Wechselwirkungen von Diltiazem

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. (Fachinformation zu Acalabrutinib, Arzneimittelwechselwirkungen)

…(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… (Fachinformation zu Alfuzosin, Gegenanzeigen)

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

• 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) ] . (Fachinformation zu Alprazolam, Gegenanzeigen)

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. (Fachinformation zu Amiodaron, Warnhinweise und Vorsichtsmaßnahmen)

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) ] . (Fachinformation zu Apixaban, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Asenapin, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Atazanavir, Gegenanzeigen)

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

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. (Fachinformation zu Betaxolol, Arzneimittelwechselwirkungen)

Concomitant administration of BIXLENVO with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (Fachinformation zu Bictegravir, Emtricitabin und Tenofoviralafenamid, Arzneimittelwechselwirkungen)

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

• Strong and Moderate CYP3A Inhibitors: Avoid concomitant use with BOSULIF. (Fachinformation zu Bosutinib, Arzneimittelwechselwirkungen)

Concomitant use of strong CYP3A4 inhibitors (e.g., azole antimycotics, HIV protease inhibitors) with CYCLOSET should be avoided. (Fachinformation zu Bromocriptin, Arzneimittelwechselwirkungen)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Fachinformation zu Buprenorphin, Arzneimittelwechselwirkungen)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex. (Fachinformation zu Butalbital, Acetylsalicylsäure, Koffein und Codein, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Butalbital, Paracetamol, Koffein und Codein, Boxed Warning (umrahmter Warnhinweis))

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… (Fachinformation zu Cabozantinib, Arzneimittelwechselwirkungen)

• Calcium Channel Blockers: Avoid concomitant use with Calcium Chloride Injection. (Fachinformation zu Calciumchlorid, Arzneimittelwechselwirkungen)

Proarrhythmic effects Like many other drugs (including all other Class Ia antiarrhythmics), quinidine prolongs the QT c interval, and this can lead to torsades de pointes , a life-threatening ventricular arrhythmia (see OVERDOSAGE ). (Fachinformation zu Chinidin, Warnhinweise)

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 ) (Fachinformation zu Clarithromycin, Warnhinweise und Vorsichtsmaßnahmen)

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 )]. (Fachinformation zu Clozapin, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Codein, Boxed Warning (umrahmter Warnhinweis))

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) ] . (Fachinformation zu Colchicin, Gegenanzeigen)

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) ] . (Fachinformation zu Dabigatran, Warnhinweise und Vorsichtsmaßnahmen)

The concomitant use of RYANODEX and calcium channel blockers is not recommended during the treatment of malignant hyperthermia. (Fachinformation zu Dantrolen, Arzneimittelwechselwirkungen)

Strong CYP3A4 inhibitors: Avoid concomitant use. (Fachinformation zu Daridorexant, Arzneimittelwechselwirkungen)

Avoid concomitant use of strong CYP3A4 inhibitors. (Fachinformation zu Dasatinib, Arzneimittelwechselwirkungen)

• Avoid concomitant use of strong CYP3A4 inhibitors or inducers. (Fachinformation zu Dexamethason, Arzneimittelwechselwirkungen)

QT Prolongation: Monitor ECG if concomitant use of drugs that prolong QT interval cannot be avoided or if concomitant CYP3A4 inhibitors used. (Fachinformation zu Dextromethorphan und Chinidin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Dihydroergotamin, Boxed Warning (umrahmter Warnhinweis))

Considering the known proarrhythmic properties of Norpace or Norpace CR and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of Norpace or Norpace CR as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias. (Fachinformation zu Disopyramid, Boxed Warning (umrahmter Warnhinweis))

Concomitant use of Docetaxel Injection and drugs that inhibit CYP3A4 may increase exposure to docetaxel and should be avoided. (Fachinformation zu Docetaxel, Arzneimittelwechselwirkungen)

Avoid concomitant use of Doxorubicin Hydrochloride Injection with inhibitors of CYP3A4, CYP2D6, or P-gp. (Fachinformation zu Doxorubicin, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Dutasterid und Tamsulosin, Warnhinweise und Vorsichtsmaßnahmen)

Table 2: Oral drugs that can be administered concomitantly with Ferric Citrate Tablets Amlodipine Aspirin Atorvastatin Calcitriol Clopidogrel Digoxin Diltiazem Doxercalciferol Enalapril Fluvastatin Glimepiride Levofloxacin Losartan Metoprolol Pravastatin Propranolol Sitagliptin Warfarin Oral drugs that have to be separated from Ferric Citrate Tablets and meals… (Fachinformation zu Eisen(III)-citrat, Arzneimittelwechselwirkungen)

• 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) ]. (Fachinformation zu Eletriptan, Gegenanzeigen)

…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)… (Fachinformation zu Eplerenon, Gegenanzeigen)

…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… (Fachinformation zu Eptifibatid, Gegenanzeigen)

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. (Fachinformation zu Ergotamin und Koffein, Boxed Warning (umrahmter Warnhinweis))

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). (Fachinformation zu Erlotinib, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Esmolol, Gegenanzeigen)

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

Strong CYP3A inhibitor and P-gp inhibitor : Avoid coadministration. (Fachinformation zu Everolimus, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Ezetimib und Simvastatin, Gegenanzeigen)

• Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of fentanyl. (Fachinformation zu Fentanyl, Boxed Warning (umrahmter Warnhinweis))

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) ]. (Fachinformation zu Fesoterodin, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Flibanserin, Boxed Warning (umrahmter Warnhinweis))

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fachinformation zu Fluticason, Arzneimittelwechselwirkungen)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (Fachinformation zu Fluticason und Salmeterol, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Fosamprenavir, Gegenanzeigen)

