Diltiazem interactions

…(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… (Alfuzosin label, Contraindications)

• 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) ] . (Alprazolam label, Contraindications)

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. (Amiodarone label, Warnings and precautions)

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) ] . (Apixaban label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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). (Asenapine label, Warnings and precautions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

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

Concomitant administration of BIXLENVO with combined P-gp, UGT1A1, and strong CYP3A inhibitors is not recommended. (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Evaluate patients starting CYP3A4 inhibitors or stopping CYP3A4 inducers at frequent intervals for respiratory depression. (Buprenorphine label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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 ) (Clarithromycin label, Warnings and precautions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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 )]. (Clozapine label, Boxed warning)

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. (Codeine label, Boxed warning)

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) ] . (Colchicine label, Contraindications)

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) ] . (Dabigatran label, Warnings and precautions)

The concomitant use of RYANODEX and calcium channel blockers is not recommended during the treatment of malignant hyperthermia. (Dantrolene label, Drug interactions)

Strong CYP3A4 inhibitors: Avoid concomitant use. (Daridorexant label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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. (Dihydroergotamine label, Boxed warning)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

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) ]. (Dutasteride and tamsulosin label, Warnings and precautions)

• 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) ]. (Eletriptan label, Contraindications)

…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)… (Eplerenone label, Contraindications)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

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

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) ]. (Fesoterodine label, Drug interactions)

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) ] . (Flibanserin label, Boxed warning)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Fluticasone label, Drug interactions)

Avoid strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): May increase risk of systemic corticosteroid and cardiovascular effects. (Fluticasone and salmeterol label, Drug interactions)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

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 )] . (Fosfomycin label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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. (Hydrocodone and acetaminophen label, Boxed warning)

Antiarrhythmics Disopyramide Dofetilide Dronedarone Quinidine Contraindicated during and 2 weeks after TOLSURA treatment. (Itraconazole label, Drug interactions)

• Ivabradine: Avoid concomitant use. (Diltiazem label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

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

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions ( 7.1 )]. (Lurasidone label, Contraindications)

Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . (Macitentan label, Drug interactions)

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. (Meperidine label, Boxed warning)

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. (Metolazone label, Warnings)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

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

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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 )]. (Moxifloxacin label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

…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… (Nirmatrelvir and ritonavir label, Contraindications)

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. (Nisoldipine label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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. (Oxycodone label, Boxed warning)

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. (Oxycodone and acetaminophen label, Boxed warning)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• 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. (Propafenone label, Boxed warning)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

• Strong CYP3A4 Inhibitors: Avoid concomitant administration. (Rimegepant label, Drug interactions)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

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) ] . (Rivaroxaban label, Warnings and precautions)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

• Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. (Salmeterol label, Drug interactions)

• Statins: Avoid statins metabolized by CYP3A4. (Diltiazem label, Drug interactions)

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

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 )] . (Solifenacin label, Drug interactions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

…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 ),… (Tadalafil label, Warnings and precautions)

• Should not be used in combination with strong inhibitors of CYP3A4. (Tamsulosin label, Warnings and precautions)

• Concomitant administration with IV beta-blockers. (Diltiazem label, Contraindications)

Coadministration of diltiazem with rifampin or any known CYP3A4 inducer should be avoided when possible, and alternative therapy considered [see Clinical Pharmacology (12.3)]. a Strong and moderate inhibitors increase the AUC of sensitive substrates of CYP3A4 by ≥ 5 and ≥ 2-fold, respectively b These examples are a guide and not considered a comprehensive list… (Diltiazem label, Drug interactions)

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex. (Tramadol label, Boxed warning)

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… (Trazodone label, Warnings and precautions)

• Strong CYP3A Inhibitors and Inducers: Avoid coadministration with strong CYP3A inhibitors and inducers. (Tretinoin label, Drug interactions)

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) ] . (Triazolam label, Warnings and precautions)

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. (Ubrogepant label, Contraindications)

For patients with atopic dermatitis, coadministration of RINVOQ 30 mg once daily with strong CYP3A4 inhibitors is not recommended. (Upadacitinib label, Drug interactions)

QT Prolongation : Patients with congenital QT syndrome or taking class IA or III antiarrhythmics should avoid using vardenafil hydrochloride tablets. (Vardenafil label, Warnings and precautions)

CYP3A4 inhibitors: Use with caution in combination due to increased exposure of alosetron. (Alosetron label, Drug interactions)

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. (Amlodipine label, Drug interactions)

CYP3A4 Inhibitors : Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. (Amlodipine and benazepril label, Drug interactions)

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 ) (Aripiprazole label, Drug interactions)

Antihypertensive Drugs Prevention or Management Increase the frequency of monitoring blood pressure and adjust atomoxetine oral solution dosage as clinically appropriate. (Atomoxetine label, Drug interactions)

