sacubitril/valsartan (Rx)

Brand and Other Names:Entresto
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

sacubitril/valsartan

film-coated tablet

  • 24mg/26mg
  • 49mg/51mg
  • 97mg/103mg

Heart Failure

Indicated to reduce risk of cardiovascular death and hospitalization in chronic heart failure (CHF); benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal

Recommended starting dose: 49 mg/51 mg PO BID

Target maintenance dose: After 2-4 weeks, double the dose to 97 mg/103 mg PO BID as tolerated

Dosage Modifications

Patients not taking an ACE inhibitor or other ARB, or previously taking a low dose of these agents when initiating treatment

  • Reduce starting dose to 24 mg/26 mg BID
  • Double the dose every 2-4 weeks to target maintenance dose of 97 mg/103 mg BID as tolerated

Renal impairment

  • Mild-to-moderate (eGFR ≥30 mL/min/1.73 m²): No starting dose adjustment required
  • Severe (eGFR <30 mL/min/1.73 m²): Reduce starting dose to 24 mg/26 mg BID; double the dose every 2-4 weeks to target maintenance dose of 97 mg/103 mg BID as tolerated

Hepatic impairment

  • Mild (Child-Pugh A): No starting dose adjustment required
  • Moderate (Child-Pugh B): Reduce starting dose to 24 mg/26 mg BID; double the dose every 2-4 weeks to target maintenance dose of 97 mg/103 mg BID as tolerated
  • Severe (Child-Pugh C): Not recommended

Dosing Considerations

LVEF varies; treat based on clinical judgment

Contraindicated with concomitant use of an ACE inhibitor; if switching from an ACE inhibitor to sacubitril/valsartan, allow a washout period of 36 hr between administration of the 2 drugs

Usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB

sacubitril/valsartan

tablet

  • 24mg/26mg
  • 49mg/51mg
  • 97mg/103mg

Heart Failure

Indicated for symptomatic heart failure with systemic left ventricular systolic dysfunction in pediatric patients aged ≥1 year; reduces NT-proBNP and is expected to improve cardiovascular outcomes

<1 year: Safety and efficacy not established

≥1 year

  • Adjust dose q2Weeks, as tolerated
  • <40 kg
    • Recommended mg/kg doses are of the combined amount of both sacubitril and valsartan
    • Use extemporaneously compounded oral suspension 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL)
    • Starting dose: 1.6 mg/kg PO BID
    • Second titration: 2.3 mg/kg PO BID
    • Not to exceed 3.1 mg/kg PO BID
  • ≥40 kg and <50 kg
    • Starting dose: 24/26 mg PO BID
    • Second titration: 49/51 mg PO BID
    • Not to exceed 72/78 mg (three 24/26-mg tablets) PO BID
  • ≥50 kg
    • Starting dose: 49/51 mg PO BID
    • Second titration: 72/78 mg (three 24/26-mg tablets) PO BID
    • Not to exceed 97/103 mg PO BID

Dosage Modifications

Patients not taking an ACE inhibitor or other ARB, or previously taking a low dose of these agents when initiating treatment

  • Start at half the recommended starting dose
  • After initiation, increase dose as per the recommended dose escalation thereafter
  • Patients weighing 40-50 kg who meet this criterion: Initiate at 0.8 mg/kg BID using oral suspension

Renal impairment

  • Mild-to-moderate (eGFR ≥30 mL/min/1.73 m2): No starting dose adjustment required
  • Severe (eGFR <30 mL/min/1.73 m2)
    • Start at half the recommended starting dose
    • After initiation, increase dose as per the recommended dose escalation thereafter
    • Patients weighing 40-50 kg who meet this criterion: Initiate at 0.8 mg/kg BID using oral suspension

Hepatic impairment

  • Mild (Child-Pugh A): No starting dose adjustment required
  • Moderate (Child-Pugh B)
    • Start at half the recommended starting dose
    • After initiation, increase dose as per the recommended dose escalation thereafter
    • Patients weighing 40-50 kg who meet this criterion: Initiate at 0.8 mg/kg BID using oral suspension
  • Severe (Child-Pugh C): Not recommended

Dosing Considerations

Contraindicated with concomitant use of an ACE inhibitor; if switching from an ACE inhibitor to sacubitril/valsartan, allow a washout period of 36 hr between the administrations of the 2 drugs

Usually administered in conjunction with other heart failure therapies, in place of an ACE inhibitor or other ARB

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Interactions

Interaction Checker

and sacubitril/valsartan

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            Contraindicated (11)

            • aliskiren

              sacubitril/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.

