Vérapamil : interactions médicamenteuses

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

…(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)

Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent. (notice Amiodarone, Mises en garde et précautions)

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)

The use of SAPHRIS should be avoided in combination with other drugs known to prolong QTc including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and antibiotics (e.g., gatifloxacin, moxifloxacin). (notice Asénapine, Mises en garde et précautions)

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)

Literature reports suggest that oral calcium antagonists may be used in combination with beta-adrenergic blocking agents when heart function is normal, but should be avoided in patients with impaired cardiac function. (notice Bétaxolol, Interactions médicamenteuses)

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)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (notice Buprénorphine, Interactions médicamenteuses)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (notice Butalbital, aspirine, caféine et codéine, Mise en garde encadrée)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (notice Butalbital, paracétamol, caféine et codéine, Mise en garde encadrée)

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)

• Calcium Channel Blockers: Avoid concomitant use with Calcium Chloride Injection. (notice Chlorure de calcium, Interactions médicamenteuses)

QT Prolongation : Avoid clarithromycin tablets in patients with known QT prolongation or receiving drugs known to prolong the QT interval, ventricular arrhythmia ( torsades de pointes ), hypokalemia/hypomagnesemia, significant bradycardia, or taking Class IA or III antiarrhythmics ( 5.2 ) (notice Clarithromycine, Mises en garde et précautions)

Use CLOZARIL cautiously in patients with cardiovascular or cerebrovascular disease or conditions predisposing to hypotension (e.g., dehydration, use of antihypertensive medications) [see Dosage and Administration ( 2.2 , 2.6 ), Warnings and Precautions ( 5.2 )]. (notice Clozapine, Mise en garde encadrée)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (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)

…Syndrome The development of a potentially life-threatening serotonin syndrome has been reported with cyclobenzaprine when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. (notice Cyclobenzaprine, Mises en garde et précautions)

Avoid use of PRADAXA Capsules and P-gp inhibitors in patients with severe renal impairment (CrCl 15-30 mL/min) [see Drug Interactions (7.1) and Use in Specific Populations (8.6) ] . (notice Dabigatran, Mises en garde et précautions)

The concomitant use of RYANODEX and calcium channel blockers is not recommended during the treatment of malignant hyperthermia. (notice Dantrolène, Interactions médicamenteuses)

Strong CYP3A4 inhibitors: Avoid concomitant use. (notice Daridorexant, Interactions médicamenteuses)

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

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

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

Until further data are obtained, avoid combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy. (notice Vérapamil, Interactions médicamenteuses)

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)

Disopyramide Until data on possible interactions between verapamil and disopyramide are obtained, do not administer disopyramide within 48 hours before or 24 hours after verapamil administration. (notice Vérapamil, Interactions médicamenteuses)

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

The concomitant use of verapamil or the cation transport system inhibitors cimetidine, trimethoprim (alone or in combination with sulfamethoxazole), or ketoconazole with dofetilide is contraindicated (see WARNINGS and PRECAUTIONS, Drug-Drug Interactions ), as each of these drugs cause a substantial increase in dofetilide plasma concentrations. (notice Dofétilide, 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)

…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)

…of active abnormal bleeding within the previous 30 days Severe hypertension (systolic blood pressure >200 mm Hg or diastolic blood pressure >110 mm Hg) not adequately controlled on antihypertensive therapy Major surgery within the preceding 6 weeks History of stroke within 30 days or any history of hemorrhagic stroke Current or planned administration of another… (notice Eptifibatide, 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)

IV administration of cardiodepressant calcium-channel antagonists (e.g., verapamil) and BREVIBLOC in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving BREVIBLOC and intravenous verapamil. (notice Esmolol, Contre-indications)

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)

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. (notice Évérolimus, Interactions médicamenteuses)

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)

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. (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)

Fosamprenavir calcium is contraindicated when coadministered with the following drugs: Alpha 1-adrenoreceptor antagonist: Alfuzosin Antiarrhythmics: Flecainide (with ritonavir ), propafenone (with ritonavir ) Antimycobacterial: Rifampin Antipsychotic: Lurasidone (with ritonavir ), pimozide Ergot derivatives: Dihydroergotamine, ergonovine, ergotamine, methylergonovine… (notice Fosamprénavir, Contre-indications)

Avoid co-administration of CONTEPO with drugs known to prolong the QT interval, such as class IA or class III antiarrhythmic medications, tricyclic antidepressants, macrolides, and antipsychotics [see Warnings and Precautions ( 5.2 )] . (notice Fosfomycine, Interactions médicamenteuses)

Cytochrome P450 3A4 Interaction The concomitant use of HYSINGLA ER with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (notice Hydrocodone, Mise en garde encadrée)

Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Polistirex and Chlorpheniramine Polistirex with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. (notice Hydrocodone et chlorphénamine, Mise en garde encadrée)

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and homatropine methylbromide with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. (notice Hydrocodone et homatropine, Mise en garde encadrée)

Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Bitartrate and Ibuprofen Tablets with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which may cause potentially fatal respiratory depression. (notice Hydrocodone et ibuprofène, Mise en garde encadrée)

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and acetaminophen tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (notice Hydrocodone et paracétamol, Mise en garde encadrée)

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

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine Contraindicated during and 2 weeks after TOLSURA treatment. (notice Itraconazole, Interactions médicamenteuses)

Avoid concomitant use of ivabradine and verapamil. (notice Vérapamil, Interactions médicamenteuses)

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

IV administration of non-dihydropyridine calcium-channel antagonists (e.g., verapamil) Hypersensitivity reactions, including anaphylaxis, to labetalol Bronchial asthma ( 4 ) (notice Labétalol, Contre-indications)

These conditions include patients with hypokalemia or hypomagnesemia, with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products with known risk for QT prolongation/ Torsades de Pointes, and cumulative high-dose anthracycline therapy. (notice Lapatinib, Mises en garde et précautions)

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)

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)

Alpha 1- Adrenoreceptor Antagonist: alfuzosin Antianginal: ranolazine Antiarrhythmic: dronedarone Anti-gout: colchicine Antipsychotics: lurasidone, pimozide Ergot Derivatives: dihydroergotamine, ergotamine, methylergonovine GI Motility Agent: cisapride Hepatitis C direct acting antiviral: elbasvir/grazoprevir HMG-CoA Reductase Inhibitors: lovastatin, simvastatin… (notice Lopinavir et ritonavir, Contre-indications)

