Primidone : interactions médicamenteuses

CYP3A4 Inducers: Avoid concomitant strong CYP3A4 inducers during YONSA treatment. (notice Abiratérone, Interactions médicamenteuses)

• CYP3A Inducers: Avoid co-administration with strong CYP3A inducers. (notice Acalabrutinib, Interactions médicamenteuses)

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. (notice Acide valproïque, Mise en garde encadrée)

L'association de l'alcool avec des médicaments sédatifs (opioïdes, benzodiazépines, somnifères, myorelaxants) peut provoquer une somnolence dangereuse, un ralentissement de la respiration et un surdosage. (NIAAA, Harmful Interactions: Mixing Alcohol with Medicines)

CYP3A4 Inducers : Avoid coadministration of VIJOICE with a strong CYP3A4 inducer. (notice Alpélisib, Interactions médicamenteuses)

• 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. (notice Alprazolam, Mises en garde et précautions)

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

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 ) (notice Aprémilast, Mises en garde et précautions)

CYP3A4 Inducers : Avoid concomitant use for greater than 14 days ( 7.1 ) (notice Aripiprazole, Interactions médicamenteuses)

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

• 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. (notice Azélastine et fluticasone, Mises en garde et précautions)

…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… (notice Belladone et opium, Mise en garde encadrée)

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. (notice Bictégravir, emtricitabine et ténofovir alafénamide, Contre-indications)

Strong CYP3A4 Inducers: Avoid concomitant use. (notice Bortézomib, Interactions médicamenteuses)

• Strong CYP3A Inducers: Avoid concomitant use with BOSULIF. (notice Bosutinib, Interactions médicamenteuses)

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. (notice Buprénorphine, Mise en garde encadrée)

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)] . (notice Bupropion, Contre-indications)

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. (notice Butalbital, aspirine, caféine et codéine, Mise en garde encadrée)

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. (notice Butalbital, paracétamol, caféine et codéine, Mise en garde encadrée)

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. (notice Butorphanol, Mise en garde encadrée)

…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… (notice Cabotégravir, Contre-indications)

Avoid chronic co-administration of strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. (notice Cabozantinib, Interactions médicamenteuses)

CNS Depressants The concomitant use of EQUETRO and other CNS depressants can increase the risk of respiratory depression, profound sedation, hypotension, and syncope. (notice Carbamazépine, Interactions médicamenteuses)

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. (notice Carbinoxamine, Mises en garde et précautions)

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

Avoid concurrent use of QUZYTTIR with alcohol or other CNS depressants because additional reduction in alertness and additional impairment of CNS performance may occur. (notice Cétirizine, Mises en garde et précautions)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Chlordiazépoxide, Mises en garde)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Chlordiazépoxide et clidinium, Mises en garde)

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.). (notice Chlorpromazine, Contre-indications)

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 )]. (notice Ciprofloxacine, Interactions médicamenteuses)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Clobazam, Mises en garde et précautions)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Clonazépam, Mises en garde)

Avoid use with other central nervous system (CNS) depressants ( 5.3 ) (notice Clonidine, Mises en garde et précautions)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Clorazépate, Mises en garde)

• Concomitant use of Strong CYP3A4 Inducers is not recommended. (notice Clozapine, Interactions médicamenteuses)

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. (notice Codéine, Mise en garde encadrée)

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… (notice Cyclobenzaprine, Interactions médicamenteuses)

Moderate or Strong CYP3A4 inducers: Avoid concomitant use. (notice Daridorexant, Interactions médicamenteuses)

…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… (notice Darunavir, Contre-indications)

Co-administration of PREZCOBIX or PREZCOBIX PED with CYP3A inducers may lead to lower exposures of darunavir and cobicistat and potential loss of efficacy of darunavir and possible resistance. (notice Darunavir et cobicistat, Contre-indications)

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

Avoid use of moderate or strong CYP3A4 inducers with EMFLAZA, as they may reduce efficacy ( 7.1 ) (notice Déflazacort, Interactions médicamenteuses)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Diazépam, Mises en garde)

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 ). (notice Diphénoxylate et atropine, Contre-indications)

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. (notice Divalproate de sodium (valproate), Mise en garde encadrée)

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) ] . (notice Doravirine, Contre-indications)

• Avoid concomitant use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp ( 7.1 ) (notice Doxorubicine, Interactions médicamenteuses)

Central nervous system (CNS) depressants: Concurrent use with alcohol or other CNS depressants is not recommended ( 5.1 ) (notice Doxylamine et pyridoxine, Mises en garde et précautions)

• CYP3A inducers: Avoid concomitant use. (notice Dronédarone, Interactions médicamenteuses)

Therefore, concomitant use with strong CYP3A inducers is not recommended [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . (notice Élexacaftor, tézacaftor et ivacaftor, Mises en garde et précautions)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine Herbal Products: St. (notice Elvitégravir, cobicistat, emtricitabine et ténofovir, Contre-indications)

…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)… (notice Emtricitabine, rilpivirine et ténofovir, Contre-indications)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Estazolam, Mises en garde)

The use of LUNESTA with other sedative-hypnotics at bedtime or the middle of the night is not recommended. (notice Eszopiclone, Mises en garde et précautions)

IT IS NOT KNOWN WHETHER CONCOMITANT USE OF OTHER ANTIEPILEPTIC DRUGS AND/OR OTHER DRUGS AFFECT THE INCIDENCE OF HEPATIC FAILURE. (notice Felbamate, Mise en garde encadrée)

• 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. (notice Fentanyl, Mise en garde encadrée)

Preventing or Managing DI The concomitant use of ADDYI with CYP3A4 inducers is not recommended. (notice Flibansérine, Interactions médicamenteuses)

…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). (notice Fosamprénavir, Contre-indications)

