nebivolol/valsartan (Rx)

Brand and Other Names:Byvalson
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

nebivolol/valsartan

tablet

  • 5mg/80mg

Hypertension

Indicated for hypertension, to lower blood pressure and reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarction

May be used as initial therapy (if not controlled on valsartan 80 mg or ≤10 mg nebivolol) or be substituted for its components in patients already receiving nebivolol 5 mg and valsartan 80 mg

1 tablet (ie, 5 mg/80 mg) PO qDay

Dosage Modifications

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate (Child-Pugh B): Not recommended as initial treatment because recommended starting dose for these patients is nebivolol 2.5 mg/day
  • Severe (Child-Pugh C): Contraindicated

Renal impairment

  • Mild or moderate (CrCl >60 mL/min): No dosage adjustment required
  • Moderate and severe: Not studied

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and nebivolol/valsartan

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            Contraindicated (1)

            • 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.

            Serious - Use Alternative (43)

            • acebutolol

              acebutolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • atenolol

              atenolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • 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.

            • betaxolol

              betaxolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • bisoprolol

              bisoprolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • 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.

            • carvedilol

              carvedilol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • celiprolol

              celiprolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • clonidine

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

            • dacomitinib

              dacomitinib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

            • digoxin

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

            • diltiazem

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

            • 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.

            • esmolol

              esmolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • fexinidazole

              fexinidazole, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to induce bradycardia. .

            • fluoxetine

              fluoxetine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • givosiran

              givosiran will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

            • labetalol

              labetalol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • 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, nebivolol. 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.

            • lumefantrine

              lumefantrine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • 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.

            • metoprolol

              metoprolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • nadolol

              nadolol and nebivolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • penbutolol

              nebivolol and penbutolol both increase anti-hypertensive channel blocking. 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.

            • pindolol

              nebivolol and pindolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • potassium phosphates, IV

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

            • propranolol

              nebivolol and propranolol both increase anti-hypertensive channel blocking. 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.

            • quinidine

              quinidine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Monitor blood pressure. Reduced doses of nebivolol may be necessary.

            • 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.

            • rivastigmine

              nebivolol increases toxicity of rivastigmine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive bradycardia effect may result in syncope.

            • sotalol

              nebivolol and sotalol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • timolol

              nebivolol and timolol both increase anti-hypertensive channel blocking. Avoid or Use Alternate Drug.

            • 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.

            • verapamil

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

            Monitor Closely (290)

            • abiraterone

              abiraterone increases levels of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • acebutolol

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

              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.

              aceclofenac decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • acemetacin

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

              acemetacin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • albuterol

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

              nebivolol decreases effects of albuterol by pharmacodynamic antagonism. Use Caution/Monitor.

            • aldesleukin

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

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

            • alfuzosin

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

            • 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.

            • aluminum hydroxide

              aluminum hydroxide decreases levels of nebivolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • amifostine

              amifostine, nebivolol. 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

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

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

            • amiodarone

              amiodarone will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Monitor cardiac function carefully and observe for signs of bradycardia or heart block when amiodarone and a beta adrenergic blocker are coadministered. Amiodarone should be used with caution in patients receiving a beta adrenergic blocker, particularly if there is suspicion of underlying dysfunction of the sinus node, such as bradycardia or sick sinus syndrome, or if there is partial AV block.

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

            • 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.

            • amlodipine

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

            • amobarbital

              amobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of amobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • arformoterol

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

              nebivolol decreases effects of arformoterol by pharmacodynamic antagonism. Use Caution/Monitor.

            • asenapine

              asenapine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

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

            • aspirin

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

              aspirin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

              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.

            • aspirin rectal

              aspirin rectal decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

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

            • aspirin/citric acid/sodium bicarbonate

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

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

              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.

              aspirin/citric acid/sodium bicarbonate decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • atazanavir

              atazanavir increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypotension, bradycardia, AV block, and prolonged PR interval. Consider lowering beta blocker dose.

