valsartan/amlodipine (Rx)

Brand and Other Names:Exforge
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Dosing & Uses

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Dosage Forms & Strengths

amlodipine/valsartan

tablet

  • 5mg/160mg
  • 5mg/320mg
  • 10mg/160mg
  • 10mg/320mg

Hypertension

Initiate with 5 mg/160 mg PO qDay OR

Substitute for individually titrated components

May increase dose after at least 2 weeks, not to exceed 10 mg/day amlodipine and 320 mg/day valsartan

May be adminsitered concomitantly with other antihypertensive agents

Dosage modifications

Renal impairment

  • Mild or moderate (CrCl >30 mL/min): Dose adjustment not necessary
  • Severe (CrCl <30 mL/min): Not studied

Hepatic impairment

  • Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination
  • Amlodipine: Exposure is increased with hepatic insufficiency, consider decreasing dose
  • Valsartan: Exposure increased with mild-to-moderate hepatic insufficiency does not require dosage adjustment; unknown for severe hepatic impairment

Safety and efficacy not established

Not recommended for initial therapy; amlodipine 2.5 mg is not an available strength with available dosage forms for this drug combination

Base initial dose on 2.5 mg of amlodipine PO qDay

No overall difference in the efficacy or safety of valsartan has been observed, but greater sensitivity of some older individuals cannot be ruled out

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Interactions

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            Contraindicated (2)

            • aliskiren

              valsartan decreases effects of aliskiren by Other (see comment). Contraindicated. Comment: Aliskiren use contraindicated with ARBs in patients with diabetes; avoid coadministration with ARBs if GFR. In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, coadministration of ARBS 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, amlodipine. 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.

            Serious - Use Alternative (29)

            • abametapir

              abametapir will increase the level or effect of amlodipine 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.

            • apalutamide

              apalutamide will decrease the level or effect of amlodipine 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.

            • baricitinib

              valsartan will increase the level or effect of baricitinib by decreasing elimination. Avoid or Use Alternate Drug. Coadministration of baricitinib with strong organic anion transporter 3 (OAT3) inhibitors is not recommended.

            • benazepril

              valsartan, benazepril. 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.

            • captopril

              valsartan, captopril. 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.

            • chloramphenicol

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

            • chloroquine

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

            • conivaptan

              conivaptan will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.

            • diltiazem

              diltiazem will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Concomitant use with amlodipine and diltiazem reported an a 60% increase in amlodipine AUC. Monitor increased effects and toxicities (eg, bradycardia, sinus arrest, decreased cardiac output) if amiodarone is concomitantly used with nondihydropyridine calcium channel blocker (ie, diltiazem).

            • eluxadoline

              valsartan increases levels of eluxadoline by decreasing metabolism. Avoid or Use Alternate Drug. Decrease eluxadoline dose to 75 mg PO BID if coadministered with OATP1B1 inhibitors. .

            • enalapril

              valsartan, enalapril. 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.

            • enzalutamide

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

            • fexinidazole

              fexinidazole will increase the level or effect of amlodipine 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.

            • fosinopril

              valsartan, fosinopril. 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.

            • idelalisib

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

            • ivosidenib

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

            • lisinopril

              valsartan, lisinopril. 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.

            • lithium

              valsartan increases toxicity of lithium by decreasing renal clearance. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine, amlodipine. 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, valsartan. 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.

            • lonafarnib

              amlodipine will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

              lonafarnib will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

            • moexipril

              valsartan, moexipril. 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.

            • nifedipine

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

            • perindopril

              valsartan, perindopril. 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.

            • potassium phosphates, IV

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

            • quinapril

              valsartan, quinapril. 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.

            • ramipril

              valsartan, ramipril. 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.

            • simvastatin

              amlodipine increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Benefits of combination therapy should be carefully weighed against the potential risks of combination. Potential for increased risk of myopathy/rhabdomyolysis. Limit simvastatin dose to no more than 20 mg/day when used concurrently.

            • trandolapril

              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.

            • voxelotor

              voxelotor will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            Monitor Closely (260)

            • acebutolol

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

              valsartan and acebutolol both increase serum potassium. Use Caution/Monitor.

              acebutolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • aceclofenac

              valsartan and aceclofenac both increase serum potassium. Use Caution/Monitor.