• Respiratory Depression: May occur with NEURONTIN when used with concomitant central nervous system (CNS) depressants, including opioids, or in the setting of underlying respiratory impairment. (notice Gabapentine, Mises en garde et précautions)

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. (notice Hydrocodone, Mise en garde encadrée)

…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;… (notice Hydrocodone et chlorphénamine, Mise en garde encadrée)

…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… (notice Hydrocodone et homatropine, Mise en garde encadrée)

…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,… (notice Hydrocodone et ibuprofène, Mise en garde encadrée)

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. (notice Hydrocodone et paracétamol, Mise en garde encadrée)

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 . (notice Hydromorphone, Mise en garde encadrée)

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

• Strong CYP3A4 Inducers: Do not administer strong CYP3A4 inducers with CAMPTOSAR. (notice Irinotécan, Interactions médicamenteuses)

To avoid phenytoin intoxication, appropriate adjustment of the anticonvulsant should be made 5,6 . (notice Isoniazide, Interactions médicamenteuses)

Anticonvulsants Carbamazepine Not recommended 2 weeks before, during, and 2 weeks after TOLSURA treatment. (notice Itraconazole, Interactions médicamenteuses)

Avoid concomitant use of CYP3A4 inducers when using Corlanor. (notice Ivabradine, Interactions médicamenteuses)

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death. (notice Kétamine, Interactions médicamenteuses)

This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. (notice Kétoconazole, Contre-indications)

Avoid strong CYP3A4 inducers. (notice Lapatinib, Interactions médicamenteuses)

Strong CYP3A4 Inducers: Avoid coadministration of strong CYP3A4 inducers with VITRAKVI. (notice Larotrectinib, Interactions médicamenteuses)

Strong or moderate CYP3A inducers: Avoid concomitant use. (notice Lemborexant, Interactions médicamenteuses)

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) ] . (notice Lénacapavir, Contre-indications)

Avoid concurrent use of alcohol or other central nervous system depressants with XYZAL. (notice Lévocétirizine, Mises en garde et précautions)

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. (notice Lévorphanol, Mise en garde encadrée)

…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… (notice Lopinavir et ritonavir, Contre-indications)

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 ) (notice Lorazépam, Mises en garde et précautions)

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

CONTRAINDICATIONS Loxapine is contraindicated in comatose or severe drug-induced depressed states (alcohol, barbiturates, narcotics, etc.). Loxapine is contraindicated in individuals with known hypersensitivity to dibenzoxazepines. (notice Loxapine, Contre-indications)

CYP3A4 inducers: Avoid concomitant use with CAPLYTA. (notice Lumatépérone, Interactions médicamenteuses)

Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. (notice Lurasidone, Contre-indications)

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). (notice Macitentan, Interactions médicamenteuses)

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. (notice Métaxalone, Mises en garde et précautions)

Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )]. (notice Méthadone, Mise en garde encadrée)

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… (notice Midazolam, Mise en garde encadrée)

CYP3A inducers: Do not use mifepristone with CYP3A inducers ( 7.3 ). (notice Mifépristone, Interactions médicamenteuses)

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. (notice Morphine, Mise en garde encadrée)

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. (notice Nalbuphine, Mise en garde encadrée)

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. (notice Naldémédine, Interactions médicamenteuses)

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. (notice Nalméfène, Mises en garde et précautions)

Strong CYP3A4 inducers (e.g., rifampin) : Decreased concentrations of naloxegol; concomitant use is not recommended. (notice Naloxégol, Interactions médicamenteuses)

…(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). (notice Naltrexone et bupropion, Contre-indications)

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 ). (notice Nifédipine, Interactions médicamenteuses)

Strong CYP3A Inducers: Avoid concomitant use with CAVHANZA. (notice Nilotinib, Interactions médicamenteuses)

…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. (notice Nirmatrelvir et ritonavir, Contre-indications)

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 ) (notice Noréthistérone et éthinylestradiol, Interactions médicamenteuses)

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. (notice Olicéridine, Mise en garde encadrée)

• Avoid concurrent use of alcohol or other central nervous system depressants with olopatadine hydrochloride nasal solution (nasal spray) ( 5.2 ). (notice Olopatadine, Mises en garde et précautions)

• 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. (notice Olopatadine et mométasone, Mises en garde et précautions)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Oxazépam, Mises en garde)

• Central Nervous System Depression Xyrem (sodium oxybate) is a CNS depressant. (notice Oxybate de sodium, Mise en garde encadrée)

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. (notice Oxycodone, Mise en garde encadrée)

…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… (notice Oxycodone et paracétamol, Mise en garde encadrée)

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. (notice Oxymorphone, Mise en garde encadrée)

• CYP3A Inducers: Avoid concurrent use of IBRANCE with strong CYP3A inducers. (notice Palbociclib, Interactions médicamenteuses)

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. (notice Palipéridone, Interactions médicamenteuses)

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. (notice Paracétamol et codéine, Mise en garde encadrée)

VOTRIENT is not recommended if chronic use of strong CYP3A4 inducers cannot be avoided. (notice Pazopanib, Interactions médicamenteuses)

…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… (notice Pentazocine et naloxone, Mise en garde encadrée)

CONTRAINDICATIONS Perphenazine products are contraindicated in comatose or greatly obtunded patients and in patients receiving large doses of central nervous system depressants (barbiturates, alcohol, narcotics, analgesics, or antihistamines); in the presence of existing blood dyscrasias, bone marrow depression, or liver damage; and in patients who have shown… (notice Perphénazine, Contre-indications)

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. (notice Péthidine, Mise en garde encadrée)

Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics. (notice Phénelzine, Contre-indications)

CONTRAINDICATIONS Primidone is contraindicated in: 1) patients with porphyria and 2) patients who are hypersensitive to phenobarbital (see ACTIONS ). (notice Primidone, Contre-indications)

