Pérampanel : interactions médicamenteuses

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. (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)

Patients taking FYCOMPA should avoid the use of alcohol [see Drug Interactions (7.3) ] . (notice Pérampanel, Mises en garde et précautions)

…(Childs-Pugh categories B and C), since alfuzosin blood levels are increased in these patients [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3) ]. with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir, since alfuzosin blood levels are increased [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . in… (notice Alfuzosine, Contre-indications)

Concomitant use of almotriptan tablets and potent CYP3A4 inhibitors should be avoided in patients with renal or hepatic impairment [see Clinical Pharmacology ( 12.3 )] . (notice Almotriptan, Interactions médicamenteuses)

• taking strong cytochrome P450 3A (CYP3A) inhibitors (e.g., ketoconazole, itraconazole), except ritonavir [see Dosage and Administration (2.5) , Warnings and Precautions (5.5) , Drug Interactions (7.1) ] . (notice Alprazolam, Contre-indications)

For patients receiving ELIQUIS at a dose of 2.5 mg twice daily, avoid coadministration with combined P-gp and strong CYP3A4 inhibitors [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] . (notice Apixaban, Interactions médicamenteuses)

Drug Class Drugs within class that are contraindicated with REYATAZ Alpha 1-adrenoreceptor antagonist Alfuzosin Anticonvulsants Carbamazepine, phenobarbital, phenytoin Antiarrhythmics Amiodarone (with ritonavir), quinidine (with ritonavir) Antimycobacterials Rifampin Antineoplastics Apalutamide, encorafenib, irinotecan, ivosidenib Antipsychotics Lurasidone (with… (notice Atazanavir, Contre-indications)

Do not use avanafil in patients taking strong CYP3A4 inhibitors [see Warnings and Precautions ( 5.2 ) and Dosage and Administration ( 2.3 )]. (notice Avanafil, Interactions médicamenteuses)

• 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 with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (notice Bictégravir, emtricitabine et ténofovir alafénamide, Interactions médicamenteuses)

Co-administration of such combinations of a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor with TRACLEER is not recommended. (notice Bosentan, Interactions médicamenteuses)

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

Concomitant use of strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) with CYCLOSET should be avoided. (notice Bromocriptine, 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 taking a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) while taking COMETRIQ or reduce the dosage of COMETRIQ if concomitant use with strong CYP3A4 inhibitors cannot be avoided [see Dosage and Administration ( 2.2 ), Clinical Pharmacology… (notice Cabozantinib, 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)

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)

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)

Avoid use with other central nervous system (CNS) depressants ( 5.3 ) (notice Clonidine, 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 Codéine, Mise en garde encadrée)

Patients with renal or hepatic impairment should not be given colchicine capsules with drugs that inhibit both P-glycoprotein and CYP3A4 inhibitors [see Drug Interactions (7) ] . (notice Colchicine, Contre-indications)

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)

Strong CYP3A4 inhibitors: 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)

Alpha 1-adrenoreceptor antagonist: alfuzosin Anticonvulsants: carbamazepine, phenobarbital, phenytoin Anti-gout: colchicine, in patients with renal and/or hepatic impairment Antimycobacterial: rifampin Antipsychotics: lurasidone, pimozide Cardiac Disorders: dronedarone, ivabradine, ranolazine Ergot derivatives, e.g. dihydroergotamine, ergotamine, methylergonovine… (notice Darunavir et cobicistat, Contre-indications)

Avoid concomitant use of strong CYP3A4 inhibitors. (notice Dasatinib, Interactions médicamenteuses)

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (notice Dexaméthasone, Interactions médicamenteuses)

QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (notice Dextrométhorphane et quinidine, Mises en garde et précautions)

WARNING: PERIPHERAL ISCHEMIA FOLLOWING COADMINISTRATION WITH POTENT CYP3A4 INHIBITORS Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of dihydroergotamine with potent CYP3A4 inhibitors including protease inhibitors and macrolide antibiotics. (notice Dihydroergotamine, Mise en garde encadrée)

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)

Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. (notice Docétaxel, Interactions médicamenteuses)

These drugs include, but are not limited to, the following: the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin the androgen receptor inhibitor enzalutamide the antimycobacterials rifampin, rifapentine the cytotoxic agent mitotane St. (notice Doravirine, Contre-indications)