            • atenolol

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

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

            • atenolol

              atenolol and nebivolol both increase serum potassium. 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 nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

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

            • bendroflumethiazide

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

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

            • betaxolol

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

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

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

            • bismuth subsalicylate

              bismuth subsalicylate, nebivolol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Blockage of renal prostaglandin synthesis; may cause severe hypertension.

            • bisoprolol

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

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

            • bisoprolol

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

            • bretylium

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

              valsartan, 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

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

            • bumetanide

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

            • bupropion

              bupropion will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • butabarbital

              butabarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butabarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • butalbital

              butalbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of butalbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • calcium acetate

              calcium acetate decreases effects of nebivolol by unspecified interaction mechanism. Use Caution/Monitor.

            • calcium carbonate

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

              calcium carbonate decreases levels of nebivolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • calcium chloride

              calcium chloride decreases effects of nebivolol by unspecified interaction mechanism. Use Caution/Monitor.

            • calcium citrate

              calcium citrate decreases effects of nebivolol by unspecified interaction mechanism. Use Caution/Monitor.

            • calcium gluconate

              calcium gluconate decreases effects of nebivolol by unspecified interaction mechanism. Use Caution/Monitor.

            • canagliflozin

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

            • candesartan

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

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

            • carbamazepine

              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

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

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

            • carbidopa

              carbidopa increases effects of nebivolol 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

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

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

            • carvedilol

              carvedilol and nebivolol 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

            • celecoxib

              nebivolol 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.

              celecoxib decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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.

              celecoxib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • celiprolol

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

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

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

            • chloroquine

              chloroquine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • chlorothiazide

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

            • chlorothiazide

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

            • chlorthalidone

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

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

            • choline magnesium trisalicylate

              nebivolol 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.

              choline magnesium trisalicylate decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • cimetidine

              cimetidine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • clarithromycin

              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

              nebivolol, clevidipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • clonidine

              nebivolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

              clonidine, nebivolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

            • cyclopenthiazide

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

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

            • cyclosporine

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

            • darifenacin

              darifenacin will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • 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.

            • dasiglucagon

              nebivolol decreases effects of dasiglucagon by unknown mechanism. Use Caution/Monitor. Dasiglucagon may stimulate catecholamine release; whereas beta blockers may inhibit catecholamines released in response to dasiglucagon. Coadministration may also transiently increase pulse and BP.

            • desflurane

              desflurane, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • desvenlafaxine

              desvenlafaxine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

            • 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.

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

              diclofenac decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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

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

              diflunisal decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

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

            • digoxin

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

              nebivolol increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Enhanced bradycardia.

              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

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

            • dobutamine

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

            • diphenhydramine

              diphenhydramine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • dobutamine

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

              nebivolol decreases effects of dobutamine by pharmacodynamic antagonism. Use Caution/Monitor.

            • dopexamine

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

              nebivolol decreases effects of dopexamine by pharmacodynamic antagonism. Use Caution/Monitor.

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

            • doxazosin

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

            • drospirenone

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

            • dronedarone

              dronedarone will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • drospirenone

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

            • duloxetine

              duloxetine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • eliglustat

              eliglustat increases levels of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

            • 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 nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • 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.

            • ephedrine

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

              nebivolol decreases effects of ephedrine by pharmacodynamic antagonism. Use Caution/Monitor.

            • epinephrine

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

              nebivolol decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor.

            • epinephrine racemic

              nebivolol increases and epinephrine racemic decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              nebivolol decreases effects of epinephrine racemic by pharmacodynamic antagonism. 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.

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

              eprosartan and nebivolol 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

            • esmolol

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

            • 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 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 stearate

              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

            • 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.

            • ethacrynic acid

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

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

            • ether

              nebivolol, ether. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both beta blockers and ether depress the myocardium; consider lowering beta blocker dose if ether used for anesthesia.

            • 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.