• 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)

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

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)

Other Antihypertensive Drugs When metolazone tablets, USP, are used with other antihypertensive drugs, particular care must be taken to avoid excessive reduction of blood pressure, especially during initial therapy. (notice Métolazone, Mises en garde)

Considering the known proarrhythmic properties of mexiletine and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of mexiletine as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmia. (notice Mexilétine, Mise en garde encadrée)

Le millepertuis peut affaiblir ces médicaments en accélérant leur dégradation, ce qui peut se traduire par un rejet d'organe, des caillots ou une perte d'effet. (NCCIH, St. John's Wort)

Minoxidil should be reserved for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and two other antihypertensive agents. (notice Minoxidil, Mise en garde encadrée)

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

Therefore, moxifloxacin should be avoided with Class IA and Class III antiarrhythmics [see Warnings and Precautions ( 5.6 ), Nonclinical Toxicology ( 13.2 ), and Patient Counseling Information ( 17 )]. (notice Moxifloxacine, Interactions médicamenteuses)

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)

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)

…concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7.3) ] : • Alpha 1-adrenoreceptor antagonist: alfuzosin • Antianginal: ranolazine • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine • Anti-gout: colchicine (in patients with renal and/or hepatic impairment [see Table 2 , Drug Interactions… (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)

Cytochrome P450 3A4 Interaction The concomitant use of Oxycodone Hydrochloride Oral Solution with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (notice Oxycodone, Mise en garde encadrée)

Cytochrome P450 3A4 Interaction The concomitant use of oxycodone hydrochloride tablets with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (notice Oxycodone et paracétamol, Mise en garde encadrée)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (notice Paracétamol et codéine, Mise en garde encadrée)

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

Cytochrome P450 3A4 Interaction The concomitant use of DEMEROL Injection with all cytochrome P450 3A4 inhibitors may result in an increase in meperidine plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. (notice Péthidine, Mise en garde encadrée)

Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of procainamide as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. (notice Procaïnamide, Mise en garde encadrée)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine. (notice Prométhazine et codéine, Mise en garde encadrée)

• The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) or other antiarrhythmic drugs is uncertain, but at present, it is prudent to consider any IC antiarrhythmic to have a significant proarrhythmic risk in patients with structural heart disease. (notice Propafénone, Mise en garde encadrée)

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, Interactions médicamenteuses)

Until further data are obtained, avoid combined therapy of verapamil and quinidine in patients with hypertrophic cardiomyopathy. (notice Vérapamil, Interactions médicamenteuses)

• 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)

When used concomitantly, inhalation anesthetics and calcium antagonists, such as verapamil, titrate slowly to avoid excessive cardiovascular depression. (notice Vérapamil, 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)

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)

…coadministration of an alpha-blocker and CIALIS for the treatment of BPH has not been adequately studied, and due to the potential vasodilatory effects of combined use resulting in blood pressure lowering, the combination of CIALIS and alpha-blockers is not recommended for the treatment of BPH. [see Dosage and Administration ( 2.7 ), Drug Interactions ( 7.1 ),… (notice Tadalafil, Mises en garde et précautions)

Effect of Other Drugs on TALZENNA Effect of P-gp Inhibitors Breast Cancer Avoid coadministration of TALZENNA with the following P-gp inhibitors: itraconazole, amiodarone, carvedilol, clarithromycin, itraconazole, and verapamil. (notice Talazoparib, Interactions médicamenteuses)

• Should not be used in combination with strong inhibitors of CYP3A4. (notice Tamsulosine, Mises en garde et précautions)

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)

Avoid concomitant use HYCAMTIN capsules with P-gp inhibitors or BCRP inhibitors. (notice Topotécan, Interactions médicamenteuses)

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)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (notice Tramadol, Mise en garde encadrée)

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (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)

Strong CYP 3A Inhibitors Triazolam is contraindicated in patients receiving strong inhibitors of CYP 3A such as ketoconazole, itraconazole, nefazodone, ritonavir, indinavir, nelfinavir, saquinavir, and lopinavir [see Contraindications (4) , Drug Interactions (7.1) ] . (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)

QT Prolongation : Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil hydrochloride tablets. (notice Vardénafil, Mises en garde et précautions)

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)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Intervention: During concomitant use of mefenamic acid with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions ( 5.6 )] . (notice Acide méfénamique, Interactions médicamenteuses)

Epinephrine may antagonize the neuronal blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter. (notice Adrénaline, Interactions médicamenteuses)

P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (notice Afatinib, Interactions médicamenteuses)

Alcohol Verapamil has been found to significantly inhibit ethanol elimination resulting in elevated blood ethanol concentrations that may prolong the intoxicating effects of alcohol. (notice Vérapamil, Interactions médicamenteuses)

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, Interactions médicamenteuses)

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

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

The pressor effects of diethylpropion and those of other drugs may be additive when the drugs are used concomitantly; conversely, diethylpropion may interfere with antihypertensive drugs (i.e., guanethidine, a-methyldopa). (notice Amfépramone, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, 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, Interactions médicamenteuses)

Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs. (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, 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)

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

CYP2D6 inhibitors and CYP3A4 Inhibitors : See full prescribing information for ABILIFY MAINTENA dosage modifications when used concomitantly with CYP2D6 inhibitors and/or CYP3A4 inhibitors for greater than 14 days ( 7.1 ) (notice Aripiprazole, Interactions médicamenteuses)

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

Aspirin In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone. (notice Vérapamil, Interactions médicamenteuses)

Aspirin In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone. (notice Vérapamil, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Antihypertensive Drugs Prevention or Management Increase the frequency of monitoring blood pressure and adjust atomoxetine oral solution dosage as clinically appropriate. (notice Atomoxétine, Interactions médicamenteuses)

Lower starting and maintenance doses of other CYP3A4 substrates (e.g., atorvastatin) may be required as verapamil may increase the plasma concentration of these drugs. (notice Vérapamil, Interactions médicamenteuses)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, 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)