Avoid concomitant use of Doxorubicin Hydrochloride Injection with inhibitors of CYP3A4, CYP2D6, or P-gp. (notice Doxorubicine, Interactions médicamenteuses)

Drug-Drug Interactions Strong Inhibitors of Cytochrome P450 (CYP) 3A4 Tamsulosin-containing products, including JALYN, should not be coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole) as this can significantly increase tamsulosin exposure [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ]. (notice Dutastéride et tamsulosine, Mises en garde et précautions)

• Recent use (i.e., within at least 72 hours) of the following potent CYP3A4 inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, or nelfinavir [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ]. (notice Élétriptan, Contre-indications)

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)

…Patients Eplerenone is contraindicated in all patients with: • serum potassium > 5.5 mEq/L at initiation, • creatinine clearance ≤ 30 mL/min, or • concomitant administration of strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir) [see Drug Interactions (7.1) , Clinical Pharmacology (12.3)… (notice Éplérénone, Contre-indications)

WARNING Serious and/or life-threatening peripheral ischemia has been associated with the coadministration of ergotamine tartrate and caffeine tablets with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. (notice Ergotamine et caféine, Mise en garde encadrée)

Avoid co-administering erlotinib with strong CYP3A4 inhibitors (e.g., boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit or grapefruit juice) or a combined CYP3A4 and CYP1A2 inhibitor (e.g., ciprofloxacin). (notice Erlotinib, Interactions médicamenteuses)

Consequently, estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A (see CONTRAINDICATIONS ). (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)

VYTORIN is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (notice Ézétimibe et simvastatine, Contre-indications)

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)

CYP3A4 Inhibitors Doses of Toviaz greater than 4 mg are not recommended in adult patients taking strong CYP3A4 inhibitors, such as ketoconazole, itraconazole, and clarithromycin [see Dosage and Administration (2.5) ]. (notice Fésotérodine, Interactions médicamenteuses)

Contraindicated with Strong or Moderate CYP3A4 Inhibitors The concomitant use of ADDYI and moderate or strong CYP3A4 inhibitors increases flibanserin concentrations, which can cause severe hypotension and syncope [see Warnings and Precautions (5.2) ] . (notice Flibansérine, Mise en garde encadrée)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (notice Fluticasone, Interactions médicamenteuses)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (notice Fluticasone et salmétérol, 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)

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 Inhibitors: Do not administer strong CYP3A4 inhibitors 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)

…bradycardia [see Warnings and Precautions ( 5.3 )] • Severe hepatic impairment [see Use in Specific Populations ( 8.6 )] • Pacemaker dependence (heart rate maintained exclusively by the pacemaker) [see Drug Interactions ( 7.3 )] • Concomitant use of strong cytochrome P450 3A4 (CYP3A4) inhibitors [see Drug Interactions ( 7.1 )] Acute decompensated heart failure ( 4 ) (notice Ivabradine, Contre-indications)

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 inhibitors. (notice Lapatinib, Interactions médicamenteuses)

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

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

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)

Concomitant administration of JUXTAPID with moderate or strong CYP3A4 inhibitors, as this can increase JUXTAPID exposure [see Warnings and Precautions (5.6) , Drug Interactions (7.1) , and Clinical Pharmacology (12.3) ]. (notice Lomitapide, Contre-indications)

…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)

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. (notice Lorlatinib, Interactions médicamenteuses)

Concomitant administration with strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone and cobicistat-containing products) (see WARNINGS , Myopathy/Rhabdomyolysis ). (notice Lovastatine, Contre-indications)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (notice Lurasidone, Contre-indications)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (notice Macitentan, Interactions médicamenteuses)

SELZENTRY is contraindicated in patients with severe renal impairment or ESRD (creatinine clearance [CrCl] less than 30 mL per minute) who are concomitantly taking potent CYP3A inhibitors or inducers [see Warnings and Precautions ( 5.3 )]. (notice Maraviroc, Contre-indications)

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)

Although there have been no reports of such interactions with methylergonovine alone, strong and moderate CYP 3A4 inhibitors should not be co-administered with methylergonovine. (notice Méthylergométrine, Interactions médicamenteuses)

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)

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. (notice Mitapivat, 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)

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)

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

…(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)

Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 , 7.2 )] . (notice Nilotinib, Mise en garde encadrée)

Therefore, the concomitant administration of NYMALIZE and strong CYP3A4 inhibitors should generally be avoided [ see Warnings and Precautions (5.3) ]. (notice Nimodipine, Interactions médicamenteuses)

…(selective blocker of Na v 1.8 sodium channels): suzetrigine • Opioid antagonists: naloxegol • PDE5 inhibitor: sildenafil (Revatio ® ) when used for pulmonary arterial hypertension (PAH) • Sedative/hypnotics: triazolam, oral midazolam • Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin • Vasopressin receptor antagonists: tolvaptan ➢ Drugs that… (notice Nirmatrelvir et ritonavir, Contre-indications)

CYP3A4 inhibitors and inducers : SULAR is substrate of CYP3A4 and coadministration of SULAR with any known inducer or inhibitor of CYP3A4 should be avoided in general. (notice Nisoldipine, 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)

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

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)

Strong CYP3A4 Inhibitors : Avoid coadministration of VOTRIENT with strong CYP3A4 inhibitors. (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)

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)

…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)

• Avoid simultaneous use of propafenone with both a cytochrome P450 2D6 (CYP2D6) inhibitor and a 3A4 inhibitor (CYP3A4). (notice Propafénone, Mises en garde et précautions)

If concomitant administration with carbamazepine or phenobarbital cannot be avoided, frequent monitoring of anticonvulsant drug concentrations is recommended. (notice Quinine, 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 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 CYP3A4 Inhibitors: Avoid concomitant administration. (notice Rimégépant, 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)

Use with P-gp and Strong CYP3A Inhibitors or Inducers Avoid concomitant use of XARELTO with known combined P-gp and strong CYP3A inhibitors [see Drug Interactions (7.2) ] . (notice Rivaroxaban, Mises en garde et précautions)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (notice Salmétérol, Interactions médicamenteuses)

Severe renal impairment (CCr < 30 mL/min) Severe hepatic impairment (Child-Pugh score ≥ 10) Concomitant administration with strong Cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ketoconazole, clarithromycin, itraconazole, ritonavir) [see DRUG INTERACTIONS (7.1) ] Patients with a history of hypersensitivity to silodosin or any of the ingredients in silodosin capsules… (notice Silodosine, Contre-indications)

ZOCOR is contraindicated in the following conditions: Concomitant use of strong CYP3A4 inhibitors (select azole anti-fungals, macrolide antibiotics, anti-viral medications, and nefazodone) [see Drug Interactions (7.1) ] . (notice Simvastatine, Contre-indications)

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)

The dosage of Solifenacin succinate tablets greater than 5 mg once daily is not recommended when concomitantly used with strong CYP3A4 inhibitors [see Dosage and Administration ( 2.4 )] . (notice Solifénacine, Interactions médicamenteuses)

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . (notice Suzétrigine, Contre-indications)

• Should not be used in combination with strong inhibitors of CYP3A4. (notice Tamsulosine, 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 Tapentadol, Mise en garde encadrée)

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)

…dominant polycystic kidney disease (ADPKD) outside of FDA-approved REMS [see Warnings and Precautions (5.2) ] Unable to sense or respond to thirst Hypovolemic hyponatremia Taking strong CYP3A inhibitors [see Warnings and Precautions (5.5) ] Anuria Hypersensitivity (e.g., anaphylactic shock, rash generalized) to tolvaptan or any components of the product [see Adverse… (notice Tolvaptan, Contre-indications)

Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] . (notice Torémifène, Mise en garde encadrée)

CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 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)

The use of RALDESY Should be avoided in patients with known QT prolongation or in combination with other drugs that are inhibitors of CYP3A4 (e.g., itraconazole, clarithromycin, voriconazole), or known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic… (notice Trazodone, Mises en garde et précautions)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (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)

UBRELVY is contraindicated: With concomitant use of strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 )] In patients with a history of serious hypersensitivity to ubrogepant or any component of UBRELVY. (notice Ubrogépant, Contre-indications)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (notice Upadacitinib, Interactions médicamenteuses)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (notice Vepdégestrant, Mises en garde et précautions)

Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. (notice Vincristine, Interactions médicamenteuses)

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)

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

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)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (notice Alosétron, Interactions médicamenteuses)

