Maleate Extended-Release Oral Suspension with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur. (Carbinoxamine label, Warnings and precautions)

Intervention: Concomitant use of VRAYLAR with a CYP3A4 inducer is not recommended [see Dosage and Administration ( 2.1 , 2.6 ) ] . (Cariprazine label, Drug interactions)

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)

Table 8: Drugs That are Affected by and Affecting Ciprofloxacin Drugs That are Affected by Ciprofloxacin Drug(s) Recommendation Comments Tizanidine Contraindicated Concomitant administration of tizanidine and ciprofloxacin is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see Contraindications ( 4.2 )]. (Ciprofloxacin label, Drug interactions)

Avoid use with other central nervous system (CNS) depressants ( 5.3 ) (Clonidine label, Warnings and precautions)

• Concomitant use of Strong CYP3A4 Inducers is not recommended. (Clozapine label, Drug interactions)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Codeine label, Boxed warning)

Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the… (Cyclobenzaprine label, Drug interactions)

Moderate or Strong CYP3A4 inducers: Avoid concomitant use. (Daridorexant label, Drug interactions)

…elbasvir/grazoprevir Lipid modifying agents: lomitapide, lovastatin, simvastatin Opioid Antagonist: naloxegol PDE-5 inhibitor: sildenafil when used for treatment of pulmonary arterial hypertension Sedatives/hypnotics: orally administered midazolam, triazolam Co-administration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance… (Darunavir label, Contraindications)

Anticonvulsants with CYP3A induction effects that are NOT contraindicated: e.g. eslicarbazepine, oxcarbazepine ↓ cobicistat darunavir: effect unknown Consider alternative anticonvulsant or antiretroviral therapy to avoid potential changes in exposures. (Darunavir and cobicistat label, Drug interactions)

If concomitant administration of a strong CYP3A4 inducer cannot be avoided, consider a dose increase [see Dosage and Administration ( 2.3 )] . (Dasatinib label, Drug interactions)

Avoid use of moderate or strong CYP3A4 inducers with EMFLAZA, as they may reduce efficacy ( 7.1 ) (Deflazacort label, Drug interactions)

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)

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. (Divalproex (valproate) label, Boxed warning)

PIFELTRO is contraindicated when co-administered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of PIFELTRO [see Warnings and Precautions (5.2) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ] . (Doravirine label, Contraindications)

• Avoid concomitant use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp ( 7.1 ) (Doxorubicin label, Drug interactions)

• CYP3A inducers: Avoid concomitant use. (Dronedarone label, Drug interactions)

Therefore, concomitant use with strong CYP3A inducers is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St. (Elvitegravir, cobicistat, emtricitabine, and tenofovir label, Contraindications)

…virologic response and possible resistance to COMPLERA or to the class of NNRTIs [see Warnings and Precautions (5.7) , Drug Interactions (7) , and Clinical Pharmacology (12.3) ]: Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin Antimycobacterials: rifampin, rifapentine Glucocorticoid (systemic): dexamethasone (more than a single-dose)… (Emtricitabine, rilpivirine, and tenofovir label, Contraindications)

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended. (Eszopiclone label, Warnings and precautions)

IT IS NOT KNOWN WHETHER CONCOMITANT USE OF OTHER ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECT THE INCIDENCE OF HEPATIC FAILURE. (Felbamate label, Boxed warning)

• Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Fentanyl label, Boxed warning)

Preventing or Managing DI The concomitant use of ADDYI with CYP3A4 inducers is not recommended. (Flibanserin label, Drug interactions)

…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)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Hydrocodone label, Boxed warning)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Hydrocodone and acetaminophen label, Boxed warning)

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;… (Hydrocodone and chlorpheniramine label, Boxed warning)

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Hydrocodone bitartrate and homatropine methylbromide exposes patients and… (Hydrocodone and homatropine label, Boxed warning)

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P4503A4 INTERACTION; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; and SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE AND IBUPROFEN TABLETS Addiction,… (Hydrocodone and ibuprofen label, Boxed warning)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death . (Hydromorphone label, Boxed warning)

Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other CNS depressants. (Hydroxyzine label, Precautions)

• Strong CYP3A4 Inducers: Do not administer strong CYP3A4 inducers with CAMPTOSAR. (Irinotecan label, Drug interactions)

To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made 5,6 . (Isoniazid label, Drug interactions)

Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. (Itraconazole label, Drug interactions)

Avoid concomitant use of CYP3A4 inducers when using Corlanor. (Ivabradine label, Drug interactions)

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death. (Ketamine label, Drug interactions)

This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. (Ketoconazole label, Contraindications)

Avoid strong CYP3A4 inducers. (Lapatinib label, Drug interactions)

Strong CYP3A4 Inducers: Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. (Larotrectinib label, Drug interactions)

Strong or moderate CYP3A inducers: Avoid concomitant use. (Lemborexant label, Drug interactions)

Concomitant administration of SUNLENCA with strong CYP3A inducers is contraindicated due to decreased lenacapavir plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to SUNLENCA [see Drug Interactions (7.1) ] . (Lenacapavir label, Contraindications)

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

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Levorphanol label, Boxed warning)

…Non-opioid Analgesic (selective blocker of Nav1.8 sodium channels): suzetrigine PDE5 Inhibitor: sildenafil (Revatio ® ) when used for the treatment of pulmonary arterial hypertension Sedative/Hypnotics: triazolam, orally administered midazolam KALETRA is contraindicated with drugs that are potent CYP3A inducers where significantly reduced lopinavir plasma concentrations… (Lopinavir and ritonavir label, Contraindications)