Use of Cytochrome P450 3A4 Inhibitors Ritonavir and other strong cytochrome P450 3A4 (CYP3A4) inhibitors can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Drug Interactions ( 7.2 ) and Clinical Pharmacology ( 12.3 )] . (notice Azélastine et fluticasone, Mises en garde et précautions)

…bradyarrhythmias or uncompensated heart failure • patients on drugs known to prolong the QT interval • patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. (notice Azithromycine, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Amphetamines may decrease the hypotensive effect of antihypertensives. (notice Benzfétamine, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Hypotension: Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration. (notice Bortézomib, Mises en garde et précautions)

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (e.g., elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medication), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and… (notice Brexpiprazole, Mises en garde et précautions)

Antihypertensives/Cardiac Glycosides Because brimonidine tartrate ophthalmic solution 0.1% and 0.15% may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with brimonidine tartrate ophthalmic solution 0.1% and 0.15% is advised. (notice Brimonidine, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Central Nervous System (CNS) depressants Antihistamines have additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, antianxiety agents, etc.). Antihypertensive drugs Sympathomimetic may reduce the effects of antihypertensive drugs. (notice Bromphéniramine, pseudoéphédrine et dextrométhorphane, Interactions médicamenteuses)

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)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Inhibitors of CYP3A4 Clinical Impact: The concomitant use of buprenorphine and CYP3A4 inhibitors can increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when an inhibitor is added after a stable dose of buprenorphine and naloxone sublingual tablet is achieved. (notice Buprénorphine et naloxone, Interactions médicamenteuses)

Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of: antidepressants (e.g., venlafaxine, nortriptyline, imipramine, desipramine, paroxetine, fluoxetine, sertraline), antipsychotics (e.g., haloperidol, risperidone, thioridazine), beta-blockers (e.g., metoprolol), and Type 1C antiarrhythmics (e.g., propafenone, flecainide). (notice Bupropion, Interactions médicamenteuses)

This finding is consistent with the in vivo interactions observed between buspirone and the following: Diltiazem and verapamil: In a study of nine healthy volunteers, coadministration of buspirone (10 mg as a single dose) with verapamil (80 mg t.i.d.) or diltiazem (60 mg t.i.d.) increased plasma buspirone concentrations (verapamil increased AUC and C max of buspirone… (notice Buspirone, Interactions médicamenteuses)

Aspirin In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone. (notice Vérapamil, Interactions médicamenteuses)

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Carbamazepine Verapamil therapy may increase carbamazepine concentrations during combined therapy. (notice Vérapamil, Interactions médicamenteuses)

Symptomatic postural hypotension has occurred when carbidopa, given with levodopa or carbidopa-levodopa combination products, was added to the treatment of a patient receiving antihypertensive drugs. (notice Carbidopa, Interactions médicamenteuses)

Antihypertensive drugs: May cause symptomatic postural hypotension. (notice Carbidopa et lévodopa, Interactions médicamenteuses)

Antihypertensive Agents Symptomatic postural hypotension has occurred when carbidopa/levodopa was added to the treatment of patients receiving antihypertensive drugs. (notice Carbidopa, lévodopa et entacapone, Interactions médicamenteuses)

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (e.g., elderly patients, patients with dehydration, hypovolemia, and concomitant treatment with antihypertensive medications), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and… (notice Cariprazine, Mises en garde et précautions)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Intervention: During concomitant use of VYSCOXA with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions (5.6) ]. (notice Célécoxib, Interactions médicamenteuses)

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

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

In a drug interaction study, co-administration of orally inhaled ciclesonide and oral ketoconazole, a potent inhibitor of cytochrome P450 3A4, increased the exposure (AUC) of des-ciclesonide by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. (notice Ciclésonide, Interactions médicamenteuses)

Cyclosporine Verapamil therapy may increase serum levels of cyclosporine. (notice Vérapamil, 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)

…syndrome, uncorrected electrolyte imbalance, such as hypokalemia or hypomagnesemia and cardiac disease, such as heart failure, myocardial infarction, or bradycardia), and patients receiving Class IA antiarrhythmic agents (quinidine, procainamide), or Class III antiarrhythmic agents (amiodarone, sotalol), tricyclic antidepressants, macrolides, and antipsychotics. (notice Ciprofloxacine, Mises en garde et précautions)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

The absorption of verapamil can be reduced by the cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic drug regimens. (notice Vérapamil, Interactions médicamenteuses)

Such drugs include Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone). (notice Citalopram, 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)

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

Monitor heart rate in patients receiving concomitant verapamil and clonidine. (notice Vérapamil, Interactions médicamenteuses)

The absorption of verapamil can be reduced by the cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic drug regimens. (notice Vérapamil, Interactions médicamenteuses)

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

Co-administration of darunavir and ritonavir and other drugs that inhibit CYP3A, or P-gp may decrease the clearance of darunavir and ritonavir and may result in increased plasma concentrations of darunavir and ritonavir (see Table 10 ). (notice Darunavir, Interactions médicamenteuses)

Co-administration of PREZCOBIX or PREZCOBIX PED and other drugs that inhibit CYP3A may result in increased plasma concentrations of darunavir and cobicistat (see Table 2 ). (notice Darunavir et cobicistat, Interactions médicamenteuses)

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

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

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (notice Désogestrel et éthinylestradiol, Interactions médicamenteuses)

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)

• Antihypertensive Drugs: Monitor blood pressure. (notice Dexméthylphénidate, Interactions médicamenteuses)

Intervention: During concomitant use of ZIPSOR with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions ( 5.6 ) ]. (notice Diclofénac, Interactions médicamenteuses)

Intervention: During concomitant use of diclofenac sodium/misoprostol with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.7) ] . (notice Diclofénac et misoprostol, Interactions médicamenteuses)

Other Drugs with Anticholinergic Activity The following agents may increase certain actions or side effects of anticholinergic drugs including dicyclomine hydrochloride: amantadine, antiarrhythmic agents of Class I (e.g., quinidine), antihistamines, antipsychotic agents (e.g., phenothiazines), benzodiazepines, MAO inhibitors, narcotic analgesics (e.g., meperidine),… (notice Dicyclovérine, Interactions médicamenteuses)

Digoxin levels can increase by 50 to 75%; reduce digoxin dose ( 7.5 ) (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. (notice Doravirine, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