            • benazepril

              sacubitril/valsartan, benazepril. Either increases toxicity of the other by pharmacodynamic synergism. Contraindicated. Dual blockade of renin-angiotensin system increases risks of hypotension, hyperkalemia, and renal impairment. Increased risk of angioedema. Discontinue ACE Inhibitor therapy for at least 36 hours prior to sacubitril/valsartan administration.

              sacubitril/valsartan, benazepril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • captopril

              sacubitril/valsartan, captopril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • enalapril

              sacubitril/valsartan, enalapril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • fosinopril

              sacubitril/valsartan, fosinopril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • lisinopril

              sacubitril/valsartan, lisinopril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • moexipril

              sacubitril/valsartan, moexipril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • perindopril

              sacubitril/valsartan, perindopril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • quinapril

              sacubitril/valsartan, quinapril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • ramipril

              sacubitril/valsartan, ramipril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            • trandolapril

              sacubitril/valsartan, trandolapril. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Coadministration of neprilysin inhibitors (eg, sacubitril) with ACE inhibitors may increase angioedema risk; do not administer ACE inhibitors within 36 hr of switching to or from sacubitril/valsartan.

            Serious - Use Alternative (13)

            • captopril

              sacubitril/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.

            • eluxadoline

              sacubitril/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

              sacubitril/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.

            • fosinopril

              sacubitril/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.

            • lisinopril

              sacubitril/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

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

              sacubitril/valsartan increases levels of lithium by unknown mechanism. Avoid or Use Alternate Drug.

            • lofexidine

              lofexidine, sacubitril/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.

            • moexipril

              sacubitril/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.

            • perindopril

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

            • potassium phosphates, IV

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

            • quinapril

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

            • ramipril

              sacubitril/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.

            • trandolapril

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

            Monitor Closely (171)

            • acebutolol

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

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

            • aceclofenac

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

            • albiglutide

              sacubitril/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

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

            • aldesleukin

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

            • amifostine

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

            • amiloride

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

            • arformoterol

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

            • aspirin

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

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

              aspirin decreases effects of sacubitril/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

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

            • aspirin/citric acid/sodium bicarbonate

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

              sacubitril/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.

              aspirin/citric acid/sodium bicarbonate decreases effects of sacubitril/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.

            • atenolol

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

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

            • atorvastatin

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

              atorvastatin will increase the level or effect of sacubitril/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

            • avanafil

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

            • bendroflumethiazide

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

            • betaxolol

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

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

            • bisoprolol

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

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

            • bretylium

              sacubitril/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 sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • bumetanide

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

            • canagliflozin

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

            • candesartan

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

            • carbamazepine

              carbamazepine will increase the level or effect of sacubitril/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

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

            • carbidopa

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

            • carvedilol

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

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

            • caspofungin

              caspofungin will increase the level or effect of sacubitril/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

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

              sacubitril/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 decreases effects of sacubitril/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.

            • celiprolol

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

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

            • chlorothiazide

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

            • chlorthalidone

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

            • choline magnesium trisalicylate

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

              sacubitril/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 sacubitril/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.

            • clarithromycin

              clarithromycin will increase the level or effect of sacubitril/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

            • cyclopenthiazide

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

            • cyclosporine

              cyclosporine, sacubitril/valsartan. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration may potentiate the hyperkalemic effects of cyclosporine or valsartan.

            • dalteparin

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

            • diclofenac

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

              sacubitril/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.

              diclofenac decreases effects of sacubitril/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.

            • diflunisal

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

              sacubitril/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.

              diflunisal decreases effects of sacubitril/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.

