trandolapril/verapamil (Rx)

Brand and Other Names:Tarka

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

trandolapril/verapamil

tablet

  • 2mg/180mg
  • 1mg/240mg
  • 2mg/240mg
  • 4mg/240mg

Combines an immediate-release formulation of an angiotensin converting enzyme inhibitor, trandolapril and a slow-release formulation of a calcium channel blocker, verapamil hydrochloride

Hypertension

Not indicated for initial therapy

Usual dose: Trandolapril 1- 4 mg/verapamil HCl ER 180-240 mg PO qDay

For convenience, patients receiving trandolapril (up to 8 mg) and verapamil (up to 240 mg) in separate tablets, administered qDay, may instead receive tablets of combination containing the same component doses

Clinical trials with combination have explored only qDay dosing

Dosage Modifications

Renal or hepatic impairment: This combination product has not been studied in patients with renal or hepatic impairment

<18 years: Safety and efficacy not established

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Interactions

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            Contraindicated (8)

            • aliskiren

              trandolapril, aliskiren. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Aliskiren use contraindicated with ACEIs in patients with diabetes; avoid coadministration with ACEIs if GFR <60 mL/min; dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

              trandolapril decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ACE-inhibitors in patients with diabetes; avoid coadministration with ACE-inhibitors if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ACE-inhibitors with drugs that affect RAAS may increase the risk of renal impairment (including acute renal failure) and cause loss of antihypertensive effect. Monitor renal function periodically.

            • dantrolene

              dantrolene, verapamil. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Contraindicated. Rare incidence of cardiovascular collapse and marked hyperkalemia observed when coadministered; may be higher risk with nondihydropyridine calcium channel blockers.

            • fezolinetant

              verapamil will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

            • flibanserin

              verapamil will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Coadministration of flibanserin with moderate or strong CYP3A4 inhibitors is contraindicated. Severe hypotension or syncope can occur.

            • lomitapide

              verapamil increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Increases lomitapide levels several folds.

            • lonafarnib

              verapamil will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lonafarnib is a sensitive CYP3A4 substrate. Coadministration with strong or moderate CYP3A4 inhibitors is contraindicated.

            • pimozide

              verapamil increases levels of pimozide by decreasing metabolism. Contraindicated. Risk of QT interval prolongation.

            • protein a column

              trandolapril, protein a column. Other (see comment). Contraindicated. Comment: Risk of anaphylactic reaction. Mechanism: buildup of bradykinin d/t deactivation of kininase by ACE inhibitors. D/C ACE inhibitor 72h prior to use of protein A column.

            Serious - Use Alternative (136)

            • abametapir

              abametapir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • afatinib

              verapamil increases levels of afatinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Reduce afatinib daily dose by 10 mg if not tolerated when coadministered with P-gp inhibitors.

            • alosetron

              verapamil will increase the level or effect of alosetron by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • apalutamide

              apalutamide will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • aspirin

              aspirin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • aspirin rectal

              aspirin rectal, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • atenolol

              verapamil, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • avapritinib

              verapamil will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of avapritinib with strong CYP3A4 inhibitors.

            • axitinib

              verapamil increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unable to avoid coadministration with moderate CYP3A4 inhibitors, monitor closely and reduce dose if necessary .

            • azilsartan

              azilsartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • betaxolol

              verapamil, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • bisoprolol

              verapamil, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • bosutinib

              verapamil increases levels of bosutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil increases levels of bosutinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • candesartan

              candesartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • carbamazepine

              carbamazepine will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • celecoxib

              celecoxib, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ceritinib

              ceritinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • choline magnesium trisalicylate

              choline magnesium trisalicylate, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • cimetidine

              cimetidine will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • cobimetinib

              verapamil will increase the level or effect of cobimetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concurrent short term (14 days or less) use of moderate CYP3A inhibitors is unavoidable for patients who are taking cobimetinib 60 mg, reduce the cobimetinib dose to 20 mg. After discontinuation of a moderate CYP3A inhibitor, resume cobimetinib 60 mg. Use an alternative to a moderate CYP3A inhibitor in patients who are taking a reduced dose of cobimetinib (40 or 20 mg daily).

            • colchicine

              verapamil will increase the level or effect of colchicine by Other (see comment). Avoid or Use Alternate Drug. Colchicine is a P-gp and CYP3A4 substrate. Avoid use with drugs that are both P-gp and strong CYP3A4 inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with strong CYP3A4 inhibitors is contraindicated in patients with renal or hepatic impairment.

            • cyclobenzaprine

              verapamil and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dalteparin

              dalteparin increases toxicity of trandolapril by Other (see comment). Avoid or Use Alternate Drug. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • diclofenac

              diclofenac, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • diflunisal

              diflunisal, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • digoxin

              verapamil increases levels of digoxin by decreasing renal clearance. Avoid or Use Alternate Drug.

            • dihydroergotamine

              verapamil will increase the level or effect of dihydroergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dihydroergotamine intranasal

              verapamil will increase the level or effect of dihydroergotamine intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • dronedarone

              verapamil will increase the level or effect of dronedarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • duloxetine

              verapamil will increase the level or effect of duloxetine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • edoxaban

              verapamil will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Dose adjustment may be required with strong P-gp inhibitors. DVT/PE treatment: Decrease dose to 30 mg PO once daily. NVAF: No dose reduction recommended

            • elacestrant

              verapamil will increase the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • eliglustat

              verapamil increases levels of eliglustat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Moderate CYP3A4 inhibitors are not recommended with eliglustat poor or intermediate metabolizers; reduce eliglustat dose from 84 mg BID to 84 mg once daily in extensive metabolizers .

            • encorafenib

              verapamil will increase the level or effect of encorafenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If concomitant use of a moderate CYP3A4 inhibitor is unavoidable, reduce encorafenib dose to one-half of the dose (eg, reduce from 450 mg/day to 225 mg/day). After discontinuing the inhibitor for 3-5 elimination half-lives, resume previous encorafenib dose.

            • entrectinib

              verapamil will increase the level or effect of entrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of moderate CYP3A4 inhibitors with entrectinib, a CYP3A4 substrate. If coadministration unavoidable, reduce dose to 200 mg/day for patients aged 12 y or older with BSA >1.50m2. Resume previous entrectinib dose after discontinuing moderate CYP3A inhibitor for 3-5 elimination half-lives.

            • eprosartan

              eprosartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • erdafitinib

              erdafitinib will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.

            • ergotamine

              verapamil will increase the level or effect of ergotamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin base

              erythromycin base will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil will increase the level or effect of erythromycin base by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil will increase the level or effect of erythromycin ethylsuccinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil will increase the level or effect of erythromycin lactobionate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil will increase the level or effect of erythromycin stearate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • esmolol

              verapamil, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • etodolac

              etodolac, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • everolimus

              verapamil will increase the level or effect of everolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use of a moderate 3A4 inhibitor such as verapamil may significantly increase the plasma concentrations of everolimus following oral administration.

              verapamil will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Everolimus prescribing information lists indication-specific dosing recommendations.

              verapamil, everolimus. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: With concomitant use of mTOR inhibitors, consider appropriate dose reductions of both medications.

            • fenoprofen

              fenoprofen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • fentanyl

              verapamil will increase the level or effect of fentanyl by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl intranasal

              verapamil will increase the level or effect of fentanyl intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transdermal

              verapamil will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fentanyl transmucosal

              verapamil will increase the level or effect of fentanyl transmucosal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

            • fexinidazole

              fexinidazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • flurbiprofen

              flurbiprofen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ibrutinib

              verapamil increases levels of ibrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of ibrutinib and strong CYP3A4 inhibitors. If a strong CYP3A4 inhibitor must be used short-term (eg, anti-infectives for =7 days), interrupt ibrutinib therapy until strong CYP3A4 inhibitor is discontinued.

            • ibuprofen

              ibuprofen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ibuprofen IV

              ibuprofen IV, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • idelalisib

              idelalisib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

            • indomethacin

              indomethacin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • infigratinib

              verapamil will increase the level or effect of infigratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irbesartan

              irbesartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • irinotecan

              verapamil will increase the level or effect of irinotecan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • irinotecan liposomal

              verapamil will increase the level or effect of irinotecan liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • itraconazole

              itraconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Observe the patient for development of toxicity associated with verapamil (peripheral edema, dizziness, hypotension, flushing, headache). Consider reducing the dose of verapamil or withdrawing one of the agents.

