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Drug Interactions between perindopril and valsartan

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

valsartan perindopril

Applies to: valsartan and perindopril

GENERALLY AVOID: Coadministration of angiotensin converting enzyme inhibitors (ACEIs) with angiotensin II receptor blockers (ARBs) may increase the risk of hyperkalemia, severe hypotension, and renal failure due to additive or synergistic effects on the renin-angiotensin system, particularly in patients with diabetes and/or renal impairment. A multicenter double-blind, randomized, controlled study evaluating the efficacy of combination-therapy with losartan (an ARB) and lisinopril (an ACEI) in slowing the progression of proteinuric diabetic nephropathy was stopped early on account of safety concerns due to increased rates of serious adverse events in the combination-therapy treatment group (hyperkalemia and acute kidney injury). Hyperkalemia occurred in 9.9% of patients in the combination-therapy group compared to 4.4% in the monotherapy group, and acute kidney injury events occurred in 18% of the combination-group compared to 11% in the monotherapy group.

MANAGEMENT: Coadministration of angiotensin converting enzyme inhibitors (ACEIs) with angiotensin II receptor blockers (ARBs) should generally be avoided, especially in patients with diabetic nephropathy and/or moderate to severe renal impairment (GFR <60 mL/min/1.73 m2). Some authorities consider this combination contraindicated in such patients. However, if the combination is considered medically necessary, serum electrolytes, blood pressure, and renal function should be closely monitored particularly in the elderly, patients with worsening heart failure, or those at risk for dehydration. Additionally, potassium supplementation should generally be avoided unless potassium levels are closely monitored. Patients and their caregivers should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia (e.g., weakness, tingling of the extremities, irregular heartbeat) and/or acute kidney injury (e.g., reduced urine output, lower extremity edema). Individual product labeling should be consulted for further guidance.

References

  1. (2001) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals
  2. (2001) "Product Information. Atacand (candesartan)." Astra-Zeneca Pharmaceuticals
  3. (2001) "Product Information. Micardis (telmisartan)." Boehringer-Ingelheim
  4. Laverman GD, Navis G, Henning RH, De Jong PE, De Zeeuw D (2002) "Dual renin-angiotensin system blockade at optimal doses for proteinuria." Kidney Int, 62, p. 1020-5
  5. Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving HH (2003) "Dual blockade of the renin-angiotensin system versus maximal recommended dose of ACE inhibition in diabetic nephropathy." Kidney Int, 63, p. 1874-80
  6. Rossing K, Jacobsen P, Pietraszek L, Parving HH (2003) "Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial." Diabetes Care, 26, p. 2268-74
  7. Jacobsen P, Andersen S, Jensen BR, Parving HH (2003) "Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy." J Am Soc Nephrol, 14, p. 992-9
  8. McMurray JJ, Ostergren J, Swedberg K, et al. (2003) "Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial." Lancet, 362, p. 767-71
  9. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. (2003) "Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both." N Engl J Med, 349, p. 1893-1906
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  11. ONTARGET Investigators, Yusuf S, Teo KK, et al. (2008) "Telmisartan, ramipril, or both in patients at high risk for vascular events." N Engl J Med, 358, p. 1547-59
  12. Mann JF, Schmieder RE, McQueen M, et al. (2008) "Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial." Lancet, 372, p. 547-53
  13. Guthrie RM (2009) "Review of ONTARGET: treating patients at high risk for vascular events with telmisartan, ramipril, or both. Commentary." Postgrad Med, 121, p. 202-4
  14. National Kidney Foundation (2012) "KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 update." Am J Kidney Dis, 60, p. 850-86
  15. EMA. European Medicines Agency (2014) PRAC recommends against combined use of medicines affecting the renin-angiotensin (RAS) system: recommendation will now be considered by CHMP for final opinion. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Renin-angiotensin_sys
  16. MHRA. Medicines and Healthcare Regulatory Agency (2014) Combination use of medicines from different classes of renin-angiotensin system blocking agents: risk of hyperkalaemia, hypotension, and impaired renal function--new warnings. http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON426905
  17. (2021) "Product Information. Irbesartan (irbesartan)." Alembic Pharmaceuticals
  18. (2021) "Product Information. Aprovel (irbesartan)." Sanofi
  19. (2021) "Product Information. Valsartan (valsartan)." Alembic Pharmaceuticals
  20. (2023) "Product Information. Auro-Valsartan (valsartan)." Auro Pharma Inc
  21. (2023) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals UK Ltd
  22. (2020) "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals Pty Ltd
  23. (2023) "Product Information. Telmisartan (telmisartan)." Alembic Pharmaceuticals
  24. (2023) "Product Information. Ach-Telmisartan (telmisartan)." Accord Healthcare Inc
  25. (2023) "Product Information. Micardis (telmisartan)." Boehringer Ingelheim Ltd
  26. (2022) "Product Information. Micardis (telmisartan)." Boehringer Ingelheim Pty Ltd
  27. (2022) "Product Information. Olmesartan Medoxomil (olmesartan)." ASCEND LABORATORIES S.P.A.
  28. (2022) "Product Information. Olmesartan Medoxomil (olmesartan)." Thornton & Ross Ltd
  29. (2022) "Product Information. IXIA (olmesartán)." MENARINI INTERNATIONAL OPERATIONS LUXEMBOURG, S.A.
  30. (2024) "Product Information. Losartan Potassium (losartan)." Strides Pharma Inc.
  31. (2023) "Product Information. Auro-Losartan (losartan)." Auro Pharma Inc
  32. (2022) "Product Information. Cozaar (losartan)." Organon Pharma (UK) Ltd
  33. (2022) "Product Information. Eprosartan (eprosartan)." Amarox Ltd
  34. (2021) "Product Information. Candesartan Cilexetil (candesartan)." Alembic Pharmaceuticals
  35. (2022) "Product Information. Amias (candesartan)." Neon Healthcare Ltd
  36. (2022) "Product Information. Edarbi (azilsartan)." Takeda UK Ltd
  37. Fried L, Emanuele N, Zhang J, brophy m, Conner TA, Duckworth W, et al. (2024) Combined angiotensin inhibition for the treatment of diabetic nephropathy https://www.nejm.org/doi/10.1056/NEJMoa1303154?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200www.ncbi.nlm.nih.gov#f02
View all 37 references

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Drug and food interactions

Moderate

valsartan food

Applies to: valsartan

GENERALLY AVOID: 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. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: 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.

References

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

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Moderate

perindopril food

Applies to: perindopril

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

References

  1. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  2. Good CB, McDermott L (1995) "Diet and serum potassium in patients on ACE inhibitors." JAMA, 274, p. 538
  3. Ray K, Dorman S, Watson R (1999) "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens, 13, p. 717-20

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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