            • digoxin

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

            • dobutamine

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

            • dopexamine

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

            • drospirenone

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

            • eltrombopag

              eltrombopag will decrease the level or effect of sacubitril/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

            • enoxaparin

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

            • ephedrine

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

            • epinephrine

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

            • epinephrine racemic

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

            • eplerenone

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

            • eprosartan

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

            • erythromycin base

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

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of sacubitril/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 sacubitril/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 sacubitril/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

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

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

            • ethacrynic acid

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

            • etodolac

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

              sacubitril/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 decreases effects of sacubitril/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.

            • exenatide injectable solution

              sacubitril/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

              sacubitril/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.

            • fenbufen

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

            • fenoprofen

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

              sacubitril/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.

              fenoprofen decreases effects of sacubitril/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.

            • flurbiprofen

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

              sacubitril/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 decreases effects of sacubitril/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.

            • fluvastatin

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

            • formoterol

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

            • furosemide

              sacubitril/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 sacubitril/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

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

            • glyburide

              glyburide will increase the level or effect of sacubitril/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

            • heparin

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

            • hydrochlorothiazide

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

            • ibuprofen

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

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

              ibuprofen decreases effects of sacubitril/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 sacubitril/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.

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

              sacubitril/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.

            • indapamide

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

            • indinavir

              indinavir will increase the level or effect of sacubitril/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

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

              sacubitril/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.

              indomethacin decreases effects of sacubitril/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.

            • insulin aspart

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

            • insulin aspart protamine/insulin aspart

              sacubitril/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

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

              sacubitril/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

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

            • insulin detemir

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

            • insulin glargine

              sacubitril/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

              sacubitril/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

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

              sacubitril/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

              sacubitril/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

              sacubitril/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

              sacubitril/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

              sacubitril/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

              sacubitril/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.

            • irbesartan

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

            • isoproterenol

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

            • ketoconazole

              ketoconazole will increase the level or effect of sacubitril/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

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

              sacubitril/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.

              ketoprofen decreases effects of sacubitril/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

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

              sacubitril/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 sacubitril/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

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

              sacubitril/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 sacubitril/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.

            • labetalol

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

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

            • levalbuterol

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

            • levodopa

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

            • liraglutide

              sacubitril/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.

            • lornoxicam

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

            • losartan

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

            • lovastatin

              lovastatin will increase the level or effect of sacubitril/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 sacubitril/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 sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            • maraviroc

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

            • meclofenamate

              meclofenamate decreases effects of sacubitril/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.

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

              sacubitril/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.

            • mefenamic acid

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

              sacubitril/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.

              mefenamic acid decreases effects of sacubitril/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.

            • meloxicam

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

              sacubitril/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 decreases effects of sacubitril/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.

            • metaproterenol

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

            • methyclothiazide

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

            • methylphenidate

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

            • metolazone

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

            • metoprolol

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

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

            • metyrapone

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

            • mifepristone

              mifepristone will increase the level or effect of sacubitril/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

            • nabumetone

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

              sacubitril/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.

              nabumetone decreases effects of sacubitril/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.

            • nadolol

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

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

            • naproxen

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

              sacubitril/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.

              naproxen decreases effects of sacubitril/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

              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.

            • nelfinavir

              nelfinavir will increase the level or effect of sacubitril/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

            • nitroglycerin rectal

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

            • norepinephrine

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

            • olmesartan

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

            • oxaprozin

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

              sacubitril/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.

              oxaprozin decreases effects of sacubitril/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.

            • paclitaxel

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

            • parecoxib

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

            • pazopanib

              pazopanib will increase the level or effect of sacubitril/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

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

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

            • pindolol

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

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

            • pioglitazone

              pioglitazone will increase the level or effect of sacubitril/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

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

            • piroxicam

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

              sacubitril/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.

              piroxicam decreases effects of sacubitril/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.