            • ivabradine

              verapamil will increase the level or effect of ivabradine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of ivabradine with moderate CYP3A4 inhibitors.

            • ivosidenib

              ivosidenib will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • ketoprofen

              ketoprofen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ketorolac

              ketorolac, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ketorolac intranasal

              ketorolac intranasal, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • larotrectinib

              verapamil will increase the level or effect of larotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • lasmiditan

              lasmiditan increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lemborexant

              verapamil will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lemborexant with moderate or strong CYP3A inhibitors.

            • levobunolol

              verapamil, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • lofexidine

              lofexidine, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              lofexidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

            • lopinavir

              lopinavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • losartan

              losartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • lovastatin

              verapamil will increase the level or effect of lovastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed 20 mg of lovastatin

            • lurbinectedin

              verapamil will increase the level or effect of lurbinectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • mavacamten

              verapamil, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • meclofenamate

              meclofenamate, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • mefenamic acid

              mefenamic acid, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • meloxicam

              meloxicam, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • metoprolol

              verapamil, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • midazolam intranasal

              verapamil will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of moderate CYP3A4 inhibitors with midazolam intranasal causes higher midazolam systemic exposure, which may prolong sedation.

            • mobocertinib

              verapamil will increase the level or effect of mobocertinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use of moderate CYP3A4 inhibitor unavoidable, reduce mobocertinib dose by ~50% (eg, 160 to 80 mg); closely monitor QTc interval.

            • nabumetone

              nabumetone, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • nadolol

              verapamil, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • naloxegol

              verapamil will increase the level or effect of naloxegol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministation of naloxegol with moderate CYP3A4 inhibitors is unavoidable, reduce naloxegol dose to 12.5 mg qDay

            • naproxen

              naproxen, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • nebivolol

              verapamil, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • nefazodone

              nefazodone will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • neratinib

              verapamil will increase the level or effect of neratinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of neratinib with strong/moderate CYP3A4 inhibitors.

            • olaparib

              verapamil will increase the level or effect of olaparib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A inhibitors cannot be avoided, reduce olaparib dose to 200 mg (capsule) or 150 mg (tablet) PO BID. Do not substitute tablets with capsules.

            • olmesartan

              olmesartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • omaveloxolone

              verapamil will increase the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If unavoidable, reduce omaveloxolone dose to 100 mg/day. Closely monitor for adverse effects. If adverse effects emerge, further reduce to 50 mg/day.

            • oxaprozin

              oxaprozin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • ozanimod

              ozanimod increases toxicity of verapamil by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • pacritinib

              verapamil will increase the level or effect of pacritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • pazopanib

              verapamil will increase the level or effect of pazopanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of pazopanib with strong CYP3A4 inhibitors if possible; if must coadminister, decrease pazopanib dose to 400 mg/day

            • pemigatinib

              verapamil will increase the level or effect of pemigatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pemigatinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pemigatinib dose.

            • pexidartinib

              verapamil will increase the level or effect of pexidartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors is unavoidable, reduce pexidartinib dose (refer to drug monograph dosage modifications). After discontinuing the CYP3A4 inhibitor for 3 elimination half-lives, may resume previous pexidartinib dose.

            • piroxicam

              piroxicam, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • pomalidomide

              verapamil increases levels of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • ponesimod

              ponesimod, verapamil. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Generally, should not be initiated in patients who are concurrently taking QT prolonging drugs with known arrhythmogenic properties, such as HR-lowering calcium channel blockers (eg, verapamil, diltiazem).

            • potassium phosphates, IV

              trandolapril and potassium phosphates, IV both increase serum potassium. Avoid or Use Alternate Drug.

            • pregabalin

              trandolapril, pregabalin. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration results in additive risk of developing angioedema of face, mouth, and neck. Angioedema may result in respiratory compromise.

            • propranolol

              verapamil, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • ranolazine

              verapamil will increase the level or effect of ranolazine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rifabutin

              rifabutin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rifampin

              rifampin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • rimegepant

              verapamil will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • riociguat

              verapamil will increase the level or effect of riociguat by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of riociguat (substrate of CYP isoenzymes 1A1, 2C8, 3A, 2J2) with strong CYP inhibitors may require a decreased initial dose of 0.5 mg PO TID; monitor for signs of hypotension and reduce dose if needed

            • sacubitril/valsartan

              sacubitril/valsartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • salsalate

              salsalate, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • saquinavir

              saquinavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • selumetinib

              verapamil will increase the level or effect of selumetinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with strong or moderate CYP3A4 inhibitors cannot be avoided, reduce selumetinib dosage (refer to selumetinib monograph for further information). After discontinuation of the strong or moderate CYP3A4 inhibitor for 3 elimination half-lives, resume selumetinib dose that was taken before initiating the inhibitor.

            • silodosin

              verapamil will increase the level or effect of silodosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • simvastatin

              verapamil will increase the level or effect of simvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Do not exceed simvastatin 10 mg daily when given concurrently. Potential for increased risk of myopathy/rhabdomyolysis.

            • siponimod

              siponimod, verapamil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Because of the potential additive effects on heart rate, siponimod should generally not be initiated in patients taking QT prolonging drugs with known arrhythmogenic properties, heart rate lowering calcium channel blockers, or other drugs that may decrease heart rate. If treatment considered, obtain cardiology consult regarding switching to non-heart-rate lowering drugs or appropriate monitoring for treatment initiation.

              verapamil will increase the level or effect of siponimod by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of siponimod with a moderate or strong CYP3A4 inhibitor PLUS a moderate or strong CYP2C9 inhibitor is not recommended.

            • sirolimus

              verapamil will increase the level or effect of sirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              verapamil, sirolimus. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: With concomitant use of mTOR inhibitors, consider appropriate dose reductions of both medications.

            • sotalol

              verapamil, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • sotorasib

              sotorasib will decrease the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • St John's Wort

              St John's Wort will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • sulbactam/durlobactam

              verapamil will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

            • sulindac

              sulindac, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • talazoparib

              verapamil will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration with certain P-gp inhibitors (ie, amiodarone, carvedilol, clarithromycin, itraconazole, verapamil) cannot be avoided, reduce talazoparib dose to 0.75 mg qDay. Once P-gp inhibitors are discontinued, increase talazoparib dose (after 3-5 half-lives of the inhibitor) to dose used prior to initiating the P-gp inhibitor(s).

            • tazemetostat

              verapamil will increase the level or effect of tazemetostat by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of tazemetostat with moderate CYP3A4 inhibitors. If coadministration is unavoidable, reduce tazemetostat current dose (see drug monograph Dosage Modifications).

            • telmisartan

              telmisartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • temsirolimus

              verapamil will increase the level or effect of temsirolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              verapamil, temsirolimus. Either increases levels of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: With concomitant use of mTOR inhibitors, consider appropriate dose reductions of both medications.

            • tepotinib

              tepotinib will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • timolol

              verapamil, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

            • tizanidine

              verapamil will increase the level or effect of tizanidine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug.

            • tolmetin

              tolmetin, trandolapril. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration may result in a significant decrease in renal function. NSAIDs may diminish the antihypertensive effect of ACE inhibitors. The mechanism of these interactions is likely related to the ability of NSAIDs to reduce the synthesis of vasodilating renal prostaglandins.

            • tolvaptan

              verapamil will increase the level or effect of tolvaptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • topotecan

              verapamil will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Product labeling for PO topotecan recommends avoiding concomitant use of P-gp inhibitors; the interaction with IV topotecan may be less severe but is still likely of clinical significance

            • tucatinib

              tucatinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • valsartan

              valsartan, trandolapril. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment.

            • venetoclax

              verapamil will increase the level or effect of venetoclax by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If a moderate CYP3A inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

              verapamil will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.

            Monitor Closely (374)

            • acalabrutinib

              verapamil will increase the level or effect of acalabrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease acalabrutinib dose to 100 mg once daily if coadministered with a moderate CYP3A inhibitor.

            • acebutolol

              acebutolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • aldesleukin

              aldesleukin increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              aldesleukin increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • alfentanil

              verapamil will increase the level or effect of alfentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. The risk of significant hypotension and/or bradycardia during therapy with alfentanil may be increased in patients receiving calcium-channel blockers.

            • alfuzosin

              trandolapril, alfuzosin. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

            • alfuzosin

              alfuzosin and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • aliskiren

              verapamil will increase the level or effect of aliskiren by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • almotriptan

              verapamil will increase the level or effect of almotriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • alprazolam

              verapamil will increase the level or effect of alprazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aluminum hydroxide

              aluminum hydroxide decreases effects of trandolapril by unspecified interaction mechanism. Use Caution/Monitor.