Caution patients receiving LOREEV XR against operating machinery or driving a motor vehicle as well to avoid the concomitant use of alcohol and other CNS depressant drugs during treatment ( 5.4 , 7 ) (Lorazepam label, Warnings and precautions)

Effect of Other Drugs on LORBRENA Strong CYP3A Inducers LORBRENA is contraindicated in patients taking strong CYP3A inducers [see Contraindication (4) ] . (Lorlatinib label, Drug interactions)

CYP3A4 inducers: Avoid concomitant use with CAPLYTA. (Lumateperone label, Drug interactions)

Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. (Lurasidone label, Contraindications)

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). (Macitentan label, Drug interactions)

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Meperidine label, Boxed warning)

If concomitant use with another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. (Metaxalone 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)

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS Personnel and Equipment for Monitoring and Resuscitation Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer… (Midazolam label, Boxed warning)

CYP3A inducers: Do not use mifepristone with CYP3A inducers ( 7.3 ). (Mifepristone label, Drug interactions)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Morphine label, Boxed warning)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Nalbuphine label, Boxed warning)

John's Wort) Clinical Impact Significant decrease in plasma naldemedine concentrations, which may reduce efficacy [see Clinical Pharmacology (12.3) ] Intervention Avoid use of SYMPROIC with strong CYP3A inducers. (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)

Strong CYP3A4 inducers (e.g., rifampin) : Decreased concentrations of naloxegol; concomitant use is not recommended. (Naloxegol label, Drug interactions)

…(e.g., buprenorphine) use, or acute opiate withdrawal [see Warnings and Precautions (5.4) and Drug Interactions (7.2) ] Patients undergoing an abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.7) ] Concomitant administration of monoamine oxidase inhibitors (MAOI). (Naltrexone and bupropion label, Contraindications)

John’s Wort reduce the bioavailability and efficacy of nifedipine; therefore nifedipine should not be used in combination with strong CYP3A inducers such as rifampin (See CONTRAINDICATIONS ). (Nifedipine label, Drug interactions)

Strong CYP3A Inducers: Avoid concomitant use with CAVHANZA. (Nilotinib label, Drug interactions)

…contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. (Nirmatrelvir and ritonavir label, Contraindications)

Counsel patients to use a back-up method or alternative method of contraception when enzyme inducers are used with COCs ( 7.1 ) -- - ---------- ------ USE IN SPECIFIC POPULATIONS---- -- -- --------- ---- Lactation: Not recommended; Lo Loestrin Fe can decrease milk production ( 8.2 ) (Norethindrone and ethinyl estradiol label, Drug interactions)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Oliceridine 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)

APTIOM is contraindicated in patients with a hypersensitivity to eslicarbazepine acetate or oxcarbazepine [see Warnings and Precautions ( 5.2 , 5.3 , and 5.4 )]. (Eslicarbazepine label, Contraindications)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Oxycodone label, Boxed warning)

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Oxycodone hydrochloride tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Oxycodone and acetaminophen label, Boxed warning)

Risks From Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Oxymorphone label, Boxed warning)

• CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. (Palbociclib label, Drug interactions)

Strong CYP3A4 and P-glycoprotein (P-gp) inducers : Avoid using a strong inducer of CYP3A4 and/or P-gp during a dosing interval for ERZOFRI. (Paliperidone label, Drug interactions)

VOTRIENT is not recommended if chronic use of strong CYP3A4 inducers cannot be avoided. (Pazopanib label, Drug interactions)

…MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Pentazocine and Naloxone Tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to… (Pentazocine and naloxone label, Boxed warning)

Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. (Phenelzine label, Contraindications)

Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of NUPLAZID. (Pimavanserin label, Drug interactions)

• Patients taking strong Cytochrome P450 3A enzyme (CYP3A) inducers, such as rifampin, [see Warnings and Precautions ( 5.6 ) and Drug Interactions ( 7.1 , 7.2 )] . (Praziquantel label, Contraindications)

…PROMETHAZINE AND RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Promethazine HCl and Codeine Phosphate Oral Solution exposes patients and other users to the risks… (Promethazine and codeine label, Boxed warning)

If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. (Quinine label, Drug interactions)

ASPRUZYO Sprinkle is contraindicated in patients: Taking strong inhibitors of CYP3A [see Drug Interactions (7.1)] Taking inducers of CYP3A [see Drug Interactions (7.1)] With liver cirrhosis [see Use in Specific Populations (8.6)] Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, nelfinavir) (4, 7.1) (Ranolazine label, Contraindications)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Remifentanil label, Boxed warning)

Table 2: Drugs That are Contraindicated with EDURANT and EDURANT PED Drug Class Contraindicated Drugs in Class Clinical Comment Anticonvulsants Carbamazepine Oxcarbazepine Phenobarbital Phenytoin Potential for significant decreases in rilpivirine plasma concentrations due to CYP3A enzyme induction, which may result in loss of virologic response. (Rilpivirine label, Contraindications)

• Strong and Moderate CYP3A Inducers: Avoid concomitant administration. (Rimegepant label, Drug interactions)

• Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended. (Ritlecitinib label, Drug interactions)

WARNING: DRUG-DRUG INTERACTIONS LEADING TO POTENTIALLY SERIOUS AND/OR LIFE THREATENING REACTIONS Co-administration of NORVIR with several classes of drugs including sedative hypnotics, antiarrhythmics, or ergot alkaloid preparations may result in potentially serious and/or life-threatening adverse events due to possible effects of NORVIR on the hepatic metabolism… (Ritonavir label, Boxed warning)

Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions (7.3) ] . (Rivaroxaban label, Warnings and precautions)

• Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. (Roflumilast label, Warnings and precautions)

Intervention: Avoid the use of VARUBI in patients who require chronic administration of strong CYP3A4 inducers. (Rolapitant label, Drug interactions)

• Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ). (Romidepsin label, Drug interactions)

Interaction with Strong Inhibitors and Inducers of CYP3A4 and/or P-gp Avoid concomitant use of sirolimus with strong inhibitors of CYP3A4 and/or P-gp (such as ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin) or strong inducers of CYP3A4 and/or P-gp (such as rifampin or rifabutin) [ see Drug Interactions (7.2) ]. (Sirolimus label, Warnings and precautions)

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )]. (Sodium oxybate label, Boxed warning)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (Sofosbuvir and velpatasvir label, Drug interactions)

• Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. (Sorafenib label, Drug interactions)

Inducers of CYP3A4 Strong CYP3A4 inducers should not be used with tamoxifen. (Tamoxifen label, Drug interactions)

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Tapentadol label, Boxed warning)

Strong CYP3A4 inducers (e.g., rifampin): Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers, because of decreased exposure ( 7.2 , 12.3 ) (Tasimelteon label, Drug interactions)

Avoid co-administration of strong CYP3A4 inhibitors (e.g., itraconazole, clarithromycin, ritonavir) and strong CYP3A4 inducers (e.g., rifampin, phenytoin) with TEPADINA due to the potential effects on efficacy and toxicity [see Clinical Pharmacology ( 12.3 ) ] . (Thiotepa label, Drug interactions)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (Ticagrelor label, Drug interactions)

Avoid concomitant use of SAMSCA with strong CYP3A inducers. (Tolvaptan label, Drug interactions)

Coadministration with a strong CYP3A4 inducer may result in a relevant decrease in FARESTON exposure and should be avoided. (Toremifene label, Drug interactions)

CYP3A inducers: Avoid concomitant strong CYP3A inducers ( 7.1 ) (Trabectedin label, Drug interactions)

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Tramadol label, Boxed warning)

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. (Tramadol and acetaminophen label, Boxed warning)

Avoid concomitant use with strong CYP3A inducers if possible. (Tretinoin label, Drug interactions)

• Effects on Driving and Operating Heavy Machinery : Patients receiving triazolam should be cautioned against driving or operating heavy machinery, as well as avoiding concomitant use with alcohol and other CNS depressant drugs. (Triazolam label, Warnings and precautions)

Strong CYP3A4 Inducers: Should be avoided as concomitant use will result in reduction of ubrogepant exposure. (Ubrogepant label, Drug interactions)

Ella should not be administered with CYP3A4 inducers [see Drug interactions (7.1) and Clinical Pharmacology (12.3) ] . (Ulipristal label, Warnings and precautions)

Strong CYP3A4 Inducers : Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. (Upadacitinib label, Drug interactions)

Use of strong CYP3A4 inducers with INGREZZA or INGREZZA SPRINKLE Concomitant use is not recommended. (Valbenazine label, Drug interactions)

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. (Valproic acid label, Boxed warning)

Strong CYP3A Inducers : Avoid concomitant use with strong CYP3A inducers. (Vepdegestrant label, Drug interactions)

The use of zaleplon with other sedative-hypnotics at bedtime or the middle of the night is not recommended (see ). (Zaleplon label, Warnings)

The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended. (Zolpidem label, Warnings and precautions)

By decreasing the gastrointestinal absorption of primidone, acetazolamide may decrease serum concentrations of primidone and its metabolites, with a consequent possible decrease in anticonvulsant effect. (Acetazolamide label, Drug interactions)

Risk of Neurologic Symptoms: Neurocysticercosis patients may experience cerebral hypertensive episodes, seizures or focal neurologic deficits after initiation of therapy; begin appropriate steroid and anticonvulsant therapy. (Albendazole label, Warnings and precautions)

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)

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

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine and atorvastatin label, Drug interactions)

Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers (e.g. rifampicin, St. (Amlodipine and benazepril label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Amlodipine and olmesartan label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is coadministered with CYP3A inducers (e.g. rifampicin, St. (Amlodipine and valsartan label, Drug interactions)

Amoxapine may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (Amoxapine label, Drug interactions)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine Monoamine Oxidase Inhibitors, Nonselective Beta-Adrenergic… (Articaine and epinephrine label, Drug interactions)

Anticonvulsants Salicylic acid can displace protein-bound phenytoin and valproic acid, leading to a decrease in the total concentration of phenytoin and an increase in serum valproic acid levels. (Aspirin and dipyridamole label, Drug interactions)

CYP3A4/5 Inducers Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. (Axitinib label, Drug interactions)

Patients should also be cautioned that the central nervous system depressant effects of intrathecal baclofen may be additive to those of alcohol and other CNS depressants. (Baclofen label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. (Beclomethasone label, Warnings and precautions)

Clinically Significant Interactions with Bexagliflozin Tablets UGT Enzyme Inducers Clinical Impact UGT Enzyme Inducers may significantly reduce exposure to bexagliflozin and lead to a decreased efficacy [ see Clinical Pharmacology ( 12.3 )]. (Bexagliflozin label, Drug interactions)

Strong CYP3A4 inducers Double the recommended dosage and further adjust based on clinical response. (Brexpiprazole label, Drug interactions)

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)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Therefore, potent inhibitors or inducers of CYP3A4 may increase or reduce the circulating levels of CYCLOSET, respectively. (Bromocriptine label, Drug interactions)