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

Monitor for increased dronabinol-related adverse reactions when dronabinol oral solution is co-administered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole) and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice). (notice Dronabinol, Interactions médicamenteuses)

• Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability. (notice Dronédarone, Interactions médicamenteuses)

…development of prolonged QT syndrome, such as: 1) clinically significant bradycardia (less than 50 bpm), 2) any clinically significant cardiac disease, 3) treatment with Class I and Class III antiarrhythmics, 4) treatment with monoamine oxidase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to prolong the QT interval (see PRECAUTIONS,… (notice Dropéridol, Mises en garde)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (notice Drospirénone et éthinylestradiol, Mises en garde et précautions)

The risk of BP decreases may be greater in patients taking concomitant medications that induce orthostatic hypotension (such as antihypertensives) or are potent CYP1A2 inhibitors [see Drug Interactions ( 7.1 )] and in patients taking duloxetine delayed-release capsules at doses above 60 mg daily. (notice Duloxétine, Mises en garde et précautions)

Calcium Channel Antagonists Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. (notice Dutastéride, Interactions médicamenteuses)

P-gp Inhibitors Treatment of NVAF Based on clinical experience from the ENGAGE AF-TIMI 48 study, dose reduction in patients concomitantly receiving P-gp inhibitors resulted in edoxaban blood levels that were lower than in patients who were given the full dose. (notice Édoxaban, Interactions médicamenteuses)

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

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

Coadministration of GENVOYA with other drugs that inhibit CYP3A may decrease the clearance and increase the plasma concentration of cobicistat. (notice Elvitégravir, cobicistat, emtricitabine et ténofovir, Interactions médicamenteuses)

Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. (notice Emtricitabine et ténofovir, Interactions médicamenteuses)

Drugs Inducing or Inhibiting CYP3A Enzymes Rilpivirine is primarily metabolized by cytochrome P450 (CYP) 3A, and drugs that induce or inhibit CYP3A may thus affect the clearance of RPV [see Contraindications (4) , Warnings and Precautions (5.7) , and Clinical Pharmacology (12.3) ] . (notice Emtricitabine, rilpivirine et ténofovir, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Following initiation and titration of Epogen, approximately 25% of patients on dialysis required initiation of or increases in antihypertensive therapy; hypertensive encephalopathy and seizures have been reported in patients with CKD receiving Epogen. (notice Époétine alfa, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics, and electrolyte abnormalities. (notice Éribuline, Mises en garde et précautions)

Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents. (notice Érythromycine, Mises en garde)

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

Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and may result in side effects. (notice Estradiol, Interactions médicamenteuses)

…exposure at steady state. [See Clinical Pharmacology (12.3).] Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors like azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem,… (notice Estradiol et diénogest, Interactions médicamenteuses)

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (notice Estradiol et noréthistérone, Interactions médicamenteuses)

Concomitant administration of itraconazole, a strong CYP3A4 inhibitor, with DUAVEE, resulted in increases in bazedoxifene exposure (40%) and, to a lesser extent, conjugated estrogens exposure (9% for baseline-adjusted total estrone, 5% for total equilin), compared to DUAVEE alone [see Pharmacokinetics (12.3) ] . (notice Estrogènes conjugués et bazédoxifène, Interactions médicamenteuses)

The dose of LUNESTA should be reduced in patients who are administered potent inhibitors of CYP3A4, such as ketoconazole, while taking LUNESTA. (notice Eszopiclone, Mises en garde et précautions)

Concomitant administration of strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma estrogen and/or progestin concentrations. (notice Étonogestrel et éthinylestradiol, Interactions médicamenteuses)

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

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, 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)

Intervention: During concomitant use of FENOPROFEN CALCIUM with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions ( 5.6 ) ]. (notice Fénoprofène, Interactions médicamenteuses)

Concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) via P-gp inhibition; however, concomitant P-gp inhibitor use had no attributable effect on safety or treatment outcome of fidaxomicin-treated adult patients in controlled clinical trials. (notice Fidaxomicine, Interactions médicamenteuses)

Flecainide A study in healthy volunteers showed that the concomitant administration of flecainide and verapamil may have additive effects on myocardial contractility, AV conduction, and repolarization. (notice Vérapamil, Interactions médicamenteuses)

Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. (notice Fluconazole, Interactions médicamenteuses)

Coadministration of fluoxetine with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. (notice Fluoxétine, Interactions médicamenteuses)

Intervention: During concomitant use of flurbiprofen with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions (5) ]. (notice Flurbiprofène, Interactions médicamenteuses)

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)

…prolongation and the potential for torsades de pointes, the use of FOSCAVIR should be avoided in combination with agents known to prolong the QT interval including Class IA (e.g., quinidine or procainamide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents, phenothiazines, tricyclic antidepressants, and certain macrolides and fluoroquinolones. (notice Foscarnet, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

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

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

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

Calcium Channel Blockers : Administration of calcium may reduce the response. (notice Gluconate de calcium, 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)

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

…Interactions: Effect of other Drugs on INTUNIV Concomitant Drug Name or Drug Class Clinical Rationale and Magnitude of Drug Interaction Clinical Recommendation Strong and moderate CYP3A4 inhibitors, e.g., ketoconazole, fluconazole Guanfacine is primarily metabolized by CYP3A4 and its plasma concentrations can be significantly affected resulting in an increase… (notice Guanfacine, Interactions médicamenteuses)

The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme may be additive. (notice Halopéridol, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, 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)

Intervention: During concomitant use of CALDOLOR with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions ( 5.6 ) ]. (notice Ibuprofène, Interactions médicamenteuses)

Intervention: During concomitant use of ibuprofen and famotidine tablet with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions ( 5.7 )] . (notice Ibuprofène et famotidine, Interactions médicamenteuses)

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

…FANAPT should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to… (notice Ilopéridone, Mises en garde et précautions)

Interactions With Drugs Metabolized by CYP3A4 Gleevec will increase plasma concentration of CYP3A4 metabolized drugs (e.g., triazolo-benzodiazepines, dihydropyridine calcium channel blockers, certain HMG-CoA reductase inhibitors, etc.). Use caution when administering Gleevec with CYP3A4 substrates that have a narrow therapeutic window. (notice Imatinib, Interactions médicamenteuses)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Monitor patients to assure diuretic efficacy including antihypertensive effects ( 7 ) (notice Indométacine, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, 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)