Intervention Avoid concomitant use of FOCINVEZ Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy… (Fachinformation zu Fosaprepitant, Arzneimittelwechselwirkungen)

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 )] . (Fachinformation zu Fosfomycin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Hydrocodon, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Hydrocodon und Chlorphenamin, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Hydrocodon und Homatropin, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Hydrocodon und Ibuprofen, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Hydrocodon und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

• Strong CYP3A4 Inhibitors: Do not administer strong CYP3A4 inhibitors with CAMPTOSAR. (Fachinformation zu Irinotecan, Arzneimittelwechselwirkungen)

Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine Contraindicated during and 2 weeks after TOLSURA treatment. (Fachinformation zu Itraconazol, Arzneimittelwechselwirkungen)

Avoid concomitant use of ivabradine and diltiazem. (Fachinformation zu Diltiazem, Arzneimittelwechselwirkungen)

IV administration of non-dihydropyridine calcium-channel antagonists (e.g., verapamil) Hypersensitivity reactions, including anaphylaxis, to labetalol Bronchial asthma ( 4 ) (Fachinformation zu Labetalol, Gegenanzeigen)

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. (Fachinformation zu Lapatinib, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A4 Inhibitors: Avoid coadministration of strong CYP3A4 inhibitors with VITRAKVI. (Fachinformation zu Larotrectinib, Arzneimittelwechselwirkungen)

Strong or moderate CYP3A inhibitors: Avoid concomitant use. (Fachinformation zu Lemborexant, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Lomitapid, Gegenanzeigen)

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… (Fachinformation zu Lopinavir und Ritonavir, Gegenanzeigen)

• Strong CYP3A Inhibitors : Avoid concomitant use; reduce LORBRENA dose if concomitant use cannot be avoided. (Fachinformation zu Lorlatinib, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Lovastatin, Gegenanzeigen)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (Fachinformation zu Lurasidon, Gegenanzeigen)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (Fachinformation zu Macitentan, Arzneimittelwechselwirkungen)

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 )]. (Fachinformation zu Maraviroc, Gegenanzeigen)

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. (Fachinformation zu Methylergometrin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Metolazon, Warnhinweise)

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. (Fachinformation zu Mexiletin, Boxed Warning (umrahmter Warnhinweis))

Minoxidil should be reserved for hypertensive patients who do not respond adequately to maximum therapeutic doses of a diuretic and two other antihypertensive agents. (Fachinformation zu Minoxidil, Boxed Warning (umrahmter Warnhinweis))

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use. (Fachinformation zu Mitapivat, Arzneimittelwechselwirkungen)

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 )]. (Fachinformation zu Moxifloxacin, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Naloxegol, Gegenanzeigen)

Avoid use of concomitant drugs known to prolong the QT interval and strong CYP3A4 inhibitors [see Drug Interactions ( 7.1 , 7.2 )] . (Fachinformation zu Nilotinib, Boxed Warning (umrahmter Warnhinweis))

Therefore, the concomitant administration of NYMALIZE and strong CYP3A4 inhibitors should generally be avoided [ see Warnings and Precautions (5.3) ]. (Fachinformation zu Nimodipin, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Nirmatrelvir und Ritonavir, Gegenanzeigen)

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. (Fachinformation zu Nisoldipin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Oxycodon, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Oxycodon und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Paracetamol und Codein, Boxed Warning (umrahmter Warnhinweis))

Strong CYP3A4 Inhibitors : Avoid coadministration of VOTRIENT with strong CYP3A4 inhibitors. (Fachinformation zu Pazopanib, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Pethidin, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Procainamid, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Promethazin und Codein, Boxed Warning (umrahmter Warnhinweis))

• 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. (Fachinformation zu Propafenon, Boxed Warning (umrahmter Warnhinweis))

• Strong CYP3A4 Inhibitors: Avoid concomitant administration. (Fachinformation zu Rimegepant, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Ritonavir, Boxed Warning (umrahmter Warnhinweis))

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) ] . (Fachinformation zu Rivaroxaban, Warnhinweise und Vorsichtsmaßnahmen)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fachinformation zu Salmeterol, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Silodosin, Gegenanzeigen)

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) ] . (Fachinformation zu Simvastatin, Gegenanzeigen)

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) ]. (Fachinformation zu Sirolimus, Warnhinweise und Vorsichtsmaßnahmen)

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 )] . (Fachinformation zu Solifenacin, Arzneimittelwechselwirkungen)

Concomitant use of JOURNAVX with strong CYP3A inhibitors is contraindicated [see Warnings and Precautions (5.1) , Drug Interactions (7.1) ] . (Fachinformation zu Suzetrigin, Gegenanzeigen)

…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 ),… (Fachinformation zu Tadalafil, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Talazoparib, Arzneimittelwechselwirkungen)

• Should not be used in combination with strong inhibitors of CYP3A4. (Fachinformation zu Tamsulosin, Warnhinweise und Vorsichtsmaßnahmen)

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 ) ] . (Fachinformation zu Thiotepa, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Tolvaptan, Gegenanzeigen)

Avoid concomitant use HYCAMTIN capsules with P-gp inhibitors or BCRP inhibitors. (Fachinformation zu Topotecan, Arzneimittelwechselwirkungen)

Drugs known to prolong the QT interval and strong CYP3A4 inhibitors should be avoided [see Warnings and Precautions (5.1) ] . (Fachinformation zu Toremifen, Boxed Warning (umrahmter Warnhinweis))

CYP3A inhibitors: Avoid concomitant strong CYP3A inhibitors ( 7.1 ) (Fachinformation zu Trabectedin, Arzneimittelwechselwirkungen)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Fachinformation zu Tramadol, Boxed Warning (umrahmter Warnhinweis))