            • amifostine

              amifostine, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

              amifostine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

            • amikacin

              verapamil will increase the level or effect of amikacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amiloride

              trandolapril, amiloride. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • amiodarone

              verapamil will increase the level or effect of amiodarone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              amiodarone will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

              amiodarone, verapamil. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of cardiotoxicity with bradycardia.

            • amitriptyline

              verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive.

            • amlodipine

              amlodipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • amobarbital

              amobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • apixaban

              verapamil will increase the level or effect of apixaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Verapamil also inhibits P-gp activity, which can further increase apixaban serum levels; since both pathways of apixaban elimination are affected, patients with renal impairment receiving apixaban with drugs that are combined P-gp and moderate CYP3A4 inhibitors may increase exposure compared to patients with normal renal function; monitor for bleeding.

            • aprepitant

              aprepitant will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • aripiprazole

              verapamil will increase the level or effect of aripiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • armodafinil

              armodafinil will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • artemether/lumefantrine

              verapamil will increase the level or effect of artemether/lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • asenapine

              trandolapril, asenapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

              asenapine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • aspirin

              trandolapril, aspirin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly with high dose aspirin, in elderly and volume depleted.

            • atazanavir

              atazanavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of atazanavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution advised, may increase risk of AV block

            • atenolol

              atenolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • atogepant

              verapamil will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • atorvastatin

              verapamil will increase the level or effect of atorvastatin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of atorvastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • avanafil

              avanafil increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              verapamil will increase the level or effect of avanafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibitors may reduce avanafil clearance increasing systemic exposure to avanafil; increased levels may result in increased associated adverse events; the maximum recommended dose of STENDRA is 50 mg, not to exceed once every 24 hours for patients taking concomitant moderate CYP3A4 inhibitors

            • azathioprine

              trandolapril, azathioprine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of neutropenia.

            • azithromycin

              azithromycin will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bazedoxifene/conjugated estrogens

              verapamil will increase the level or effect of bazedoxifene/conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of bazedoxifene/conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • berotralstat

              berotralstat will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • betaxolol

              betaxolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • betrixaban

              verapamil increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

            • bisoprolol

              bisoprolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • bortezomib

              verapamil will increase the level or effect of bortezomib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • bosutinib

              bosutinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • bretylium

              verapamil, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

              trandolapril, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

            • brexpiprazole

              verapamil will increase the level or effect of brexpiprazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP3A4 inhibitor PLUS a strong/moderate CYP2D6 inhibitor.

            • bumetanide

              trandolapril, bumetanide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypotension, renal insufficiency.

            • budesonide

              verapamil will increase the level or effect of budesonide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              budesonide will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • buprenorphine subdermal implant

              verapamil will increase the level or effect of buprenorphine subdermal implant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor patients already on buprenorphine subdermal implant who require newly-initiated treatment with CYP3A4 inhibitors for signs and symptoms of overmedication. If the dose of the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, implant removal may be necessary and the patient should then be treated with a buprenorphine dosage form that permits dose adjustments. If a CYP3A4 inhibitor is discontinued in a patient who has been stabilized on buprenorphine, monitor the patient for withdrawal.

            • buprenorphine, long-acting injection

              verapamil will increase the level or effect of buprenorphine, long-acting injection by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Patients who transfer to buprenorphine long-acting injection from transmucosal buprenorphine coadministered with CYP3A4 inhibitors should be monitored to ensure buprenorphine plasma levels are adequate. Within 2 weeks, if signs and symptoms of buprenorphine toxicity or overdose occur and the concomitant CYP3A4 inhibitor cannot be reduced or discontinued, transition the patient back to a buprenorphine formulation that permits dose adjustments.

            • buspirone

              verapamil will increase the level or effect of buspirone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider lower buspirone doses.

            • butabarbital

              butabarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • butalbital

              butalbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cabazitaxel

              verapamil will increase the level or effect of cabazitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A4 inhibitors.

            • cabozantinib

              verapamil will increase the level or effect of cabozantinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • calcium acetate

              calcium acetate decreases effects of verapamil by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium carbonate

              calcium carbonate decreases effects of verapamil by pharmacodynamic antagonism. Use Caution/Monitor.

              calcium carbonate decreases effects of trandolapril by unspecified interaction mechanism. Use Caution/Monitor.

            • calcium chloride

              calcium chloride decreases effects of verapamil by pharmacodynamic antagonism. Use Caution/Monitor.

            • canagliflozin

              trandolapril and canagliflozin both increase serum potassium. Use Caution/Monitor.

            • calcium citrate

              calcium citrate decreases effects of verapamil by pharmacodynamic antagonism. Use Caution/Monitor.

            • calcium gluconate

              calcium gluconate decreases effects of verapamil by pharmacodynamic antagonism. Use Caution/Monitor.

            • cannabidiol

              verapamil will increase the level or effect of cannabidiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Consider reducing the cannabidiol dose when coadministered with a moderate CYP3A4 inhibitor.

            • carbamazepine

              verapamil will increase the level or effect of carbamazepine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor plasma levels when used concomitantly

            • carbidopa

              carbidopa increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

              carbidopa increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

            • carvedilol

              carvedilol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • celecoxib

              trandolapril, celecoxib. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • celiprolol

              celiprolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • ceritinib

              verapamil increases levels of ceritinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • chloramphenicol

              chloramphenicol will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • chlorpropamide

              trandolapril increases effects of chlorpropamide by pharmacodynamic synergism. Use Caution/Monitor.

            • cilostazol

              verapamil will increase the level or effect of cilostazol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Consider decreasing the cilostazol dose to 50 mg twice a day.

            • cimetidine

              cimetidine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • cinacalcet

              verapamil will increase the level or effect of cinacalcet by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased effect of calcium channel blockers may lead to hypotension, edema, decreased HR, and acute kidney injury due to reduced renal blood flow

            • clevidipine

              clevidipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • clomipramine

              verapamil will increase the level or effect of clomipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • clonidine

              clonidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

              verapamil, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

            • clopidogrel

              verapamil will decrease the level or effect of clopidogrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Inhibition of CYP3A4 will reduce clopidogrel bioactivation

            • clozapine

              verapamil will increase the level or effect of clozapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of clozapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • cobicistat

              cobicistat will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conjugated estrogens

              verapamil will increase the level or effect of conjugated estrogens by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of conjugated estrogens by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • conjugated estrogens, vaginal

              verapamil will increase the level or effect of conjugated estrogens, vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of conjugated estrogens, vaginal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cortisone

              verapamil will increase the level or effect of cortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              cortisone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of cortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • crizotinib

              crizotinib increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Dose reduction may be needed for coadministered drugs that are predominantly metabolized by CYP3A.

              crizotinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              verapamil increases levels of crizotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution should be exercised with concomitant use of moderate CYP3A inhibitors. .

            • crofelemer

              crofelemer increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

            • cyclosporine

              verapamil, cyclosporine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Verapamil and cyclosporine may inhibit CYP3A4 metabolism. Coadministration of verapamil and cyclosporine may increase plasma concentrations of either drugs.

            • dabigatran

              verapamil will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Atrial fibrillation: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <30 mL/min. DVT/PE treatment: Avoid coadministering dabigatran with P-gp inhibitors if CrCl <50 mL/min

            • dabrafenib

              dabrafenib will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • daridorexant

              verapamil will increase the level or effect of daridorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Daridorexant dose should not exceed 25 mg per night when coadministered with moderate CYP3A4 inhibitors.

            • darifenacin

              darifenacin will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of darifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • darunavir

              darunavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • dasatinib

              dasatinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • daunorubicin

              verapamil will increase the level or effect of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • deferasirox

              deferasirox will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • deflazacort

              verapamil will increase the level or effect of deflazacort by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease deflazacort dose to one-third of the recommended dose if coadministered with moderate or strong CYP3A4 inhibitors.

              verapamil will increase the level or effect of deflazacort by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexamethasone

              verapamil will increase the level or effect of dexamethasone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              dexamethasone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam

              verapamil will increase the level or effect of diazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • diazepam intranasal

              verapamil will increase the level or effect of diazepam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong or moderate CYP3A4 inhibitors may decrease rate of diazepam elimination, thereby increasing adverse reactions to diazepam.