Antiarrhythmics disopyramide, dofetilide, dronedarone, quinidine digoxin Disopyramide, dofetilide, dronedarone, quinidine: The potential increase in plasma concentrations of these drugs when coadministered with ketoconazole may increase the risk of serious cardiovascular events including QT prolongation. (notice Kétoconazole, Interactions médicamenteuses)

VIMPAT should also be used with caution in patients on concomitant medications that affect cardiac conduction, including sodium channel blockers, beta-blockers, calcium channel blockers, potassium channel blockers, and medications that prolong the PR interval [see Drug Interactions (7.2) ] . (notice Lacosamide, 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)

Antiarrhythmics: amiodarone Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown Coadministration of amiodarone with ledipasvir and sofosbuvir may result in serious symptomatic bradycardia. (notice Lédipasvir et sofosbuvir, Interactions médicamenteuses)

Clinical Comment Antiarrhythmics: digoxin ↑ digoxin Use with caution and monitor digoxin therapeutic concentration. (notice Lénacapavir, Interactions médicamenteuses)

Levofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. (notice Lévofloxacine, Mises en garde et précautions)

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

CYP3A inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice The effect of grapefruit juice on CYP3A4 enzymes (e.g., strong vs. moderate inhibition) depends on its brand, concentration, and preparation. , or ketoconazole may increase systemic exposure of the estrogen and/or progestin component of CHCs. (notice Lévonorgestrel et éthinylestradiol, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Lithium Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant verapamil-lithium therapy with either no change or an increase in serum lithium levels. (notice Vérapamil, Interactions médicamenteuses)

…combination with others drugs or herbal products that are known to prolong the QT interval, including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmics, antipsychotics (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), or any other drug known to prolong the QT interval… (notice Lopéramide, Mises en garde)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (e.g., elderly patients, patients with dehydration, hypovolemia, and concomitant treatment with antihypertensive drugs), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and patients… (notice Lumatépérone, Mises en garde et précautions)

The action of Mecamylamine HCl may be potentiated by anesthesia, other antihypertensive drugs and alcohol. (notice Mécamylamine, 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)

Intervention: During concomitant use of QAMZOVA with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [ see Warnings and Precautions ( 5.6 ) ]. (notice Méloxicam, Interactions médicamenteuses)

Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (notice Méthadone, Interactions médicamenteuses)

Antihypertensive Drugs: Monitor blood pressure. (notice Méthylphénidate, Interactions médicamenteuses)

A decrease in metoprolol and propranolol clearance has been observed when either drug is administered concomitantly with verapamil. (notice Vérapamil, Interactions médicamenteuses)

A decrease in metoprolol and propranolol clearance has been observed when either drug is administered concomitantly with verapamil. (notice Vérapamil, Interactions médicamenteuses)

The half-life of midazolam increased from 5 to 7 hours when midazolam was taken in conjunction with verapamil or diltiazem. (notice Midazolam, Interactions médicamenteuses)

…mifepristone is contraindicated. [See Contraindications (4.3)] 5.6 Use of Strong CYP3A Inhibitors Mifepristone should be used with caution in patients taking ketoconazole and other strong inhibitors of CYP3A, such as itraconazole, nefazodone, ritonavir, nelfinavir, indinavir, atazanavir, amprenavir, fosamprenavir, clarithromycin, conivaptan, lopinavir/ritonavir, posaconazole,… (notice Mifépristone, Mises en garde et précautions)

REMERON/REMERONSolTab should be used with caution in patients with known cardiovascular or cerebrovascular disease that could be exacerbated by hypotension (history of myocardial infarction, angina, or ischemic stroke) and conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medication). (notice Mirtazapine, Mises en garde et précautions)

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

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

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

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

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

P-Glycoprotein (P-gp) Inhibitors Clinical Impact: The concomitant use of P-gp inhibitors can increase the exposure to morphine by two-fold and can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. (notice Morphine, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

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

Drugs Metabolized by CYP2D6: Bupropion inhibits CYP2D6 and can increase concentrations of antidepressants, (e.g., selective serotonin reuptake inhibitors and many tricyclics), antipsychotics (e.g., haloperidol, risperidone and thioridazine), beta-blockers (e.g., metoprolol) and Type 1C antiarrhythmics (e.g., propafenone and flecainide). (notice Naltrexone et bupropion, Interactions médicamenteuses)

( 5.3 Hepatotoxicity) Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. (notice Naproxène, Mises en garde et précautions)

Intervention : During concomitant use of naproxen and esomeprazole magnesium delayed-release tablets with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see Warnings and Precautions (5.6) ]. (notice Naproxène et ésoméprazole, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, 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)

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

Caution should also be used when niacin extended-release tablets are used in patients with unstable angina or in the acute phase of an MI, particularly when such patients are also receiving vasoactive drugs such as nitrates, calcium channel blockers, or adrenergic blocking agents. (notice Niacine, Mises en garde et précautions)

…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)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (notice Norelgestromine et éthinylestradiol, Interactions médicamenteuses)

Substances increasing the systemic concentrations of HCs: Co-administration of certain HCs and strong or moderate CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase the systemic concentrations of progestins, including norethindrone. (notice Noréthistérone, Interactions médicamenteuses)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (notice Noréthistérone et éthinylestradiol, Interactions médicamenteuses)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (notice Norgestimate et éthinylestradiol, Interactions médicamenteuses)

Concomitant administration of CYP3A4 inhibitors such as itraconazole, fluconazole, grapefruit juice or ketoconazole may increase plasma hormone concentrations. (notice Norgestrel et éthinylestradiol, Interactions médicamenteuses)

Beta Blocker and Calcium Channel Blockers : dose adjustment of beta blockers or calcium channel blockers may be necessary (‎ 7 ). (notice Octréotide, Interactions médicamenteuses)

Ofloxacin should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalemia, and patients receiving Class IA (quinidine, procainamide), or Class III (amiodarone, sotalol) antiarrhythmic agents. (notice Ofloxacine, Précautions)