Central Nervous System (CNS) depressants Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.). Antihypertensive drugs Sympathomimetic may reduce the effects of antihypertensive drugs. (Brompheniramine, pseudoephedrine, and dextromethorphan label, Drug interactions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, post menopausal status, tobacco use, advance age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Budesonide label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Budesonide and formoterol 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)

Warn patients of the potential danger of self-administration of benzodiazepines or other CNS depressants while under treatment with buprenorphine and naloxone sublingual tablets [see Warnings and Precautions (5.3) , Drug Interactions (7) ] . (Buprenorphine and naloxone label, Warnings and precautions)

Triazolam/flurazepam: Coadministration of buspirone with either triazolam or flurazepam did not appear to prolong or intensify the sedative effects of either benzodiazepine. (Buspirone label, Drug interactions)

Butalbital and acetaminophen may enhance the effects of:other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. (Butalbital and acetaminophen label, Drug interactions)

Butalbital, acetaminophen and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. (Butalbital, acetaminophen, and caffeine label, Drug interactions)

Other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. (Butalbital, aspirin, and caffeine label, Drug interactions)

Table 7: Clinically Significant Drug Interactions with INVOKANA UGT Enzyme Inducers Clinical Impact: UGT enzyme inducers decrease canagliflozin exposure which may reduce the effectiveness of INVOKANA. (Canagliflozin label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

• Additive sedative effects when used with other CNS depressants including alcohol (5.1) (Carisoprodol label, Warnings and precautions)

Inducers of Hepatic CYP Enzymes Rifampin : Rifampin is a potent CYP3A4 inducer and concomitant administration with caspofungin acetate for injection is expected to reduce the plasma concentrations of caspofungin acetate for injection. (Caspofungin label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Chlordiazepoxide label, Warnings)

Effects on the Ability to Drive or Operate Machinery As in the case of other preparations containing CNS-acting drugs, patients receiving Librax should be cautioned about possible combined effects with opioids, alcohol and other CNS depressants. (Chlordiazepoxide and clidinium label, Warnings)

…procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Chloroprocaine label, Precautions)

Therefore, dosage of anticonvulsants, including barbiturates, should not be reduced if chlorpromazine is started. (Chlorpromazine label, Precautions)

Chlorzoxazone use should also be discontinued if a patient develops abnormal liver enzymes (e.g., AST, ALT, alkaline phosphatase and bilirubin.) The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Chlorzoxazone label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and oral corticosteroids) should be monitored and treated with established standards of care. (Ciclesonide label, Warnings and precautions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Antiepileptics: Carbamazepine Use With Caution Carbamazepine: Concomitant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentrations of carbamazepine. (Clarithromycin label, Drug interactions)

Use with CNS Depressants Clemastine has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.). Use in Activities Requiring Mental Alertness Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc. (Clemastine label, Warnings)

Inducers of CYP3A4 and CYP3A5 Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. (Clindamycin label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

…several closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of methylphenidate or hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin), and such an effect may be anticipated with CMI as well. (Clomipramine label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. (Clorazepate label, Warnings)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations Antibiotics Anticonvulsants Other Drugs/Dietary Supplements nafcillin carbamazepine bosentan St. (Cyclosporine label, Drug interactions)

CNS Depressants Antihistamines may have additive effects with alcohol and other CNS depressants, e.g., hypnotics, sedatives, tranquilizers, antianxiety agents. (Cyproheptadine label, Warnings)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

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

Use with CNS Depressants CORPHENA Oral Solution has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc.). Use in Activities Requiring Mental Alertness Patients should be warned about engaging in activities requiring mental alertness such as driving a car or operating appliances, machinery, etc. (Dexchlorpheniramine label, Warnings)

Clinically Relevant Interactions Affecting DEXILANT When Coadministered with Other Drugs and Substances CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of dexlansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Dexlansoprazole label, Drug interactions)

As with other agents that have anticonvulsant activity, when Valium is used as an adjunct in treating convulsive disorders, the possibility of an increase in the frequency and/or severity of grand mal seizures may require an increase in the dosage of standard anticonvulsant medication. (Diazepam label, Warnings)

Exercise caution when prescribing ZIPSOR with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics). (Diclofenac label, Warnings and precautions)

Exercise caution when prescribing diclofenac sodium/misoprostol with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics). (Diclofenac and misoprostol label, Warnings and precautions)

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (Dimenhydrinate label, Warnings)

Drug Interactions Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc). (Diphenhydramine label, Drug interactions)

Concomitant medications were grouped as ACE inhibitors, oral anticoagulants, calcium channel blockers, beta blockers, cardiac glycosides, inducers of CYP3A4, substrates and inhibitors of CYP3A4, substrates and inhibitors of P-glycoprotein, nitrates, sulphonylureas, loop diuretics, potassium sparing diuretics, thiazide diuretics, substrates and inhibitors of tubular… (Dofetilide label, Drug interactions)

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose. (Doxepin label, Warnings and precautions)

Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary. (Doxercalciferol label, Drug interactions)

Barbiturates and Anti-Epileptics Barbiturates, carbamazepine, and phenytoin decrease the half-life of doxycycline. (Doxycycline label, Drug interactions)

Seizures and Seizure-like Activity : Weigh the potential risk versus benefits before prescribing dronabinol oral solution to patients with a history of seizures, including those requiring anti-epileptic medication or with other factors that lower the seizure threshold. (Dronabinol label, Warnings and precautions)

Following the administration of droperidol, the dose of other CNS depressant drugs should be reduced. (Droperidol label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. (Emtricitabine and tenofovir label, Drug interactions)