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. (Fachinformation zu Tramadol und Paracetamol, Boxed Warning (umrahmter Warnhinweis))

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… (Fachinformation zu Trazodon, Warnhinweise und Vorsichtsmaßnahmen)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (Fachinformation zu Tretinoin, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Triazolam, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Ubrogepant, Gegenanzeigen)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (Fachinformation zu Upadacitinib, Arzneimittelwechselwirkungen)

QT Prolongation : Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil hydrochloride tablets. (Fachinformation zu Vardenafil, Warnhinweise und Vorsichtsmaßnahmen)

Avoid concomitant use of VEPPANU with strong CYP3A inhibitors or drugs known to prolong the QTc interval. (Fachinformation zu Vepdegestrant, Warnhinweise und Vorsichtsmaßnahmen)

Therefore, the concomitant use of strong CYP3A inhibitors with vincristine sulfate should be avoided. (Fachinformation zu Vincristin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Epinephrine may antagonize the neuronal blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter. (Fachinformation zu Adrenalin, Arzneimittelwechselwirkungen)

P-glycoprotein (P-gp) Inhibitors : Co-administration of P-gp inhibitors can increase afatinib exposure. (Fachinformation zu Afatinib, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (Fachinformation zu Alosetron, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Amfepramon, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Amlodipin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Amlodipin und Atorvastatin, Arzneimittelwechselwirkungen)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Fachinformation zu Amlodipin und Benazepril, Arzneimittelwechselwirkungen)

• 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. (Fachinformation zu Amlodipin und Olmesartan, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Amlodipin und Valsartan, Arzneimittelwechselwirkungen)

Use of CINVANTI with strong or moderate CYP3A4 inhibitors (e.g., ketoconazole, diltiazem) may increase plasma concentrations of aprepitant and result in an increased risk of adverse reactions related to CINVANTI. (Fachinformation zu Aprepitant, Warnhinweise und Vorsichtsmaßnahmen)

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 ) (Fachinformation zu Aripiprazol, Arzneimittelwechselwirkungen)

There was also a slightly greater proportion of patients on NUVIGIL requiring new or increased use of antihypertensive medications (2.9%) compared to patients on placebo (1.8%). (Fachinformation zu Armodafinil, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Antihypertensive Drugs Prevention or Management Increase the frequency of monitoring blood pressure and adjust atomoxetine oral solution dosage as clinically appropriate. (Fachinformation zu Atomoxetin, Arzneimittelwechselwirkungen)

LIPITOR plasma levels can be significantly increased with concomitant administration of inhibitors of CYP3A4 and transporters. (Fachinformation zu Atorvastatin, Arzneimittelwechselwirkungen)

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

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 )] . (Fachinformation zu Azelastin und Fluticason, Warnhinweise und Vorsichtsmaßnahmen)

…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. (Fachinformation zu Azithromycin, Warnhinweise und Vorsichtsmaßnahmen)

The thiazide component of Lotensin HCT may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. (Fachinformation zu Benazepril und Hydrochlorothiazid, Warnhinweise)

Amphetamines may decrease the hypotensive effect of antihypertensives. (Fachinformation zu Benzfetamin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Hypotension: Use caution when treating patients taking antihypertensives, with a history of syncope, or with dehydration. (Fachinformation zu Bortezomib, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Brexpiprazol, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Brimonidin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Brompheniramin, Pseudoephedrin und Dextromethorphan, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Budesonid, Warnhinweise und Vorsichtsmaßnahmen)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Fachinformation zu Budesonid und Formoterol, Warnhinweise und Vorsichtsmaßnahmen)

Antihypertensives Bumetanide may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs. (Fachinformation zu Bumetanid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Buprenorphin und Naloxon, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Bupropion, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Buspiron, Arzneimittelwechselwirkungen)

Calcium Channel Blockers : Administration of calcium may reduce the response. (Fachinformation zu Calciumgluconat, Arzneimittelwechselwirkungen)

It may be necessary to reduce the EQUETRO dose if used concomitantly with inhibitors of CYP3A4 and/or epoxide hydrolase. (Fachinformation zu Carbamazepin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Carbidopa, Arzneimittelwechselwirkungen)

Antihypertensive drugs: May cause symptomatic postural hypotension. (Fachinformation zu Carbidopa und Levodopa, Arzneimittelwechselwirkungen)

Antihypertensive Agents Symptomatic postural hypotension has occurred when carbidopa/levodopa was added to the treatment of patients receiving antihypertensive drugs. (Fachinformation zu Carbidopa, Levodopa und Entacapon, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Cariprazin, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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) ]. (Fachinformation zu Celecoxib, Arzneimittelwechselwirkungen)

Quinine sulfate is not recommended for use with other drugs known to cause QT prolongation, including Class IA antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide), and Class III antiarrhythmic agents (e.g., amiodarone, sotalol, dofetilide). (Fachinformation zu Chinin, Warnhinweise und Vorsichtsmaßnahmen)

Thiazides may add to or potentiate the action of other antihypertensive drugs. (Fachinformation zu Chlorothiazid, Warnhinweise)

Effect of chlorthalidone on other drugs Chlorthalidone may add to or potentiate the action of other antihypertensive drugs. (Fachinformation zu Chlortalidon, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Ciclesonid, Arzneimittelwechselwirkungen)

Drugs That Increase Cyclosporine Concentrations Calcium Channel Blockers Antifungals Antibiotics Glucocorticoids Other Drugs diltiazem fluconazole azithromycin methylprednisolone Allopurinol nicardipine itraconazole clarithromycin Amiodarone verapamil ketoconazole erythromycin Bromocriptine voriconazole quinupristin/ dalfopristin colchicine danazol imatinib metoclopramide… (Fachinformation zu Ciclosporin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Cilostazol, Arzneimittelwechselwirkungen)