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

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)

Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (notice Amlodipine, Interactions médicamenteuses)

Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (notice Amlodipine et atorvastatine, Interactions médicamenteuses)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (notice Amlodipine et bénazépril, Interactions médicamenteuses)

• Increased exposure of amlodipine when coadministered with CYP3A inhibitors Olmesartan medoxomil ( 7.2 ): • Nonsteroidal anti-inflammatory drugs (NSAIDS) may lead to increased risk of renal impairment and loss of antihypertensive effect. (notice Amlodipine et olmésartan, Interactions médicamenteuses)

Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (notice Amlodipine et valsartan, Interactions médicamenteuses)

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)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

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)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, 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)

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)

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)

LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. (notice Atorvastatine, Interactions médicamenteuses)

CYP3A4/5 Inhibitors Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. (notice Axitinib, Interactions médicamenteuses)

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)

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)

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)

Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. (notice Bortézomib, Interactions médicamenteuses)

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)

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)

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)

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)

Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the co-administration of PULMICORT FLEXHALER with ketoconazole, and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to… (notice Budésonide, Mises en garde et précautions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

…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)

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)

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)

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)

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)

Inhibitors of CYP3A4 or CYP2C19 Inhibitors of CYP3A4 Coadministration of strong (e.g., ketoconazole) and moderate (e.g., erythromycin, diltiazem and grapefruit juice) CYP3A4 inhibitors can increase exposure to cilostazol. (notice Cilostazol, Interactions médicamenteuses)

Co-administration with a strong CYP3A4 inhibitor may increase serum levels of cinacalcet. (notice Cinacalcet, 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)

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)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (notice Clindamycine, Interactions médicamenteuses)

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)

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)

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)

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)

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)

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)

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)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (notice Darifénacine, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of EMFLAZA ( 7.1 ) (notice Déflazacort, Interactions médicamenteuses)

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)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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

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)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of dexlansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (notice Dexlansoprazole, Interactions médicamenteuses)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

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)

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)

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)

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)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (notice Doxazosine, Interactions médicamenteuses)

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)

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

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)

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)

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)

Effects of Other Drugs on Dronedarone Ketoconazole and Other Potent CYP3A Inhibitors Concomitant use of ketoconazole as well as other potent CYP3A inhibitors such as itraconazole, voriconazole, ritonavir, clarithromycin, and nefazodone is contraindicated because exposure to dronedarone is significantly increased [see Contraindications (4) , Clinical Pharmacology… (notice Dronédarone, Interactions médicamenteuses)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (notice Élexacaftor, tézacaftor et ivacaftor, Mises en garde et précautions)

Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. (notice Pérampanel, Interactions médicamenteuses)

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

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Coadministration of CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin, grapefruit juice, cimetidine) with felodipine may lead to several-fold increases in the plasma levels of felodipine, either due to an increase in bioavailability or due to a decrease in metabolism. (notice Félodipine, Interactions médicamenteuses)

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)

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

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)

Potential Pimozide Interaction Pimozide is metabolized by the cytochrome P4503A4 isoenzyme, and it has been demonstrated that ketoconazole, a potent inhibitor of CYP3A4, blocks the metabolism of this drug, resulting in increased plasma concentrations of parent drug. (notice Fluvoxamine, 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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

• CYP3A4 Inhibitor: Monitor adverse reactions if concomitant use with IRESSA. (notice Géfitinib, 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)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

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)

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)

Concomitant administration of inhibitors of CYP3A4 may lead to increases in serum concentrations of ALKINDI SPRINKLE and increase the risk of adverse reactions associated with the use of excessive doses. (notice Hydrocortisone, Interactions médicamenteuses)

• CYP3A4 Inhibitors: Use in combination with CYP3A4 inhibitors could decrease the effectiveness of ifosfamide. (notice Ifosfamide, Interactions médicamenteuses)

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)

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)

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)

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)

Potential for other drugs to affect ivacaftor CYP3A inhibitors: Reduce KALYDECO dosage in patients aged 6 months and older when co-administered with strong CYP3A inhibitors (e.g., ketoconazole) or moderate CYP3A inhibitors (e.g., fluconazole). (notice Ivacaftor, Interactions médicamenteuses)

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)