            • pitavastatin

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

            • potassium acid phosphate

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

            • potassium chloride

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

            • potassium citrate

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

            • potassium citrate/citric acid

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

            • potassium iodide

              potassium iodide and sacubitril/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

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

              pravastatin will increase the level or effect of sacubitril/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

            • propranolol

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

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

            • repaglinide

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

            • rifampin

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

              ritonavir will increase the level or effect of sacubitril/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

            • rosiglitazone

              rosiglitazone will increase the level or effect of sacubitril/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

            • salicylates (non-asa)

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

            • salmeterol

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

            • salsalate

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

              sacubitril/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 decreases effects of sacubitril/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.

            • saquinavir

              saquinavir will increase the level or effect of sacubitril/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

            • simvastatin

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

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of sacubitril/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 sacubitril/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.

            • sotalol

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

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

            • spironolactone

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

            • succinylcholine

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

            • sulfasalazine

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

              sacubitril/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 decreases effects of sacubitril/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.

            • sulindac

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

              sacubitril/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.

              sulindac decreases effects of sacubitril/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

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

            • tacrolimus

              tacrolimus will increase the level or effect of sacubitril/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

            • tadalafil

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

            • telmisartan

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

            • terbutaline

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

            • timolol

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

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

            • tizanidine

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

            • tolfenamic acid

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

            • tolmetin

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

              sacubitril/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.

              tolmetin decreases effects of sacubitril/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

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

            • torsemide

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

            • treprostinil

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

            • triamterene

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

            • trimethoprim

              sacubitril/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.

            • voclosporin

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

              voclosporin, sacubitril/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 sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor.

            Minor (9)

            • agrimony

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

            • cornsilk

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

            • entecavir

              sacubitril/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.

            • food

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

            • noni juice

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

            • octacosanol

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

            • reishi

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

            • shepherd's purse

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

            • simvastatin

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

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            Adverse Effects

            >10%

            Hypotension (18%)

            Hyperkalemia (12%)

            1-10%

            Cough (9%)

            Dizziness (6%)

            Orthostasis (2.1%)

            Falls (1.9%)

            <1%

            Angioedema, all patients (0.5%); in black patients (2.4%)

            Hypersensitivity (rash, pruritus, anaphylaxis)

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            Warnings

            Black Box Warnings

            Fetal toxicity

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

            Contraindications

            Hypersensitivity to any component

            History of angioedema related to previous ACE inhibitor or ARB therapy

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

            Concomitant use with aliskiren in patients with diabetes

            Cautions

            Can cause fetal harm when administered to a pregnant woman; use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Black Box Warnings)

            Not for use in patients with hereditary angioedema; observe for signs and symptoms of angioedema; if angioedema occurs, discontinue drug immediately, provide appropriate therapy, and monitor for airway compromise

            Sacubitril/valsartan lowers blood pressure and may cause symptomatic hypotension; patients who are volume-depleted or salt-depleted, or those taking diuretics, are at greater risk

            Drug interaction overview

            • Dual blockade of the renin-angiotensin-aldosterone system
              • Coadministration with an ACE inhibitor is contraindicated because of the increased risk of angioedema
              • Avoid use with an ARB, because drug contains the angiotensin II receptor blocker valsartan
              • Concomitant use with aliskiren is contraindicated in patients with diabetes
            • Potassium-sparing diuretics
              • As with other drugs that block angiotensin II or its effects, concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to increases in serum potassium
            • Nonsteroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors (COX-2 inhibitors)
              • In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, concomitant use of NSAIDs, including COX-2 inhibitors, with sacubitril/valsartan may result in worsening of renal function, including possible acute renal failure
              • Effects are usually reversible; monitor renal function periodically
            • Lithium
              • Increases in serum lithium concentrations and lithium toxicity have been reported during coadministration of lithium with angiotensin II receptor antagonists; monitor serum lithium levels
              • Monitor renal function and potassium levels in susceptible patients (eg, diabetes, hypoaldosteronism, high-potassium diet, renal artery stenosis); dosage reduction or interruption may be required
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            Pregnancy

            Pregnancy

            Discontinue as soon as pregnancy detected; during the second and third trimesters of pregnancy, resulting oligohydramnios may cause fetal injury (eg, hypotension, neonatal skull hypoplasia, anuria, reversible and irreversible renal failure) and death

            Neonates with a history of in utero exposure: Direct attention toward support of blood pressure and renal perfusion; exchange transfusions or dialysis may be required