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

…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. (Fachinformation zu Ciprofloxacin, Warnhinweise und Vorsichtsmaßnahmen)

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). (Fachinformation zu Citalopram, Warnhinweise und Vorsichtsmaßnahmen)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (Fachinformation zu Clindamycin, Arzneimittelwechselwirkungen)

Drugs that affect sinus node function or AV node conduction (e.g., digitalis, calcium channel blockers, beta blockers) Clinical Implication Concomitant use of drugs that affect sinus node function or AV node conduction with clonidine potentiate bradycardia and risk of AV block [see Warnings and Precautions (5.1) ]. (Fachinformation zu Clonidin, Arzneimittelwechselwirkungen)

…concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the antihypertensive action of these drugs. (Fachinformation zu Cyclobenzaprin, Arzneimittelwechselwirkungen)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (Fachinformation zu Darifenacin, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Darunavir, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Darunavir und Cobicistat, Arzneimittelwechselwirkungen)

Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of EMFLAZA ( 7.1 ) (Fachinformation zu Deflazacort, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Desogestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of dexlansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Dexlansoprazol, Arzneimittelwechselwirkungen)

• Antihypertensive Drugs: Monitor blood pressure. (Fachinformation zu Dexmethylphenidat, Arzneimittelwechselwirkungen)

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 ) ]. (Fachinformation zu Diclofenac, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Diclofenac und Misoprostol, Arzneimittelwechselwirkungen)

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),… (Fachinformation zu Dicycloverin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Inhibitors of this isoenzyme (e.g., macrolide antibiotics, azole antifungal agents, protease inhibitors, serotonin reuptake inhibitors, amiodarone, cannabinoids, diltiazem, grapefruit juice, nefazadone, norfloxacin, quinine, zafirlukast) should be cautiously co-administered with dofetilide as they can potentially increase dofetilide levels. (Fachinformation zu Dofetilid, Arzneimittelwechselwirkungen)

Co-administration of PIFELTRO and drugs that are inhibitors of CYP3A may result in increased plasma concentrations of doravirine. (Fachinformation zu Doravirin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (Fachinformation zu Doxazosin, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Dronabinol, Arzneimittelwechselwirkungen)

• Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability. (Fachinformation zu Dronedaron, Arzneimittelwechselwirkungen)

…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,… (Fachinformation zu Droperidol, Warnhinweise)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (Fachinformation zu Drospirenon und Ethinylestradiol, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Duloxetin, Warnhinweise und Vorsichtsmaßnahmen)

Calcium Channel Antagonists Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. (Fachinformation zu Dutasterid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Edoxaban, Arzneimittelwechselwirkungen)

Calcium channel blockers: Diltiazem Others (e.g., felodipine, nicardipine, nifedipine, verapamil) ↓ diltiazem * ↓ desacetyl diltiazem * ↓ N-monodesmethyl diltiazem * ↓ calcium channel blocker Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Fachinformation zu Efavirenz, Arzneimittelwechselwirkungen)

Calcium channel blockers: Diltiazem ↓ diltiazem ↓ desacetyl diltiazem ↓ N-monodesmethyldiltiazem Diltiazem dose adjustments should be guided by clinical response (refer to the full prescribing information for diltiazem). (Fachinformation zu Efavirenz, Lamivudin und Tenofovir, Arzneimittelwechselwirkungen)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (Fachinformation zu Elexacaftor, Tezacaftor und Ivacaftor, Warnhinweise und Vorsichtsmaßnahmen)

Coadministration of GENVOYA with other drugs that inhibit CYP3A may decrease the clearance and increase the plasma concentration of cobicistat. (Fachinformation zu Elvitegravir, Cobicistat, Emtricitabin und Tenofovir, Arzneimittelwechselwirkungen)

Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. (Fachinformation zu Emtricitabin und Tenofovir, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Emtricitabin, Rilpivirin und Tenofovir, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Epoetin alfa, Warnhinweise und Vorsichtsmaßnahmen)

Additional reductions in blood pressure may occur when VELETRI is administered with diuretics, antihypertensive agents, or other vasodilators. (Fachinformation zu Epoprostenol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Eribulin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Erythromycin, Warnhinweise)

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. (Fachinformation zu Estradiol, Arzneimittelwechselwirkungen)

…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,… (Fachinformation zu Estradiol und Dienogest, Arzneimittelwechselwirkungen)

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration. (Fachinformation zu Estradiol und Norethisteron, Arzneimittelwechselwirkungen)

The dose of LUNESTA should be reduced in patients who are administered potent inhibitors of CYP3A4, such as ketoconazole, while taking LUNESTA. (Fachinformation zu Eszopiclon, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Etonogestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

CCR5 antagonists maraviroc ↔ etravirine ↓ maraviroc When Etravirine is co-administered with maraviroc in the absence of a potent CYP3A inhibitor (e.g., ritonavir boosted protease inhibitor), the recommended dose of maraviroc is 600 mg twice daily. (Fachinformation zu Etravirin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Felodipin, Arzneimittelwechselwirkungen)

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 ) ]. (Fachinformation zu Fenoprofen, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Fidaxomicin, Arzneimittelwechselwirkungen)

Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists. (Fachinformation zu Fluconazol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Fluoxetin, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Flurbiprofen, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Fluvoxamin, Warnhinweise und Vorsichtsmaßnahmen)

…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. (Fachinformation zu Foscarnet, Arzneimittelwechselwirkungen)

The thiazide component of fosinopril sodium and hydrochlorothiazide may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic-blocking drugs. (Fachinformation zu Fosinopril und Hydrochlorothiazid, Warnhinweise)