Patients with History of Allergy or Rash to Other Antiepileptic Drugs The risk of rash may be increased in patients with a history of allergy or rash to other AEDs. (notice Lamotrigine, Mises en garde et précautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [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)

Anticonvulsants: carbamazepine oxcarbazepine phenobarbital phenytoin ↓ lenacapavir Concomitant administration of carbamazepine, oxcarbazepine, phenobarbital, or phenytoin may result in loss of therapeutic effect and development of resistance. (notice Lénacapavir, Interactions médicamenteuses)

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)

Strong CYP3A4 inhibitors : Maximum recommended dosage is 80 mg once daily ( 7 ). (notice Lévomilnacipran, Interactions médicamenteuses)

Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see Clinical Pharmacology (12.3) ] . (notice Pérampanel, Interactions médicamenteuses)

Contraceptives With concomitant use, FYCOMPA at a dose of 12 mg per day reduced levonorgestrel exposure by approximately 40% [see Clinical Pharmacology (12.3) ] . (notice Pérampanel, 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)

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)

Drug Interactions Effects of Other Drugs on Loperamide Concomitant use of loperamide hydrochloride capsules with inhibitors of CYP3A4 (e.g., itraconazole) or CYP2C8 (e.g., gemfibrozil) or inhibitors of P-glycoprotein (e.g., quinidine, ritonavir) can increase exposure to loperamide. (notice Lopéramide, Interactions médicamenteuses)

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)

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)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Ketoconazole (Potent Inhibitor of CYP3A4) Coadministration of a single 500 mg oral dose of mefloquine with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in an increase in the mean C max and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours. (notice Méfloquine, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, 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)

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)

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)

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)

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)

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

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (notice Mométasone, Mises en garde et précautions)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate (e.g., fluconazole, atazanavir, aprepitant, diltiazem, erythromycin) and Strong (e.g., itraconazole, ketoconazole, clarithromycin, ritonavir, saquinavir) CYP3A Inhibitors Clinical Impact Increase in plasma naldemedine concentrations [see Clinical Pharmacology (12.3) ] Intervention Monitor for potential naldemedine-related adverse reactions [see Adverse… (notice Naldémédine, Interactions médicamenteuses)

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)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact : Increased exposure of esomeprazole [see Clinical Pharmacology (12.3) ]. (notice Naproxène et ésoméprazole, Interactions médicamenteuses)

…Astemizole, Cisapride, and Pimozide Interactions Terfenadine, astemizole, cisapride, and pimozide are all metabolized by the cytochrome P450 3A4 (CYP3A4) isozyme, and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of CYP3A4 can block the metabolism of these drugs, which can result in increased plasma concentrations of parent drug. (notice Néfazodone, Mises en garde)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

…as ketoconazole, fluconazole, itraconazole, clarithromycin, erythromycin (Azithromycin, although structurally related to the class of macrolide antibiotic is void of clinically relevant CYP3A4 inhibition), grapefruit, nefazodone, fluoxetine, saquinavir, indinavir, nelfinavir, and ritonavir may result in increased exposure to nifedipine when co-administered. (notice Nifédipine, Interactions médicamenteuses)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (notice Nintédanib, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

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)

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)

• Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): • Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. (notice Olmésartan, amlodipine et hydrochlorothiazide, Interactions médicamenteuses)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (notice Oméprazole, Interactions médicamenteuses)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (notice Oméprazole et bicarbonate de sodium, 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)

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)

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)

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)

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)

Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic exposure of oxybutynin. (notice Oxybutynine, Interactions médicamenteuses)

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)

Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . (notice Paricalcitol, Interactions médicamenteuses)

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)

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)

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)

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)

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)

Alcohol and Other CNS Depressants The concomitant use of FYCOMPA and CNS depressants including alcohol may increase CNS depression. (notice Pérampanel, Interactions médicamenteuses)

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)

• Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. (notice Pioglitazone, Interactions médicamenteuses)

Strong CYP2C8 inhibitors (e.g., gemfibrozil) increase pioglitazone concentrations. (notice Pioglitazone et glimépiride, Interactions médicamenteuses)

Strong CYP2C8 inhibitors (e.g., gemfibrozil): Limit ACTOPLUS MET dose to 15 mg/850 mg daily. (notice Pioglitazone et metformine, Interactions médicamenteuses)