            • etodolac

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

              etodolac decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • etomidate

              etomidate, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • 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 nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • felodipine

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

            • fenbufen

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

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

            • fenoprofen

              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.

              fenoprofen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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.

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

            • fingolimod

              nebivolol increases effects of fingolimod by pharmacodynamic synergism. Use Caution/Monitor. Both medications decrease heart rate. Monitor patients on concomitant therapy, particularly in the first 6 hours after fingolimod is initiated or after a treatment interruption of at least two weeks, for bradycardia and atrioventricular block. To identify underlying risk factors of bradycardia and AV block, obtain a new or recent ECG in patients using beta-blockers prior to starting fingolimod.

            • 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.

            • flurbiprofen

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

              flurbiprofen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • fluvastatin

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

            • formoterol

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

              nebivolol decreases effects of formoterol by pharmacodynamic antagonism. 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

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

              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

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

            • gentamicin

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

            • glucagon

              glucagon decreases toxicity of nebivolol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Coadministration of glucagon with beta-blockers may have transiently increased pulse and blood pressure.

            • glucagon intranasal

              glucagon intranasal decreases toxicity of nebivolol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Coadministration of glucagon with beta-blockers may have transiently increased pulse and blood pressure.

            • 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

            • haloperidol

              haloperidol will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 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.

            • hydralazine

              hydralazine increases effects of nebivolol by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

            • hydrochlorothiazide

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

              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.

              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.

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

              ibuprofen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • ibuprofen IV

              ibuprofen IV decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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.

            • imatinib

              imatinib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • indapamide

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

            • indacaterol, inhaled

              indacaterol, inhaled, nebivolol. Other (see comment). Use Caution/Monitor. Comment: Beta-blockers and indacaterol may interfere with the effect of each other when administered concurrently. Beta-blockers may produce severe bronchospasm in COPD patients. Therefore, patients with COPD should not normally be treated with beta-blockers. However, under certain circumstances, e.g. as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.

            • indapamide

              nebivolol 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, 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.

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

              indomethacin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

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

            • 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 degludec

              nebivolol, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

            • 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.

              nebivolol, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

            • 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 inhaled

              nebivolol, insulin inhaled. Other (see comment). Modify Therapy/Monitor Closely. Comment: Beta-blockers may either increase or decrease the blood glucose lowering effect of insulin; beta-blockers can prolong hypoglycemia (interference with glycogenolysis) or cause hyperglycemia (insulin secretion inhibited).

            • 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.

            • iodixanol

              nebivolol increases toxicity of iodixanol by unspecified interaction mechanism. Use Caution/Monitor. Use of beta-blockers lowers the threshold for and increases the severity of contrast reactions, and reduces the responsiveness of treatment of hypersensitivity reactions with epinephrine. .

            • irbesartan

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

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

            • isoproterenol

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

              nebivolol decreases effects of isoproterenol by pharmacodynamic antagonism. Use Caution/Monitor.

            • isradipine

              nebivolol, isradipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • ivabradine

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

            • ketamine

              ketamine, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • 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

            • ketoprofen

              ketoprofen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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.

              nebivolol 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.

            • ketorolac

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

              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 decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • ketorolac intranasal

              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.

              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.

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

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

              ketorolac intranasal decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • labetalol

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

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

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

            • lasmiditan

              nebivolol increases effects of lasmiditan by pharmacodynamic synergism. Use Caution/Monitor. Lasmiditan has been associated with a lowering of heart rate (HR). In a drug interaction study, addition of a single 200-mg dose of lasmiditan to propranolol decreased HR by an additional 5 bpm compared to propranolol alone, for a mean maximum of 19 bpm.

            • letermovir

              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.

              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.

            • levalbuterol

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

              nebivolol decreases effects of levalbuterol by pharmacodynamic antagonism. Use Caution/Monitor.

            • levodopa

              levodopa increases effects of nebivolol 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.

            • 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.

