in no way [10%:<60 mL/minute/1.73 m 2 ); pregnancy. Dosing: Adult Note: Entresto contains sacubitril (24 mg, 49 mg, or 97 mg) and valsartan (26 mg, 51 mg, or 103 mg). Use caution when prescribing since dosing in clinical trials was based on the total amount of both components (ie, 24/26 mg, 49/51 mg and 97/103 mg were referred to as 50 mg, 100 mg, and 200 mg, respectively). To reduce the risk of errors, include the doses of both ingredients (eg, Entresto 24/26 mg) when prescribing Entresto. The valsartan in Entresto is more bioavailable than the valsartan in other marketed tablet formulations; valsartan 26 mg, 51 mg, and 103 mg in Entresto is equivalent to valsartan 40 mg, 80 mg, and 160 mg in other marketed tablet formulations, respectively. Heart failure: Oral: Patients previously taking> 10 mg/day of enalapril or >160 mg/day of valsartan or equivalent dose of another ACE inhibitor or ARB: Initial: Sacubitril 49 mg and valsartan 51 mg twice daily. Double the dose as tolerated after 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg and valsartan 103 mg twice daily. Note: Concomitant use of an ACE inhibitor is contraindicated; allow a 36 hour washout period when switching from or to an ACE inhibitor. Patients previously taking low doses of an ACE inhibitor ( 10 mg/day of enalapril or an equivalent dose of another ACE inhibitor) or ARB ( 160 mg/day of valsartan or an equivalent dose of another ARB): Initial: Sacubitril 24 mg and valsartan 26 mg twice daily. Double the dose as tolerated every 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg and valsartan 103 mg twice daily. Patients not currently taking an ACE inhibitor or an ARB: Initial: Sacubitril 24 mg and valsartan 26 mg twice daily. Double the dose as tolerated every 2 to 4 weeks to the target maintenance dose of sacubitril 97 mg and valsartan 103 mg twice daily. Dosing: Geriatric Refer to adult dosing. Dosing: Renal Impairment eGFR 30 mL/minute/1.73 m 2 : No dosage adjustment necessary. eGFR <30 mL/minute/1.73 m 2 : Initial: Sacubitril 24 mg and valsartan 26 mg twice daily Dosing: Hepatic Impairment Mild impairment (Child-Pugh class A): No dosage adjustment necessary. Moderate impairment (Child-Pugh class B): Initial: Sacubitril 24 mg and valsartan 26 mg twice daily Severe impairment (Child-Pugh class C): Use not recommended (has not been studied). Administration Oral: Administer with or without food. Storage Store at 25 C (77 F); excursions permitted between 15 C and 30 C (59 F and 86 F) . Protect from moisture. Drug Interactions Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Aliskiren: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Aliskiren may enhance the nephrotoxic effect of Angiotensin II Receptor Blockers. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Angiotensin-Converting Enzyme Inhibitors: May enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Avoid combination Antihepaciviral Combination Products: May increase the serum concentration of Valsartan. Management: Per antihepaciviral combination product US prescribing information, consider decreasing the valsartan dose and monitoring for evidence of hypotension and worsening renal function if these agents are used in combination. Consider therapy modification Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Canagliflozin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Canagliflozin may enhance the hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy Ciprofloxacin (Systemic): Angiotensin II Receptor Blockers may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy CycloSPORINE (Systemic): Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of CycloSPORINE (Systemic). Monitor therapy Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin II Receptor Blockers. Monitor therapy Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Drospirenone: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Drospirenone. Monitor therapy DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy Eplerenone: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Gemfibrozil: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy Heparin: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy HydroCHLOROthiazide: May enhance the hypotensive effect of Valsartan. Valsartan may increase the serum concentration of HydroCHLOROthiazide. Monitor therapy Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy Lithium: Angiotensin II Receptor Blockers may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an angiotensin II receptor antagonist. Consider therapy modification Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nicorandil: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy Nonsteroidal Anti-Inflammatory Agents: Angiotensin II Receptor Blockers may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Angiotensin II Receptor Blockers. The combination of these two agents may also significantly decrease glomerular filtration and renal function. Monitor therapy Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Potassium Salts: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Potassium-Sparing Diuretics: Angiotensin II Receptor Blockers may enhance the hyperkalemic effect of Potassium-Sparing Diuretics. Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Sodium Phosphates: Angiotensin II Receptor Blockers may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ARBs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy Tolvaptan: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Trimethoprim: May enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Adverse Reactions Also see individual agents.