CONTRAINDICATIONS Primidone is contraindicated in: 1) patients with porphyria and 2) patients who are hypersensitive to phenobarbital (see ACTIONS ). (notice Primidone, Contre-indications)

…spasms in the urinary tract collection system, inactivation of nerve and muscle cells after administration of drugs to relax the muscles (depolarization block after depolarizing muscle relaxants), in case of intoxication due to “irreversibly acting” cholinesterase inhibitors (drugs used to treat dementia), intoxication with phosphoric acid esters or barbiturates. (notice Physostigmine, Contre-indications)

Strong or Moderate CYP3A4 Inducers: Avoid concomitant use of NUPLAZID. (notice Pimavansérine, Interactions médicamenteuses)

• 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 )] . (notice Praziquantel, Contre-indications)

• Respiratory Depression : May occur with LYRICA when used with concomitant CNS depressants or in the setting of underlying respiratory impairment. (notice Prégabaline, Mises en garde et précautions)

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.). Do not use in pediatric surgery. (notice Prochlorpérazine, Contre-indications)

…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… (notice Prométhazine et codéine, Mise en garde encadrée)

If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. (notice Quinine, Interactions médicamenteuses)

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) (notice Ranolazine, Contre-indications)

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. (notice Rémifentanil, Mise en garde encadrée)

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. (notice Rilpivirine, Contre-indications)

• Strong and Moderate CYP3A Inducers: Avoid concomitant administration. (notice Rimégépant, Interactions médicamenteuses)

• Certain CYP3A inducers: Coadministration with strong inducers of CYP3A is not recommended. (notice Ritlécitinib, Interactions médicamenteuses)

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… (notice Ritonavir, Mise en garde encadrée)

Avoid concomitant use of XARELTO with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions (7.3) ] . (notice Rivaroxaban, Mises en garde et précautions)

• Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. (notice Roflumilast, Mises en garde et précautions)

Intervention: Avoid the use of VARUBI in patients who require chronic administration of strong CYP3A4 inducers. (notice Rolapitant, Interactions médicamenteuses)

• Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ). (notice Romidepsine, Interactions médicamenteuses)

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) ]. (notice Sirolimus, Mises en garde et précautions)

Anticonvulsants: carbamazepine phenytoin phenobarbital ↓ sofosbuvir ↓ velpatasvir ↓ voxilaprevir Coadministration is not recommended. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

• Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. (notice Sorafénib, Interactions médicamenteuses)

Inducers of CYP3A4 Strong CYP3A4 inducers should not be used with tamoxifen. (notice Tamoxifène, Interactions médicamenteuses)

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. (notice Tapentadol, Mise en garde encadrée)

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 ) (notice Tasimeltéon, Interactions médicamenteuses)

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. (notice Témazépam, Mises en garde)

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 ) ] . (notice Thiotépa, Interactions médicamenteuses)

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. (notice Ticagrélor, Interactions médicamenteuses)

Avoid concomitant use of SAMSCA with strong CYP3A inducers. (notice Tolvaptan, Interactions médicamenteuses)

Coadministration with a strong CYP3A4 inducer may result in a relevant decrease in FARESTON exposure and should be avoided. (notice Torémifène, Interactions médicamenteuses)

CYP3A inducers: Avoid concomitant strong CYP3A inducers ( 7.1 ) (notice Trabectédine, Interactions médicamenteuses)

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. (notice Tramadol, Mise en garde encadrée)

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. (notice Tramadol et paracétamol, Mise en garde encadrée)

Avoid concomitant use with strong CYP3A inducers if possible. (notice Trétinoïne, Interactions médicamenteuses)

• 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. (notice Triazolam, Mises en garde et précautions)

CONTRAINDICATIONS A known hypersensitivity to phenothiazines, comatose or greatly depressed states due to central nervous system depressants and, in cases of existing blood dyscrasias, bone marrow depression and preexisting liver damage. (notice Trifluopérazine, Contre-indications)

Strong CYP3A4 Inducers: Should be avoided as concomitant use will result in reduction of ubrogepant exposure. (notice Ubrogépant, Interactions médicamenteuses)

Ella should not be administered with CYP3A4 inducers [see Drug interactions (7.1) and Clinical Pharmacology (12.3) ] . (notice Ulipristal, Mises en garde et précautions)

Strong CYP3A4 Inducers : Coadministration of RINVOQ/RINVOQ LQ with strong CYP3A4 inducers is not recommended. (notice Upadacitinib, Interactions médicamenteuses)

Use of strong CYP3A4 inducers with INGREZZA or INGREZZA SPRINKLE Concomitant use is not recommended. (notice Valbénazine, Interactions médicamenteuses)

Strong CYP3A Inducers : Avoid concomitant use with strong CYP3A inducers. (notice Vepdégestrant, Interactions médicamenteuses)

• Long-acting barbiturates • Rifabutin • Rifampin • Ritonavir Concomitant use with high-dose ritonavir (400 mg every 12 hours) is contraindicated. (notice Voriconazole, Contre-indications)

The use of zaleplon with other sedative-hypnotics at bedtime or the middle of the night is not recommended (see ). (notice Zaléplone, Mises en garde)

The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended. (notice Zolpidem, Mises en garde et précautions)

Caution is advised when beginning, discontinuing, or changing the dose of acetazolamide in patients receiving primidone. (notice Acétazolamide, Interactions médicamenteuses)

Effects of VYKOURA on Other Drugs Certain Antiepileptic Drugs Increase monitoring for seizure activity in patients taking certain concomitant antiepileptic drugs. (notice Acide folinique, Interactions médicamenteuses)

Ces médicaments antiépileptiques abaissent les taux de folates, et les compléments d'acide folique peuvent à leur tour abaisser les taux sanguins du médicament. (NIH Office of Dietary Supplements, Folate)