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine… (Fachinformation zu Fosphenytoin, Arzneimittelwechselwirkungen)

Monitor for changes in blood pressure and adjust the dose of other antihypertensive drugs if needed. (Fachinformation zu Furosemid, Arzneimittelwechselwirkungen)

• CYP3A4 Inhibitor: Monitor adverse reactions if concomitant use with IRESSA. (Fachinformation zu Gefitinib, Arzneimittelwechselwirkungen)

Antihypertensives: Possible additive hypotensive effects. (Fachinformation zu Glyceroltrinitrat (Nitroglycerin), Arzneimittelwechselwirkungen)

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. (Fachinformation zu Glycopyrroniumbromid, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Guanfacin, Arzneimittelwechselwirkungen)

The effect of CYP3A4 inhibition and of decreased CYP2D6 enzyme may be additive. (Fachinformation zu Haloperidol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Hydrocortison, Arzneimittelwechselwirkungen)

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 ) ]. (Fachinformation zu Ibuprofen, Arzneimittelwechselwirkungen)

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 )] . (Fachinformation zu Ibuprofen und Famotidin, Arzneimittelwechselwirkungen)

• CYP3A4 Inhibitors: Use in combination with CYP3A4 inhibitors could decrease the effectiveness of ifosfamide. (Fachinformation zu Ifosfamid, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Iloperidon, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Imatinib, Arzneimittelwechselwirkungen)

Drug Interactions Other Antihypertensives: Indapamide may add to or potentiate the action of other antihypertensive drugs. (Fachinformation zu Indapamid, Arzneimittelwechselwirkungen)

Monitor patients to assure diuretic efficacy including antihypertensive effects ( 7 ) (Fachinformation zu Indometacin, Arzneimittelwechselwirkungen)

Calcium Antagonists FORANE may lead to marked hypotension in patients treated with calcium antagonists. (Fachinformation zu Isofluran, Arzneimittelwechselwirkungen)

Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. (Fachinformation zu Isosorbidmononitrat, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Ivacaftor, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Ketoconazol, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Konjugierte Estrogene und Bazedoxifen, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Lacosamid, Warnhinweise und Vorsichtsmaßnahmen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Lansoprazol, Arzneimittelwechselwirkungen)

Antiarrhythmics: amiodarone Effect on amiodarone, ledipasvir, and sofosbuvir concentrations unknown Coadministration of amiodarone with ledipasvir and sofosbuvir may result in serious symptomatic bradycardia. (Fachinformation zu Ledipasvir und Sofosbuvir, Arzneimittelwechselwirkungen)

Clinical Comment Antiarrhythmics: digoxin ↑ digoxin Use with caution and monitor digoxin therapeutic concentration. (Fachinformation zu Lenacapavir, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Levofloxacin, Warnhinweise und Vorsichtsmaßnahmen)

Strong CYP3A4 inhibitors : Maximum recommended dosage is 80 mg once daily ( 7 ). (Fachinformation zu Levomilnacipran, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Levonorgestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

When a diuretic is added to the therapy of a patient receiving lisinopril, an additional antihypertensive effect is usually observed (see DOSAGE AND ADMINISTRATION ). (Fachinformation zu Lisinopril und Hydrochlorothiazid, Arzneimittelwechselwirkungen)

Calcium Channel Blocking Agents (CCB) Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. (Fachinformation zu Lithium, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Loperamid, Warnhinweise)

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… (Fachinformation zu Lumateperon, Warnhinweise und Vorsichtsmaßnahmen)

The action of Mecamylamine HCl may be potentiated by anesthesia, other antihypertensive drugs and alcohol. (Fachinformation zu Mecamylamin, Arzneimittelwechselwirkungen)

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 )] . (Fachinformation zu Mefenaminsäure, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Mefloquin, Arzneimittelwechselwirkungen)

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 ) ]. (Fachinformation zu Meloxicam, Arzneimittelwechselwirkungen)

Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Fachinformation zu Methadon, Arzneimittelwechselwirkungen)

Antihypertensive Drugs: Monitor blood pressure. (Fachinformation zu Methylphenidat, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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

…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,… (Fachinformation zu Mifepriston, Warnhinweise und Vorsichtsmaßnahmen)

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). (Fachinformation zu Mirtazapin, Warnhinweise und Vorsichtsmaßnahmen)

However, a retrospective analysis of the use of antihypertensive medication in these studies showed that a greater proportion of patients on PROVIGIL required new or increased use of antihypertensive medications (2.4%) compared to patients on placebo (0.7%). (Fachinformation zu Modafinil, Warnhinweise und Vorsichtsmaßnahmen)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Fachinformation zu Mometason, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Morphin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Naldemedin, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Naltrexon und Bupropion, Arzneimittelwechselwirkungen)

( 5.3 Hepatotoxicity) Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. (Fachinformation zu Naproxen, Warnhinweise und Vorsichtsmaßnahmen)

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) ]. (Fachinformation zu Naproxen und Esomeprazol, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

…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. (Fachinformation zu Nefazodon, Warnhinweise)

Antiarrhythmics: Amiodarone, disopyramide, lidocaine Plasma concentrations may be decreased. (Fachinformation zu Nevirapin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Nicotinsäure (Niacin), Warnhinweise und Vorsichtsmaßnahmen)

Calcium Channel Blockers Diltiazem: Pre-treatment of healthy volunteers with 30 mg or 90 mg t.i.d. diltiazem p.o. increased the AUC of nifedipine after a single dose of 20 mg nifedipine by factors of 2.2 and 3.1, respectively. (Fachinformation zu Nifedipin, Arzneimittelwechselwirkungen)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (Fachinformation zu Nintedanib, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norelgestromin und Ethinylestradiol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Norethisteron, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (Fachinformation zu Norethisteron und Ethinylestradiol, Arzneimittelwechselwirkungen)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norgestimat und Ethinylestradiol, Arzneimittelwechselwirkungen)