            • lorcaserin

              lorcaserin will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lornoxicam

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

              lornoxicam decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • losartan

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

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

            • 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 nebivolol 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.

            • maitake

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

            • maraviroc

              maraviroc will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • maraviroc

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

            • marijuana

              marijuana will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • meclofenamate

              meclofenamate decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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, 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.

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

            • mefenamic acid

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

              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.

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

              mefenamic acid decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • mefloquine

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

            • 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.

            • meloxicam

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

              meloxicam decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • metaproterenol

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

              nebivolol decreases effects of metaproterenol by pharmacodynamic antagonism. Use Caution/Monitor.

            • methyclothiazide

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

              nebivolol 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 valsartan by pharmacodynamic antagonism. Use Caution/Monitor. Methylphenidate may diminish antihypertensive effects. Monitor BP.

            • metolazone

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

            • metolazone

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

            • metoprolol

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

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

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

            • 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

            • mirabegron

              mirabegron will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • 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

            • moxisylyte

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

            • nabumetone

              nabumetone decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

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

              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.

            • nadolol

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

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

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

            • naproxen

              nebivolol 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.

              naproxen decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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

              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.

            • nicardipine

              nebivolol, nicardipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • 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

            • nifedipine

              nebivolol, nifedipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • nilotinib

              nilotinib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • nimodipine

              nebivolol, nimodipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • nisoldipine

              nebivolol, nisoldipine. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure.

            • nitroglycerin rectal

              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 rectal, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects. If beta-blockers are used with nitroglycerin in patients with angina pectoris, additional hypotensive effects may occur.

            • norepinephrine

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

              nebivolol decreases effects of norepinephrine by pharmacodynamic antagonism. Use Caution/Monitor.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir 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

            • olmesartan

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

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

            • oxaprozin

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

              oxaprozin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              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.

            • oxymetazoline topical

              oxymetazoline topical increases and nebivolol decreases sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • 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

            • panobinostat

              panobinostat will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

            • parecoxib

              parecoxib decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

              parecoxib will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              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

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

            • penbutolol

              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 decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of pentobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • perphenazine

              perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • phenobarbital

              phenobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of phenobarbital. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • phenoxybenzamine

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

            • phentolamine

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

            • 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.

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

            • 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

            • pirbuterol

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

              nebivolol decreases effects of pirbuterol by pharmacodynamic antagonism. Use Caution/Monitor.

            • piroxicam

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

              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.

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

              piroxicam decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • pitavastatin

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

            • ponesimod

              ponesimod and nebivolol both increase pharmacodynamic synergism. Use Caution/Monitor. Beta-blockers may have additive effects on lowering HR. Consider resting HR before initiating ponesimod in patients on stable dose of beta-blocker. Refer to the ponesimod prescribing information for more dosing information.

            • potassium acid phosphate

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

              nebivolol and potassium acid phosphate both increase serum potassium. Modify Therapy/Monitor Closely.

            • potassium chloride

              nebivolol and potassium chloride both increase serum potassium. Modify Therapy/Monitor Closely.

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

            • potassium citrate

              nebivolol and potassium citrate both increase serum potassium. Modify Therapy/Monitor Closely.

              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.

            • prazosin

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

            • 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.

            • primidone

              primidone decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Consider a higher beta-blocker dose during coadministration of secobarbital. Consider a higher beta-blocker dose during coadministration of primidone. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • propafenone

              propafenone will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Reduced doses of nebivolol may be necessary.

            • propofol

              propofol, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • propranolol

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

              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.

            • quinacrine

              quinacrine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • 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

            • ranolazine

              ranolazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 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

            • ritonavir

              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 will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              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

            • rolapitant

              rolapitant will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • 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

            • sacubitril/valsartan

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

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

            • salicylates (non-asa)

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

              salicylates (non-asa) decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

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

            • salmeterol

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

              nebivolol decreases effects of salmeterol by pharmacodynamic antagonism. 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.