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. (notice Acide lévofolinique, Interactions médicamenteuses)

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. (notice Albendazole, Mises en garde et précautions)

Inform patients also that the central nervous system depressant effects of allopurinol tablets may be additive to those of alcohol and other CNS depressants. (notice Allopurinol, Mises en garde et précautions)

25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (notice Aminophylline, Interactions médicamenteuses)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (notice Amlodipine, Interactions médicamenteuses)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (notice Amlodipine et atorvastatine, Interactions médicamenteuses)

Blood pressure should be monitored when amlodipine is coadministered with CYP3A4 inducers (e.g. rifampicin, St. (notice Amlodipine et bénazépril, Interactions médicamenteuses)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (notice Amlodipine et olmésartan, Interactions médicamenteuses)

Blood pressure should be closely monitored when amlodipine is coadministered with CYP3A inducers (e.g. rifampicin, St. (notice Amlodipine et valsartan, Interactions médicamenteuses)

Amoxapine may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (notice Amoxapine, Interactions médicamenteuses)

…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… (notice Articaïne et adrénaline, Interactions médicamenteuses)

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. (notice Aspirine et dipyridamole, Interactions médicamenteuses)

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

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. (notice Baclofène, Mises en garde et précautions)

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. (notice Béclométasone, Mises en garde et précautions)

Alcohol, barbiturates or narcotics: Concomitant administration of thiazide diuretics with alcohol, barbiturates, or narcotics may potentiate orthostatic hypotension. (notice Bénazépril et hydrochlorothiazide, Interactions médicamenteuses)

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 )]. (notice Bexagliflozine, Interactions médicamenteuses)

Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur. (notice Bisoprolol et hydrochlorothiazide, Précautions)

Strong CYP3A4 inducers Double the recommended dosage and further adjust based on clinical response. (notice Brexpiprazole, Interactions médicamenteuses)

Use with CNS depressants may result in an additive or potentiating effect. (notice Brimonidine, Interactions médicamenteuses)

Use with CNS depressants may result in an additive or potentiating effect. (notice Brimonidine et timolol, Interactions médicamenteuses)

Therefore, potent inhibitors or inducers of CYP3A4 may increase or reduce the circulating levels of CYCLOSET, respectively. (notice Bromocriptine, Interactions médicamenteuses)

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. (notice Bromphéniramine, pseudoéphédrine et dextrométhorphane, Interactions médicamenteuses)

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. (notice Budésonide, Mises en garde et précautions)

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. (notice Budésonide et formotérol, Mises en garde et précautions)

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. (notice Bupivacaïne, Mises en garde et précautions)

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. (notice Bupivacaïne et adrénaline, Mises en garde et précautions)

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) ] . (notice Buprénorphine et naloxone, Mises en garde et précautions)

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

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. (notice Butalbital et paracétamol, Interactions médicamenteuses)

Other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression. (notice Butalbital, aspirine et caféine, Interactions médicamenteuses)

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. (notice Butalbital, paracétamol et caféine, Interactions médicamenteuses)

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. (notice Canagliflozine, Interactions médicamenteuses)

Interactions with Hydrochlorothiazide Alcohol, barbiturates, or narcotics − Potentiation of orthostatic hypotension may occur. (notice Candésartan et hydrochlorothiazide, Interactions médicamenteuses)

Other CNS depressants, including alcohol, could potentiate the somnolence and sedation effect of EPIDIOLEX. (notice Cannabidiol (sur ordonnance), Mises en garde et précautions)

• Additive sedative effects when used with other CNS depressants including alcohol (5.1) (notice Carisoprodol, Mises en garde et précautions)

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. (notice Caspofungine, Interactions médicamenteuses)

Concomitant use with other CNS depressants or alcohol may have additive effects. (notice Cénobamate, Mises en garde et précautions)

…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 (notice Chloroprocaïne, Précautions)

Alcohol, Barbiturates, or Narcotics - potentiation of orthostatic hypotension may occur. (notice Chlorothiazide, Interactions médicamenteuses)

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. (notice Chlorzoxazone, Mises en garde et précautions)

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. (notice Ciclésonide, Mises en garde et précautions)

Drugs/Dietary Supplements That Decrease Cyclosporine Concentrations Antibiotics Anticonvulsants Other Drugs/Dietary Supplements nafcillin carbamazepine bosentan St. (notice Ciclosporine, Interactions médicamenteuses)

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. (notice Clarithromycine, Interactions médicamenteuses)

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. (notice Clémastine, Mises en garde)

Inducers of CYP3A4 and CYP3A5 Inducers of CYP3A4 and/or CYP3A5 may reduce plasma concentrations of clindamycin. (notice Clindamycine, Interactions médicamenteuses)

…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. (notice Clomipramine, Interactions médicamenteuses)

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

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. (notice Désogestrel et éthinylestradiol, Interactions médicamenteuses)

Alcohol or other sedating drugs: May have additive sedation and somnolence ( 7.5 ) (notice Deutétrabénazine, Interactions médicamenteuses)

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. (notice Dexchlorphéniramine, Mises en garde)

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) ] . (notice Dexlansoprazole, Interactions médicamenteuses)

Exercise caution when prescribing ZIPSOR with concomitant drugs that are known to be potentially hepatotoxic (e.g., acetaminophen, antibiotics, antiepileptics). (notice Diclofénac, Mises en garde et précautions)

Exercise caution when prescribing diclofenac sodium/misoprostol with concomitant drugs that are known to be potentially hepatotoxic (e.g., antibiotics, anti-epileptics). (notice Diclofénac et misoprostol, Mises en garde et précautions)