> 10%: Cardiovascular: Hypotension (18%) Endocrine & metabolic: Increased serum potassium (4% to 16%), hyperkalemia (12%) Renal: Increased serum creatinine (1% to 16%) 1% to 10%: Cardiovascular: Orthostatic hypotension (2%) Central nervous system: Dizziness (6%), falling (2%) Hematologic & oncologic: Decreased hematocrit ( 5%), decreased hemoglobin ( 5%) Hypersensitivity: Angioedema (black patients: 2%; others: <1%) Renal: Renal failure (5%) Respiratory: Cough (9%) ALERT: U.S. Boxed Warning Fetal toxicity: Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. When pregnancy is detected, discontinue sacubitril/valsartan as soon as possible. Warnings/Precautions Concerns related to adverse effects: Angioedema: Angioedema has been reported rarely with some angiotensin II receptor antagonists (ARBs) and may occur at any time during treatment (especially following first dose). It may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). Patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE-inhibitor therapy may be at an increased risk. Prolonged frequent monitoring may be required, especially if tongue, glottis, or larynx are involved, as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Discontinue therapy immediately if angioedema occurs. Aggressive early management is critical. Intramuscular (IM) administration of epinephrine may be necessary. Do not readminister to patients who have had angioedema with ARBs. Hyperkalemia: May occur; risk factors include renal dysfunction, diabetes mellitus, hypoaldosteronism, high potassium diet, concomitant use of aliskiren (contraindicated), potassium-sparing diuretics, potassium supplements, and/or potassium containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Hypotension: During the initiation of therapy, hypotension may occur, particularly in patients with heart failure or post-MI patients. Symptomatic hypotension may occur upon initiation in patients who are salt- or volume-depleted (eg, those treated with high-dose diuretics); correct volume depletion prior to administration or initiate at a lower dose. This transient hypotensive response is not a contraindication to further treatment with sacubitril and valsartan. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Disease-related concerns: Aortic/mitral stenosis: Use with caution in patients with significant aortic/mitral stenosis. Heart failure: Use caution when initiating in heart failure; may need to adjust dose, and/or concurrent diuretic therapy, because of valsartan-induced hypotension. Careful monitoring of BUN, serum creatinine, and potassium is necessary especially if preexisting renal disease exists. Hepatic impairment: Use with caution and reduce dosage in patients with moderate hepatic impairment; use is not recommended in patients with severe hepatic impairment. Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in preexisting renal insufficiency; reduce initial dosage for severe impairment (eGFR> <30 mL/minute/1.73 m 2 ). Concurrent drug therapy issues: Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations: Pregnancy: [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Surgical patients: In patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Monitoring Parameters Baseline and periodic serum potassium, renal function, BP. 2013 ACCF/AHA Heart Failure guideline recommendations: Within 1 to 2 weeks after initiation of an ARB, reassess blood pressure (including postural blood pressure changes), renal function, and serum potassium; follow closely after dose changes. Patients with systolic blood pressure> <80 mm Hg, low serum sodium, diabetes mellitus, and impaired renal function should be closely monitored (Yancy, 2013). Note: Sacubitril/valsartan was not available for use at the time of the publication of these guidelines. Pregnancy Considerations [US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Refer to the valsartan monograph for additional information. Patient Education Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) Patient may experience cough. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), dizziness, passing out, or severe loss of strength and energy (HCAHPS). Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Next Interactions Print this page Add to My Med List More about sacubitril/valsartan Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 16 Reviews Add your own review/rating Drug class: angiotensin receptor blockers and neprilysin inhibitors Consumer resources Sacubitril and valsartan Sacubitril and valsartan (Advanced Reading) Professional resources Sacubitril and Valsartan (AHFS Monograph) Other brands: Entresto Related treatment guides Heart Failure> ]} Drug Status Rx Availability Prescription only N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Sacubitril / valsartan Rating 16 User Reviews 5.1 /10 16 User Reviews 5.1 Rate it! Drug Class Angiotensin receptor blockers and neprilysin inhibitors Related Drugs angiotensin receptor blockers and neprilysin inhibitors Entresto , sacubitril / valsartan Heart Failure amlodipine , lisinopril , furosemide , carvedilol , metoprolol , diltiazem , Lasix , spironolactone , warfarin , triamcinolone , Norvasc , nitroglycerin , valsartan , benazepril , hydralazine , digoxin , Nitrostat , Coreg , enalapril , Diovan , nifedipine , ramipril , Coumadin , isosorbide mononitrate , More...} } exercise session
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