            • salsalate

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

              salsalate decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • saquinavir

              saquinavir, nebivolol. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Use alternatives if available. Increased risk of PR prolongation and cardiac arrhythmias.

              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

            • secobarbital

              secobarbital decreases levels of nebivolol by increasing metabolism. Use Caution/Monitor. Atenolol, sotalol, nadolol less likely to be affected than other beta blockers.

            • 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

            • sertraline

              sertraline will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • sevoflurane

              sevoflurane, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

            • sildenafil

              nebivolol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.

            • silodosin

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

            • siponimod

              siponimod, nebivolol. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Caution when siponimod is initiated in patients receiving beta-blocker treatment because of additive effects on lowering heart rate. Temporary interruption of beta-blocker may be needed before initiating siponimod. Beta-blocker treatment can be initiated in patients receiving stable doses of siponimod.

            • sodium bicarbonate

              sodium bicarbonate decreases levels of nebivolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sodium citrate/citric acid

              sodium citrate/citric acid decreases levels of nebivolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. Separate by 2 hours.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              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

              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. .

            • sotalol

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

              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.

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

            • succinylcholine

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

            • 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.

            • sulfasalazine

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

              sulfasalazine decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • sulindac

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

              sulindac decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

              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.

            • synthetic human angiotensin II

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

            • tadalafil

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

            • tadalafil

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

            • telmisartan

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

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

            • terazosin

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

            • terbinafine

              terbinafine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

            • terbutaline

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

              nebivolol decreases effects of terbutaline by pharmacodynamic antagonism. Use Caution/Monitor.

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

            • theophylline

              nebivolol, theophylline. Other (see comment). Use Caution/Monitor. Comment: Beta blockers (esp. non selective) antagonize theophylline effects, while at the same time increasing theophylline levels and toxicity (mechanism: decreased theophylline metabolism). Smoking increases risk of interaction.

            • timolol

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

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

            • thioridazine

              thioridazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • timolol

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

            • tipranavir

              tipranavir will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tizanidine

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

            • tolfenamic acid

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

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

              tolfenamic acid decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

            • tolmetin

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

              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.

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

              tolmetin decreases effects of nebivolol by pharmacodynamic antagonism. Use Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin synthesis.

              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.

            • tolvaptan

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

              nebivolol 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.

              nebivolol 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

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

            • triamterene

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

            • 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.

            • valsartan

              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.

            • venlafaxine

              venlafaxine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • verapamil

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

            • 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.

            • xipamide

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

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

            Minor (35)

            • adenosine

              nebivolol, adenosine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Bradycardia.

            • agrimony

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

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

            • brimonidine

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

            • cornsilk

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

            • cevimeline

              cevimeline increases effects of nebivolol by unspecified interaction mechanism. Minor/Significance Unknown.

            • ciprofloxacin

              ciprofloxacin increases levels of nebivolol by decreasing metabolism. Minor/Significance Unknown.

            • cocaine

              nebivolol increases effects of cocaine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of angina.

            • cornsilk

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

            • dihydroergotamine

              dihydroergotamine, nebivolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive vasospasm.

            • dihydroergotamine intranasal

              dihydroergotamine intranasal, nebivolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive vasospasm.

            • dipyridamole

              dipyridamole, nebivolol. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of bradycardia.

            • 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.

            • escitalopram

              escitalopram increases levels of nebivolol by decreasing metabolism. Minor/Significance Unknown.

            • fenoldopam

              fenoldopam increases effects of nebivolol by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

            • 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 nebivolol by pharmacodynamic synergism. Minor/Significance Unknown.

            • guanfacine

              nebivolol, guanfacine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

            • imaging agents (gadolinium)

              nebivolol, imaging agents (gadolinium). Mechanism: unknown. Minor/Significance Unknown. Increased risk of anaphylaxis from contrast media.

            • levobetaxolol

              levobetaxolol increases effects of nebivolol by pharmacodynamic synergism. Minor/Significance Unknown.