MOTOFEN ® may potentiate the action of barbiturates, tranquilizers, narcotics, and alcohol. (notice Difénoxine et atropine, Interactions médicamenteuses)

The concomitant use of alcohol or other central nervous system depressants may have an additive effect. (notice Dimenhydrinate, Mises en garde)

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

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… (notice Dofétilide, Interactions médicamenteuses)

Potential additive effects when used in combination with CNS depressants or sedating antihistamines. (notice Doxépine, Mises en garde et précautions)

Examples Glutethimide and phenobarbital Intervention If a patient initiates or discontinues therapy with an enzyme inducer, dose adjustment of doxercalciferol may be necessary. (notice Doxercalciférol, Interactions médicamenteuses)

Barbiturates, carbamazepine and phenytoin decrease the half-life of doxycycline. (notice Doxycycline, Interactions médicamenteuses)

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. (notice Dronabinol, Mises en garde et précautions)

CNS Depressant Drugs: Other CNS depressant drugs (e.g. barbiturates, tranquilizers, opioids and general anesthetics) have additive or potentiating effects with droperidol. (notice Dropéridol, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampin, topiramate and products containing St. (notice Drospirénone et éthinylestradiol, Interactions médicamenteuses)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions ( 7.1 ) ] . (notice Éfavirenz, Mises en garde et précautions)

Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels [see Drug Interactions (7.5) ] . (notice Éfavirenz, lamivudine et ténofovir, Mises en garde et précautions)

Other Agents Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ TAF Consider alternative anticonvulsant. (notice Emtricitabine et ténofovir, Interactions médicamenteuses)

Hydrochlorothiazide When administered concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics Potentiation of orthostatic hypotension may occur. (notice Énalapril et hydrochlorothiazide, Interactions médicamenteuses)

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

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. (notice Ertapénem, Mises en garde et précautions)

Phenobarbital or Primidone: Higher dosage of APTIOM may be necessary. (notice Eslicarbazépine, Interactions médicamenteuses)

Table 4: Clinically Relevant Interactions Affecting Esomeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (notice Ésoméprazole, Interactions médicamenteuses)

Women who take medications that are strong CYP3A4 inducers should not choose Natazia as their oral contraceptive while using these inducers and for at least 28 days after discontinuation of these inducers due to the possibility of increased breakthrough bleeding and/or decreased contraceptive efficacy. (notice Estradiol et diénogest, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. (notice Étonogestrel et éthinylestradiol, Interactions médicamenteuses)

Strong CYP3A inducer and P-gp inducer : Increase the dosage as recommended. (notice Évérolimus, Interactions médicamenteuses)

Strong CYP 3A4 inducers: Concomitant use of strong CYP 3A4 inducers decreases exemestane exposure. (notice Exémestane, Interactions médicamenteuses)

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. (notice Félodipine, Interactions médicamenteuses)

Phenobarbital Clinical Impact: Chronic administration of phenobarbital, a known enzyme inducer, may be associated with a decrease in the plasma half-life of fenoprofen. (notice Fénoprofène, Interactions médicamenteuses)

CYP3A4 Inducers No dosing adjustments are recommended in the presence of CYP3A4 inducers, such as rifampin and carbamazepine. (notice Fésotérodine, Interactions médicamenteuses)

Limited data in patients receiving known enzyme inducers ( phenytoin, phenobarbital, carbamazepine ) indicate only a 30% increase in the rate of flecainide elimination. (notice Flécaïnide, Interactions médicamenteuses)

Barbiturates, phenytoin, or rifampin —increased metabolic clearance of fludrocortisone acetate because of the induction of hepatic enzymes. (notice Fludrocortisone, Interactions médicamenteuses)

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. (notice Flumazénil, Mises en garde)

Anticonvulsants: Potential for elevated phenytoin and carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (notice Fluoxétine, Interactions médicamenteuses)

Moreover, it should be remembered that reduced amounts of anesthetics or central nervous system depressants may be necessary. (notice Fluphénazine, Précautions)

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. (notice Fluticasone, Mises en garde et précautions)

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. (notice Fluticasone et salmétérol, Mises en garde et précautions)

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. (notice Fosaprépitant, Mises en garde et précautions)

Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. (notice Fosphénytoïne, Mises en garde et précautions)

• CYP3A4 Inducer: Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer. (notice Géfitinib, Interactions médicamenteuses)

…including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic… (notice Glimépiride, Interactions médicamenteuses)

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. (notice Glycopyrronium, Interactions médicamenteuses)

Barbiturates usually depress griseofulvin activity by decreasing plasma levels and concomitant administration may require a dosage adjustment of the antifungal agent. (notice Griséofulvine, Interactions médicamenteuses)

Consider the potential for additive sedative effects with CNS depressant drugs. (notice Guanfacine, Mises en garde et précautions)

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. (notice Halopéridol, Interactions médicamenteuses)

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. (notice Hydrocortisone, Interactions médicamenteuses)

• CYP3A4 Inducers: Monitor for increased toxicity when used in combination with CYP3A4 inducers. (notice Ifosfamide, Interactions médicamenteuses)

CYP3A4 inducers may decrease Gleevec C max and area under curve (AUC). (notice Imatinib, Interactions médicamenteuses)

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 ). (notice Imipénem et cilastatine, Mises en garde et précautions)

Imipramine hydrochloride may enhance the CNS depressant effects of alcohol. (notice Imipramine, Mises en garde)

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. (notice Ivacaftor, Mises en garde et précautions)

Anyone considering prescribing VIMPAT or any other AED must balance this risk with the risk of untreated illness. (notice Lacosamide, Mises en garde et précautions)

Carbamazepine, phenytoin, phenobarbital, primidone, and rifampin decrease lamotrigine concentrations by approximately 40%. (notice Lamotrigine, Interactions médicamenteuses)