…of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, and conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications) where the occurrence of syncope, or hypotension and/or bradycardia might put the patient at increased medical risk. (notice Olanzapine, Mises en garde et précautions)

…and fluoxetine capsules should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemia, heart failure, or conduction abnormalities), cerebrovascular disease, or conditions that would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications). (notice Olanzapine et fluoxétine, Mises en garde et précautions)

Risk of Use in Patients with Decreased Cytochrome P450 2D6 Function or Concomitant Use or Discontinuation with Cytochrome P450 3A4 Inhibitors and Inducers Risk of Increased Oliceridine Plasma Concentrations Increased plasma concentrations of oliceridine, which may result in prolonged opioid adverse reactions and exacerbated respiratory depression, may occur when… (notice Olicéridine, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Concomitant administration of CYP3A4 inhibitors may inhibit the metabolism of, and increase the mometasone furoate plasma concentration and potentially increase the risk for adverse reactions. (notice Olopatadine et mométasone, 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)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

Aspirin In a few reported cases, coadministration of verapamil with aspirin has led to increased bleeding times greater than observed with aspirin alone. (notice Vérapamil, Interactions médicamenteuses)

Monitor electrocardiograms (ECG) in patients with congestive heart failure, bradyarrhythmias, and electrolyte abnormalities and in patients taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics [see Drug Interactions (7.1)] . (notice Oxaliplatine, Mises en garde et précautions)

Intervention: During concomitant use of OXAPROZIN CAPSULES with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects [see WARNINGS AND PRECAUTIONS (5.6) ]. (notice Oxaprozine, Interactions médicamenteuses)

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

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

Concomitant administration of R verapamil can decrease the clearance of paclitaxel. (notice Vérapamil, Interactions médicamenteuses)

…paliperidone should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to… (notice Palipéridone, Mises en garde et précautions)

Grapefruit juice may significantly increase verapamil levels ( 7.3 ) (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

• Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. (notice Paracétamol et ibuprofène, 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)

Adjustments in the dose of drugs known to slow the heart rate (e.g., beta-blockers, calcium channel blockers) and correction of electrolyte disturbances may be necessary when initiating or during the course of SIGNIFOR LAR treatment. (notice Pasiréotide, Mises en garde et précautions)

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

…hydrochloride desipramine hydrochloride imipramine hydrochloride doxepin carbamazepine cyclobenzaprine HCl amoxapine maprotiline HCl trimipramine maleate protriptyline HCl mirtazapine Phenelzine sulfate should be used with caution in combination with antihypertensive drugs, including thiazide diuretics and β-blockers, since exaggerated hypotensive effects may result. (notice Phénelzine, Mises en garde)

Phenobarbital Phenobarbital therapy may increase verapamil clearance. (notice Vérapamil, Interactions médicamenteuses)

Phenobarbital Phenobarbital therapy may increase verapamil clearance. (notice Vérapamil, Interactions médicamenteuses)

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

Antagonistic Effects (decrease in BIORPHEN blood pressure effect) can occur with α-adrenergic antagonists, phosphodiesterase Type 5 inhibitors, mixed α- and β-receptor antagonists, calcium channel blockers, benzodiazepines and ACE inhibitors, centrally acting sympatholytic agents. (notice Phényléphrine, Interactions médicamenteuses)

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

The use of NUPLAZID should be avoided in patients with known QT prolongation or in combination with other drugs known to prolong QT interval including Class 1A antiarrhythmics (e.g., quinidine, procainamide) or Class 3 antiarrhythmics (e.g., amiodarone, sotalol), certain antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), and certain… (notice Pimavansérine, Mises en garde et précautions)

DRUG INTERACTIONS Because pimozide prolongs the QT interval of the electrocardiogram, an additive effect on QT interval would be anticipated if administered with other drugs, such as phenothiazines, tricyclic antidepressants or antiarrhythmic agents, which prolong the QT interval. (notice Pimozide, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Monitor patients to assure diuretic efficacy including antihypertensive effects (7) (notice Piroxicam, Interactions médicamenteuses)

Experience with PONVORY is limited in patients receiving concurrent therapy with drugs that decrease heart rate (e.g., beta-blockers, non-dihydropyridine calcium channel blockers - diltiazem and verapamil, and other drugs that may decrease heart rate such as digoxin). (notice Ponésimod, Mises en garde et précautions)

Calcium Channel Blockers that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Posaconazole may increase the plasma concentrations of calcium channel blockers that are substrates of CYP3A4. (notice Posaconazole, Interactions médicamenteuses)

Syncopal episodes have usually occurred within 30 to 90 minutes of the initial dose of the drug; occasionally, they have been reported in association with rapid dosage increases or the introduction of another antihypertensive drug into the regimen of a patient taking high doses of prazosin hydrochloride capsules. (notice Prazosine, Mises en garde)

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)

The absorption of verapamil can be reduced by the cyclophosphamide, oncovin, procarbazine, prednisone (COPP) and the vindesine, adriamycin, cisplatin (VAC) cytotoxic drug regimens. (notice Vérapamil, 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)

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

Patients with Hypertrophic Cardiomyopathy In 120 patients with hypertrophic cardiomyopathy, idiopathic hypertrophic subaortic stenosis (IHSS) (most of them refractory or intolerant to propranolol) who received therapy with verapamil at doses up to 720 mg/day, a variety of serious adverse effects were seen. (notice Vérapamil, Mises en garde et précautions)

Quetiapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications). (notice Quétiapine, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

…disease and preexisting conduction system abnormalities, elderly patients with sick sinus syndrome, patients with atrial fibrillation with slow ventricular response, patients with myocardial ischemia or patients receiving drugs known to prolong the PR interval (e.g. verapamil) or QRS interval (e.g. flecainide or quinidine) [see CLINICAL PHARMACOLOGY ( 12.2 )] . (notice Quinine, Mises en garde et précautions)

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (notice Rameltéon, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Moderate CYP3A Inhibitors Limit the dose of ASPRUZYO Sprinkle to 500 mg twice daily in patients on moderate CYP3A inhibitors, including diltiazem, verapamil, erythromycin, fluconazole, and grapefruit juice or grapefruit-containing products [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)]. (notice Ranolazine, Interactions médicamenteuses)

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)