…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. (Azithromycin label, Warnings and precautions)

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… (Brexpiprazole label, Warnings and precautions)

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. (Brimonidine label, Drug interactions)

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… (Budesonide label, Warnings and precautions)

Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. (Budesonide and formoterol label, Warnings and precautions)

Antihypertensives Bumetanide may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs. (Bumetanide label, Drug interactions)

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. (Buprenorphine and naloxone label, Drug interactions)

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). (Bupropion label, Drug interactions)

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… (Buspirone label, Drug interactions)

Antihypertensive drugs: May cause symptomatic postural hypotension. (Carbidopa and levodopa label, Drug interactions)

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… (Cariprazine label, Warnings and precautions)

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) ]. (Celecoxib label, Drug interactions)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

Effect of chlorthalidone on other drugs Chlorthalidone may add to or potentiate the action of other antihypertensive drugs. (Chlorthalidone label, Drug interactions)

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. (Cilostazol label, Drug interactions)

Strong or moderate CYP 3A inhibitors a Examples b : Ketoconazole, itraconazole, cimetidine Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with strong or moderate inhibitors of CYP3A4. (Diltiazem label, Drug interactions)

…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. (Ciprofloxacin label, Warnings and precautions)

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). (Citalopram label, Warnings and precautions)

Inhibitors of CYP3A4 and CYP3A5 Inhibitors of CYP3A4 and/or CYP3A5 may increase plasma concentrations of clindamycin [ see Clinical Pharmacology (12.3) ]. (Clindamycin label, Drug interactions)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

Clonidine Increased risk of bradycardia. (Diltiazem label, Drug interactions)

…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. (Cyclobenzaprine label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

CYP3A4 Inhibitors The systemic exposure of darifenacin from darifenacin extended-release tablets is increased in the presence of CYP3A4 inhibitors. (Darifenacin label, Drug interactions)

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

• Antihypertensive Drugs: Monitor blood pressure. (Dexmethylphenidate label, Drug interactions)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

Intervention: During concomitant use of Diclofenac Potassium 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) ] . (Diclofenac label, Drug interactions)

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),… (Dicyclomine label, Drug interactions)

Carvedilol 16% 14% Conivaptan 33% 43% Diltiazem 20% NA Indomethacin 40% NA Mirabegron 29% 27% Nefazodone 27% 15% Nifedipine 45% NA Propantheline 24% 24% Quinine NA 33% Rabeprazole 29% 19% Saquinavir 27% 49% Spironolactone 25% NA Telmisartan 20 to 49% NA Ticagrelor 31% 28% Tolvaptan 30% 20% Trimethoprim 22 to 28% NA Digoxin Concentrations Increased, but Magnitude… (Digoxin label, Drug interactions)

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. (Dofetilide label, Drug interactions)

Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. (Doxazosin label, Drug interactions)

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). (Dronabinol label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

Consider monitoring serum potassium concentration in high-risk patients who take a strong CYP3A4 inhibitor long-term and concomitantly. (Drospirenone and ethinyl estradiol label, Warnings and precautions)

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 Warnings and Precautions ( 5.12 ) and Drug Interactions ( 7.1 )] and in patients taking CYMBALTA at doses above 60 mg daily. (Duloxetine label, Warnings and precautions)

Calcium Channel Antagonists Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. (Dutasteride label, Drug interactions)

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. (Edoxaban label, Drug interactions)

Concomitant Use with CYP3A Inhibitors Exposure to elexacaftor, tezacaftor and ivacaftor are increased when used concomitantly with strong or moderate CYP3A inhibitors. (Elexacaftor, tezacaftor, and ivacaftor label, Warnings and precautions)

Coadministration of DESCOVY with other drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentration of TAF. (Emtricitabine and tenofovir label, Drug interactions)

Epinephrine may antagonize the neuronal blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter. (Epinephrine label, Drug interactions)

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. (Epoetin alfa label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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. (Estradiol label, Drug interactions)

The dose of LUNESTA should be reduced in patients who are administered potent inhibitors of CYP3A4, such as ketoconazole, while taking LUNESTA. (Eszopiclone label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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. (Felodipine label, Drug interactions)

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. (Fidaxomicin label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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. (Fluoxetine label, Drug interactions)

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. (Fluvoxamine label, Warnings and precautions)

Monitor for changes in blood pressure and adjust the dose of other antihypertensive drugs if needed. (Furosemide label, Drug interactions)

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

…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… (Guanfacine label, Drug interactions)

Orthostatic vital signs should be monitored in patients who are at risk for hypotension (e.g., geriatric patients, patients with dehydration, hypovolemia, and concomitantly treated with antihypertensive medications), patients with known cardiovascular disease (history of myocardial infarction, ischemic heart disease, heart failure, or conduction abnormalities), and… (Haloperidol label, Warnings and precautions)