            • aldesleukin

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

            • acemetacin

              valsartan and acemetacin both increase serum potassium. Use Caution/Monitor.

            • albiglutide

              valsartan increases effects of albiglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • aldesleukin

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

            • alfuzosin

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

            • amifostine

              amifostine, amlodipine. 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, valsartan. 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.

            • amiloride

              valsartan and amiloride both increase serum potassium. Modify Therapy/Monitor Closely.

            • asenapine

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

            • apalutamide

              apalutamide will decrease the level or effect of valsartan by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

            • aspirin

              valsartan and aspirin both increase serum potassium. Use Caution/Monitor.

              aspirin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, aspirin. 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.

            • aspirin rectal

              valsartan and aspirin rectal both increase serum potassium. Use Caution/Monitor.

            • aspirin/citric acid/sodium bicarbonate

              aspirin/citric acid/sodium bicarbonate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and aspirin/citric acid/sodium bicarbonate both increase serum potassium. Use Caution/Monitor.

              valsartan, aspirin/citric acid/sodium bicarbonate. 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.

            • atenolol

              atenolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              atenolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              valsartan and atenolol both increase serum potassium. Use Caution/Monitor.

            • atogepant

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

            • atorvastatin

              atorvastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              valsartan increases toxicity of atorvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • avanafil

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

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

            • avapritinib

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

            • bendroflumethiazide

              valsartan increases and bendroflumethiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • axitinib

              amlodipine increases levels of axitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • betaxolol

              betaxolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              betaxolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              valsartan and betaxolol both increase serum potassium. Use Caution/Monitor.

            • bisoprolol

              bisoprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

              bisoprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

              valsartan and bisoprolol both increase serum potassium. Use Caution/Monitor.

            • bosentan

              bosentan will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor for decreased effects of amlodipine (CYP3A4 substrate) if bosentan is initiated/dose increased. Also, monitor toxicities of amlodipine if bosentan is discontinued/dose decreased.

            • bretylium

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

            • bretylium

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

            • brimonidine

              brimonidine increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • bumetanide

              valsartan increases and bumetanide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • butabarbital

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

            • butalbital

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

            • calcium acetate

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

            • calcium carbonate

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

            • calcium chloride

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

            • calcium citrate

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

            • calcium gluconate

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

            • canagliflozin

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

            • carbamazepine

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

              carbamazepine will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • carbenoxolone

              valsartan increases and carbenoxolone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbidopa

              carbidopa increases effects of amlodipine 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, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

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

              valsartan and carvedilol both increase serum potassium. Use Caution/Monitor.

            • caspofungin

              caspofungin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • celiprolol

              celiprolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • celecoxib

              valsartan and celecoxib both increase serum potassium. Use Caution/Monitor.

              celecoxib decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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

              valsartan and celiprolol both increase serum potassium. Use Caution/Monitor.

              celiprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • cenobamate

              cenobamate will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • chlorothiazide

              valsartan increases and chlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chlorthalidone

              valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • choline magnesium trisalicylate

              valsartan and choline magnesium trisalicylate both increase serum potassium. Use Caution/Monitor.

              choline magnesium trisalicylate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, choline magnesium trisalicylate. 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.

            • clarithromycin

              clarithromycin will increase the level or effect of amlodipine 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

              clarithromycin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • clevidipine

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

            • cyclopenthiazide

              valsartan increases and cyclopenthiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • cobicistat

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

            • crizotinib

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

            • cyclosporine

              cyclosporine and valsartan both increase Other (see comment). Use Caution/Monitor. Cyclosporine and valsartan both increase the risk of hyperkalemia and nephrotoxicity.

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

              amlodipine increases levels of cyclosporine by unspecified interaction mechanism. Modify Therapy/Monitor Closely. A prospective study in renal transplant recipients averaged a 40% increase in cyclosporine trough levels.

            • dabrafenib

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

            • dalteparin

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

            • darunavir

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

            • deferasirox

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

            • dichlorphenamide

              dichlorphenamide and amlodipine both decrease serum potassium. Use Caution/Monitor.

            • diclofenac

              valsartan and diclofenac both increase serum potassium. Use Caution/Monitor.

              diclofenac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • diflunisal

              valsartan and diflunisal both increase serum potassium. Use Caution/Monitor.

              diflunisal decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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

              valsartan will increase the level or effect of digoxin by decreasing renal clearance. Use Caution/Monitor. Monitor digoxin levels closely when coadministered with drugs that may decrease glomerular filtration or tubular secretion.