            • diclofenac

              trandolapril, diclofenac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • dienogest/estradiol valerate

              verapamil will increase the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for potential adverse effects such as nausea, irregular uterine bleeding, breast tenderness and headache.

            • diflunisal

              trandolapril, diflunisal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • digoxin

              verapamil will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Toxicity characterized by gastrointestinal and neuropsychiatric symptoms, and cardiac arrhythmias may result.

              digoxin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

              trandolapril increases levels of digoxin by unspecified interaction mechanism. Use Caution/Monitor.

            • diltiazem

              diltiazem will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of diltiazem by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. These agents have additive hypotensive effects that may be beneficial however, it is important to monitor patients carefully.

              diltiazem and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor. Antihypertensives may enhance the hypotensive effects of other antihypertensive agents when used together.

            • doxazosin

              trandolapril, doxazosin. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

            • disopyramide

              verapamil will increase the level or effect of disopyramide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Avoid disopyramide administration within 48 hours before or 24 hours after verapamil administration.

            • docetaxel

              verapamil will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dofetilide

              dofetilide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • doxazosin

              doxazosin and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • doxorubicin

              verapamil will increase the level or effect of doxorubicin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil increases levels of doxorubicin by decreasing metabolism. Use Caution/Monitor. Coadministration of doxorubicin and calcium channel blockers may increase the risk of doxorubicin cardiotoxicity. .

            • doxorubicin liposomal

              verapamil will increase the level or effect of doxorubicin liposomal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil increases toxicity of doxorubicin liposomal by decreasing metabolism. Use Caution/Monitor. Coadministration of doxorubicin and calcium channel blockers may increase the risk of doxorubicin cardiotoxicity. .

            • dronedarone

              dronedarone will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • drospirenone

              trandolapril, drospirenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • duvelisib

              duvelisib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

              verapamil will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • efavirenz

              efavirenz will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              elagolix decreases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • eletriptan

              verapamil will increase the level or effect of eletriptan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eliglustat

              eliglustat increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

              encorafenib, verapamil. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

            • enoxaparin

              enoxaparin increases toxicity of trandolapril by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • enzalutamide

              enzalutamide will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eplerenone

              verapamil will increase the level or effect of eplerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Plasma concentrations and pharmacologic or toxic effects of eplerenone may be increased by verapamil.

              trandolapril, eplerenone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • erlotinib

              verapamil will increase the level or effect of erlotinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ethacrynic acid

              trandolapril, ethacrynic acid. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypotension, renal insufficiency.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil decreases levels of eslicarbazepine acetate by increasing metabolism. Modify Therapy/Monitor Closely.

            • esmolol

              esmolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • estradiol

              verapamil will increase the level or effect of estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estrogens conjugated synthetic

              verapamil will increase the level or effect of estrogens conjugated synthetic by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of estrogens conjugated synthetic by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • estrogens esterified

              verapamil will increase the level or effect of estrogens esterified by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • estropipate

              verapamil will increase the level or effect of estropipate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of estropipate by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ethanol

              verapamil increases levels of ethanol by decreasing metabolism. Use Caution/Monitor.

            • etodolac

              trandolapril, etodolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • etonogestrel

              verapamil will increase the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • etoposide

              verapamil will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • etravirine

              verapamil will increase the level or effect of etravirine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              etravirine will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • everolimus

              trandolapril, everolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

              everolimus will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Everolimus prescribing information lists indication-specific dosing recommendations.

            • fedratinib

              fedratinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fenoprofen

              trandolapril, fenoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • felodipine

              verapamil will increase the level or effect of felodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              felodipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • fesoterodine

              verapamil will increase the level or effect of fesoterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • finerenone

              verapamil will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or moderate CYP3A4 inhibitors. Adjust finererone dosage as needed.

              trandolapril and finerenone both increase serum potassium. Modify Therapy/Monitor Closely. Finerenone dose adjustment based on current serum potassium concentration. Monitor serum potassium and adjust finerenone dose as described in the prescribing information as necessary.

            • fluconazole

              fluconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • furosemide

              trandolapril, furosemide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypotension, renal insufficiency.

            • fludrocortisone

              verapamil will increase the level or effect of fludrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              fludrocortisone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of fludrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosamprenavir

              fosamprenavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosaprepitant

              fosaprepitant will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fostamatinib

              fostamatinib will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • gentamicin

              verapamil will increase the level or effect of gentamicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • glecaprevir/pibrentasvir

              verapamil will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • glimepiride

              trandolapril increases effects of glimepiride by pharmacodynamic synergism. Use Caution/Monitor.

            • glipizide

              trandolapril increases effects of glipizide by pharmacodynamic synergism. Use Caution/Monitor.

            • glyburide

              trandolapril increases effects of glyburide by pharmacodynamic synergism. Use Caution/Monitor.

            • gold sodium thiomalate

              trandolapril, gold sodium thiomalate. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Combo of ACE inhibitors and injectable gold has caused rare cases of nitritoid reaction (flushing, N/V, hypot'n).

            • grapefruit

              grapefruit will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • green tea

              verapamil increases levels of green tea by decreasing elimination. Use Caution/Monitor. (Caffeine). Verapamil reduces clearance of caffeine and increases serum caffeine concentrations, presumably via inhibition of hepatic metabolism. May advise patients to limit or minimize the intake of caffeinated products to minimize caffeine-related side effects.

            • griseofulvin

              griseofulvin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • guanfacine

              verapamil will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.

            • hawthorn

              hawthorn increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor.

            • heparin

              heparin increases toxicity of trandolapril by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • hydrocortisone

              verapamil will increase the level or effect of hydrocortisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              hydrocortisone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • hydroxyprogesterone caproate (DSC)

              verapamil will increase the level or effect of hydroxyprogesterone caproate (DSC) by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ibuprofen

              trandolapril, ibuprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ibuprofen IV

              ibuprofen IV decreases effects of trandolapril by pharmacodynamic synergism. Modify Therapy/Monitor Closely. NSAIDs decrease sysnthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertenisve effect.

              trandolapril, ibuprofen IV. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • icatibant

              icatibant decreases effects of trandolapril by pharmacodynamic antagonism. Use Caution/Monitor. Icatibant has potential to have a pharmacodynamic interaction with ACE inhibitors where it may attenuate the antihypertensive effect of ACE inhibitors.

            • ifosfamide

              verapamil decreases effects of ifosfamide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Use of a CYP3A4 inhibitor may decrease metabolism of ifosfamide, potentially reducing ifosfamide therapeutic effects.

            • iloperidone

              verapamil will increase the level or effect of iloperidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              iloperidone increases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

              verapamil will increase the level or effect of imatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • imipramine

              verapamil will increase the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. TCA level may be increased.

            • indacaterol, inhaled

              verapamil increases levels of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: Data suggests that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities. No dose adjustment is warranted at the 75 mcg dose.

            • indinavir

              indinavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of indinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • indomethacin

              trandolapril, indomethacin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • insulin aspart

              trandolapril increases effects of insulin aspart by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin degludec

              trandolapril, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin degludec/insulin aspart

              trandolapril, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin detemir

              trandolapril increases effects of insulin detemir by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin glargine

              trandolapril increases effects of insulin glargine by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin glulisine

              trandolapril increases effects of insulin glulisine by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin inhaled

              trandolapril, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs decrease blood glucose.

            • insulin lispro

              trandolapril increases effects of insulin lispro by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin NPH

              trandolapril increases effects of insulin NPH by pharmacodynamic synergism. Use Caution/Monitor.

            • insulin regular human

              trandolapril increases effects of insulin regular human by pharmacodynamic synergism. Use Caution/Monitor.

            • irinotecan

              verapamil will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • irinotecan liposomal

              verapamil will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isavuconazonium sulfate

              verapamil will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • isradipine

              isradipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              verapamil will increase the level or effect of itraconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              itraconazole will increase the level or effect of verapamil by Other (see comment). Modify Therapy/Monitor Closely. CCBs elicit negative inotropic effects which may be additive to those of itraconazole; additionally, itraconazole can inhibit the metabolism of calcium channel blockers. Monitor for adverse reactions. Concomitant drug dose reduction may be necessary.

            • ivabradine

              verapamil, ivabradine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.

            • ivacaftor

              verapamil will increase the level or effect of ivacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce ivacaftor dose if coadministered with moderate CYP3A4 inhibitors. See specific ivacaftor-containing product for precise dosage modification.

              ivacaftor increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ivermectin

              verapamil will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ivosidenib

              verapamil will increase the level or effect of ivosidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with moderate CYP3A4 inhibitors may increase ivosidenib plasma concentrations, thus increasing the risk of QTc prolongation. Monitor for increased risk of QTc interval prolongation.