            Animal data

            • Treatment during organogenesis resulted in increased embryo-fetal lethality in rats at doses greater than or equal to 49 mg sacubitril/51 mg valsartan/kg/day (less than or equal to 0.06 [LBQ657, the active metabolite] and 0.72 [valsartan]-fold the maximum recommended human dose [MRHD] of 97/103 mg twice-daily on the basis of the area under the plasma drug concentration-time curve [AUC]) and rabbits at doses greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day (2-fold and 0.03-fold the MRHD on the basis of valsartan and LBQ657 AUC, respectively)
            • Drug is teratogenic based on a low incidence of fetal hydrocephaly, associated with maternally toxic doses, which was observed in rabbits at a dose of greater than or equal to 5 mg sacubitril/5 mg valsartan/kg/day
            • The adverse embryo-fetal effects are attributed to the angiotensin receptor antagonist activity;
            • Pre- and postnatal development studies in rats at sacubitril doses up to 750 mg/kg/day (2.2-fold the MRHD on the basis of LBQ657 AUC) and valsartan at doses up to 600 mg/kg/day (0.86-fold the MRHD on the basis of AUC) indicate that treatment during organogenesis, gestation, and lactation may affect pup development and survival

            Lactation

            Unknown if distributed in human breast milk; not recommended

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            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

            Combination is an angiotensin receptor-neprilysin inhibitor (ARNi)

            Sacubitril: Neprilysin inhibitor; neprilysin is responsible for degradation of atrial and brain natriuretic peptide; the cardiovascular and renal effects of sacubitril’s active metabolite (LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic peptide); administration results in increased natriuresis, increased urine cGMP, and decreased plasma MR-proANP and NT-proBNP

            Valsartan: Angiotensin II receptor type I inhibitor; decreases blood pressure and blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II

            Absorption

            Absolute bioavailability

            • Sacubitril: ≥60%
            • Valsartan in Entresto is more bioavailable than the valsartan in other marketed tablet formulations; 26 mg, 51 mg, and 103 mg of valsartan in Entresto is equivalent to 40 mg, 80 mg, and 160 mg of valsartan in other marketed tablet formulations, respectively

            Steady-state

            • Reached in 3 days
            • At steady state, sacubitril and valsartan do not accumulate significantly, whereas LBQ657 accumulates by 1.6-fold

            Peak plasma concentration

            • Sacubitril: 0.5 hr
            • LBQ657: 2 hr
            • Valsartan: 1.5 hr

            Distribution

            Protein bound

            • Sacubitril: 94-97%
            • LBQ657: 94-97%; LBQ657 crosses the blood-brain barrier to a limited extent (0.28%)
            • Valsartan: 94-97%

            Vd

            • Sacubitril: 103 L
            • Valsartan: 75 L

            Metabolism

            Sacubitril is a prodrug that is metabolized by esterases to the active metabolite LBQ657

            LBQ657 is not further metabolized to a significant extent

            Valsartan is minimally metabolized; only about 20% of the dose is recovered as metabolites; a hydroxyl metabolite has been identified in plasma at low concentrations (<10%)

            Elimination

            Half-life

            • Sacubitril: 1.4 hr
            • LBQ657: 11.5 hr
            • Valsartan: 9.9 hr

            Excretion

            • Sacubitril: 52-68% (primarily as LBQ657) in urine; 37-48% (primarily as LBQ657) in feces
            • Valsartan: 13% in urine; 86% in feces
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            Administration

            Oral Suspension Preparation

            Oral suspension can be substituted in patients unable to swallow tablets

            Prepare an oral suspension in a concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL)

            Transfer eight 49/51-mg tablets into a mortar

            Crush tablets into a fine powder using a pestle

            Add 60 mL of Ora-Plus into mortar and triturate gently with pestle for 10 min, to form a uniform suspension

            Add 140 mL of Ora-Sweet into mortar and triturate with pestle for another 10 min, to form a uniform suspension; resulting in a final concentration of 4 mg/mL (sacubitril/valsartan 1.96/2.04 mg/mL)