            • maitake

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

            • melatonin

              melatonin decreases toxicity of nebivolol by pharmacodynamic antagonism. Minor/Significance Unknown. Melatonin may correct beta blocker induced sleep disturbances.

            • metipranolol ophthalmic

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

            • neostigmine

              nebivolol, neostigmine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive bradycardia.

            • noni juice

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

              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 nebivolol by pharmacodynamic synergism. Minor/Significance Unknown.

            • ombitasvir/paritaprevir/ritonavir & dasabuvir

              ombitasvir/paritaprevir/ritonavir & dasabuvir 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

            • physostigmine

              nebivolol, physostigmine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive bradycardia.

            • pilocarpine

              pilocarpine increases effects of nebivolol by pharmacodynamic synergism. Minor/Significance Unknown.

            • reishi

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

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

            • shepherd's purse

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

              shepherd's purse, valsartan. 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.

            • tizanidine

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

            • treprostinil

              treprostinil increases effects of nebivolol 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.

            • yohimbe

              nebivolol decreases toxicity of yohimbe by pharmacodynamic antagonism. Minor/Significance Unknown.

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            Adverse Effects

            1-10%

            Increased serum potassium by >20% (4.4%)

            Frequency Not Defined

            Symptomatic hypotension

            Postmarketing Reports

            Nebivolol

            • Cardiac: Atrioventricular block (both second and third degree), myocardial infarction
            • Central nervous system: Somnolence, syncope, vertigo
            • Circulatory: Raynaud phenomenon, peripheral ischemia/claudication, thrombocytopenia
            • Dermatologic: Pruritus, psoriasis, various rashes and skin disorders
            • Digestive: Vomiting Hepatic: Abnormal hepatic function (including increased AST, ALT and bilirubin)
            • Hypersensitivity: Hypersensitivity (including urticaria, allergic vasculitis, and rare reports of angioedema)
            • Renal: Acute renal failure
            • Respiratory: Acute pulmonary edema, bronchospasm
            • Sexual dysfunction: Erectile dysfunction

            Valsartan

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

            Black Box Warnings

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

            Contraindications

            Severe bradycardia

            Heart block greater than first degree (if no pacemaker)

            Patients with cardiogenic shock

            Decompensated cardiac failure

            Sick sinus syndrome (unless a permanent pacemaker is in place)

            Patients with severe hepatic impairment (Child-Pugh >B)

            Patients who are hypersensitive to any component of this product

            Do not coadminister aliskiren with an angiotensin receptor blocker (ARB) (eg, valsartan) in patients with diabetes; dual blockade of renin-angiotensin system increases risk of hypotension, hyperkalemia, and renal impairment

            Cautions

            Fetal toxicity: ARB (eg, valsartan) use during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black Box Warnings, Pregnancy)

            Increased risk of symptomatic hypotension in patients with activated renin-angiotensin-aldosterone system (eg, volume/ and/or salt-depleted)

            Do not abruptly discontinue nebivolol in patients with coronary artery disease; severe exacerbation of angina, myocardial infarction, and ventricular arrhythmias reported

            Worsening heart failure or fluid retention may occur during nebivolol therapy because of its beta-blocking effects

            Generally, patients with bronchospastic diseases should not receive beta-blockers

            Long-term beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures

            Beta-blockers may mask manifestations of hypoglycemia, particularly tachycardia

            Beta-blockers may mask clinical signs of hyperthyroidism (eg, tachycardia)

            Do not abruptly discontinue beta-blockers

            While taking beta-blockers, patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated accidental, diagnostic, or therapeutic challenge; these patients may be unresponsive to the usual doses of epinephrine used to treat allergic reactions

            In patients with known or suspected pheochromocytoma, initiate an alpha-blocker prior to the use of any beta-blocker