Concomitant administration of CYP3A4 inhibitors such as itraconazole, fluconazole, grapefruit juice or ketoconazole may increase plasma hormone concentrations. (Fachinformation zu Norgestrel und Ethinylestradiol, Arzneimittelwechselwirkungen)

Beta Blocker and Calcium Channel Blockers : dose adjustment of beta blockers or calcium channel blockers may be necessary (‎ 7 ). (Fachinformation zu Octreotid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Ofloxacin, Vorsichtsmaßnahmen)

…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. (Fachinformation zu Olanzapin, Warnhinweise und Vorsichtsmaßnahmen)

…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). (Fachinformation zu Olanzapin und Fluoxetin, Warnhinweise und Vorsichtsmaßnahmen)

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… (Fachinformation zu Oliceridin, Warnhinweise und Vorsichtsmaßnahmen)

• Increased amlodipine exposure when coadministered with CYP3A inhibitors Hydrochlorothiazide ( 7.3 ): • Antidiabetic drugs: Dosage adjustment of antidiabetic may be required. (Fachinformation zu Olmesartan, Amlodipin und Hydrochlorothiazid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Olopatadin und Mometason, Arzneimittelwechselwirkungen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Fachinformation zu Omeprazol, Arzneimittelwechselwirkungen)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Fachinformation zu Omeprazol und Natriumhydrogencarbonat, Arzneimittelwechselwirkungen)

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)] . (Fachinformation zu Oxaliplatin, Warnhinweise und Vorsichtsmaßnahmen)

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) ]. (Fachinformation zu Oxaprozin, Arzneimittelwechselwirkungen)

Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic exposure of oxybutynin. (Fachinformation zu Oxybutynin, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Paliperidon, Warnhinweise und Vorsichtsmaßnahmen)

• Hypertension : Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. (Fachinformation zu Paracetamol und Ibuprofen, Warnhinweise und Vorsichtsmaßnahmen)

Exposure of Paricalcitol Injection will increase upon coadministration with strong CYP3A inhibitors [see Clinical Pharmacology (12.3) ] . (Fachinformation zu Paricalcitol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Pasireotid, Warnhinweise und Vorsichtsmaßnahmen)

Small decreases in blood pressure have been observed in some patients treated with pentoxifylline extended-release tablets; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensive therapy. (Fachinformation zu Pentoxifyllin, Arzneimittelwechselwirkungen)

…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. (Fachinformation zu Phenelzin, Warnhinweise)

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. (Fachinformation zu Phenylephrin, Arzneimittelwechselwirkungen)

Phenytoin when given with the combination of fosamprenavir and ritonavir may increase the concentration of amprenavir Calcium channel blockers Nifedipine, nimodipine, nisoldipine, verapamil Other Albendazole (decreases active metabolite), chlorpropamide, clozapine, cyclosporine, digoxin, disopyramide, folic acid, methadone, mexiletine, praziquantel, quetiapine… (Fachinformation zu Phenytoin, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Pimavanserin, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Pimozid, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Monitor patients to assure diuretic efficacy including antihypertensive effects (7) (Fachinformation zu Piroxicam, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Ponesimod, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Posaconazol, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Prazosin, Warnhinweise)

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. (Fachinformation zu Prednisolon, Arzneimittelwechselwirkungen)

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

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. (Fachinformation zu Primaquin, Arzneimittelwechselwirkungen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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). (Fachinformation zu Quetiapin, Warnhinweise und Vorsichtsmaßnahmen)

The thiazide component of quinapril and hydrochlorothiazide tablets may potentiate the action of other antihypertensive drugs, especially ganglionic or peripheral adrenergic- blocking drugs. (Fachinformation zu Quinapril und Hydrochlorothiazid, Warnhinweise)

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (Fachinformation zu Ramelteon, Arzneimittelwechselwirkungen)

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)]. (Fachinformation zu Ranolazin, Arzneimittelwechselwirkungen)

CYP2C8 and CYP3A4 Inhibitors Intervention: Repaglinide tablets dose reductions and increased frequency of glucose monitoring may be required when co‑administered. (Fachinformation zu Repaglinid, Arzneimittelwechselwirkungen)

Effect of Other Drugs on Rifabutin Pharmacokinetics Some drugs that inhibit CYP3A may significantly increase the plasma concentration of rifabutin. (Fachinformation zu Rifabutin, Arzneimittelwechselwirkungen)

…non-hormonal methods of birth control during rifampin therapy Estrogens Decrease exposure Progestins Anticonvulsants Phenytoin Administered with rifampin 450 mg daily Decrease exposure Antiarrhythmics Disopyramide Decrease exposure Mexiletine Decrease exposure Quinidine Decrease exposure Propafenone Decrease AUC by 50%-67% Tocainide Decrease exposure Antiestrogens… (Fachinformation zu Rifampicin, Arzneimittelwechselwirkungen)

…Antimalarials Quinine Azole Antifungals Fluconazole, itraconazole, ketoconazole Antipsychotics Haloperidol Barbiturates Phenobarbital Benzodiazepines Diazepam Beta-Blockers Propranolol Calcium Channel Blockers Diltiazem, nifedipine, verapamil Cardiac Glycoside Preparations Digoxin Corticosteroids Prednisone Fibrates Clofibrate Oral Hypoglycemics Sulfonylureas (e.g.,… (Fachinformation zu Rifapentin, Arzneimittelwechselwirkungen)