CYP3A4 Inducers Pre-treatment with a CYP3A4 inducer prior to erlotinib decreased erlotinib exposure [see Clinical Pharmacology (12.3) ]. (Erlotinib label, Drug interactions)

If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of INVANZ re-examined to determine whether it should be decreased or discontinued. (Ertapenem label, Warnings and precautions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Although behaviors such as sleep-driving may occur with sedative-hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with sedative-hypnotics appears to increase the risk of such behaviors, as does the use of sedative-hypnotics at doses exceeding the maximum recommended dose. (Estazolam label, Warnings)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Strong CYP3A inducer and P-gp inducer : Increase the dosage as recommended. (Everolimus label, Drug interactions)

Strong CYP 3A4 inducers: Concomitant use of strong CYP 3A4 inducers decreases exemestane exposure. (Exemestane label, Drug interactions)

Dose adjustment of simvastatin and lovastatin may be needed if a clinically significant change in lipids is noted. (Eslicarbazepine label, Drug interactions)

Anticonvulsants - In a pharmacokinetic study, maximum plasma concentrations of felodipine were considerably lower in epileptic patients on long-term anticonvulsant therapy (e.g., phenytoin, carbamazepine, or phenobarbital) than in healthy volunteers. (Felodipine label, Drug interactions)

Phenobarbital Clinical Impact: Chronic administration of phenobarbital, a known enzyme inducer, may be associated with a decrease in the plasma half-life of fenoprofen. (Fenoprofen label, Drug interactions)

CYP3A4 Inducers No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. (Fesoterodine label, Drug interactions)

Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination. (Flecainide label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning. (Flumazenil label, Warnings)

Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (Fluoxetine label, Drug interactions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids), should be monitored and treated with established standards of care. (Fluticasone label, Warnings and precautions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care. (Fluticasone and salmeterol label, Warnings and precautions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

CYP3A4 Interactions: Fosaprepitant is a weak inhibitor of CYP3A4, and aprepitant, the active moiety, is a substrate, inhibitor, and inducer of CYP3A4; see Full Prescribing Information for recommendations regarding contraindications, risk of adverse reactions, and dosage adjustment of FOCINVEZ and concomitant drugs. (Fosaprepitant label, Warnings and precautions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

• CYP3A4 Inducer: Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer. (Gefitinib label, Drug interactions)

Other Anticholinergic Drugs There is potential for an additive interaction between glycopyrrolate and concomitantly used anticholinergic drugs (e.g., tricyclic antidepressants, anti-epileptics, class I antiarrhythmics, anti­-spasmodics, amantadine) resulting in increased anticholinergic adverse reactions. (Glycopyrrolate label, Drug interactions)

…and its plasma concentrations can be significantly affected resulting in an increase in exposure Consider dose reduction [see Dosage and administration (2.7) ] Strong and moderate CYP3A4 inducers, e.g., rifampin, efavirenz Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in a decrease in exposure… (Guanfacine label, Drug interactions)

Drugs that May Decrease Haloperidol Plasma Concentrations Coadministration of haloperidol with potent enzyme inducers of CYP3A4 may gradually decrease the plasma concentrations of haloperidol to such an extent that efficacy may be reduced. (Haloperidol label, Drug interactions)

Concomitant administration of inducers of CYP3A4 may lead to decreases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions, including adrenal crisis. (Hydrocortisone label, Drug interactions)

• CYP3A4 Inducers: Monitor for increased toxicity when used in combination with CYP3A4 inducers. (Ifosfamide label, Drug interactions)

CYP3A4 inducers may decrease Gleevec C max and area under curve (AUC). (Imatinib label, Drug interactions)

If focal tremors, myoclonus, or seizures occur, patients should be evaluated neurologically, placed on anticonvulsant therapy if not already instituted, and the dosage of PRIMAXIN re-examined to determine whether it should be decreased, or the antibacterial drug discontinued ( 5.2 ). (Imipenem and cilastatin label, Warnings and precautions)

The plasma concentration of imipramine may increase when the drug is given concomitantly with hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine) and decrease by concomitant administration with hepatic enzyme inducers (e.g., barbiturates, phenytoin), and adjustment of the dosage of imipramine may therefore be necessary. (Imipramine label, Drug interactions)

Concomitant Use with CYP3A Inducers Use of KALYDECO with strong CYP3A inducers, such as rifampin, substantially decreases the exposure of ivacaftor, which may reduce the therapeutic effectiveness of KALYDECO. (Ivacaftor label, Warnings and precautions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Clinically Relevant Interactions Affecting PREVACID or PREVACID SoluTab When Coadministered with Other Drugs CYP2C19 OR CYP3A4 Inducers Clinical Impact: Decreased exposure of lansoprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ ledipasvir ↓ sofosbuvir Coadministration of ledipasvir and sofosbuvir with carbamazepine, phenytoin, or phenobarbital is expected to decrease the concentration of ledipasvir and sofosbuvir, leading to reduced therapeutic effect of ledipasvir and sofosbuvir. (Ledipasvir and sofosbuvir label, Drug interactions)

Effects of VYKOURA on Other Drugs Certain Antiepileptic Drugs Increase monitoring for seizure activity in patients taking certain concomitant antiepileptic drugs. (Leucovorin label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Effects of Leucovorin Products on Other Drugs Antiepileptic Drugs Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children. (Levoleucovorin label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

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)

…prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sufonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Lidocaine and prilocaine label, Drug interactions)

Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). (Linagliptin label, Drug interactions)