            • diltiazem

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

            • dobutamine

              valsartan increases and dobutamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              valsartan increases and dopexamine decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • doxazosin

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

            • dronedarone

              dronedarone will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only ECG is reviewed and tolerated.

            • drospirenone

              valsartan and drospirenone both increase serum potassium. Modify Therapy/Monitor Closely.

            • efavirenz

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

            • elagolix

              elagolix will decrease the level or effect of amlodipine 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.

            • eltrombopag

              eltrombopag will decrease the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amlodipine 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 will increase the level or effect of valsartan by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

              encorafenib, amlodipine. 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 valsartan by Other (see comment). Use Caution/Monitor. Comment: Low molecular weight heparins may suppress adrenal aldosterone secretion, which can potentially cause hyperkalemia.

            • erythromycin base

              erythromycin base will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • eplerenone

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

            • eprosartan

              eprosartan and valsartan both increase serum potassium. Use Caution/Monitor.

            • erythromycin base

              erythromycin base will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              erythromycin ethylsuccinate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              erythromycin lactobionate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              erythromycin stearate will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • eslicarbazepine acetate

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

            • esmolol

              valsartan and esmolol both increase serum potassium. Use Caution/Monitor.

              esmolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • esmolol

              esmolol, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • ethacrynic acid

              valsartan increases and ethacrynic acid decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • etodolac

              valsartan and etodolac both increase serum potassium. Use Caution/Monitor.

              etodolac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • exenatide injectable solution

              valsartan increases effects of exenatide injectable solution by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • exenatide injectable suspension

              valsartan increases effects of exenatide injectable suspension by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • fedratinib

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

            • felodipine

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

            • fenbufen

              valsartan and fenbufen both increase serum potassium. Use Caution/Monitor.

            • fenoprofen

              valsartan and fenoprofen both increase serum potassium. Use Caution/Monitor.

              fenoprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • finerenone

              amlodipine 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 weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

            • flibanserin

              amlodipine will increase the level or effect of flibanserin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Increased flibanserin adverse effects may occur if coadministered with multiple weak CYP3A4 inhibitors.

            • fluconazole

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

            • flurbiprofen

              valsartan and flurbiprofen both increase serum potassium. Use Caution/Monitor.

              flurbiprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, flurbiprofen. 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.

            • fluvastatin

              valsartan increases toxicity of fluvastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • fosamprenavir

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

            • fosphenytoin

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

            • fostemsavir

              fostemsavir will increase the level or effect of valsartan by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

            • furosemide

              valsartan increases and furosemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • gemfibrozil

              gemfibrozil will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • gentamicin

              valsartan increases and gentamicin decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • glyburide

              glyburide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • griseofulvin

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

            • heparin

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

            • hydrochlorothiazide

              valsartan increases and hydrochlorothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ibuprofen

              valsartan and ibuprofen both increase serum potassium. Use Caution/Monitor.

              ibuprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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 valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and ibuprofen IV both increase serum potassium. Use Caution/Monitor.

              valsartan, 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.

            • iloperidone

              iloperidone and amlodipine both increase additive vasodilation. Use Caution/Monitor. Calcium channel blockers with iloperidone may potentiate the hypotensive effects.

            • indapamide

              valsartan increases and indapamide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • indinavir

              indinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • indomethacin

              valsartan and indomethacin both increase serum potassium. Use Caution/Monitor.

              indomethacin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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

              valsartan increases effects of insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin aspart protamine/insulin aspart

              valsartan increases effects of insulin aspart protamine/insulin aspart by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec

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

              valsartan increases effects of insulin degludec by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin degludec/insulin aspart

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

            • insulin detemir

              valsartan increases effects of insulin detemir by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin glargine

              valsartan increases effects of insulin glargine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin glulisine

              valsartan increases effects of insulin glulisine by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin inhaled

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

              valsartan increases effects of insulin inhaled by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin isophane human/insulin regular human

              valsartan increases effects of insulin isophane human/insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro

              valsartan increases effects of insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin lispro protamine/insulin lispro

              valsartan increases effects of insulin lispro protamine/insulin lispro by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin NPH

              valsartan increases effects of insulin NPH by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • insulin regular human

              valsartan increases effects of insulin regular human by unspecified interaction mechanism. Use Caution/Monitor. Concomitant use of insulin and ARBs may require insulin dosage adjustment and increased glucose monitoring.