            • ixabepilone

              verapamil will increase the level or effect of ixabepilone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ketoprofen

              trandolapril, ketoprofen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ketorolac

              trandolapril, ketorolac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • ketorolac intranasal

              trandolapril, ketorolac intranasal. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • labetalol

              labetalol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • lanthanum carbonate

              lanthanum carbonate decreases levels of trandolapril by cation binding in GI tract. Use Caution/Monitor. Administer ACE inhibitor at least 2 hr before or after lanthanum.

            • lapatinib

              lapatinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of lapatinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lefamulin

              verapamil will increase the level or effect of lefamulin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for adverse effects if lefamulin is coadministered with moderate CYP3A inhibitors.

            • lenacapavir

              lenacapavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • levamlodipine

              verapamil will increase the level or effect of levamlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with moderate and strong CYP3A inhibitors results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment.

            • levodopa

              levodopa increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              levodopa increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

            • levoketoconazole

              levoketoconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lithium

              trandolapril increases toxicity of lithium by unknown mechanism. Use Caution/Monitor. ACE inhibitor induced Na+ depletion may increase reabsorption of lithium from renal tubule.

            • lidocaine

              verapamil will increase the level or effect of lidocaine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • lomitapide

              lomitapide increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing dose when used concomitantly with lomitapide.

            • loperamide

              verapamil will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lopinavir

              verapamil will increase the level or effect of lopinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • loratadine

              verapamil will increase the level or effect of loratadine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              verapamil will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Avoid concomitant use of verapamil and lovastatin if possible. If used together, use lower doses of lovastatin and monitor for lovastatin toxicity (myositis, rhabdomyolysis).

            • lumateperone

              verapamil will increase the level or effect of lumateperone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce lumateperone dose to 21 mg/day if coadministered with moderate CYP3A4 inhibitors.

            • lumefantrine

              verapamil will increase the level or effect of lumefantrine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lurasidone

              verapamil increases levels of lurasidone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Manufacturer recommends decreasing starting dose of lurasidone to 20 mg/day and maximum daily dose of lurasidone 80 mg when coadministered with moderate CYP3A4 inhibitors. Concurrent use may increase risk of lurasidone-related adverse reactions.

              lurasidone increases effects of verapamil by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

              lurasidone increases effects of trandolapril by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

            • magnesium supplement

              magnesium supplement, verapamil. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Calcium channel blockers may increase toxic effects of magnesium; magnesium may increase hypotensive effects of calcium channel blockers.

            • maraviroc

              maraviroc, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • maraviroc

              verapamil will increase the level or effect of maraviroc by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • marijuana

              marijuana will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • meclofenamate

              trandolapril, meclofenamate. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • mefenamic acid

              trandolapril, mefenamic acid. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • mefloquine

              mefloquine increases levels of verapamil by decreasing metabolism. Use Caution/Monitor. Risk of arrhythmia.

              verapamil will increase the level or effect of mefloquine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • meloxicam

              trandolapril, meloxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • mestranol

              verapamil will increase the level or effect of mestranol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of mestranol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metformin

              trandolapril increases toxicity of metformin by unspecified interaction mechanism. Use Caution/Monitor. Increases risk for hypoglycemia and lactic acidosis.

              verapamil decreases effects of metformin by Other (see comment). Use Caution/Monitor. Comment: Verapamil may inhibit hepatic uptake of metformin by OCT1 and/or other transporters.

            • methadone

              verapamil will increase the level or effect of methadone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • methylphenidate

              methylphenidate will decrease the level or effect of trandolapril by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methylphenidate

              methylphenidate will decrease the level or effect of verapamil by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • methylphenidate transdermal

              methylphenidate transdermal decreases effects of trandolapril by anti-hypertensive channel blocking. Use Caution/Monitor.

            • methylprednisolone

              verapamil will increase the level or effect of methylprednisolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              methylprednisolone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metoprolol

              metoprolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • metronidazole

              metronidazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mexiletine

              verapamil will increase the level or effect of mexiletine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • midazolam

              verapamil will increase the level or effect of midazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mifepristone

              verapamil will increase the level or effect of mifepristone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              mifepristone will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mipomersen

              mipomersen, verapamil. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mitotane

              mitotane decreases levels of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • moxisylyte

              trandolapril, moxisylyte. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

              moxisylyte and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nabumetone

              trandolapril, nabumetone. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • nadolol

              nadolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • nafcillin

              nafcillin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nafcillin decreases levels of verapamil by increasing metabolism. Use Caution/Monitor.

            • naldemedine

              verapamil increases levels of naldemedine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with strong or moderate CYP3A4 inhibitors.

              verapamil increases levels of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor naldemedine for potential adverse effects if coadministered with P-gp inhibitors.

            • naproxen

              trandolapril, naproxen. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • nebivolol

              nebivolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • nelfinavir

              nelfinavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of nelfinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • neomycin PO

              verapamil will increase the level or effect of neomycin PO by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nesiritide

              nesiritide, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • nevirapine

              nevirapine will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nicardipine

              verapamil will increase the level or effect of nicardipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nicardipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nifedipine

              nifedipine will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nifedipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nintedanib

              verapamil increases levels of nintedanib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. If nintedanib adverse effects occur, management may require interruption, dose reduction, or discontinuation of therapy .

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for increased bradycardia, hypotension, or dizziness. If needed, temporarily pause the antihypertensive drug.

            • nisoldipine

              verapamil will increase the level or effect of nisoldipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nisoldipine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • nitroglycerin rectal

              nitroglycerin rectal, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

              nitroglycerin rectal, verapamil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Marked orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used concomitantly. Observe for possible additive hypotensive effects during concomitant use. .

            • nitroglycerin sublingual

              verapamil, nitroglycerin sublingual. Either increases toxicity of the other by additive vasodilation. Modify Therapy/Monitor Closely. Marked orthostatic hypotension reported with concomitant use.

            • oxaprozin

              trandolapril, oxaprozin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • nitroprusside sodium

              verapamil increases effects of nitroprusside sodium by pharmacodynamic synergism. Use Caution/Monitor.

            • olanzapine

              verapamil will increase the level or effect of olanzapine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • oliceridine

              verapamil will increase the level or effect of oliceridine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If concomitant use is necessary, may require less frequent oliceridine dosing. Closely monitor for respiratory depression and sedation and titrate subsequent doses accordingly. If inhibitor is discontinued, consider increase oliceridine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal.

              verapamil, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of verapamil by altering metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; clinical monitoring of patients is recommended for edema and/or signs and symptoms of hypotension. if such events occur, consider further dose reduction of calcium channel blocker or switching to alternative to calcium channel blocker m channel blocker dose if necessary

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paclitaxel

              verapamil will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paclitaxel protein bound

              verapamil will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • palbociclib

              verapamil will increase the level or effect of palbociclib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • paliperidone

              verapamil will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paromomycin

              verapamil will increase the level or effect of paromomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • penbutolol

              penbutolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenobarbital

              phenobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • phenoxybenzamine

              trandolapril, phenoxybenzamine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

              phenoxybenzamine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phentolamine

              trandolapril, phentolamine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

              phentolamine and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • phenytoin

              phenytoin will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • piroxicam

              trandolapril, piroxicam. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • pindolol

              pindolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • ponatinib

              ponatinib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • posaconazole

              posaconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • potassium acid phosphate

              trandolapril increases levels of potassium acid phosphate by decreasing elimination. Use Caution/Monitor. Risk of hyperkalemia.

            • potassium chloride

              trandolapril increases levels of potassium chloride by decreasing elimination. Use Caution/Monitor. Risk of hyperkalemia.

            • potassium citrate

              trandolapril increases levels of potassium citrate by decreasing elimination. Use Caution/Monitor. Risk of hyperkalemia.

            • potassium citrate/citric acid

              trandolapril and potassium citrate/citric acid both increase serum potassium. Use Caution/Monitor.

            • potassium iodide

              potassium iodide and trandolapril both increase serum potassium. Use Caution/Monitor. Potassium salts may increase the hyperkalemic effects of ACE inhibitors; the effect may be the result of aldosterone suppression in patients receiving ACE inhibitors.