• 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. (Fachinformation zu Rifaximin, Warnhinweise und Vorsichtsmaßnahmen)

Coadministration of EDURANT or EDURANT PED and drugs that inhibit CYP3A may result in increased plasma concentrations of rilpivirine. (Fachinformation zu Rilpivirin, Arzneimittelwechselwirkungen)

Consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or concomitant treatment with antihypertensives or strong CYP and P-gp/BCRP inhibitors [see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ] . (Fachinformation zu Riociguat, Warnhinweise und Vorsichtsmaßnahmen)

Clinically significant hypotension has been observed with concomitant use of oral RISPERDAL and antihypertensive medication. (Fachinformation zu Risperidon, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Roflumilast, Arzneimittelwechselwirkungen)

• Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). (Fachinformation zu Romidepsin, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Ropivacain, Warnhinweise und Vorsichtsmaßnahmen)

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

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Fachinformation zu Saxagliptin, Arzneimittelwechselwirkungen)

Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. (Fachinformation zu Saxagliptin und Metformin, Arzneimittelwechselwirkungen)

Calcium antagonists Sevoflurane may lead to marked hypotension in patients treated with calcium antagonists. (Fachinformation zu Sevofluran, Arzneimittelwechselwirkungen)

Caution is advised when SILDENAFIL ORAL FILM is co-administered with alpha-blockers or antihypertensives. (Fachinformation zu Sildenafil, Warnhinweise und Vorsichtsmaßnahmen)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (Fachinformation zu Sofosbuvir und Velpatasvir, Arzneimittelwechselwirkungen)

Consider temporary or permanent discontinuation for severe or persistent hypertension despite antihypertensive therapy. (Fachinformation zu Sorafenib, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

Thiazides may add to or potentiate the action of other antihypertensive drugs. (Fachinformation zu Spironolacton und Hydrochlorothiazid, Warnhinweise)

Monitor patients to assure diuretic efficacy including antihypertensive effects. (Fachinformation zu Sumatriptan und Naproxen, Arzneimittelwechselwirkungen)

Initiate and/or adjust antihypertensive therapy as appropriate. (Fachinformation zu Sunitinib, Warnhinweise und Vorsichtsmaßnahmen)

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). (Fachinformation zu Suvorexant, Arzneimittelwechselwirkungen)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (Fachinformation zu Tacrolimus, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Telmisartan und Amlodipin, Arzneimittelwechselwirkungen)

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

Risk of Hypotension with Concomitant Use of Other Antihypertensive Agents and Phospodiesterase Type 5 Inhibitors (PDE5-I): Concomitant administration of TEZRULY with antihypertensives or phosphodiesterase-5 (PDE-5) inhibitors can result in additive blood pressure lowering effects and symptomatic hypotension (5.3). (Fachinformation zu Terazosin, Warnhinweise und Vorsichtsmaßnahmen)

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 )] . (Fachinformation zu Testosteron, Warnhinweise und Vorsichtsmaßnahmen)

…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 )]. (Fachinformation zu Tetrabenazin, Warnhinweise und Vorsichtsmaßnahmen)

Concomitant use of diltiazem with beta-blockers or digitalis may result in additive effects on cardiac conduction. (Fachinformation zu Diltiazem, Warnhinweise und Vorsichtsmaßnahmen)

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. (Fachinformation zu Tinidazol, Arzneimittelwechselwirkungen)

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… (Fachinformation zu Tofacitinib, Arzneimittelwechselwirkungen)

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 ). (Fachinformation zu Tolterodin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Triamcinolon, Arzneimittelwechselwirkungen)

Thiazides may add to or potentiate the action of other antihypertensive drugs. (Fachinformation zu Triamteren und Hydrochlorothiazid, Arzneimittelwechselwirkungen)

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) ] . (Fachinformation zu Ulipristal, Arzneimittelwechselwirkungen)

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,… (Fachinformation zu Umeclidiniumbromid und Vilanterol, Warnhinweise und Vorsichtsmaßnahmen)

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 )] . (Fachinformation zu Valbenazin, Warnhinweise und Vorsichtsmaßnahmen)

Metoprolol: Possibly reduced blood-pressure lowering effect despite increased metoprolol plasma levels. (Fachinformation zu Venlafaxin, Arzneimittelwechselwirkungen)

CYP3A4 Inhibitors: The VIIBRYD dose should not exceed 20 mg once daily when co-administered with strong CYP3A4 inhibitors ( 2.4 , 7 ). (Fachinformation zu Vilazodon, Arzneimittelwechselwirkungen)

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) ]. (Fachinformation zu Viloxazin, Arzneimittelwechselwirkungen)

Inhibitors of CYP3A4: May cause earlier onset and/or increased severity of adverse reactions ( 7.1 ) (Fachinformation zu Vinorelbin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Voriconazol, Arzneimittelwechselwirkungen)

…amiodarone, amlodipine, amprenavir, aprepitant, atorvastatin, atazanavir, bicalutamide, cilostazol, cimetidine, ciprofloxacin, clarithromycin, conivaptan, cyclosporine, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fluoxetine, fluvoxamine, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir,… (Fachinformation zu Warfarin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Zafirlukast, Vorsichtsmaßnahmen)

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. (Fachinformation zu Zaleplon, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Ziprasidon, Warnhinweise und Vorsichtsmaßnahmen)

CYP3A4 Inhibitors Ketoconazole Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. (Fachinformation zu Zolpidem, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Adenosin, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Amitriptylin, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Amoxapin, Arzneimittelwechselwirkungen)

In such cases, butorphanol should be discontinued and the hypertension treated with antihypertensive drugs. (Fachinformation zu Butorphanol, Warnhinweise)

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Candesartan und Hydrochlorothiazid, Warnhinweise)