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) ] . (notice Lansoprazole, Interactions médicamenteuses)

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. (notice Lédipasvir et sofosbuvir, Interactions médicamenteuses)

Enzyme inducers (e.g., CYP3A4) : May decrease the effectiveness of TYBLUME or increase breakthrough bleeding. (notice Lévonorgestrel et éthinylestradiol, Interactions médicamenteuses)

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. (notice Lidocaïne et adrénaline, Mises en garde et précautions)

…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 (notice Lidocaïne et prilocaïne, Interactions médicamenteuses)

Strong P-glycoprotein/CYP3A4 inducer: The efficacy of TRADJENTA may be reduced when administered in combination (e.g., with rifampin). (notice Linagliptine, Interactions médicamenteuses)

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. (notice Linagliptine et metformine, Interactions médicamenteuses)

Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur. (notice Lisinopril et hydrochlorothiazide, Interactions médicamenteuses)

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. (notice Lofexidine, Mises en garde et précautions)

• 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. (notice Maraviroc, Mises en garde et précautions)

• Coadministration of meclizine hydrochloride with other CNS depressants, including alcohol, may result in increased CNS depression ( 7.1 ). (notice Méclozine, Interactions médicamenteuses)

MPA Injectable Suspension, USP can pose an additional risk in patients with risk factors for osteoporosis (e.g., metabolic bone disease, chronic alcohol and/or tobacco use, anorexia nervosa, strong family history of osteoporosis or chronic use of drugs that can reduce bone mass such as anticonvulsants or corticosteroids). (notice Médroxyprogestérone, Mises en garde et précautions)

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. (notice Méfloquine, Interactions médicamenteuses)

Inducers of CYP3A4 (e.g., phenytoin, carbamazepine, dexamethasone, rifampin, and phenobarbital) could increase the rate of elimination of donepezil. (notice Mémantine et donépézil, Interactions médicamenteuses)

…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 (notice Mépivacaïne, Interactions médicamenteuses)

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. (notice Méprobamate, Mises en garde)

ATMEKSI may potentiate the effects of CNS (central nervous system) depressants and alcohol ( 5.1 ) (notice Méthocarbamol, Mises en garde et précautions)

CYP3A4 inducers Drugs (e.g. nevirapine, rifampin) that are strong inducers of CYP3A4 are likely to decrease the pharmacological action of methylergonovine maleate. (notice Méthylergométrine, Interactions médicamenteuses)

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. (notice Méthylprednisolone, Interactions médicamenteuses)

Concurrent use of metyrosine with alcohol or other CNS depressants can increase their sedative effects. (notice Métirosine, Interactions médicamenteuses)

Concomitant use of central nervous system (CNS) depressants or drugs associated with EPS may increase this effect (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics). (notice Métoclopramide, Mises en garde et précautions)

Alcohol, Barbiturates, And Narcotics The hypotensive effects of these drugs may be potentiated by the volume contraction that may be associated with metolazone therapy. (notice Métolazone, Interactions médicamenteuses)

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) ] . (notice Mirtazapine, Interactions médicamenteuses)

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. (notice Mométasone, Mises en garde et précautions)

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. (notice Naloxone, Mises en garde et précautions)

Table 4: Clinically Significant Interactions with Esomeprazole Magnesium - Affecting Co-Administered Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact : Decreased exposure of esomeprazole when used concomitantly with strong inducers [see Clinical Pharmacology (12.3) ]. (notice Naproxène et ésoméprazole, Interactions médicamenteuses)

Anticonvulsants: Carbamazepine, clonazepam, ethosuximide Plasma concentrations of nevirapine and the anticonvulsant may be decreased. (notice Névirapine, Interactions médicamenteuses)

Possible Reduced Efficacy with Strong CYP3A4 Inducers Concomitant use of strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. (notice Nimodipine, Mises en garde et précautions)

Coadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. (notice Nintédanib, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. (notice Norelgestromine et éthinylestradiol, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of HCs include efavirenz, phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, and products containing St. (notice Noréthistérone, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. (notice Norgestimate et éthinylestradiol, Interactions médicamenteuses)

Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate rifabutin, rufinamide, aprepitant, and products containing St. (notice Norgestrel et éthinylestradiol, Interactions médicamenteuses)

Carbamazepine : Potential for elevated carbamazepine levels and clinical anticonvulsant toxicity ( 7.7 ) (notice Olanzapine et fluoxétine, Interactions médicamenteuses)

Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. (notice Olmésartan, amlodipine et hydrochlorothiazide, Interactions médicamenteuses)

Table 4: Clinically Relevant Interactions Affecting Omeprazole When Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of omeprazole when used concomitantly with strong inducers [see Clinical Pharmacology ( 12.3 )] . (notice Oméprazole, Interactions médicamenteuses)

Table 6: Clinically Relevant Interactions Affecting Omeprazole when Co-Administered with Other Drugs CYP2C19 or CYP3A4 Inducers Clinical Impact: Decreased exposure of omeprazole when used concomitantly with strong inducers [see Clinical Pharmacology ( 12.3 )] . (notice Oméprazole et bicarbonate de sodium, Interactions médicamenteuses)

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. (notice Ondansétron, Interactions médicamenteuses)

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) ]. (notice Orlistat, Mises en garde et précautions)

Therefore, if a patient develops a skin reaction while taking TRILEPTAL, consideration should be given to discontinuing TRILEPTAL use and prescribing another antiepileptic medication. (notice Oxcarbazépine, Mises en garde et précautions)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when FYCOMPA is used with other drugs with sedative properties because of potential additive effects. (notice Pérampanel, Mises en garde et précautions)

The concomitant use of alcohol or central nervous system (CNS) depressant drugs with phentermine and topiramate extended-release capsules may potentiate CNS depression or other centrally mediated effects of these agents, such as dizziness, cognitive adverse reactions, drowsiness, light-headedness, impaired coordination, and somnolence. (notice Phentermine et topiramate, Mises en garde et précautions)

Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. (notice Phénytoïne, Mises en garde et précautions)

…including glimepiride, leading to worsening glycemic control: danazol, glucagon, somatropin, protease inhibitors, atypical antipsychotic medications (e.g., olanzapine and clozapine), barbiturates, diazoxide, laxatives, rifampin, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid hormones, estrogens, oral contraceptives, phenytoin, nicotinic… (notice Pioglitazone et glimépiride, Interactions médicamenteuses)

Strong CYP3A4 Inducers: Decreased exposure of WAKIX; consider dosage adjustment of WAKIX ( 2.6 , 7.1 ) (notice Pitolisant, Interactions médicamenteuses)

Concomitant Use with Midazolam : Noxafil can prolong hypnotic/sedative effects. (notice Posaconazole, Mises en garde et précautions)

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. (notice Prednisolone, Interactions médicamenteuses)

CYP 3A4 inducers and inhibitors: May, respectively, increase or decrease clearance of corticosteroids, necessitating dose adjustment. (notice Prednisone, Interactions médicamenteuses)

…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… (notice Prilocaïne et adrénaline, Interactions médicamenteuses)

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… (notice Prométhazine, Mises en garde)

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… (notice Prométhazine et dextrométhorphane, Mises en garde)

As with other sedative medications, there is wide interpatient variability in DIPRIVAN dosage requirements, and these requirements may change with time. (notice Propofol, Mises en garde et précautions)

Protriptyline may enhance the response to alcohol and the effects of barbiturates and other CNS depressants. (notice Protriptyline, Interactions médicamenteuses)

• 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. (notice Quétiapine, Interactions médicamenteuses)

The use of alcohol and other CNS depressants may increase the risk of such behaviors. (notice Rameltéon, Mises en garde et précautions)

CYP2C8 and CYP3A4 Inducers Intervention: Repaglinide tablets dose increases and increased frequency of glucose monitoring may be required when co‑administered. (notice Répaglinide, Interactions médicamenteuses)

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. (notice Rifabutine, Interactions médicamenteuses)

…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… (notice Rifampicine, Interactions médicamenteuses)

…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… (notice Rifapentine, Interactions médicamenteuses)

Carbamazepine and other enzyme inducers decrease plasma concentrations of risperidone. (notice Rispéridone, Interactions médicamenteuses)

Reduced Rocuronium Bromide Injection activity possible : Anticonvulsants. (notice Rocuronium, Interactions médicamenteuses)

…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… (notice Ropivacaïne, Interactions médicamenteuses)

Table 6: Summary of drug-drug interactions of BANZEL with other antiepileptic drugs AED Co-administered Influence of Rufinamide on AED concentration a) Influence of AED on Rufinamide concentration Carbamazepine Decrease by 7 to 13% b) Decrease by 19 to 26% Dependent on dose of carbamazepine Lamotrigine Decrease by 7 to 13% b) No Effect Phenobarbital Increase… (notice Rufinamide, Interactions médicamenteuses)

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. (notice Ruxolitinib, Interactions médicamenteuses)

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. (notice Scopolamine, Mises en garde et précautions)

Drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution. (notice Sélégiline, Interactions médicamenteuses)

Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur. (notice Spironolactone et hydrochlorothiazide, Interactions médicamenteuses)

• CYP3A4 Inducers : Consider dose increase of SUTENT when administered with strong CYP3A4 inducers. (notice Sunitinib, Interactions médicamenteuses)

CNS Depressant Effects and Daytime Impairment: Risk of impaired alertness and motor coordination, including impaired driving; risk increases with dose; caution patients taking 20 mg against next-day driving and other activities requiring complete mental alertness ( 5.1 ). (notice Suvorexant, Mises en garde et précautions)

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. (notice Tacrolimus, Mises en garde et précautions)

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 ). (notice Tadalafil, Interactions médicamenteuses)

Patients should be monitored for adequate clinical effect when amlodipine is co-administered with CYP3A4 inducers. (notice Telmisartan et amlodipine, Interactions médicamenteuses)

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. (notice Temsirolimus, Mises en garde et précautions)

Terbinafine clearance is increased 100% by rifampin, a CYP450 enzyme inducer, and decreased 33% by cimetidine, a CYP450 enzyme inhibitor. (notice Terbinafine, Interactions médicamenteuses)

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) ] . (notice Tétrabénazine, Interactions médicamenteuses)

25% increase Diazepam Benzodiazepines increase CNS concentrations of adenosine, a potent CNS depressant, while theophylline blocks adenosine receptors. (notice Théophylline, Interactions médicamenteuses)

Severe respiratory depression and respiratory arrest have been reported when a patient was given a phenothiazine and a concomitant high dose of a barbiturate. (notice Thioridazine, Mises en garde)

Use of tiagabine HCl without enzyme-inducing antiepileptic drugs results in blood levels about twice those attained in the studies on which current dosing recommendations are based (see DOSAGE AND ADMINISTRATION ). (notice Tiagabine, Mises en garde)

Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or tinidazole dose(s) may be needed ( 7.1, 7.2 ) (notice Tinidazole, Interactions médicamenteuses)

As in the case of other CNS-acting drugs, patients receiving thiothixene should be cautioned about the possible additive effects (which may include hypotension) with CNS depressants and with alcohol. (notice Tiotixène, Mises en garde)

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 ) (notice Tizanidine, Mises en garde et précautions)

…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… (notice Tofacitinib, Interactions médicamenteuses)

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, topiramate extended-release capsules should be used with extreme caution if used in combination with alcohol and other CNS depressants. (notice Topiramate, Interactions médicamenteuses)