            • prazosin

              trandolapril, prazosin. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

              prazosin and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • prednisolone

              verapamil will increase the level or effect of prednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • silodosin

              trandolapril, silodosin. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

            • prednisone

              verapamil will increase the level or effect of prednisone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              prednisone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • procainamide

              procainamide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • propranolol

              propranolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • quetiapine

              verapamil will increase the level or effect of quetiapine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • quinidine

              verapamil will increase the level or effect of quinidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              quinidine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Use Caution/Monitor.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • repaglinide

              verapamil will increase the level or effect of repaglinide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ribociclib

              ribociclib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rifaximin

              verapamil increases levels of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rimegepant

              verapamil will increase the level or effect of rimegepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid repeating rimegepant dose within 48 hr if coadministered with a moderate CYP3A4 inhibitor.

            • risperidone

              verapamil will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rivaroxaban

              verapamil increases levels of rivaroxaban by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Verapamil also inhibits P-gp activity, which can further increase rivaroxaban serum levels; since both pathways of rivaroxaban elimination are affected, patients with renal impairment receiving rivaroxaban with drugs that are combined P-gp and moderate CYP3A4 inhibitors may increase exposure compared to patients with normal renal function; monitor for bleeding.

            • romidepsin

              verapamil will increase the level or effect of romidepsin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of romidepsin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rucaparib

              rucaparib will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • rufinamide

              rufinamide will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ruxolitinib

              verapamil will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • ruxolitinib topical

              verapamil will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • saquinavir

              verapamil will increase the level or effect of saquinavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • secobarbital

              secobarbital will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • sevelamer

              sevelamer decreases levels of verapamil by increasing elimination. Use Caution/Monitor.

            • sildenafil

              verapamil will increase the level or effect of sildenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • silodosin

              verapamil will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              silodosin and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

            • sirolimus

              trandolapril, sirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

            • sodium bicarbonate

              sodium bicarbonate decreases effects of trandolapril by unspecified interaction mechanism. Use Caution/Monitor.

            • sodium citrate/citric acid

              sodium citrate/citric acid decreases effects of trandolapril by unspecified interaction mechanism. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of trandolapril by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              verapamil, sodium sulfate/?magnesium sulfate/potassium chloride. Either decreases toxicity of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of trandolapril by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

              verapamil, sodium sulfate/potassium sulfate/magnesium sulfate. Either decreases toxicity of the other by unknown mechanism. Use Caution/Monitor. Monitor for hypotension or muscle weakness in patients receiving calcium channel blockers with elevated serum magnesium concentrations.

            • solifenacin

              verapamil will increase the level or effect of solifenacin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • spironolactone

              trandolapril, spironolactone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • sonidegib

              verapamil will increase the level or effect of sonidegib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Avoid coadministration of sonidegib with moderate CYP3A4 inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for <14 days and monitor closely for adverse reactions, particularly musculoskeletal adverse reactions.

            • sotalol

              sotalol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • sparsentan

              verapamil will increase the level or effect of sparsentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No dosage adjustment needed. Monitor blood pressure, serum potassium, edema, and kidney function regularly if sparsentan is coadministered with moderate CYP3A4 inhibitors.

            • stiripentol

              stiripentol, verapamil. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • streptomycin

              verapamil will increase the level or effect of streptomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sufentanil

              verapamil will increase the level or effect of sufentanil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. There may be an increased incidence of bradycardia and hypotension during induction with sufentanil in patients receiving calcium channel blockers such as verapamil.

            • sufentanil SL

              verapamil will increase the level or effect of sufentanil SL by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of sufentanil SL with any CYP3A4 inhibitor may increase sufentanil plasma concentration, and, thereby increase or prolonged adverse effects, including potentially fatal respiratory depression.

            • sulindac

              trandolapril, sulindac. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • sunitinib

              verapamil will increase the level or effect of sunitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • suvorexant

              verapamil will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors

            • synthetic human angiotensin II

              trandolapril increases effects of synthetic human angiotensin II by unspecified interaction mechanism. Use Caution/Monitor.

            • tacrolimus

              verapamil will increase the level or effect of tacrolimus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tadalafil

              tadalafil increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              verapamil will increase the level or effect of tadalafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Risk of hypotension.

            • tamoxifen

              verapamil will increase the level or effect of tamoxifen by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. CYP3A4 inhibition decreases metabolism of tamoxifen to N-desmethyl tamoxifen (active metabolite with similar biologic activity)

            • temsirolimus

              trandolapril, temsirolimus. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration increases risk of angioedema.

            • tapentadol

              verapamil and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • tazemetostat

              tazemetostat will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • teniposide

              verapamil will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tenofovir DF

              tenofovir DF increases levels of verapamil by decreasing renal clearance. Use Caution/Monitor. Potential for increased toxicity. .

            • terazosin

              terazosin and verapamil both increase anti-hypertensive channel blocking. Use Caution/Monitor.

              trandolapril, terazosin. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

            • tezacaftor

              verapamil will increase the level or effect of tezacaftor by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust tezacaftor dosage regimen if coadministered with a moderate CYP3A inhibitor.

            • tolazamide

              trandolapril increases effects of tolazamide by pharmacodynamic synergism. Use Caution/Monitor.

            • theophylline

              verapamil will increase the level or effect of theophylline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

              verapamil will increase the level or effect of theophylline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • timolol

              timolol and verapamil both increase anti-hypertensive channel blocking. Modify Therapy/Monitor Closely.

            • tinidazole

              verapamil will increase the level or effect of tinidazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tipranavir

              verapamil will increase the level or effect of tipranavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              tipranavir, verapamil. Other (see comment). Use Caution/Monitor. Comment: Verapamil levels may incr or decr, due to contradictory effects of tipranavir on hepatic CYP3A4 and P glycoprotein.

              tipranavir will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tobramycin

              verapamil will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tofacitinib

              verapamil increases levels of tofacitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. No specific dose adjustment recommended when tofacitinib coadministered with moderate CYP3A4 inhibitors; decrease tofacitinib dose if coadministered with both moderate CYP3A4 and potent CYP2C19 inhibitors .

            • tolbutamide

              trandolapril increases effects of tolbutamide by pharmacodynamic synergism. Use Caution/Monitor.

            • tolmetin

              trandolapril, tolmetin. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: May result in renal function deterioration, particularly in elderly or volume depleted individuals.

            • tolterodine

              verapamil will increase the level or effect of tolterodine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolvaptan

              verapamil will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Coadministration of moderate CYP 3A inhibitors, such as Verapamil with Tolvaptan should be avoided.

            • topiramate

              topiramate will decrease the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • torsemide

              trandolapril, torsemide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypotension, renal insufficiency.

            • trabectedin

              verapamil will increase the level or effect of trabectedin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trazodone

              verapamil will increase the level or effect of trazodone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triamcinolone acetonide injectable suspension

              verapamil will increase the level or effect of triamcinolone acetonide injectable suspension by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • triamterene

              trandolapril, triamterene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of hyperkalemia.

            • triazolam

              verapamil will increase the level or effect of triazolam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • trimagnesium citrate anhydrous

              trimagnesium citrate anhydrous, verapamil. Either increases effects of the other by sedation. Use Caution/Monitor. Possible additive effect of magnesium and calcium channel blockers on reduction of ionic calcium may increase risk of hypotension or muscle weakness.

            • trimethoprim

              trimethoprim and trandolapril both increase serum potassium. Use Caution/Monitor. Trimethoprim decreases urinary potassium excretion. May cause hyperkalemia, particularly with high doses, renal insufficiency, or when combined with other drugs that cause hyperkalemia.

            • tucatinib

              tucatinib will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • vardenafil

              verapamil will increase the level or effect of vardenafil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Vardenafil dose may need to be reduced if coadministered with moderate or strong CYP3A4 inhibitors

            • vemurafenib

              verapamil increases levels of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              vemurafenib increases levels of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vinblastine

              verapamil will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine

              verapamil will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vincristine liposomal

              verapamil will increase the level or effect of vincristine liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • voclosporin

              verapamil will increase the level or effect of voclosporin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce voclosporin daily dosage to 15.8 mg PO in AM and 7.9 mg PO in PM.

              voclosporin and trandolapril both increase serum potassium. Use Caution/Monitor.

              voclosporin, trandolapril. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

            • voriconazole

              voriconazole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Combo may increase risk of hypotension, bradycardia, AV block.

              voriconazole increases levels of verapamil by decreasing metabolism. Use Caution/Monitor.

            • xipamide

              xipamide increases effects of trandolapril by pharmacodynamic synergism. Use Caution/Monitor.

            • xipamide

              xipamide increases effects of verapamil by pharmacodynamic synergism. Use Caution/Monitor.