Concomitant Use with Midazolam : Noxafil can prolong hypnotic/sedative effects. (notice Posaconazole, 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)

CYP 3A4 inhibitors (e.g., ketoconazole, macrolide antibiotics): Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects. (notice Prednisolone, Interactions médicamenteuses)

CYP 3A4 Inhibitors (e.g., Ketoconazole, Macrolide Antibiotics) Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to increased risk of corticosteroid side effects. (notice Prednisone, Interactions médicamenteuses)

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)

…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)

Published clinical reports indicate primaquine may inhibit CYP3A4 enzyme activity and thus may lead to increased exposure of oral CYP3A4 substrate drugs when co-administered with Primaquine phosphate Tablets. (notice Primaquine, Interactions médicamenteuses)

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)

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)

Contraceptives: 12 mg once daily may decrease the effectiveness of hormonal contraceptives containing levonorgestrel ( 7.1 ) (notice Pérampanel, Interactions médicamenteuses)

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)

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)

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)

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)

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)

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)

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

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

Moderate and Strong CYP3A4 Inducers (including carbamazepine, oxcarbazepine, and phenytoin): increase clearance of perampanel and decrease perampanel plasma concentrations. (notice Pérampanel, Interactions médicamenteuses)

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)

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

Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic exposure and may result in increased adverse reactions. (notice Roflumilast, Interactions médicamenteuses)

• Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). (notice Romidepsine, Interactions médicamenteuses)

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)

…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)

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)

Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue JAKAFI/JAKAFI XR doses as recommended except in patients with acute or chronic graft-versus-host-disease. (notice Ruxolitinib, Interactions médicamenteuses)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (notice Saxagliptine, Interactions médicamenteuses)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (notice Saxagliptine et metformine, Interactions médicamenteuses)

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)

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)

CYP3A4 inhibitors (e.g., ritonavir, ketoconazole, itraconazole, erythromycin) increase SILDENAFIL ORAL FILM exposure. (notice Sildénafil, Interactions médicamenteuses)

Monitor QT interval more frequently when SUTENT is concomitantly administered with strong CYP3A4 inhibitors or drugs known to prolong QT interval. (notice Sunitinib, 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 risk for nephrotoxicity may increase when ASTAGRAF XL is concomitantly administered with CYP3A inhibitors (by increasing tacrolimus whole blood concentrations) or drugs associated with nephrotoxicity (e.g., aminoglycosides, ganciclovir, amphotericin B, cisplatin, nucleotide reverse transcriptase inhibitors, protease inhibitors). (notice Tacrolimus, Mises en garde et précautions)

…Physicians should be aware that CIALIS for once daily use provides continuous plasma tadalafil levels and should consider this when evaluating the potential for interactions with medications (e.g., nitrates, alpha-blockers, anti-hypertensives and potent inhibitors of CYP3A4) and with substantial consumption of alcohol [see Drug Interactions ( 7.1 , 7.2 , 7.3 )] . (notice Tadalafil, 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)

CYP3A4 Inhibitors Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. (notice Telmisartan et amlodipine, Interactions médicamenteuses)

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)

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)

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)

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

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)

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)

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

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)

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)

Table 7: Clinically Significant Interactions Affecting XELJANZ/XELJANZ XR When Concomitantly Used with Other Drugs Strong CYP3A4 Inhibitors (e.g., ketoconazole) Clinical Impact Increased exposure to tofacitinib Intervention Dosage modification of XELJANZ/XELJANZ XR is recommended [see Dosage and Administration (2) , Clinical Pharmacology, Figure 3 (12.3) ] Moderate… (notice Tofacitinib, Interactions médicamenteuses)

Drug Interactions CYP3A4 Inhibitors Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions ). (notice Toltérodine, Interactions médicamenteuses)

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)

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)

Co-administration of other strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin, cobicistat-containing products) with KENALOG-40 Injection may cause increased plasma concentration of triamcinolone leading to adverse reactions. (notice Triamcinolone, Interactions médicamenteuses)

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)

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

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)

Increase in Plasma Concentrations of ella Associated with Co-Administered Drugs CYP3A4 inhibitors such as itraconazole or ketoconazole increase plasma concentrations of ella [see Pharmacokinetics (12.3) ] . (notice Ulipristal, Interactions médicamenteuses)