Inducers of P-glycoprotein or CYP3A4 Enzymes Clinical Impact Rifampin decreased linagliptin exposure, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-gp or CYP3A4 inducer. (Linagliptin and metformin label, Drug interactions)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs : Lofexidine tablets potentiates the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs. (Lofexidine label, Warnings and precautions)

Dose adjustment of simvastatin and lovastatin may be needed if a clinically significant change in lipids is noted. (Eslicarbazepine label, Drug interactions)

• If patients with severe renal impairment or ESRD receiving SELZENTRY (without concomitant CYP3A inducers or inhibitors) experience postural hypotension, the dose of SELZENTRY should be reduced from 300 mg twice daily to 150 mg twice daily. (Maraviroc label, Warnings and precautions)

• Coadministration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression ( 7.1 ). (Meclizine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Anticonvulsants In patients taking an anticonvulsant (e.g., valproic acid, carbamazepine, phenobarbital or phenytoin), the concomitant use of mefloquine may reduce seizure control by lowering the plasma levels of the anticonvulsant. (Mefloquine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Inducers of CYP3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil. (Memantine and donepezil label, Drug interactions)

…procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine (Mepivacaine label, Drug interactions)

Additive Effects Since the effects of meprobamate and alcohol or meprobamate and other CNS depressants or psychotropic drugs may be additive,appropriate caution should be exercised with patients who take more than one of these agents simultaneously. (Meprobamate label, Warnings)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

Patients receiving ATMEKSI (methocarbamol) Oral Suspension should be cautioned about combined effects with alcohol and other CNS depressants [ see Drug Interactions (7.1) ]. (Methocarbamol label, Warnings and precautions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

CYP3A4 inducers Drugs (e.g. nevirapine, rifampin) that are strong inducers of CYP3A4 are likely to decrease the pharmacological action of methylergonovine maleate. (Methylergonovine label, Drug interactions)

Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin) : Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. (Methylprednisolone label, Drug interactions)

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

John's Wort, tramadol, tryptophan, buspirone Strong CYP3A Inducers Clinical Impact The concomitant use of strong CYP3A inducers with REMERON/REMERONSolTab decreases the plasma concentration of mirtazapine [see Clinical Pharmacology (12.3) ] . (Mirtazapine label, Drug interactions)

Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants and corticosteroids) should be monitored and treated with established standards of care. (Mometasone label, Warnings and precautions)

WARNINGS AND PRECAUTIONS Risk of Recurrent Respiratory and CNS Depression : Due to the duration of action of naloxone relative to the opioid, respiratory and CNS depression may recur after the first dose of naloxone. (Naloxone label, Warnings and precautions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Anticonvulsants: Carbamazepine, clonazepam, ethosuximide Plasma concentrations of nevirapine and the anticonvulsant may be decreased. (Nevirapine label, Drug interactions)

Possible Reduced Efficacy with Strong CYP3A4 Inducers Concomitant use of strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. (Nimodipine label, Warnings and precautions)

Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. (Nintedanib label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

Carbamazepine : Potential for elevated carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (Olanzapine and fluoxetine label, Drug interactions)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (Olmesartan, amlodipine, and hydrochlorothiazide label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Phenytoin, Carbamazepine, and Rifampin In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. (Ondansetron label, Drug interactions)

Drug Interactions and Decreased Vitamin Absorption ORLISTAT may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs [see Drug Interactions (7) ]. (Orlistat label, Warnings and precautions)

Patients should be warned that the effects of alcohol or other CNS-depressant drugs may be additive to those of Oxazepam, possibly requiring adjustment of dosage or elimination of such agents. (Oxazepam label, Warnings)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

If the patient is being treated with an anticonvulsant agent, increased dosage of that agent may be required when perphenazine products are used concomitantly. (Perphenazine label, Warnings)

Phenobarbital or Primidone: Higher dosage of APTIOM may be necessary. (Eslicarbazepine label, Drug interactions)

Phenobarbital or Primidone: Higher dosage of APTIOM may be necessary. (Eslicarbazepine label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Phenytoin: Higher dosage of APTIOM may be necessary and dose adjustment may be needed for phenytoin. (Eslicarbazepine label, Drug interactions)

Strong CYP3A4 Inducers: Decreased exposure of WAKIX; consider dosage adjustment of WAKIX ( 2.6 , 7.1 ) (Pitolisant label, Drug interactions)

Concomitant Use with Midazolam : Noxafil can prolong hypnotic/sedative effects. (Posaconazole label, Warnings and precautions)

CYP 3A4 inducers (e.g. barbiturates, phenytoin, carbamazepine, and rifampin): Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Orapred be increased. (Prednisolone label, Drug interactions)

CYP 3A4 inducers and inhibitors: May, respectively, increase or decrease clearance of corticosteroids, necessitating dose adjustment. (Prednisone label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine The administration of local anesthetic injections containing… (Prilocaine and epinephrine label, Drug interactions)

Phenobarbital or Primidone: Higher dosage of APTIOM may be necessary. (Eslicarbazepine label, Drug interactions)

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. (Prochlorperazine label, Precautions)

Hormonal Contraceptives: APTIOM may decrease the effectiveness of hormonal contraceptives. (Eslicarbazepine label, Drug interactions)

The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine… (Promethazine label, Warnings)

The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine… (Promethazine and dextromethorphan label, Warnings)

As with other sedative medications, there is wide interpatient variability in DIPRIVAN dosage requirements, and these requirements may change with time. (Propofol label, Warnings and precautions)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (Protriptyline label, Drug interactions)

• Concomitant use of strong CYP3A4 inducers: Increase quetiapine dose up to 5 fold when used in combination with a chronic treatment (more than 7-14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. (Quetiapine label, Drug interactions)