            • zafirlukast

              zafirlukast will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • zanubrutinib

              verapamil will increase the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce zanubrutinib (a CYP3A4 substrate) to 80 mg PO BID to when coadministered with a moderate CYP3A4 inhibitor. Interrupt dose as recommended for adverse reactions. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.

            • zotepine

              trandolapril, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Exaggerated first dose hypotensive response.

            Minor (127)

            • aceclofenac

              aceclofenac decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • acemetacin

              acemetacin decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • acetazolamide

              acetazolamide will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • agrimony

              agrimony increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

              agrimony increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • alfuzosin

              verapamil will increase the level or effect of alfuzosin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • alosetron

              verapamil will increase the level or effect of alosetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • alvimopan

              verapamil will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • ambrisentan

              verapamil will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • amitriptyline

              verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

            • amoxapine

              verapamil increases levels of amoxapine by decreasing metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • antipyrine

              verapamil will increase the level or effect of antipyrine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • armodafinil

              verapamil will increase the level or effect of armodafinil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              verapamil will increase the level or effect of armodafinil by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • asenapine

              verapamil will increase the level or effect of asenapine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • aspirin

              verapamil increases effects of aspirin by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • aspirin rectal

              verapamil increases effects of aspirin rectal by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • aspirin/citric acid/sodium bicarbonate

              verapamil increases effects of aspirin/citric acid/sodium bicarbonate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • atracurium

              verapamil increases effects of atracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • balsalazide

              verapamil increases effects of balsalazide by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • berotralstat

              verapamil increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

            • bosentan

              verapamil will increase the level or effect of bosentan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

              brimonidine increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • caffeine

              verapamil will increase the level or effect of caffeine by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • capsicum

              capsicum, trandolapril. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increase ACE inhibitor induced cough.

            • cevimeline

              verapamil will increase the level or effect of cevimeline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • chlorpromazine

              chlorpromazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • choline magnesium trisalicylate

              verapamil increases effects of choline magnesium trisalicylate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • cisatracurium

              verapamil increases effects of cisatracurium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • clarithromycin

              verapamil will increase the level or effect of clarithromycin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • clomipramine

              verapamil will increase the level or effect of clomipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              verapamil increases levels of clomipramine by decreasing metabolism. Minor/Significance Unknown.

            • colesevelam

              colesevelam decreases levels of verapamil by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown. (Sustained release form of verapamil).

            • cornsilk

              cornsilk increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

              cornsilk increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

            • creatine

              creatine, trandolapril. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. (Theoretical interaction) Combination may have additive nephrotoxic effects.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of verapamil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dapsone

              verapamil will increase the level or effect of dapsone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • darolutamide

              verapamil will increase the level or effect of darolutamide by Other (see comment). Minor/Significance Unknown. Darolutamide is a P-gp and CYP3A4 substrate. Closely monitor for increased adverse reactions and modify dose of darolutamide as needed when coadministered with drugs that are both P-gp and strong or moderate CYP3A4 inhibitors.

            • desipramine

              verapamil increases levels of desipramine by decreasing metabolism. Minor/Significance Unknown.

            • diflunisal

              verapamil increases effects of diflunisal by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • docetaxel

              verapamil will increase the level or effect of docetaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • donepezil

              verapamil will increase the level or effect of donepezil by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dosulepin

              verapamil increases levels of dosulepin by decreasing metabolism. Minor/Significance Unknown.

            • doxepin

              verapamil increases levels of doxepin by decreasing metabolism. Minor/Significance Unknown.

            • dutasteride

              verapamil will increase the level or effect of dutasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • efavirenz

              verapamil will increase the level or effect of efavirenz by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • encainide

              verapamil increases levels of encainide by decreasing metabolism. Minor/Significance Unknown.

            • entecavir

              trandolapril, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.

            • estradiol vaginal

              verapamil will increase the level or effect of estradiol vaginal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eucalyptus

              verapamil will increase the level or effect of eucalyptus by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fexofenadine

              verapamil will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • finasteride

              verapamil will increase the level or effect of finasteride by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fluphenazine

              fluphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • fo-ti

              fo-ti increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • forskolin

              forskolin increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • frovatriptan

              verapamil will increase the level or effect of frovatriptan by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • galantamine

              verapamil will increase the level or effect of galantamine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydrochlorothiazide

              hydrochlorothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • imatinib

              verapamil will increase the level or effect of imatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • imipramine

              verapamil increases levels of imipramine by decreasing metabolism. Minor/Significance Unknown.

            • isradipine

              verapamil will increase the level or effect of isradipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • itraconazole

              verapamil will increase the level or effect of itraconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketoconazole

              verapamil will increase the level or effect of ketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levoketoconazole

              verapamil will increase the level or effect of levoketoconazole by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lily of the valley

              verapamil, lily of the valley. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown.

            • lithium

              verapamil increases toxicity of lithium by pharmacodynamic synergism. Minor/Significance Unknown. Increased risk of neurotoxicity.

            • lofepramine

              verapamil increases levels of lofepramine by decreasing metabolism. Minor/Significance Unknown.

            • loratadine

              verapamil will increase the level or effect of loratadine by P-glycoprotein (MDR1) efflux transporter. Minor/Significance Unknown.

            • lornoxicam

              lornoxicam decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • maitake

              maitake increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

              maitake increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

            • maprotiline

              verapamil increases levels of maprotiline by decreasing metabolism. Minor/Significance Unknown.

            • octacosanol

              octacosanol increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

            • memantine

              memantine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • mesalamine

              verapamil increases effects of mesalamine by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • metformin

              metformin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • methyclothiazide

              methyclothiazide will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • metipranolol ophthalmic

              metipranolol ophthalmic increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • midodrine

              midodrine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • montelukast

              verapamil will increase the level or effect of montelukast by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              verapamil will increase the level or effect of nifedipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nimodipine

              verapamil will increase the level or effect of nimodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nitrendipine

              verapamil will increase the level or effect of nitrendipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nortriptyline

              verapamil increases levels of nortriptyline by decreasing metabolism. Minor/Significance Unknown.

            • octacosanol

              octacosanol increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

            • ofloxacin

              ofloxacin will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • onabotulinumtoxinA

              verapamil increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • ondansetron

              verapamil will increase the level or effect of ondansetron by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

              verapamil will increase the level or effect of ondansetron by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxcarbazepine

              verapamil decreases levels of oxcarbazepine by increasing metabolism. Minor/Significance Unknown.

            • oxybutynin

              verapamil will increase the level or effect of oxybutynin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel

              verapamil will increase the level or effect of paclitaxel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • paclitaxel protein bound

              verapamil will increase the level or effect of paclitaxel protein bound by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pancuronium

              verapamil increases effects of pancuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • parecoxib

              verapamil will increase the level or effect of parecoxib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              parecoxib decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • patiromer

              patiromer, trandolapril. cation binding in GI tract. Minor/Significance Unknown. No observed clinically important interaction. No separation of dosing required.

            • pimozide

              verapamil will increase the level or effect of pimozide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • perphenazine

              perphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • pioglitazone

              verapamil will increase the level or effect of pioglitazone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • porfimer

              verapamil decreases levels of porfimer by unspecified interaction mechanism. Minor/Significance Unknown.

            • pramipexole

              pramipexole will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • probenecid

              probenecid increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • prochlorperazine

              prochlorperazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • promazine

              promazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • promethazine

              promethazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • propafenone

              verapamil will increase the level or effect of propafenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • protriptyline

              verapamil increases levels of protriptyline by decreasing metabolism. Minor/Significance Unknown.

            • quinine

              verapamil will increase the level or effect of quinine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              quinine will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • ramelteon

              verapamil will increase the level or effect of ramelteon by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rapacuronium

              verapamil increases effects of rapacuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • reishi

              reishi increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

              reishi increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

            • rifampin

              rifampin decreases levels of trandolapril by increasing metabolism. Minor/Significance Unknown.

            • riluzole

              verapamil will increase the level or effect of riluzole by affecting hepatic enzyme CYP1A2 metabolism. Minor/Significance Unknown.

