Sacubitril + Valsartan interactions

Food & lifestyle

• alcohol

  Moderate

  Synergy

  Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

  What to do: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

  8 sources

  1. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595

• Food High in Potassium

  Moderate

  Synergy

  Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion.

  What to do: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

  2 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):

Conditions

Conditions in which Sacubitril + Valsartan needs care, as documented in this source.

• Angioedema

  Major

  The use of these agents is contraindicated in patients with a history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) therapy or in patients with hereditary angioedema. Patients with a history of angioedema unrelated to these agents may be at increased risk of angioedema while receiving angiotensin II receptor (AR) antagonists. Patients should be advised to immediately report any signs or symptoms suggestive of angioedema (swelling of face, extremities, eyes, lips, or tongue, or difficulty swallowing or breathing) and to stop taking the medication until otherwise directed by their physician. Emergency therapy and/or measures to prevent airway obstruction are required for angioedema involving the tongue, glottis, or larynx. Treatment with angiotensin II receptor (AR) antagonists should be discontinued permanently if angioedema develops in association with therapy.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Diabetes Mellitus

  Major

  The coadministration of some angiotensin II receptor blocker agents with aliskiren is contraindicated in patients with diabetes.

  7 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Hypotension

  Major

  Angiotensin II receptor (AR) antagonists can cause symptomatic hypotension in patients with an activated renin-angiotensin system, such as volume- and/or sodium-depleted patients. Therapy with AR antagonists should be administered cautiously in such patients and in those predisposed to hypovolemic or hyponatremic states (e.g., patients on diuretic therapy, especially if high doses were used or if recently instituted; those on dietary salt restriction; renal dialysis patients). Volume and/or sodium depletion should be corrected prior to initiating therapy with AR antagonists, and the patient should be hemodynamically stable. Ideally, patients at risk for excessive hypotension should initiate AR antagonist therapy under close medical supervision, preferably with a lower dose, and followed closely for the first 2 weeks of treatment and whenever the dosage of AR antagonist or diuretic is increased.

  27 sources

  1. Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G, et al. "Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients." Hypertension 25 (1995): 37-46
  2. Doig JK, MacFadyen RJ, Sweet CS, Lees KR, Reid JL "Dose-ranging study of the angiotensin type I receptor antagonist losartan (DuP753/MK954), in salt-deplete normal man." J Cardiovasc Pharmacol 21 (1993): 732-8
  3. Goldberg AI, Dunlay MC, Sweet CS "Safety and tolerability of losartan potassium, and angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension." Am J Cardiol 75 (1995): 793-5
  4. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  5. Weber MA, Bryyny RL, Pratt JH, et al. "Blood pressure effects of the angiotensin II receptor blocker, losartan." Arch Intern Med 155 (1995): 405-11
  6. Mcintyre M, Macfadyen RJ, Meredith PA, Menard J, Brunner HR, Insuasty J, Reid JL "Comparison of the oral angiotensin II receptor antagonist UP 269-6 or enalapril 20 mg on blood pressure and neurohormonal effects in salt-deplete man." J Cardiovasc Pharmacol 25 (1995): 994-1000
  7. Goldberg AI, Dunlay MC, Sweet CS "Safety and tolerability of losartan compared with atenolol, felodipine and angiotensin converting enzyme inhibitors." J Hypertens 13 Suppl (1995): s77-80
  8. Tikkanen I, Omvik P, Jensen HA "Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension." J Hypertens 13 (1995): 1343-51