The use of alcohol and other CNS depressants may increase the risk of such behaviors. (Ramelteon label, Warnings and precautions)

CYP2C8 and CYP3A4 Inducers Intervention: Repaglinide tablets dose increases and increased frequency of glucose monitoring may be required when co‑administered. (Repaglinide label, Drug interactions)

Drug Interactions Effect of Rifabutin on the Pharmacokinetics of Other Drugs Rifabutin induces CYP3A enzymes and therefore may reduce the plasma concentrations of drugs metabolized by those enzymes. (Rifabutin label, Drug interactions)

…Hormonal Contraceptives Prevention or Management: Advise patients to change to non-hormonal methods of birth control during rifampin therapy Estrogens Decrease exposure Progestins Anticonvulsants Phenytoin Administered with rifampin 450 mg daily Decrease exposure Antiarrhythmics Disopyramide Decrease exposure Mexiletine Decrease exposure Quinidine Decrease exposure… (Rifampin label, Drug interactions)

…Disopyramide, mexiletine, quinidine, tocainide Antibiotics Chloramphenicol, clarithromycin, dapsone, doxycycline; Fluoroquinolones (such as ciprofloxacin) Oral Anticoagulants Warfarin Anticonvulsants Phenytoin Antimalarials Quinine Azole Antifungals Fluconazole, itraconazole, ketoconazole Antipsychotics Haloperidol Barbiturates Phenobarbital Benzodiazepines Diazepam… (Rifapentine label, Drug interactions)

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (Risperidone label, Drug interactions)

Reduced Rocuronium Bromide Injection activity possible : Anticonvulsants. (Rocuronium label, Drug interactions)

…cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants Phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine NAROPIN should be used with caution in patients receiving… (Ropivacaine label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Strong CYP3A4 Inducers Concomitant use of JAKAFI/JAKAFI XR with strong CYP3A4 inducers may decrease ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may reduce efficacy of JAKAFI/JAKAFI XR. (Ruxolitinib label, Drug interactions)

Weigh this potential risk against the benefits before prescribing TRANSDERM SCŌP to patients with a history of seizures, including those receiving anti-epileptic medication or who have risk factors that can lower the seizure threshold. (Scopolamine label, Warnings and precautions)

Drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution. (Selegiline label, Drug interactions)

Dose adjustment of simvastatin and lovastatin may be needed if a clinically significant change in lipids is noted. (Eslicarbazepine label, Drug interactions)

• CYP3A4 Inducers : Consider dose increase of SUTENT when administered with strong CYP3A4 inducers. (Sunitinib label, Drug interactions)

Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. (Suvorexant label, Warnings and precautions)

Risk of Rejection with Strong CYP3A Inducers and Risk of Serious Adverse Reactions with Strong CYP3A Inhibitors The concomitant use of strong CYP3A inducers may increase the metabolism of tacrolimus, leading to lower whole blood trough concentrations and greater risk of rejection. (Tacrolimus label, Warnings and precautions)

CYP3A4 inhibitors (e.g. ketoconazole, ritonavir) increase CIALIS exposure ( 2.7 , 5.10 , 7.2 ) requiring dose adjustment: CIALIS for use as needed: no more than 10 mg every 72 hours CIALIS for once daily use: dose not to exceed 2.5 mg CYP3A4 inducers (e.g. rifampin) decrease CIALIS exposure ( 7.2 ). (Tadalafil label, Drug interactions)

Patients should be monitored for adequate clinical effect when amlodipine is co-administered with CYP3A4 inducers. (Telmisartan and amlodipine label, Drug interactions)

Although behaviors such as “sleep-driving” may occur with temazepam capsules alone at therapeutic doses, the use of alcohol and other CNS depressants with temazepam capsules appear to increase the risk of such behaviors, as does the use of temazepam capsules at doses exceeding the maximum recommended dose. (Temazepam label, Warnings)

Co-administration with Inducers or Inhibitors of CYP3A Metabolism Agents Inducing CYP3A Metabolism: Strong inducers of CYP3A4/5 such as dexamethasone, carbamazepine, phenytoin, phenobarbital, rifampin, rifabutin, and rifampacin may decrease exposure of the active metabolite, sirolimus. (Temsirolimus label, Warnings and precautions)

Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. (Terbinafine label, Drug interactions)

Abnormal Thyroid Function Tests Dose-dependent decreases in serum T3 and T4 (free and total) values have been observed in patients taking APTIOM. (Eslicarbazepine label, Warnings and precautions)

Alcohol or Other Sedating Drugs Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence [see Warnings and Precautions (5.7) ] . (Tetrabenazine label, Drug interactions)

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

DRUG INTERACTIONS Hepatic microsomal enzyme inducing agents, such as carbamazepine, were found to significantly increase the clearance of thiothixene. (Thiothixene label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1, 7.2 ) (Tinidazole label, Drug interactions)

Sedation: Zanaflex may interfere with everyday activities; sedative effects of Zanaflex, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 ) (Tizanidine label, Warnings and precautions)

…exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Strong CYP3A4 Inducers (e.g., rifampin) Clinical Impact Decreased exposure to tofacitinib and may result in loss of or reduced clinical response Intervention Concomitant use with XELJANZ/XELJANZ… (Tofacitinib label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Excessive reduction of blood glucose (additive effect) f CNS depressant agents (including opioids, alcohol, sedatives, hypnotics) Use with caution d Increased CNS depression Dietary supplements containing sympathomimetics Contraindicated a Antidepressants including but not limited to: Other MAOIs (e.g., linezolid, intravenous methylene blue, selective MAOIs)… (Tranylcypromine label, Drug interactions)

