Skip to main content

Drug Interactions between enalaprilat and Valturna

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

enalapril valsartan

Applies to: enalaprilat and Valturna (aliskiren / valsartan)

GENERALLY AVOID: Coadministration of an ACE inhibitor in combination with an angiotensin II receptor antagonist may increase the risk of hyperkalemia, hypotension, syncope, and renal dysfunction due to additive or synergistic effects on the renin-angiotensin system.

MANAGEMENT: Dual blockade of the renin-angiotensin-aldosterone system by adding an ACE inhibitor to an angiotensin II receptor antagonist is not recommended, especially in patients with diabetic nephropathy. Most patients receiving the combination do not obtain any additional benefit compared to monotherapy. However, if the combination is considered medically necessary, serum electrolytes, blood pressure, and renal function should be closely monitored. Routine monitoring of electrolytes and renal function may be indicated in the elderly or patients with worsening heart failure or a risk for dehydration. Potassium supplementation should generally be avoided unless it is closely monitored, and patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as weakness, listlessness, confusion, tingling of the extremities, and irregular heartbeat.

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
View all 16 references

Switch to consumer interaction data

Major

enalapril aliskiren

Applies to: enalaprilat and Valturna (aliskiren / valsartan)

CONTRAINDICATED: In patients with type 2 diabetes and renal impairment, coadministration of aliskiren with ACE inhibitors or angiotensin receptor blockers (ARBs) has been associated with an increased risk of adverse events including renal complications, hyperkalemia, and hypotension. Interim review of data from the ALTITUDE study after 18 to 24 months revealed no additional benefit and a higher incidence of adverse events when aliskiren 300 mg daily, as opposed to placebo, was added to optimal cardiovascular treatment including an ACE inhibitor or ARB. Another preliminary finding was a slight excess of death or stroke in the aliskiren group; however, the relationship to aliskiren treatment has not been established. ALTITUDE was a multinational study in 8,606 patients from 36 countries evaluating the potential benefits of aliskiren to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes and renal impairment, who are known to be at high risk of cardiovascular and renal events. The trial was halted in December 2011 per recommendation of the independent data monitoring committee overseeing the study.

GENERALLY AVOID: In patients without diabetes, coadministration of aliskiren with ACE inhibitors or ARBs may also be associated with increased risk of symptomatic hypotension, hyperkalemia, and changes in renal function including acute renal failure. All drugs inhibiting the renin-angiotensin system (RAS) can have these effects, which may be additive during concomitant administration. The risk of symptomatic hypotension is increased in the presence of marked volume and/or salt depletion. Elevations in serum potassium levels to greater than 5.5 mEq/L were infrequent with aliskiren alone (0.9% compared to 0.6% with placebo), but increased to 5.5% when used in combination with an ACE inhibitor in a diabetic population. Patients whose renal function may depend in part on the activity of the RAS, including those with renal artery stenosis, severe heart failure, postmyocardial infarction or volume depletion, may be at particular risk for developing acute renal failure with these drugs.

MANAGEMENT: The use of aliskiren with ACE inhibitors or ARBs is considered contraindicated in patients with diabetes and should be avoided in general, particularly in patients with moderate to severe renal impairment (i.e., creatinine clearance (CrCl) < 60 mL/min). Prescribers should not initiate aliskiren in diabetic patients who are taking an ACE inhibitor or an ARB, and should stop any aliskiren-containing treatment if these patients are already receiving the combination. Alternative antihypertensive treatment should be considered as necessary. Most patients do not obtain any additional benefit from combination therapy relative to monotherapy; therefore, the potential risks should be thoroughly assessed when aliskiren is prescribed with ACE inhibitors or ARBs for the treatment of essential hypertension in patients without diabetes. Volume or salt depletion should be corrected prior to initiation of treatment. Routine monitoring of blood pressure, electrolytes, and renal function are recommended, particularly in the elderly or patients with worsening heart failure or a risk for dehydration. Potassium supplementation should generally be avoided unless it is closely monitored, and patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as weakness, listlessness, confusion, tingling of the extremities, and irregular heartbeat.

References

  1. (2007) "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals
  2. Novartis International AG (2012) Novartis announces termination of ALTITUDE study with Rasilez Tekturna in high-risk patients with diabetes and renal impairment. http://cardiobrief.files.wordpress.com/2011/12/novartis-aliskiren-altitude-pr.pdf
  3. Chief Scientific Officer and Senior Vice-President Clinical and Regulatory Affairs, Health Canada, Leclerc JM (2012) Potential risks of cardiovascular and renal adverse events in patients with type 2 diabetes treated with aliskiren (RASILEZ) or aliskiren/hydrochlorothiazide (RASILEZ HCT). http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2012/r
  4. National Kidney Foundation (2012) "KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 update." Am J Kidney Dis, 60, p. 850-86
  5. 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
  6. 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
View all 6 references

Switch to consumer interaction data

Major

valsartan aliskiren

Applies to: Valturna (aliskiren / valsartan) and Valturna (aliskiren / valsartan)