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. (Hydrocortisone label, Drug interactions)

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 ) ]. (Ibuprofen label, Drug interactions)

…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… (Iloperidone label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

Drug Interactions Other Antihypertensives: Indapamide may add to or potentiate the action of other antihypertensive drugs. (Indapamide label, Drug interactions)

Monitor patients to assure diuretic efficacy including antihypertensive effects ( 7 ) (Indomethacin label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. (Isosorbide mononitrate label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

Strong or moderate CYP 3A inhibitors a Examples b : Ketoconazole, itraconazole, cimetidine Patients currently receiving diltiazem therapy should be carefully monitored for a change in pharmacological effect when initiating and discontinuing therapy with strong or moderate inhibitors of CYP3A4. (Diltiazem label, Drug interactions)

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) ] . (Lacosamide label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of lansoprazole is expected when used concomitantly with strong inhibitors [see Clinical Pharmacology (12.3) ] . (Lansoprazole label, Drug interactions)

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. (Levofloxacin label, Warnings and precautions)

Strong CYP3A4 inhibitors : Maximum recommended dosage is 80 mg once daily ( 7 ). (Levomilnacipran label, Drug interactions)

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. (Levonorgestrel and ethinyl estradiol label, Drug interactions)

When a diuretic is added to the therapy of a patient receiving lisinopril, an additional antihypertensive effect is usually observed (see DOSAGE AND ADMINISTRATION ). (Lisinopril and hydrochlorothiazide label, Drug interactions)

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. (Lithium label, Drug interactions)

…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… (Loperamide label, Warnings)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

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… (Lumateperone label, Warnings and precautions)

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 ) ]. (Meloxicam label, Drug interactions)

Examples: Drugs known to have potential to prolong QT interval: Class I and III antiarrhythmics, some neuroleptics and tricyclic antidepressants, and calcium channel blockers. (Methadone label, Drug interactions)

Antihypertensive Drugs: Monitor blood pressure. (Methylphenidate label, Drug interactions)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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). (Mirtazapine label, Warnings and precautions)

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

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. (Morphine label, Drug interactions)

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… (Naldemedine label, Drug interactions)

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). (Naltrexone and bupropion label, Drug interactions)

( 5.3 Hepatotoxicity) Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. (Naproxen label, Warnings and precautions)

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. (Niacin label, Warnings and precautions)

CYP3A inhibitors such as fluconazole, itraconazole, clarithromycin, erythromycin, nefazodone, fluoxetine, saquinavir, indinavir, and nelfinavir may result in increased exposure to nifedipine when co-administered. (Nifedipine label, Drug interactions)

Coadministration of P-gp and CYP3A4 inhibitors may increase nintedanib exposure. (Nintedanib label, Drug interactions)

Antihypertensives: Possible additive hypotensive effects. (Nitroglycerin label, Drug interactions)

CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. (Norethindrone and ethinyl estradiol label, Drug interactions)

CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. (Norgestimate and ethinyl estradiol label, Drug interactions)

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. (Ofloxacin label, Precautions)

…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. (Olanzapine label, Warnings and precautions)

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… (Oliceridine label, Warnings and precautions)

CYP2C19 or CYP3A4 Inhibitors Clinical Impact: Increased exposure of omeprazole [see Clinical Pharmacology ( 12.3 )] . (Omeprazole label, Drug interactions)

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

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

…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… (Paliperidone label, Warnings and precautions)

Use caution with concomitant use of BRISDELLE with other drugs that are metabolized by CYP2D6, including nortriptyline, amitriptyline, imipramine, desipramine, fluoxetine, phenothiazines, risperidone, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide). (Paroxetine label, Drug interactions)

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. (Pentoxifylline label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

…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. (Phenelzine label, Warnings)

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. (Phenylephrine label, Drug interactions)

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… (Pimavanserin label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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. (Prazosin label, Warnings)

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. (Prednisolone label, Drug interactions)

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. (Prednisone label, Drug interactions)

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). (Quetiapine label, Warnings and precautions)

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (Ramelteon label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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

• 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. (Rifaximin label, Warnings and precautions)

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) ] . (Riociguat label, Warnings and precautions)

Clinically significant hypotension has been observed with concomitant use of oral RISPERDAL and antihypertensive medication. (Risperidone label, Warnings and precautions)

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. (Roflumilast label, Drug interactions)

Caution is advised when SILDENAFIL ORAL FILM is co-administered with alpha-blockers or antihypertensives. (Sildenafil label, Warnings and precautions)