            • rocuronium

              verapamil increases effects of rocuronium by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • salicylates (non-asa)

              verapamil increases effects of salicylates (non-asa) by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

              salicylates (non-asa) decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • salsalate

              verapamil increases effects of salsalate by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • shepherd's purse

              shepherd's purse, trandolapril. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

            • saxagliptin

              verapamil will increase the level or effect of saxagliptin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • shepherd's purse

              shepherd's purse, verapamil. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

            • succinylcholine

              verapamil increases effects of succinylcholine by pharmacodynamic synergism. Minor/Significance Unknown. Ca Channel Blockers interfere w/Ach release from prejunctional axon.

            • sulfamethoxazole

              sulfamethoxazole will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • sulfasalazine

              sulfasalazine decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

              verapamil increases effects of sulfasalazine by unknown mechanism. Minor/Significance Unknown. Enhanced antiplatelet activity.

            • thioridazine

              thioridazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • tizanidine

              tizanidine increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

            • tizanidine

              tizanidine increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

            • tolfenamic acid

              tolfenamic acid decreases effects of trandolapril by pharmacodynamic antagonism. Minor/Significance Unknown. NSAIDs decrease prostaglandin synthesis.

            • trazodone

              verapamil increases levels of trazodone by decreasing metabolism. Minor/Significance Unknown.

            • treprostinil

              treprostinil increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

              treprostinil increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

            • triamterene

              triamterene will increase the level or effect of verapamil by basic (cationic) drug competition for renal tubular clearance. Minor/Significance Unknown.

            • trifluoperazine

              trifluoperazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            Previous
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            Adverse Effects

            >10%

            Verapamil

            • Headache (1-12 %)
            • Gingival hyperplasia (≤ 19%)
            • Constipation (7-12%)

            Trandolapril

            • Hypotension (1-11%)
            • Dizziness (1-23%)
            • Increased uric acid (15%)
            • Cough (2-35%)

            1-10%

            Verapamil

            • Dizziness (4%)
            • Dyspepsia (3%)
            • Edema (2%)
            • Fatigue (2%)
            • Lethargy (3%)
            • Pain (2%)
            • Sleep disturbance (1%)
            • Increased liver enzymes (1%)
            • Pulmonary edema (2%)
            • Flushing (1%)
            • Hypotension (4%)
            • Nausea (3%)

            Trandolapril

            • Syncope (6%)
            • Bradycardia (1-5%)
            • Stroke (3%)
            • Gastritis (4%)
            • Diarrhea (1%)
            • Weakness (3%)
            • Myalgia (5%)

            < 1%

            Trandolapril

            • Angioedema
            • ARF if renal artery stenosis
            • Cough

            Verapamil

            • Abdominal discomfort
            • Arthralgia
            • Extrapyramidal symptoms
            • Gastrointestinal distress
            • Hyperkeratosis
            • Gynecomastia
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            Warnings

            Black Box Warnings

            Trandolapril: Discontinue as soon as possible when pregnancy is detected; affects renin-angiotensin system causing oligohydramnios, which may result in fetal injury and/or death

            Contraindications

            Hypersensitivity to either component

            Second- or third-degree AV block (unless permanent pacemaker in place)

            Hypotension (systolic pressure less than 90 mmHg) or cardiogenic shock

            Concomitant use with aliskiren in patients with diabetes mellitus

            Sick sinus syndrome (unless permanent pacemaker in place)

            Patients with atrial flutter or atrial fibrillation and an accessory bypass tract (e.g. Wolff-Parkinson-White, Lown-Ganong-Levine syndromes)

            Do not coadminister with aliskiren in patients with diabetes

            History of angioedema

            Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan

            Severe left ventricular dysfunction

            Patients taking flibanserin

            Cautions

            Aortic stenosis, hypotension (initially or after dose increases) reported

            Persistent progressive dermatologic reactions reported

            Avoid taking with grapefruit juice

            Use caution in heart failure or compromised ventricular function

            Use caution in liver or renal impairment

            Use caution and monitor closely if adminstered with concurrent beta blocker therapy

            Excessive hypotension may occur if administered with concomitant diuretics, hypovolemia, hyponatremia

            Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for hypotension, hyperkalemia, and renal function changes (including acute renal failure) compared to monotherapy

            Avoid concomitant use of verapamil and quinidine in patients with hypertrophic cardiomyopathy; may cause significant hypotension

            Hemodialysis with high flux membrane and low-density lipoprotein apharesis associated with anaphylactoid reactions

            Avoid verapamil in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%, pulmonary wedge pressure above 20 mmHg, or severe symptoms of cardiac failure) and in patients with any degree of ventricular dysfunction if they are receiving a beta adrenergic blocker

            ACE inhibitors may cause excessive hypotension in patients with congestive heart failure

            Verapamil may produce a decrease in blood pressure below normal levels which may result in dizziness or symptomatic hypotension

            ACE inhibitors rarely associated with syndrome of cholestatic jaundice, fulminant hepatic necrosis, and death; mechanism of this syndrome is not understood; patients receiving ACE inhibitors who develop jaundice should discontinue therapy

            Not for administration to patients with paroxysmal and/or chronic atrial fibrillation or atrial flutter and a coexisting accessory AV pathway

            Reduce dose if marked first-degree block or progressive development to second-or third-degree AV block; in rare instances, discontinuation of verapamil HCl and institution of appropriate therapy depending upon clinical situation may be necessary

            Patients receiving coadministration of an ACE inhibitor with an mTOR (mammalian target of rapamycin) inhibitor (e.g., temsirolimus, sirolimus, everolimus) may be at increased risk for angioedema

            Discontinue immediately if If laryngeal stridor or angioedema of the face, tongue or glottis occurs

            Administration of other ACE inhibitors have been associated with agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen-vascular disease such as systemic lupus erythematosus or scleroderma; consider periodic monitoring of white blood cell counts in patients with collagen-vascular disease and/or renal disease

            Acceleration of ventricular rate and/or ventricular fibrillation has been reported in patients with atrial flutter or atrial fibrillation and a coexisting accessory AV pathway

            Drug interaction overview

            • Moderate CYP3A4 inhibitor such as verapamil with flibanserin significantly increases flibanserin concentrations, which can lead to severe hypotension and syncope; concomitant use is contraindicated at least 2 weeks prior to starting flibanserin; do not administer therapy within 2 days of discontinuing flibanserin
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            Pregnancy & Lactation

            Pregnancy Category: C (1st trimester); D (2nd and 3rd trimester)

            Lactation: excreted in breast milk, use caution

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Trandolapril/verapamil hydrochloride ER combines a slow release formulation of a calcium channel blocker, verapamil hydrochloride, and an immediate release formulation of an angiotensin converting enzyme inhibitor, trandolapril

            Trandolapril competitively inhibits angiotensin-converting enzymes resulting in decreased plasma angiotensin II concentrations and consequently, blood pressure may be reduced in part through decreased vasoconstriction, increased renin activity, and decreased aldosterone secretion

            Verapamil, a nondihydropyridine calcium-channel blocker, inhibits transmembrane influx of extracellular Ca ions across membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating main coronary and systemic arteries

            Pharmacokinetics

            Trandolapril

            • Half-life: 6 (trandolapril); 22.5 hr (trandolaprilat)
            • Onset: 1-2 hr
            • Duration: 72 hr
            • Vd: 18 L
            • Peak plasma time: 1 hr (trandolapril); 4-10 hr (trandolaprilat)
            • Bioavailability: 10% (trandolapril); 70% (trandolaprilat)
            • Protein bound: 80% (trandolapril); 65-94% (trandolaprilat)
            • Metabolism: Liver, undergoes hepatic biotransformation to trandolaprilat
            • Metabolites: Trandolaprilat (active)
            • Clearance: 52 L/hr (total body); 1-4 L/hr (renal)
            • Excretion: Urine 33%, feces 66%
            • Dialyzable: Yes

            Verapamil

            • Half-life: 4-12 hr (parent drug); 6-10 hr (norverapamil); increases to 14-16 hr in liver disease patients (norverapamil)
            • Bioavailability: 20-35%
            • Onset: 1-2 hr (peak effect)
            • Duration: 6-8 hr (PO); 10-20 min (IV)
            • Vd: 3.9 L/kg
            • Peak plasma time: 1-2 hr (immediate release); 11 hr (extended release); 4-5 hr (delayed release); 5-9 hr (sustained release)
            • Protein bound: 90%
            • Metabolism: Liver via P450 enzyme CYP3A4
            • Metabolites: Norverapamil (active)
            • Clearance: 0.5-1 L/kg
            • Excretion: Urine (70%); feces (16%)
            • Dialyzable: HD No
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            Administration

            Oral Administration

            Administer with food

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            Images

            No images available for this drug.
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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.