            • isavuconazonium sulfate

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

            • isradipine

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

            • istradefylline

              istradefylline will increase the level or effect of amlodipine 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.

            • itraconazole

              itraconazole will increase the level or effect of amlodipine 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.

            • ketoconazole

              ketoconazole will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • ketoprofen

              valsartan and ketoprofen both increase serum potassium. Use Caution/Monitor.

              ketoprofen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • labetalol

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

            • ketorolac

              valsartan and ketorolac both increase serum potassium. Use Caution/Monitor.

              ketorolac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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

              valsartan and ketorolac intranasal both increase serum potassium. Use Caution/Monitor.

              ketorolac intranasal decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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

              valsartan and labetalol both increase serum potassium. Use Caution/Monitor.

              labetalol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • lemborexant

              amlodipine will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.

            • lesinurad

              lesinurad decreases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • letermovir

              letermovir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              letermovir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

              valsartan increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

            • levodopa

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

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

            • levoketoconazole

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

              levoketoconazole will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • liraglutide

              valsartan increases effects of liraglutide by Other (see comment). Use Caution/Monitor. Comment: Angiotensin II receptor antagonists may enhance hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. Monitor patients for changes in glycemic control.

            • lomitapide

              amlodipine increases levels of lomitapide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lomitapide dose should not exceed 30 mg/day.

            • lopinavir

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

            • lorlatinib

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

            • lornoxicam

              valsartan and lornoxicam both increase serum potassium. Use Caution/Monitor.

            • lovastatin

              lovastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • lurasidone

              lurasidone increases effects of amlodipine 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 valsartan 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, amlodipine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Calcium channel blockers may increase toxic effects of magnesium; magnesium may increase hypotensive effects of calcium channel blockers.

            • maitake

              maitake increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • maraviroc

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

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

            • meclofenamate

              meclofenamate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan and meclofenamate both increase serum potassium. Use Caution/Monitor.

              valsartan, 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.

            • mefloquine

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

            • mefenamic acid

              valsartan and mefenamic acid both increase serum potassium. Use Caution/Monitor.

              mefenamic acid decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • meloxicam

              valsartan and meloxicam both increase serum potassium. Use Caution/Monitor.

              meloxicam decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • metformin

              amlodipine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

            • methyclothiazide

              valsartan increases and methyclothiazide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • methylphenidate

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

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

            • methylphenidate transdermal

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

            • midazolam intranasal

              amlodipine will increase the level or effect of midazolam intranasal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of mild CYP3A4 inhibitors with midazolam intranasal may cause higher midazolam systemic exposure, which may prolong sedation.

            • metolazone

              valsartan increases and metolazone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metoprolol

              valsartan and metoprolol both increase serum potassium. Use Caution/Monitor.

              metoprolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • metyrapone

              metyrapone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • mifepristone

              mifepristone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • mitotane

              mitotane decreases levels of amlodipine 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.

            • nabumetone

              valsartan and nabumetone both increase serum potassium. Use Caution/Monitor.

              nabumetone decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • moxisylyte

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

            • nadolol

              nadolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

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

              valsartan and nadolol both increase serum potassium. Use Caution/Monitor.

            • naproxen

              valsartan and naproxen both increase serum potassium. Use Caution/Monitor.

              naproxen decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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, amlodipine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • nebivolol

              valsartan and nebivolol both increase serum potassium. Use Caution/Monitor.

              nebivolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • nefazodone

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

            • nelfinavir

              nelfinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • nevirapine

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

            • nicardipine

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

            • nifedipine

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

            • nilotinib

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

            • nirmatrelvir

              nirmatrelvir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce amlodipine dose by 50% during coadministration and for 3 more days after the last nirmatrelvir/ritonavir dose.