  Show all 27 sourcesShow fewer sources

  9. Schaefer KL, Porter JA "Angiotensin II receptor antagonists: the prototype losartan." Ann Pharmacother 30 (1996): 625-36
  10. Weir MR, Elkins M, Liss C, Vrecenak AJ, Barr E, Edelman JM "Efficacy, tolerability, and quality of life of losartan, alone or with hydrochlorothiazide, versus nifedipine GITS in patients with essential hypertension." Clin Ther 18 (1996): 411-28
  11. Waeber B, Brunner HR "Angiotensin II antagonists: a new class of antihypertensive agent." Br J Clin Pract 50 (1996): 265-8
  12. Gibbs CR, Ferner RE, Beevers DG "Angiotensin receptor antagonists - a new class of antihypertensive drug." J Clin Pharm Ther 21 (1996): 127-30
  13. Ellis ML, Patterson H "A new class of antihypertensive therapy: angiotensin II receptor antagonists." Pharmacotherapy 16 (1996): 849-60
  14. Holwerda NJ, Fogari R, Angeli P, et al. "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril." J Hypertens 14 (1996): 1147-115
  15. Oparil S, Barr E, Elkins M, Liss C, Vrecenak A, Edelman J "Efficacy, tolerability, and effects on quality of life of losartan, alone or with hydrochlorothiazide, versus amlodipine, alone or with hydrochlorothiazide, in patients with essential hypertension." Clin Ther 18 (1996): 608-25
  16. Waeber B, Burnier M, Nussberger J, Brunner HR "Experience with angiotensin II antagonists in hypertensive patients." Clin Exp Pharmacol Physiol 23 ( Suppl (1996): s142-6
  17. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  18. van den Meiracker AH, Admiraal PJ, Janssen JA, Kroodsma JM, de Ronde WA, Boomsma F, Sissmann J, Blankestijn PJ, Mulder PG, Man In 't Veld AJ "Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension." Hypertension 25 (1995): 22-9
  19. McIntyre M, MacFadyen RJ, Meredith PA, Brouard R, Reid JL "Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormona effects in salt-deplete men." J Cardiovasc Pharmacol 28 (1996): 101-6
  20. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  21. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  22. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  23. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  24. Karlberg BE, Lins LE, Hermansson K "Efficacy and safety of telmisartan, a selective AT(1) receptor antagonist, compared with enalapril in elderly patients with primary hypertension." J Hypertens 17 (1999): 293-302
  25. McClellan KJ, Markham A "Telmisartan." Drugs 56 (1998): 1039-44
  26. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  27. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Heart Failure

  Moderate

  Angiotensin II receptor (AR) antagonists can cause renal impairment in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system. In addition, symptomatic hypotension can occur in susceptible individuals, which may compromise renal and myocardial perfusion. In patients with severe congestive heart failure (CHF), treatment with AR antagonists has been associated with oliguria and/or progressive azotemia and, rarely, renal failure, myocardial ischemia, and death. Therapy with AR antagonists should be initiated cautiously in patients with severe CHF, especially when accompanied by volume and/or sodium depletion. In patients who experience a decline in renal function, discontinuation of AR antagonist therapy is usually not required provided there is symptomatic improvement of the heart failure and renal deterioration is well-tolerated. Transient hypotension is also not a contraindication to further treatment with AR antagonists, since therapy can usually be reinstated without difficulty after blood pressure stabilizes.

  28 sources

  1. Weber MA, Byyny RL, Pratt JH, Faison EP, Snavely DB, Goldberg AI, Nelson EB "Blood pressure effects of the angiotensin II receptor blocker, losartan." Arch Intern Med 155 (1995): 405-11
  2. Crozier I, Ikram H, Awan N, Cleland J, Stephen N, Dickstein K, Frey M, Young J, Klinger G, Makris L, et al. "Losartan in heart failure. Hemodynamic effects and tolerability. Losartan Hemodynamic Study Group." Circulation 91 (1995): 691-7
  3. Gottlieb SS, Dickstein K, Fleck E, Kostis J, Levine TB, LeJemtel T, DeKock M "Hemodynamic and neurohormonal effects of the angiotensin II antagonist losartan in patients with congestive heart failure." Circulation 88 (1993): 1602-9
  4. Goldberg MR, Bradstreet TE, McWilliams EJ, Tanaka WK, Lipert S, Bjornsson TD, Waldman SA, Osborne B, Pivadori L, Lewis G, et al. "Biochemical effects of losartan, a nonpeptide angiotensin II receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients." Hypertension 25 (1995): 37-46
  5. Goldberg MR, Tanaka W, Barchowsky A, Bradstreet TE, McCrea J, Lo MW, McWilliams EJ Jr, Bjornsson TD "Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers." Hypertension 21 (1993): 704-13
  6. Doig JK, MacFadyen RJ, Sweet CS, Lees KR, Reid JL "Dose-ranging study of the angiotensin type I receptor antagonist losartan (DuP753/MK954), in salt-deplete normal man." J Cardiovasc Pharmacol 21 (1993): 732-8
  7. Dickstein K, Gottlieb S, Fleck E, Kostis J, Levine B, DeKock M, LeJemtel T "Hemodynamic and neurohumoral effects of the angiotensin II antagonist losartan in patients with heart failure." J Hypertens Suppl 12 (1994): s31-5
  8. Abdelrahman AM, Burrell LM, Johnston CI "Blockade of the renin-angiotensin system at different sites: effect on renin, angiotensin and aldosterone." J Hypertens 11 Suppl 3 (1993): s23-6