Drug Interactions with Strong Cytochrome P450 3A4 Inhibitors Caution should be exercised when considering the coadministration of Umeclidinium and Vilanterol ELLIPTA with ketoconazole and other known strong cytochrome P450 3A4 (CYP3A4) inhibitors (including, but not limited to, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone,… (notice Uméclidinium et vilantérol, Mises en garde et précautions)

In patients taking a strong CYP2D6 or CYP3A4 inhibitor, or who are CYP2D6 poor metabolizers, INGREZZA and INGREZZA SPRINKLE concentrations may be higher and QT prolongation clinically significant [see Clinical Pharmacology ( 12.2 )] . (notice Valbénazine, Mises en garde et précautions)

Potential for Drug Interactions with Strong or Moderate CYP3A4 Inhibitors Concomitant administration with strong CYP3A4 inhibitors (such as ritonavir, indinavir, cobicistat, ketoconazole) or moderate CYP3A4 inhibitors (such as erythromycin) increases plasma concentrations of vardenafil. (notice Vardénafil, Mises en garde et précautions)

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and ODV. (notice Venlafaxine, Interactions médicamenteuses)

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)

CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). (notice Vilazodone, Interactions médicamenteuses)

CYP3A4 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP3A4 which increases the exposure of CYP3A4 substrates when coadministered [see Clinical Pharmacology (12.3) ]. (notice Viloxazine, Interactions médicamenteuses)

Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) (notice Vinorelbine, Interactions médicamenteuses)

Eszopiclone (CYP3A4 Inhibition) Not Studied In Vivo or In Vitro , but Drug Plasma Exposure Likely to be Increased which may Increase the Sedative Effect of Eszopiclone Dose reduction of eszopiclone is recommended. (notice Voriconazole, Interactions médicamenteuses)

Closely monitor INR if a concomitant drug is a CYP2C9, 1A2, and/or 3A4 inhibitor or inducer. (notice Warfarine, Interactions médicamenteuses)

As zafirlukast is known to be an inhibitor of CYP3A4 in vitro , it is reasonable to employ appropriate clinical monitoring when these drugs are coadministered with zafirlukast. (notice Zafirlukast, 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)

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)

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)

Repaglinide (CYP2C8 Substrates) The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. (notice Clopidogrel, Interactions médicamenteuses)

Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). (notice Pérampanel, Interactions médicamenteuses)

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

Although potent inhibitors of cytochrome P450 3A4 (e.g., ketoconazole) have not been studied clinically, in vitro studies have shown that erythromycin and oleandomycin inhibit the metabolism of disopyramide. (notice Disopyramide, 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 effect of potent CYP3A4 inhibitors on dutasteride has not been studied. (notice Dutastéride, Interactions médicamenteuses)

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)

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (notice Famciclovir, Interactions médicamenteuses)

Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). (notice Pérampanel, 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)

Effect on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . (notice Léflunomide, Interactions médicamenteuses)

Patients should limit activity until they have experience with concomitant use of CNS depressants (e.g., benzodiazepines, narcotics, barbiturates, sedating antihistamines). (notice Pérampanel, Interactions médicamenteuses)

Effect of Other Drugs on the Metabolism of Donepezil Inhibitors of CYP3A4 (e.g., ketoconazole) and CYP2D6 (e.g., quinidine), inhibit donepezil metabolism in vitro . (notice Mémantine et donépézil, Interactions médicamenteuses)

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

Effects of Other Drugs on Ranolazine Strong CYP3A Inhibitors Concomitant use of ASPRUZYO Sprinkle with strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir is contraindicated [see Contraindications (4), Clinical Pharmacology (12.3)]. (notice Ranolazine, Interactions médicamenteuses)

Clinically Significant Interactions Affecting Other Drugs CYP3A Substrates Where Small Concentration Changes May Lead to Serious Adverse Reactions Clinical Impact Ritlecitinib is a CYP3A inhibitor. (notice Ritlécitinib, Interactions médicamenteuses)

Effect of AUBAGIO on CYP2C8 Substrates Teriflunomide is an inhibitor of CYP2C8 in vivo . (notice Tériflunomide, 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)

However, no formal drug-drug interaction studies between zileuton and CYP3A4 inhibitors, such as ketaconazole, have been conducted. (notice Zileuton, 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)