            • nisoldipine

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

            • nitroglycerin rectal

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

            • nitroglycerin sublingual

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. May inhibit organic anion transporter polypeptides; decrease dose of angiotensin receptor blockers and monitor patients for signs and symptoms of hypotension and/or worsening renal function; if such events occur, consider further dose reduction of angiotensin receptor blocker or switching to alternative to angiotensin receptor blocker

            • nitroprusside sodium

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; 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

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of amlodipine by altering metabolism. Modify Therapy/Monitor Closely. Decrease dose of calcium channel blocker; dose of amlodipine should be decreased by at least 50%; 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

            • oxaprozin

              valsartan and oxaprozin both increase serum potassium. Use Caution/Monitor.

              oxaprozin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • paclitaxel

              paclitaxel will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • paclitaxel protein bound

              paclitaxel protein bound will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • parecoxib

              valsartan and parecoxib both increase serum potassium. Use Caution/Monitor.

            • pazopanib

              pazopanib will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • penbutolol

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

              valsartan and penbutolol both increase serum potassium. Use Caution/Monitor.

              penbutolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • pentobarbital

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

            • pindolol

              valsartan and pindolol both increase serum potassium. Use Caution/Monitor.

              pindolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • phenobarbital

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

            • phenoxybenzamine

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

            • phentolamine

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

            • phenytoin

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

            • pindolol

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

            • pioglitazone

              pioglitazone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • piroxicam

              valsartan and piroxicam both increase serum potassium. Use Caution/Monitor.

              piroxicam decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • pitavastatin

              valsartan increases toxicity of pitavastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • posaconazole

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

            • potassium acid phosphate

              valsartan and potassium acid phosphate both increase serum potassium. Use Caution/Monitor.

            • potassium chloride

              valsartan and potassium chloride both increase serum potassium. Use Caution/Monitor.

            • potassium citrate

              valsartan and potassium citrate both increase serum potassium. Use Caution/Monitor.

            • potassium citrate/citric acid

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

            • potassium iodide

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

            • pravastatin

              pravastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              valsartan increases toxicity of pravastatin by Other (see comment). Use Caution/Monitor. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • prazosin

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

            • primidone

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

            • propranolol

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

              valsartan and propranolol both increase serum potassium. Use Caution/Monitor.

              propranolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • repaglinide

              repaglinide will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • ribociclib

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

            • rifabutin

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

            • rifampin

              rifampin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

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

            • rifapentine

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

            • ritonavir

              ritonavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              ritonavir will increase the level or effect of valsartan by Mechanism: decreasing hepatic clearance. Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic efflux transporter MRP2; coadministration of inhibitors of the efflux transporter may increase the systemic exposure to valsartan

            • ritonavir

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

            • rosiglitazone

              rosiglitazone will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • rucaparib

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

            • salicylates (non-asa)

              valsartan and salicylates (non-asa) both increase serum potassium. Use Caution/Monitor.

            • salsalate

              valsartan and salsalate both increase serum potassium. Use Caution/Monitor.

              salsalate decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, salsalate. 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.

            • saquinavir

              saquinavir will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

              saquinavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. .

            • silodosin

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

            • simvastatin

              simvastatin will increase the level or effect of valsartan by Other (see comment). Use Caution/Monitor. The results from an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1; coadministration with OATP1B1 inhibitors may increase valsartan systemic exposure

            • sodium sulfate/?magnesium sulfate/potassium chloride

              amlodipine, sodium sulfate/?magnesium sulfate/potassium chloride. Either increases effects 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/?magnesium sulfate/potassium chloride increases toxicity of valsartan 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.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              amlodipine, sodium sulfate/potassium sulfate/magnesium sulfate. Either increases effects 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 increases toxicity of valsartan 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.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of valsartan by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

            • St John's Wort

              St John's Wort will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • sotalol

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

            • sotalol

              valsartan and sotalol both increase serum potassium. Use Caution/Monitor.

              sotalol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

            • spironolactone

              valsartan and spironolactone both increase serum potassium. Modify Therapy/Monitor Closely.

            • stiripentol

              stiripentol, amlodipine. 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.

            • sulfasalazine

              valsartan and sulfasalazine both increase serum potassium. Use Caution/Monitor.

              sulfasalazine decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, sulfasalazine. 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.

            • sulindac

              valsartan and sulindac both increase serum potassium. Use Caution/Monitor.

              sulindac decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • synthetic human angiotensin II

              valsartan decreases effects of synthetic human angiotensin II by pharmacodynamic antagonism. Use Caution/Monitor.