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

Rifampin Therapy with rifampin may markedly reduce oral verapamil bioavailability. (notice Vérapamil, Interactions médicamenteuses)

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

• Concomitant P-glycoprotein (P-gp) inhibitors (e.g., cyclosporine): Caution should be exercised when concomitant use of XIFAXAN and a P-glycoprotein inhibitor is needed. (notice Rifaximine, Mises en garde et précautions)

Coadministration of EDURANT or EDURANT PED and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. (notice Rilpivirine, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Clinically significant hypotension has been observed with concomitant use of oral RISPERDAL and antihypertensive medication. (notice Rispéridone, Mises en garde et précautions)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, 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)

…anesthetics or agents structurally related to amide- type local anesthetics, since the toxic effects of these drugs are additive. [See Drug Interactions 7.0 ] Patients treated with class III antiarrhythmic drugs (e.g., amiodarone) should be under close surveillance and ECG monitoring considered, since cardiac effects may be additive. [See Drug Interactions 7.0… (notice Ropivacaïne, 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)

Caution is advised when SILDENAFIL ORAL FILM is co-administered with alpha-blockers or antihypertensives. (notice Sildénafil, Mises en garde et précautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (notice Sofosbuvir et velpatasvir, Interactions médicamenteuses)

Consider temporary or permanent discontinuation for severe or persistent hypertension despite antihypertensive therapy. (notice Sorafénib, Mises en garde et précautions)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Monitor patients to assure diuretic efficacy including antihypertensive effects. (notice Sumatriptan et naproxène, Interactions médicamenteuses)

Initiate and/or adjust antihypertensive therapy as appropriate. (notice Sunitinib, Mises en garde et précautions)

The recommended dose of BELSOMRA is 5 mg in subjects receiving moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil). (notice Suvorexant, Interactions médicamenteuses)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (notice Tacrolimus, 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)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

With concomitant use of mTOR inhibitors (e.g., sirolimus, temsirolimus, and everolimus) and verapamil, consider appropriate dose reductions of both medications. (notice Vérapamil, Interactions médicamenteuses)

Co-administration of verapamil with terazosin increases the systemic exposure of terazosin [see Clinical Pharmacology (12.3)] , which may increase the risk of hypotenstion. (notice Térazosine, Interactions médicamenteuses)

In patients with hypertension on antihypertensive therapy, TLANDO increased the mean systolic/diastolic BP by 4.8/1.6 mm Hg from baseline. [see Adverse Reactions ( 6.1 )] . (notice Testostérone, Mises en garde et précautions)

…are known to prolong QTc, including antipsychotic medications (e.g., chlorpromazine, haloperidol, thioridazine, ziprasidone), antibiotics (e.g., moxifloxacin), Class 1A (e.g., quinidine, procainamide) and Class III (e.g., amiodarone, sotalol) antiarrhythmic medications or any other medications known to prolong the QTc interval [see Drug Interactions ( 7.5 )]. (notice Tétrabénazine, Mises en garde et précautions)

Theophylline Verapamil may inhibit the clearance and increase the plasma levels of theophylline. (notice Vérapamil, Interactions médicamenteuses)

Beta blockers: reports of excess bradycardia and AV block, including complete heart block; monitor closely ( 7.4 ) (notice Vérapamil, Interactions médicamenteuses)

Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of tinidazole, increasing the plasma concentrations of tinidazole. (notice Tinidazole, Interactions médicamenteuses)

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)

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

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, 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)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

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)

Control patients with milder ventricular dysfunction, if possible, with optimum doses of digitalis and/or diuretics before verapamil treatment is started [see Drug Interactions ( 7.5 )] . (notice Vérapamil, Mises en garde et précautions)

Neuromuscular Blocking Agents Clinical data and animal studies suggest that verapamil may potentiate the activity of neuromuscular blocking agents (curare-like and depolarizing). (notice Vérapamil, Interactions médicamenteuses)

Metoprolol: Possibly reduced blood-pressure lowering effect despite increased metoprolol plasma levels. (notice Venlafaxine, Interactions médicamenteuses)

Antihypertensive Agents Verapamil administered concomitantly with oral antihypertensive agents (e.g., vasodilators, angiotensin-converting enzyme inhibitors, diuretics, beta blockers) will usually have an additive effect on lowering blood pressure. (notice Vérapamil, Interactions médicamenteuses)

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)

Dihydropyridine Calcium Channel Blockers (CYP3A4 Inhibition) In Vitro Studies Demonstrated Potential for Voriconazole to Inhibit Metabolism (Increased Plasma Exposure) Frequent monitoring for adverse reactions and toxicity related to calcium channel blockers. (notice Voriconazole, Interactions médicamenteuses)

…enoxacin, famotidine, fluvoxamine, methoxsalen, mexiletine, norfloxacin, oral contraceptives, phenylpropanolamine, propafenone, propranolol, terbinafine, thiabendazole, ticlopidine, verapamil, zileuton montelukast, moricizine, omeprazole, phenobarbital, phenytoin, cigarette smoking CYP3A4 alprazolam, amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin,… (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)

Drugs That Inhibit CYP3A4 CYP3A4 is a minor metabolic pathway for the elimination of zaleplon because the sum of desethylzaleplon (formed via CYP3A4 in vitro) and its metabolites, 5-oxo-desethylzaleplon and 5-oxo-desethylzaleplon glucuronide, account for only 9% of the urinary recovery of a zaleplon dose. (notice Zaléplone, Interactions médicamenteuses)

Ziprasidone should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications). (notice Ziprasidone, Mises en garde et précautions)

CYP3A4 Inhibitors Ketoconazole Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. (notice Zolpidem, Interactions médicamenteuses)

Effects of Adenosine on Other Drugs Adenosine injection has been given with other cardioactive drugs (such as beta adrenergic blocking agents, cardiac glycosides, and calcium channel blockers) without apparent adverse interactions, but its effectiveness with these agents has not been systematically evaluated. (notice Adénosine, Interactions médicamenteuses)

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). (notice Amitriptyline, Interactions médicamenteuses)

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine, cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). (notice Amoxapine, Interactions médicamenteuses)

In such cases, butorphanol should be discontinued and the hypertension treated with antihypertensive drugs. (notice Butorphanol, Mises en garde)