CYP3A4 Inducers: Increase in RALDESY dosage may be necessary ( 2.5 , 7 ). (Trazodone label, Drug interactions)

Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. (Treprostinil label, Warnings and precautions)

Hepatic enzyme inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Drugs which induce hepatic microsomal drug metabolizing enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. (Triamcinolone label, Drug interactions)

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. (Trifluoperazine label, Precautions)

Concurrent use of alcohol or other CNS depressants with trihexyphenidyl may cause increased sedative effects. (Trihexyphenidyl 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)

CYP3A4 inducers decrease verapamil levels ( 7.1 ) (Verapamil label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

CYP3A4 Inducers: Consider increasing VIIBRYD dosage by 2-fold, up to 80 mg once-daily over 1 to 2 weeks when used concomitantly with strong CYP3A4 inducers for greater than 14 days ( 2.4 , 7 ). (Vilazodone label, Drug interactions)

Drug Interactions The simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included vincristine sulfate has been reported to reduce blood levels of the anticonvulsant and to increase seizure activity. (Vincristine label, Drug interactions)

CYP2C19 Substrates APTIOM can inhibit CYP2C19, which can cause increased plasma concentrations of drugs that are metabolized by this isoenzyme (e.g., phenytoin, clobazam, and omeprazole) [see Clinical Pharmacology ( 12.3 )]. (Eslicarbazepine label, Drug interactions)

Pharmacokinetic Interactions Carbamazepine Carbamazepine is an inducer of CYP3A4; administration of 200 mg twice daily for 21 days resulted in a decrease of approximately 35% in the AUC of ziprasidone. (Ziprasidone label, Drug interactions)

Anyone considering prescribing APTIOM or any other AED must balance this risk with the risk of untreated illness. (Eslicarbazepine label, Warnings and precautions)

Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram – see WARNINGS section. (Amitriptyline label, Drug interactions)

Anticonvulsant therapy should be continued in patients with known seizure disorders. (Cefazolin label, Warnings and precautions)

Anticonvulsant therapy can be given if clinically indicated. (Cephalexin label, Warnings and precautions)

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

Drug Interactions If phenytoin or other hepatic enzyme inducers are taken concurrently with Norpace or Norpace CR, lower plasma levels of disopyramide may occur. (Disopyramide label, Drug interactions)

• Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (Docetaxel label, Drug interactions)

In Drug-Induced CNS and Respiratory Depression Doxapram alone may not stimulate adequate spontaneous breathing or provide sufficient arousal in patients who are severely depressed either due to respiratory failure or to CNS depressant drugs, but may be used as an adjunct to established supportive measures and resuscitative techniques. (Doxapram label, Warnings)

Concurrent use of alcohol and other CNS depressants (such as hypnotic sedatives and tranquilizers) with doxylamine succinate and pyridoxine hydrochloride delayed-release tablets is not recommended. (Doxylamine and pyridoxine label, Drug interactions)

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

Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. (Eribulin label, Drug interactions)

Seizures Although anticonvulsant effects of racemic citalopram have been observed in animal studies, Escitalopram Capsules have not been systematically evaluated in patients with a seizure disorder. (Escitalopram label, Warnings and precautions)

Potential for Glycerol Phenylbutyrate to Affect Other Drugs Drugs with narrow therapeutic index that are substrates of CYP3A4 Glycerol phenylbutyrate is a weak inducer of CYP3A4 in humans. (Glycerol phenylbutyrate label, Drug interactions)

Antiepileptics The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL. (Hydroxychloroquine label, Drug interactions)

Antiepileptic Drugs Sporadic cases of seizures have been reported during concomitant use of ketorolac tromethamine and antiepileptic drugs (phenytoin, carbamazepine). (Ketorolac label, Drug interactions)

Therefore, ambulatory patients should be warned about activities requiring alertness (e.g., operating vehicles or machinery) and about concomitant use of alcohol and other CNS depressants. (Loxapine label, Warnings)

Anticonvulsants, psychotropic, hormone preparations, corticosteroids, antithyroid agents, cyproheptadine: may affect the results of the metyrapone test. (Metyrapone label, Drug interactions)

When phenytoin or other hepatic enzyme inducers such as rifampin and phenobarbital have been taken concurrently with mexiletine, lowered mexiletine plasma levels have been reported. (Mexiletine 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)

CYP3A4 Substrates An in vitro study has suggested that rifaximin induces CYP3A4 [see Clinical Pharmacology ( 12.3 )] . (Rifaximin label, Drug interactions)

Strong CYP3A inducers: Strong inducers of CYP3A (for example, rifampin, phenytoin, carbamazepine, phenobarbital or St. (Riociguat label, Drug interactions)

These data suggest that GH may alter the clearance of compounds known to be metabolized by CYP450 liver enzymes (e.g., corticosteroids, sex steroids, anticonvulsants, and cyclosporine). (Tesamorelin label, Drug interactions)

Drugs Having No Clinically Important Interactions with SAPHRIS No dosage adjustment of SAPHRIS is necessary when administered concomitantly with paroxetine (see Table 12 in Drug Interactions ( 7.1 ) for paroxetine dosage adjustment), imipramine, cimetidine, valproate, lithium, or a CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin). (Asenapine label, Drug interactions)

CYP2C19 and CYP3A4 Inducer Co-administration of Micafungin in Sodium Chloride Injection with rifampin and ritonavir did not alter the pharmacokinetics of micafungin. (Micafungin 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)