            • tacrolimus

              amlodipine will increase the level or effect of tacrolimus by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Adjust dose when appropriate.

            • tadalafil

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

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

            • tazemetostat

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

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

            • terbutaline

              valsartan increases and terbutaline decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tecovirimat

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

            • temsirolimus

              amlodipine increases toxicity of temsirolimus by Other (see comment). Use Caution/Monitor. Comment: Combination of mTOR inhibitors with calcium channel blockers increases risk of angioedema.

            • terazosin

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

            • timolol

              timolol, valsartan. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of fetal compromise if given during pregnancy.

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

              valsartan and timolol both increase serum potassium. Use Caution/Monitor.

            • tinidazole

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

            • tizanidine

              tizanidine increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • tipranavir

              tipranavir increases levels of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Potential for increased toxicity. Tipranavir is used with ritonavir (boosted therapy) which is a potent CYP3A4 inhibitor.

            • tolfenamic acid

              valsartan and tolfenamic acid both increase serum potassium. Use Caution/Monitor.

            • tolmetin

              valsartan and tolmetin both increase serum potassium. Use Caution/Monitor.

              tolmetin decreases effects of valsartan by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. NSAIDs decrease synthesis of vasodilating renal prostaglandins, and thus affect fluid homeostasis and may diminish antihypertensive effect.

              valsartan, 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.

            • tolvaptan

              valsartan and tolvaptan both increase serum potassium. Use Caution/Monitor.

            • torsemide

              valsartan increases and torsemide decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • treprostinil

              treprostinil increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • triamterene

              valsartan and triamterene both increase serum potassium. Modify Therapy/Monitor Closely.

            • trimagnesium citrate anhydrous

              trimagnesium citrate anhydrous, amlodipine. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Possible additive effect of magnesium and calcium channel blockers on reduction of ionic calcium may increase risk of hypotension or muscle weakness.

            • trimethoprim

              valsartan and trimethoprim 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.

            • verapamil

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

            • voclosporin

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

              voclosporin, valsartan. 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 amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

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

            • xipamide

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

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

            Minor (50)

            • agrimony

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

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

            • amobarbital

              amobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cornsilk

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

            • aprepitant

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

            • armodafinil

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

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atazanavir

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

            • atracurium

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

            • brimonidine

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

            • cisatracurium

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

            • cornsilk

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

            • dasatinib

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

            • dexamethasone

              dexamethasone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • entecavir

              valsartan, 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.

            • etravirine

              etravirine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fo-ti

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

            • food

              food decreases levels of valsartan by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

            • forskolin

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

            • grapefruit

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

            • hydrocortisone

              hydrocortisone will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • incobotulinumtoxinA

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

            • lithium

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

            • maitake

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

            • metipranolol ophthalmic

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

            • nelfinavir

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

            • noni juice

              valsartan and noni juice both increase serum potassium. Minor/Significance Unknown.

            • octacosanol

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

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

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) will increase the level or effect of valsartan by decreasing elimination. Minor/Significance Unknown. May inhibit hepatic efflux transporter MRP2; decrease dose of angiotensin receptor blockers and monitor patients for signs and symptoms of hypotension and/or worsening renal function; if such events occur, consider further dose reduction of angiotensin receptor blocker or switching to alternative to angiotensin receptor blocker

            • onabotulinumtoxinA

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

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • pancuronium

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

            • porfimer

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

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rapacuronium

              amlodipine 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 amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.

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

            • rocuronium

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

            • shepherd's purse

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

            • rufinamide

              rufinamide will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ruxolitinib

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

            • ruxolitinib topical

              amlodipine will increase the level or effect of ruxolitinib topical by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital will decrease the level or effect of amlodipine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • shepherd's purse

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

            • simvastatin

              valsartan increases toxicity of simvastatin by Other (see comment). Minor/Significance Unknown. Comment: OATP1B1 inhibitors may increase risk of myopathy.

            • succinylcholine

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

            • tizanidine

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

            • treprostinil

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

            • vecuronium

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

            • verteporfin

              amlodipine increases levels of verteporfin by pharmacodynamic synergism. Minor/Significance Unknown.