Chlorpromazine may counteract the antihypertensive effect of guanethidine and related compounds. (notice Chlorpromazine, Mises en garde)

Cimetidine The interaction between cimetidine and chronically administered verapamil has not been studied. (notice Vérapamil, Interactions médicamenteuses)

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). (notice Clomipramine, Interactions médicamenteuses)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (notice Dapagliflozine, Interactions médicamenteuses)

This drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds. (notice Désipramine, Mises en garde)

Antihypertensives Amphetamines may antagonize the hypotensive effects of antihypertensives. (notice Dexamfétamine, Interactions médicamenteuses)

Drug Interactions ACE-inhibitors and Angiotensin II Anagonists Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. (notice Diflunisal, Interactions médicamenteuses)

Examples: α-adrenergic antagonists, β-adrenergic receptor antagonists, reserpine, quinidine, mephentermine Other Drug Interactions G u anethidine C linical Impact: Ephedrine may inhibit the neuron blockage produced by guanethidine, resulting in loss of antihypertensive effectiveness. (notice Éphédrine, Interactions médicamenteuses)

Drug Interactions ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (notice Étodolac, Interactions médicamenteuses)

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

…studies with acetaminophen, acetylsalicylic acid, α-blockers, angiotensin-converting enzyme (ACE) inhibitors, analgesics, anti-convulsants, beta-adrenergic blocking agents, diuretics, calcium channel blockers, cardiac nitrates, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, H 2 antagonists and quinolone anti-infectives… (notice Finastéride, Interactions médicamenteuses)

Drugs That Slow Heart Rate or Atrioventricular Conduction (e.g., beta blockers or diltiazem) Experience with GILENYA in patients receiving concurrent therapy with drugs that slow the heart rate or AV conduction (e.g., beta blockers, digoxin, or heart rate-slowing calcium channel blockers, such as diltiazem or verapamil) is limited. (notice Fingolimod, Interactions médicamenteuses)

HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. (notice Vérapamil, Interactions médicamenteuses)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (notice Glibenclamide et metformine, Interactions médicamenteuses)

These include Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmics, certain antipsychotics (e.g., ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine), certain antidepressants (e.g., citalopram, fluoxetine), certain antibiotics (e.g., azithromycin, erythromycin, clarithromycin, gatifloxacin, moxifloxacin);… (notice Hydroxyzine, Précautions)

WARNINGS Proarrhythmia: Like other antiarrhythmic agents, CORVERT Injection can induce or worsen ventricular arrhythmias in some patients. (notice Ibutilide, Mises en garde)

ACE Inhibitors FIRAZYR is a bradykinin B2 receptor antagonist and thereby has the potential to have a pharmacodynamic interaction with ACE inhibitors where FIRAZYR may attenuate the antihypertensive effect of ACE inhibitors. (notice Icatibant, Interactions médicamenteuses)

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). (notice Imipramine, Interactions médicamenteuses)

In a study in hypertensive patients, addition of isradipine to existing hydrochlorothiazide therapy did not result in any unexpected adverse effects, and isradipine had an additional antihypertensive effect. (notice Isradipine, Interactions médicamenteuses)

ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (notice Kétoprofène, Mises en garde et précautions)

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists. (notice Kétorolac, Interactions médicamenteuses)

Cardiac Rhythm and Conduction Abnormalities In vitro testing showed that lamotrigine exhibits Class IB antiarrhythmic activity at therapeutically relevant concentrations [see Clinical Pharmacology ( 12.2 )] . (notice Lamotrigine, Mises en garde et précautions)

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)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (notice Metformine, Interactions médicamenteuses)

Drug Interactions When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may occur. (notice Méthyldopa, Interactions médicamenteuses)

Drug Interactions: ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (notice Nabumétone, Interactions médicamenteuses)

The antihypertensive action of guanethidine and similar agents may be blocked. (notice Nortriptyline, Mises en garde)

Drug Interactions Metabolism of a number of medications, including antipsychotics, antidepressants, β-blockers, and antiarrhythmics, occurs through the cytochrome P450 2D6 isoenzyme (debrisoquine hydroxylase). (notice Perphénazine, Interactions médicamenteuses)

Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine. (notice Pimécrolimus, Interactions médicamenteuses)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (notice Pioglitazone et metformine, Interactions médicamenteuses)

HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. (notice Vérapamil, Interactions médicamenteuses)

HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. (notice Vérapamil, Interactions médicamenteuses)

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. (notice Prochlorpérazine, Précautions)

Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds. (notice Protriptyline, Mises en garde)

Aminoglycoside antibiotics, local and some general anesthetics, antiarrhythmic agents, and other drugs that interfere with neuromuscular transmission should be used cautiously, if at all. (notice Pyridostigmine, 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)

HMG-CoA Reductase Inhibitors The use of HMG-CoA reductase inhibitors that are CYP3A4 substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis. (notice Vérapamil, Interactions médicamenteuses)

DRUG INTERACTIONS ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (notice Salsalate, Interactions médicamenteuses)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (notice Sitagliptine et metformine, Interactions médicamenteuses)

Drug Interactions ACE-Inhibitors and Angiotensin II Antagonists Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. (notice Sulindac, Interactions médicamenteuses)

Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, antiarrhythmics class 1C (e.g., flecainide and propafenone) and monoamine oxidase inhibitors Type B. (notice Terbinafine, Interactions médicamenteuses)

Moderate or Weak CYP1A2 Inhibitors Concomitant use of Zanaflex with moderate or weak CYP1A2 inhibitors (e.g., zileuton, antiarrhythmics [amiodarone, mexiletine, propafenone, and verapamil], cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine) should be avoided. (notice Tizanidine, Interactions médicamenteuses)

DRUG INTERACTIONS ACE Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE Inhibitors. (notice Tolmétine, Interactions médicamenteuses)

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concurrently. (notice Trifluopérazine, Précautions)

The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). (notice Trimipramine, Interactions médicamenteuses)

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

Inhibitors of Cytochrome P450 3A4 In controlled clinical studies co-administration of desloratadine with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of desloratadine and 3 hydroxydesloratadine, but there were no clinically relevant changes in the safety profile of desloratadine. [See Clinical Pharmacology (12.3) .]… (notice Desloratadine, Interactions médicamenteuses)