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Captopril, Warnhinweise)

Chlorpromazine may counteract the antihypertensive effect of guanethidine and related compounds. (Fachinformation zu Chlorpromazin, Warnhinweise)

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). (Fachinformation zu Clomipramin, Arzneimittelwechselwirkungen)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (Fachinformation zu Dapagliflozin, Arzneimittelwechselwirkungen)

This drug is capable of blocking the antihypertensive effect of guanethidine and similarly acting compounds. (Fachinformation zu Desipramin, Warnhinweise)

Antihypertensives Amphetamines may antagonize the hypotensive effects of antihypertensives. (Fachinformation zu Dexamfetamin, Arzneimittelwechselwirkungen)

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

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Enalapril und Hydrochlorothiazid, Warnhinweise)

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. (Fachinformation zu Ephedrin, Arzneimittelwechselwirkungen)

Drug Interactions ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (Fachinformation zu Etodolac, Arzneimittelwechselwirkungen)

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (Fachinformation zu Famciclovir, Arzneimittelwechselwirkungen)

…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… (Fachinformation zu Finasterid, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Fingolimod, Arzneimittelwechselwirkungen)

There has been too little experience with the coadministration of flecainide acetate with nifedipine or diltiazem to recommend concomitant use. (Fachinformation zu Flecainid, Arzneimittelwechselwirkungen)

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Fosinopril, Warnhinweise)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Fachinformation zu Glibenclamid und Metformin, Arzneimittelwechselwirkungen)

When other potent parenteral antihypertensive drugs, such as diazoxide, are used in combination with hydralazine, patients should be continuously observed for several hours for any excessive fall in blood pressure. (Fachinformation zu Hydralazin, Arzneimittelwechselwirkungen)

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);… (Fachinformation zu Hydroxyzin, Vorsichtsmaßnahmen)

WARNINGS Proarrhythmia: Like other antiarrhythmic agents, CORVERT Injection can induce or worsen ventricular arrhythmias in some patients. (Fachinformation zu Ibutilid, Warnhinweise)

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. (Fachinformation zu Icatibant, Arzneimittelwechselwirkungen)

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). (Fachinformation zu Imipramin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Isradipin, Arzneimittelwechselwirkungen)

ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (Fachinformation zu Ketoprofen, Warnhinweise und Vorsichtsmaßnahmen)

Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors and/or angiotensin II receptor antagonists. (Fachinformation zu Ketorolac, Arzneimittelwechselwirkungen)

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 )] . (Fachinformation zu Lamotrigin, Warnhinweise und Vorsichtsmaßnahmen)

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 . (Fachinformation zu Memantin und Donepezil, Arzneimittelwechselwirkungen)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Fachinformation zu Metformin, Arzneimittelwechselwirkungen)

Drug Interactions When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may occur. (Fachinformation zu Methyldopa, Arzneimittelwechselwirkungen)

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Moexipril, Warnhinweise)

Drug Interactions: ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (Fachinformation zu Nabumeton, Arzneimittelwechselwirkungen)

Hypertensive patients, and patients concomitantly receiving other antihypertensive medications, may be more sensitive to the effects of sodium nitroprusside than normal subjects. (Fachinformation zu Nitroprussidnatrium, Warnhinweise)

The antihypertensive action of guanethidine and similar agents may be blocked. (Fachinformation zu Nortriptylin, Warnhinweise)

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

Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine. (Fachinformation zu Pimecrolimus, Arzneimittelwechselwirkungen)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Fachinformation zu Pioglitazon und Metformin, Arzneimittelwechselwirkungen)

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. (Fachinformation zu Prochlorperazin, Vorsichtsmaßnahmen)

Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds. (Fachinformation zu Protriptylin, Warnhinweise)

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

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Quinapril, Warnhinweise)

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. (Fachinformation zu Ritlecitinib, Arzneimittelwechselwirkungen)

DRUG INTERACTIONS ACE-inhibitors Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (Fachinformation zu Salsalat, Arzneimittelwechselwirkungen)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Fachinformation zu Sitagliptin und Metformin, Arzneimittelwechselwirkungen)

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

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. (Fachinformation zu Terbinafin, Arzneimittelwechselwirkungen)

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. (Fachinformation zu Tizanidin, Arzneimittelwechselwirkungen)

DRUG INTERACTIONS ACE Inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE Inhibitors. (Fachinformation zu Tolmetin, Arzneimittelwechselwirkungen)

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. (Fachinformation zu Trandolapril, Warnhinweise)

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concurrently. (Fachinformation zu Trifluoperazin, Vorsichtsmaßnahmen)

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). (Fachinformation zu Trimipramin, Arzneimittelwechselwirkungen)

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

…systemic and inhaled amoxicillin ampicillin, with or without sulbactam atenolol azithromycin caffeine, dietary ingestion cefaclor co-trimoxazole (trimethoprim and sulfamethoxazole) diltiazem dirithromycin enflurane famotidine felodipine finasteride hydrocortisone isoflurane isoniazid isradipine influenza vaccine ketoconazole lomefloxacin mebendazole medroxyprogesterone… (Fachinformation zu Aminophyllin, Arzneimittelwechselwirkungen)

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) .]… (Fachinformation zu Desloratadin, Arzneimittelwechselwirkungen)

…metronidazole atenolol metoprolol azithromycin nadolol caffeine, dietary ingestion nifedipine cefaclor nizatidine co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin ofloxacin diltiazem omeprazole dirithromycin prednisone, prednisolone enflurane ranitidine famotidine rifabutin felodipine roxithromycin finasteride Sorbitol (purgative doses do not inhibit hydrocortisone… (Fachinformation zu Theophyllin, Arzneimittelwechselwirkungen)