            • voclosporin

              voclosporin will increase the level or effect of valsartan by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            >10%

            Headache

            Increased BUN (6-17%)

            1-10%

            Peripheral edema (5-8%)

            Anxiety (3%)

            Nasopharyngitis (4%)

            Increased potassium (3%)

            Upper respiratory infection (3%)

            Dizziness (2%)

            Somnolence (3%)

            Diarrhea (3%)

            Nausea (3%)

            Abdominal pain (3%)

            Cough (2%)

            <1%

            Orthostatic hypotension

            Syncope

            Visual disturbance

            Tinnitus

            Exanthema

            Postmarketing Reports

            Rhabdomyolysis

            Amlodipine

            • Gynecomastia
            • Jaundice and hepatic enzyme elevations

            Valsartan

            • Hypersensitivity: Angioedema (rare)
            • Digestive: Elevated liver enzymes, hepatitis (rare)
            • Renal: Impaired renal function, renal failure
            • Clinical laboratory tests: Hyperkalemia
            • Dermatologic: Alopecia, bullous dermatitis
            • Blood and lymphatic: Thrombocytopenia (rare)
            • Vascular: Vasculitis
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            Warnings

            Black Box Warnings

            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 valsartan, amlodipine, or excipients

            Concomitant administration with aliskiren in patients with diabetes mellitus

            Cautions

            Drugs that inhibit renin-angiotensin system can cause hyperkalemia; monitor serum electrolytes periodically; some patients with heart failure have developed increases in potassium with valsartan therapy; these effects are usually minor and transient, and they are more likely to occur in patients with pre-existing renal impairment; dosage reduction and/or discontinuation of therapy may be required

            Worsening angina and acute MI may occur after starting or increasing amlodipine dose, particularly with severe obstructive CAD

            Peripheral edema may occur within 2-3 weeks of starting therapy (amlodipine)

            Use caution in heart failure, severe aortic stenosis (amlodipine), hepatic impairment, renal artery stenosis, or hypertrophic cardiomyopathy

            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; closely monitor blood pressure

            Impaired renal function

            • Changes in renal function including acute renal failure can be caused by drugs that inhibit renin-angiotensin system and by diuretics; patients whose renal function may depend in part on activity of renin­ angiotensin system (eg, patients with renal artery stenosis, chronic kidney disease, severe congestive heart failure, or volume depletion) may be at particular risk of developing acute renal failure with therapy
            • Monitor renal function periodically in these patients; consider withholding or discontinuing therapy in patients who develop a clinically significant decrease in renal function

            Hypotension

            • In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur in patients receiving angiotensin receptor blockers; volume depletion should be corrected prior to therapy administration; treatment should start under close medical supervision
            • Initiate therapy cautiously in patients with heart failure or recent myocardial infarction and in patients undergoing surgery or dialysis; patients with heart failure or post-myocardial infarction patients given valsartan commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed
            • Since vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration; nonetheless, caution, as with any other peripheral vasodilator, should be exercised when administering amlodipine, particularly in patients with severe aortic stenosis
            • If excessive hypotension occurs with therapy, place patient in a supine position and, if necessary, give intravenous normal saline; a transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized

            Fetal toxicity

            • Use during the 2nd or 3rd trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black Box Warnings)
            • Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations; potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death; when pregnancy detected, discontinue therapy as soon as possible
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            Pregnancy & Lactation

            Pregnancy

            The drug combination can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death

            Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents

            When pregnancy is detected, discontinue therapy as soon as possible

            Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (eg, need for cesarean section, and post-partum hemorrhage)

            Hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

            Fetal/neonate adverse reactions

            • Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in second and third trimesters of pregnancy can result in reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death
            • Perform serial ultrasound examinations to assess the intra-amniotic environment; fetal testing may be appropriate, based on the week of gestation; oligohydramnios may not appear until after the fetus has sustained irreversible injury
            • If oligohydramnios is observed, consider alternative drug treatment; closely observe neonates with histories of in utero exposure to the drug combination for hypotension, oliguria, and hyperkalemia; in neonates with a history of in utero exposure to the drug combination, if oliguria or hypotension occurs, support blood pressure and renal perfusion
            • Exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function

            Lactation

            There is limited information regarding presence of drug combination in human milk, effects on breastfed infant, or on milk production; valsartan is present in rat milk; limited published studies report that amlodipine is present in human milk

            Because of the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment with this drug combination

            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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            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.