            Transfer entire contents from the mortar into a clean 200 mL amber colored PET or glass bottle

            Place a press-in bottle adapter and close the bottle with a child resistant cap

            Oral Administration

            May take with or without food

            Use oral suspension for the following

            • Pediatric patients <40 kg
            • Pediatric patients 40-50 kg who are not currently taking an ACE inhibitor or an angiotensin II receptor blocker (ARB) and for patients previously taking low doses of these agents
            • Pediatric patients 40-50 kg who are renally or hepatically impaired

            Storage

            Prepared oral suspension

            • Store <25ºC (77ºF) for up to 15 days and do not refrigerate
            • Shake before each use

            Tablets

            • Store at controlled room temperature (25ºC [77ºF]), with excursions between 15-30ºC (59-86ºF) permitted
            • Protect from moisture
            • Store in the original package
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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Entresto oral
            -
            49-51 mg tablet
            Entresto oral
            -
            97-103 mg tablet
            Entresto oral
            -
            24-26 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            sacubitril-valsartan oral

            SACUBITRIL/VALSARTAN - ORAL

            (sak-UE-bi-tril/val-SAR-tan)

            COMMON BRAND NAME(S): Entresto

            WARNING: Valsartan can cause serious (possibly fatal) harm to an unborn baby if used during pregnancy. It is important to prevent pregnancy while taking this medication. Consult your doctor for more details and to discuss the use of reliable forms of birth control while taking this medication. If you are planning pregnancy, become pregnant, or think you may be pregnant, tell your doctor right away.

            USES: This product is used to treat certain types of heart failure. It may help you live longer and lower your chance of having to go to the hospital for heart failure. This product contains 2 medications: sacubitril and valsartan. Sacubitril belongs to a class of drugs called neprilysin inhibitors and valsartan belongs to a class of drugs called angiotensin receptor blockers (ARBs). They work by relaxing blood vessels so that blood can flow more easily, which makes it easier for your heart to pump blood to your body.

            HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking this product and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this product by mouth with or without food as directed by your doctor, usually twice daily. The dosage is based on your medical condition and response to treatment. Children's dosage is also based on weight.If you are using the suspension form of this medication, shake the bottle well before each dose. Carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.To reduce your risk of side effects, your doctor may direct you to start this product at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.This product should not be taken with ACE inhibitors (such as captopril, enalapril) since your risk of serious side effects may increase. Do not take this product for at least 36 hours before or after taking an ACE inhibitor. Consult your doctor or pharmacist for more details.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Tell your doctor if you do not get better or if you get worse.

            SIDE EFFECTS: Cough, dizziness, or lightheadedness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: signs of kidney problems (such as change in the amount of urine), symptoms of a high potassium blood level (such as muscle weakness, slow/irregular heartbeat), fainting.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking this product, tell your doctor or pharmacist if you are allergic to sacubitril; or to valsartan; or to other ARBs (such as candesartan, losartan); or to ACE inhibitors (such as quinapril, ramipril); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, dehydration and electrolytes imbalance, serious allergic reaction conditions that included swelling of your face/lips/tongue/throat/trouble breathing (such as angioedema, hereditary angioedema).This product may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).This product may increase your potassium levels. Before using potassium supplements or salt substitutes that contain potassium, consult your doctor or pharmacist.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This product is not recommended for use during pregnancy. It may harm an unborn baby. Consult your doctor for more details. See also Warning section.It is unknown if this product passes into breast milk. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: See also How to Use and Precautions sections.Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this medication include: aliskiren, lithium, drugs that may increase the level of potassium in the blood (such as ACE inhibitors including benazepril/lisinopril, birth control pills containing drospirenone).Some products have ingredients that could worsen your heart failure. Tell your pharmacist what products you are using, and ask how to use them safely (especially cough-and-cold products, diet aids, or NSAIDs such as ibuprofen/naproxen).

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

            NOTES: Do not share this product with others.Lab and/or medical tests (such as kidney function tests, potassium levels) should be done while you are taking this product. Keep all medical and lab appointments.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Discard any unused suspension after 15 days. Do not store the suspension in the refrigerator. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.