Antiarrhythmics: amiodarone Effect on amiodarone, sofosbuvir, velpatasvir, and voxilaprevir concentrations unknown Coadministration of amiodarone with VOSEVI may result in serious symptomatic bradycardia. (Sofosbuvir and velpatasvir label, Drug interactions)

Thiazides may add to or potentiate the action of other antihypertensive drugs. (Spironolactone and hydrochlorothiazide label, Warnings)

Monitor patients to assure diuretic efficacy including antihypertensive effects. (Sumatriptan and naproxen label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

• Hypertension: May require antihypertensive therapy; monitor relevant drug interactions. (Tacrolimus label, Warnings and precautions)

Benzodiazepines Increased exposure likely. (Diltiazem label, Drug interactions)

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). (Terazosin label, Warnings and precautions)

In patients with hypertension on antihypertensive therapy, KYZATREX® increased the mean systolic/diastolic BP by 3.4/0.7 mm Hg from baseline after 4 months of treatment and 3.1/1.0 mm Hg from baseline after 6 months of treatment. [see Adverse Reactions (6.1) ]. (Testosterone label, Warnings and precautions)

…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 )]. (Tetrabenazine label, Warnings and precautions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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. (Tinidazole label, Drug interactions)

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… (Tofacitinib label, Drug interactions)

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 ). (Tolterodine label, Drug interactions)

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. (Triamcinolone label, Drug interactions)

Thiazides may add to or potentiate the action of other antihypertensive drugs. (Triamterene and hydrochlorothiazide label, Drug interactions)

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,… (Umeclidinium and vilanterol label, Warnings and precautions)

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 )] . (Valbenazine label, Warnings and precautions)

Metoprolol: Possibly reduced blood-pressure lowering effect despite increased metoprolol plasma levels. (Venlafaxine label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

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

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) ]. (Viloxazine label, Drug interactions)

Effect of other drugs on Diltiazem Cytochrome P450 3A4 Inhibitors/ Inducers Diltiazem is a substrate of the cytochrome P450 3A4 enzyme and inhibitors/inducers may change the pharmacological effect of diltiazem Monitor. (Diltiazem label, Drug interactions)

…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,… (Warfarin label, Drug interactions)

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. (Zafirlukast label, Precautions)

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. (Zaleplon label, Drug interactions)

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). (Ziprasidone label, Warnings and precautions)

CYP3A4 Inhibitors Ketoconazole Ketoconazole, a potent CYP3A4 inhibitor, increased the exposure to and pharmacodynamic effects of zolpidem. (Zolpidem label, Drug interactions)

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). (Amitriptyline label, Drug interactions)

In such cases, butorphanol should be discontinued and the hypertension treated with antihypertensive drugs. (Butorphanol label, Warnings)

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. (Captopril label, Warnings)

Chlorpromazine may counteract the antihypertensive effect of guanethidine and related compounds. (Chlorpromazine label, Warnings)

Dapagliflozin or dapagliflozin 3-O-glucuronide did not meaningfully inhibit P-gp, OCT2, OAT1, or OAT3 active transporters. (Dapagliflozin label, Drug interactions)

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

An in vitro study using human liver microsomes suggests that famciclovir is not an inhibitor of CYP3A4 enzymes. (Famciclovir label, Drug interactions)

…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… (Finasteride label, Drug interactions)

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. (Fingolimod label, Drug interactions)

There has been too little experience with the coadministration of flecainide acetate with nifedipine or diltiazem to recommend concomitant use. (Flecainide label, Drug interactions)

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. (Fosinopril label, Warnings)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Glyburide and metformin label, Drug interactions)

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. (Hydralazine label, Drug interactions)

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);… (Hydroxyzine label, Precautions)

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. (Isradipine label, Drug interactions)

Anesthetics Depressed cardiac contractility, conductivity, and automaticity as well as the vascular dilation. (Diltiazem label, Drug interactions)

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

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 )] . (Lamotrigine label, Warnings and precautions)

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

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

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. (Moexipril label, Warnings)

Drug Interactions: ACE-inhibitors: Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. (Nabumetone label, Drug interactions)

The antihypertensive action of guanethidine and similar agents may be blocked. (Nortriptyline label, Warnings)

Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine. (Pimecrolimus label, Drug interactions)

These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Pioglitazone and metformin label, Drug interactions)

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly. (Prochlorperazine label, Precautions)

Anesthetics Depressed cardiac contractility, conductivity, and automaticity as well as the vascular dilation. (Diltiazem label, Drug interactions)

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

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. (Quinapril label, Warnings)

Examples: Thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blockers, and isoniazid. (Sitagliptin and metformin label, Drug interactions)

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. (Terbinafine label, Drug interactions)

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. (Tizanidine label, Drug interactions)

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. (Trandolapril label, Warnings)

…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… (Theophylline label, Drug interactions)