            ARBs associated with increased serum potassium levels; monitor closely

            Drug interaction overview

            • Nebivolol
              • Nebivolol is a CYP2D6 substrate; avoid coadministration with CYP2D6 inhibitors (eg, quinidine, propafenone, fluoxetine, paroxetine)
              • Do not use with other beta-blockers
              • Monitor closely if coadministered with catecholamine-depleting drugs (eg, reserpine, guanethidine); the added beta-blocking action of nebivolol may produce excessive reduction of sympathetic activity
              • If coadministered with clonidine, discontinue nebivolol for several days before the gradual tapering of clonidine
              • Digitalis glycosides: Coadministration increases risk of bradycardia; monitor
              • Nebivolol can exacerbate effects of myocardial depressants or inhibitors of atrioventricular conduction (eg, certain calcium channel blockers, especially the phenylalkylamine class [eg, verapamil] and benzothiazepine class [eg, diltiazem])
            • Valsartan
              • Concomitant use with other agents that block the renin-angiotensin system, potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium, or other agents that may increase potassium levels (eg, heparin) may result in hyperkalemia
              • Coadministration with NSAIDs or COX-2 inhibitors may result in renal function deterioration, especially in elderly patients, volume-depleted (including diuretics) patients, or those with renal impairment
              • Use of ARBs with ACE inhibitors or with aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function
              • Coadministration with aliskiren in patients with diabetes is contraindicated
              • Coadministration with lithium increase serum lithium levels and toxicity
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            Pregnancy & Lactation

            Pregnancy

            Nebivolol: Neonates of women with hypertension who are treated with beta-blockers during pregnancy may be at increased risk for hypotension, bradycardia, hypoglycemia, and respiratory depression

            Valsartan

            • Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, and skeletal deformations, including skull hypoplasia, hypotension, and death
            • In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus
            • In patients taking an ARB during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment
            • Fetal testing may be appropriate, based on the week of gestation
            • Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury

            Lactation

            Unknown if distributed in human breast milk

            Because of the potential for beta-blockers to produce serious adverse reactions in nursing infants, especially bradycardia, and the potential for valsartan to affect postnatal renal development in nursing infants, advise females not to breastfeed during treatment

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Nebivolol: Competitive and selective beta1-receptor antagonist; has little or no effect on beta2 receptors at doses <10 mg; lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations; reduces systemic vascular resistance

            Valsartan: Blocks binding of angiotensin II to type 1 angiotensin receptors, causing a lowering in blood pressure; blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II

            Absorption

            Peak plasma time: 1-6 hr (nebivolol); 2-4 hr (valsartan)

            Maximal antihypertensive effects (initial therapy): 2-4 wk

            Distribution

            Vd: 98% (nebivolol); 95% (valsartan) – mostly to albumin

            Metabolism

            Nebivolol: Predominantly metabolized via direct glucuronidation of parent and to a lesser extent via N-dealkylation and oxidation via CYP2D6

            Valsartan: CYP2C9 isozyme is responsible for the formation of the primary metabolite (valeryl-4-hydroxy valsartan), which is ~9% of the dose

            Elimination

            Half-life

            • d-Nebivolol: 12 hr (CYP2D6 extensive metabolizers [EMs]); 19 hr (CYP2D6 poor metabolizers [PMs])
            • Valsartan: 6 hr

            Clearance (valsartan)

            • Plasma clearance: 2 L/hr
            • Renal clearance: 0.62 L/hr (30% of total clearance)

            Excretion

            • Nebivolol (EMs)
              • 38% urine; 44% feces
            • Nebivolol (PMs)
              • 67% urine; 13% feces
            • Valsartan
              • 13% urine; 83% feces

            Pharmacogenomics

            Nebivolol

            • In extensive metabolizers (most of the population) and at doses ≤10 mg, nebivolol is preferentially beta1-selective
            • In poor metabolizers and at higher doses, nebivolol inhibits both beta1- and beta2- adrenergic receptors
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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store at controlled room temperature (20-25°C [68-77°F])

            Dispense in a tightly closed container

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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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.