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Drug Interactions between sacubitril / valsartan and sildenafil

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

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Interactions between your drugs

Moderate

valsartan sildenafil

Applies to: sacubitril / valsartan and sildenafil

MONITOR: Phosphodiesterase-5 (PDE5) inhibitors may potentiate the blood pressure-lowering effect of antihypertensive medications, including vasodilators. These agents inhibit PDE5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can lead to peripheral vasodilation and thus blood pressure (BP) reduction. For example, when sildenafil (100 mg) was coadministered with amlodipine (5 mg or 10 mg) to hypertensive patients, the mean additional reduction in supine BP was 8/7 mmHg. Likewise, in a group of patients whose hypertension was controlled with nifedipine slow-release (30 mg or 60 mg) once daily, the addition of vardenafil (20 mg) produced a mean additional supine BP reduction of 6/5 mmHg compared to placebo. When coadministered with amlodipine (5 mg) daily or enalapril (20 mg) daily, a single dose of avanafil (200 mg) produced a mean maximum decrease in supine systolic BP of 1.2 mmHg (amlodipine) and supine BP of 1.8/3.5 mmHg (enalapril) compared to placebo.

MANAGEMENT: Caution is advised if PDE5 inhibitors are prescribed in combination with antihypertensive agents. Patients receiving the combination should be advised to avoid rising abruptly from a sitting or recumbent position, especially following treatment initiation or a dosage increase, and to contact their doctor if they experience symptoms of hypotension such as dizziness, lightheadedness, fainting, or tachycardia.

References

  1. "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals PROD (2001):
  2. "Product Information. Levitra (vardenafil)." Bayer (2003):
  3. "Product Information. Stendra (avanafil)." Vivus Inc (2012):

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Drug and food interactions

Moderate

valsartan food

Applies to: sacubitril / 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. "Product Information. Cozaar (losartan)." Merck & Co., Inc PROD (2001):
  2. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals PROD (2001):

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Moderate

sildenafil food

Applies to: sildenafil

GENERALLY AVOID: Coadministration with grapefruit juice may slightly increase the oral bioavailability and delay the onset of action of sildenafil. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In a randomized, crossover study with 24 healthy male volunteers, ingestion of 250 mL of grapefruit juice one hour before and concurrently with a 50 mg dose of sildenafil increased the mean area under the plasma concentration-time curve (AUC) of sildenafil and its pharmacologically active N-desmethyl metabolite by 23% and 24%, respectively, compared to water. Peak plasma concentrations (Cmax) were unaltered, but the time to reach sildenafil Cmax was prolonged by 0.25 hour. The observed increase in sildenafil bioavailability is unlikely to be of clinical significance in most individuals. However, pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability and may be significant in the occasional susceptible patient. Indeed, one subject in the study had a 2.6-fold increase in sildenafil concentrations.

MANAGEMENT: It may be advisable to avoid administration of sildenafil with grapefruit juice to prevent potential toxicity and delay in onset of action.

References

  1. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. "Effects of grapefruit juice on the pharmacokinetics of sildenafil." Clin Pharmacol Ther 71 (2002): 21-29

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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.

See also

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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

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

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