CONTRAINDICATED: In patients with type 2 diabetes and renal impairment, coadministration of aliskiren with ACE inhibitors or angiotensin receptor blockers (ARBs) has been associated with an increased risk of adverse events including renal complications, hyperkalemia, and hypotension. Interim review of data from the ALTITUDE study after 18 to 24 months revealed no additional benefit and a higher incidence of adverse events when aliskiren 300 mg daily, as opposed to placebo, was added to optimal cardiovascular treatment including an ACE inhibitor or ARB. Another preliminary finding was a slight excess of death or stroke in the aliskiren group; however, the relationship to aliskiren treatment has not been established. ALTITUDE was a multinational study in 8,606 patients from 36 countries evaluating the potential benefits of aliskiren to reduce the risk of cardiovascular and renal events in patients with type 2 diabetes and renal impairment, who are known to be at high risk of cardiovascular and renal events. The trial was halted in December 2011 per recommendation of the independent data monitoring committee overseeing the study.

GENERALLY AVOID: In patients without diabetes, coadministration of aliskiren with ACE inhibitors or ARBs may also be associated with increased risk of symptomatic hypotension, hyperkalemia, and changes in renal function including acute renal failure. All drugs inhibiting the renin-angiotensin system (RAS) can have these effects, which may be additive during concomitant administration. The risk of symptomatic hypotension is increased in the presence of marked volume and/or salt depletion. Elevations in serum potassium levels to greater than 5.5 mEq/L were infrequent with aliskiren alone (0.9% compared to 0.6% with placebo), but increased to 5.5% when used in combination with an ACE inhibitor in a diabetic population. Patients whose renal function may depend in part on the activity of the RAS, including those with renal artery stenosis, severe heart failure, postmyocardial infarction or volume depletion, may be at particular risk for developing acute renal failure with these drugs.

MANAGEMENT: The use of aliskiren with ACE inhibitors or ARBs is considered contraindicated in patients with diabetes and should be avoided in general, particularly in patients with moderate to severe renal impairment (i.e., creatinine clearance (CrCl) < 60 mL/min). Prescribers should not initiate aliskiren in diabetic patients who are taking an ACE inhibitor or an ARB, and should stop any aliskiren-containing treatment if these patients are already receiving the combination. Alternative antihypertensive treatment should be considered as necessary. Most patients do not obtain any additional benefit from combination therapy relative to monotherapy; therefore, the potential risks should be thoroughly assessed when aliskiren is prescribed with ACE inhibitors or ARBs for the treatment of essential hypertension in patients without diabetes. Volume or salt depletion should be corrected prior to initiation of treatment. Routine monitoring of blood pressure, electrolytes, and renal function are recommended, particularly in the elderly or patients with worsening heart failure or a risk for dehydration. Potassium supplementation should generally be avoided unless it is closely monitored, and patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as weakness, listlessness, confusion, tingling of the extremities, and irregular heartbeat.

References

  1. (2007) "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals
  2. Novartis International AG (2012) Novartis announces termination of ALTITUDE study with Rasilez Tekturna in high-risk patients with diabetes and renal impairment. http://cardiobrief.files.wordpress.com/2011/12/novartis-aliskiren-altitude-pr.pdf
  3. Chief Scientific Officer and Senior Vice-President Clinical and Regulatory Affairs, Health Canada, Leclerc JM (2012) Potential risks of cardiovascular and renal adverse events in patients with type 2 diabetes treated with aliskiren (RASILEZ) or aliskiren/hydrochlorothiazide (RASILEZ HCT). http://www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/advisories-avis/prof/2012/r
  4. National Kidney Foundation (2012) "KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 update." Am J Kidney Dis, 60, p. 850-86
  5. 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
  6. 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
View all 6 references

Switch to consumer interaction data

Drug and food interactions

Moderate

enalapril food

Applies to: enalaprilat

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

Switch to consumer interaction data

Moderate

valsartan food

Applies to: Valturna (aliskiren / 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

Switch to consumer interaction data

Moderate

aliskiren food

Applies to: Valturna (aliskiren / valsartan)

GENERALLY AVOID: Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren. The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and/or increased ionization of aliskiren due to reduced intestinal pH. In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water. Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water. No significant differences were observed in the blood pressure or heart rate between treatments. However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose. A similar pharmacokinetic interaction has been reported with grapefruit juice. In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water. A high degree of interpatient variability was observed with all three interactions.

MONITOR: High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren. According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively. In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.

MANAGEMENT: To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals. Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.

References

  1. (2007) "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals
  2. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP (2008) "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet, 47, p. 515-31
  3. Tapaninen T, Neuvonen PJ, Niemi M (2010) "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther, 88, p. 339-42
  4. Tapaninen T, Neuvonen PJ, Niemi M (2010) "Orange and apple juices greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren." Br J Clin Pharmacol, 71, p. 718-26
View all 4 references

Switch to consumer interaction data

Moderate

enalapril food

Applies to: enalaprilat

MONITOR: 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.

MANAGEMENT: 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.

References

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

Switch to consumer interaction data

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.


Report options

Loading...
QR code containing a link to this page

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.