  Show all 28 sourcesShow fewer sources

  9. Rush JE, Rajfer SI "Theoretical basis for the use of angiotensin II antagonists in the treatment of heart failure." J Hypertens 11 Suppl 3 (1993): s69-71
  10. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  11. Crozier I, Ikram H "The acute and chronic effects of losartan in heart failure." J Hypertens 13 Suppl (1995): s59-61
  12. Saine DR, Ahrens ER "Renal impairment associated with losartan." Ann Intern Med 124 (1996): 775
  13. Schaefer KL, Porter JA "Angiotensin II receptor antagonists: the prototype losartan." Ann Pharmacother 30 (1996): 625-36
  14. Waeber B, Brunner HR "Angiotensin II antagonists: a new class of antihypertensive agent." Br J Clin Pract 50 (1996): 265-8
  15. Gibbs CR, Ferner RE, Beevers DG "Angiotensin receptor antagonists - a new class of antihypertensive drug." J Clin Pharm Ther 21 (1996): 127-30
  16. Ellis ML, Patterson H "A new class of antihypertensive therapy: angiotensin II receptor antagonists." Pharmacotherapy 16 (1996): 849-60
  17. Holwerda NJ, Fogari R, Angeli P, et al. "Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril." J Hypertens 14 (1996): 1147-115
  18. Waeber B, Burnier M, Nussberger J, Brunner HR "Experience with angiotensin II antagonists in hypertensive patients." Clin Exp Pharmacol Physiol 23 ( Suppl (1996): s142-6
  19. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  20. Pitt B, Segal R, Martinez FA, et al. "Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)." Lancet 349 (1997): 747-52
  21. van den Meiracker AH, Admiraal PJ, Janssen JA, Kroodsma JM, de Ronde WA, Boomsma F, Sissmann J, Blankestijn PJ, Mulder PG, Man In 't Veld AJ "Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension." Hypertension 25 (1995): 22-9
  22. McIntyre M, MacFadyen RJ, Meredith PA, Brouard R, Reid JL "Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormona effects in salt-deplete men." J Cardiovasc Pharmacol 28 (1996): 101-6
  23. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  24. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  25. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  26. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  27. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  28. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Hyperkalemia

  Moderate

  Drugs that inhibit the renin-angiotensin, such as angiotensin II receptor antagonist system can cause hyperkalemia. Concomitant use of these agents with drugs that increase potassium levels may increase the risk of hyperkalemia. Use caution when using these agents together and monitor serum potassium periodically.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Kidney Diseases

  Moderate

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

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):

• Liver Diseases

  Moderate

  Valsartan is primarily eliminated by biliary excretion, and a minority is excreted in the urine. Dosage adjustments are not necessary in patients with renal impairment unless they are also volume-depleted, in which case therapy should be initiated under medical supervision. Likewise, patients with mild to moderate hepatic impairment or biliary obstruction generally do not require a dosage adjustment. The manufacturer recommends administering valsartan therapy with caution in patients with impaired renal and/or liver function, particularly if these conditions are severe.

  1 source

  1. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):

• Renal Artery Obstruction

  Moderate

  In patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney, angiotensin II receptor (AR) antagonists may reduce renal perfusion to a critically low level. Increases in serum creatinine or blood urea nitrogen have been reported with ACE inhibitors, a class of drugs that also block the renin-angiotensin-aldosterone system. Although there are no long-term data on the use of AR antagonists in patients with renal artery stenosis, a similar effect should be anticipated. Renal function should be monitored closely for the first few weeks of therapy.

  8 sources

  1. "Product Information. Cozaar (losartan)." Merck & Co., Inc (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals (2001):
  3. "Product Information. Avapro (irbesartan)." Bristol-Myers Squibb (2001):
  4. "Product Information. Teveten (eprosartan)." SmithKline Beecham (2001):
  5. "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals (2001):
  6. "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim (2001):
  7. "Product Information. Benicar (olmesartan)." Sankyo Pharma (2002):
  8. "Product Information. Edarbi (azilsartan)." Takeda Pharmaceuticals America (2011):