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)… (notice Tranylcypromine, Interactions médicamenteuses)

CNS Depressants: RALDESY may enhance effects of alcohol, barbiturates, or other CNS depressants ( 7 ). (notice Trazodone, Interactions médicamenteuses)

Co-administration of a CYP2C8 enzyme inducer (e.g., rifampin) may decrease exposure to treprostinil. (notice Tréprostinil, Mises en garde et précautions)

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. (notice Triamcinolone, Interactions médicamenteuses)

Drug Interactions Cannabinoids, barbiturates, opiates, and alcohol may have additive effects with trihexyphenidyl, and thus, an abuse potential exists. (notice Trihexyphénidyle, Interactions médicamenteuses)

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. (notice Triméthobenzamide, Mises en garde et précautions)

Thiopental Reconstituted vecuronium, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions such as thiopental) in the same syringe or administered simultaneously during intravenous infusion through the same needle or through the same intravenous line (see DOSAGE AND ADMINISTRATION -COMPATIBILITY ). (notice Vécuronium, Précautions)

CYP3A4 inducers decrease verapamil levels ( 7.1 ) (notice Vérapamil, Interactions médicamenteuses)

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 ). (notice Vilazodone, Interactions médicamenteuses)

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. (notice Vincristine, Interactions médicamenteuses)

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. (notice Ziprasidone, Interactions médicamenteuses)

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when ZONISADE is used with other drugs with sedative properties because of potential additive effects. (notice Zonisamide, Mises en garde et précautions)

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

Atracurium besylate injection, which has an acid pH, should not be mixed with alkaline solutions (e.g., barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle. (notice Atracurium, Mises en garde)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Anticonvulsant therapy can be given if clinically indicated. (notice Céfalexine, Mises en garde et précautions)

Anticonvulsant therapy should be continued in patients with known seizure disorders. (notice Céfazoline, Mises en garde et précautions)

…Probenecid Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine). (notice Cidofovir, Interactions médicamenteuses)

Antihistamines Amphetamines may counteract the sedative effect of antihistamines. (notice Dexamfétamine, Interactions médicamenteuses)

A similar association, though less marked, has been suggested for barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines. (notice Diacétate d'étynodiol et éthinylestradiol, Interactions médicamenteuses)

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

• Cytochrome P450 3A4 inducers, inhibitors, or substrates: May alter docetaxel metabolism. (notice Docétaxel, Interactions médicamenteuses)

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. (notice Doxapram, Mises en garde)

The “gasping syndrome” is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. (notice Époétine alfa, Mises en garde et précautions)

Effects of Other Drugs on HALAVEN No drug-drug interactions are expected with CYP3A4 inhibitors, CYP3A4 inducers or P-glycoprotein (P-gp) inhibitors. (notice Éribuline, Interactions médicamenteuses)

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. (notice Escitalopram, Mises en garde et précautions)

Inducers of CYP3A4 such as St. (notice Estradiol, Interactions médicamenteuses)

Inducers of CYP3A4 such as St. (notice Estradiol et noréthistérone, Interactions médicamenteuses)

Inducers of CYP3A4, such as St. (notice Estrogènes conjugués et bazédoxifène, Interactions médicamenteuses)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Potential for Etravirine to Affect Other Drugs Etravirine is an inducer of CYP3A and inhibitor of CYP2C9, CYP2C19 and P-glycoprotein (P-gp). (notice Étravirine, Interactions médicamenteuses)

Antiepileptics The activity of antiepileptic drugs might be impaired if co-administered with PLAQUENIL. (notice Hydroxychloroquine, Interactions médicamenteuses)

Antiepileptic Drugs Sporadic cases of seizures have been reported during concomitant use of ketorolac tromethamine and antiepileptic drugs (phenytoin, carbamazepine). (notice Kétorolac, Interactions médicamenteuses)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. (notice Lévothyroxine, Interactions médicamenteuses)

Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. (notice Liothyronine, Interactions médicamenteuses)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Apnea/hypoventilation may be noted during induction, which may impair pulmonary ventilation; the duration of apnea may be longer than that produced by other barbiturate anesthetics. (notice Méthohexital, Mises en garde)

Anticonvulsants, psychotropic, hormone preparations, corticosteroids, antithyroid agents, cyproheptadine: may affect the results of the metyrapone test. (notice Métyrapone, Interactions médicamenteuses)

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. (notice Mexilétine, Interactions médicamenteuses)

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. (notice Phénylbutyrate de glycérol, Interactions médicamenteuses)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Pimozide may be capable of potentiating CNS depressants, including analgesics, sedatives, anxiolytics, and alcohol. (notice Pimozide, Interactions médicamenteuses)

…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),… (notice Prazosine, Interactions médicamenteuses)

CYP3A4 Substrates An in vitro study has suggested that rifaximin induces CYP3A4 [see Clinical Pharmacology ( 12.3 )] . (notice Rifaximine, Interactions médicamenteuses)

Strong CYP3A inducers: Strong inducers of CYP3A (for example, rifampin, phenytoin, carbamazepine, phenobarbital or St. (notice Riociguat, Interactions médicamenteuses)

Drug Interactions In clinical studies, no significant adverse reactions occurred with other drugs commonly used in the perioperative period, including central nervous system depressants, autonomic drugs, skeletal muscle relaxants, anti-infective agents, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs. (notice Sévoflurane, Interactions médicamenteuses)

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). (notice Tésamoréline, Interactions médicamenteuses)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

Neonatal hemorrhage, with a coagulation defect resembling vitamin K deficiency, has been described in newborns whose mothers were taking primidone and other anticonvulsants. (notice Primidone, Mises en garde)

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). (notice Asénapine, Interactions médicamenteuses)

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

…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) ]. (notice Montélukast, Interactions médicamenteuses)