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Drug Interactions between Cozaar and Envarsus XR

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

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Interactions between your drugs

Moderate

tacrolimus losartan

Applies to: Envarsus XR (tacrolimus) and Cozaar (losartan)

MONITOR: Coadministration of tacrolimus with ACE inhibitors or angiotensin II receptor antagonists may increase the risk of hyperkalemia associated with the use of these drugs, particularly in patients with renal impairment. Mild to severe hyperkalemia was reported in 31% and 21% of kidney transplant recipients and in 45% and 13% of liver transplant recipients treated with tacrolimus in U.S. and European randomized trials, respectively, and in 8% of heart transplant recipients in a European randomized trial.

MANAGEMENT: Serum potassium levels and renal function should be monitored regularly when tacrolimus is used in combination with ACE inhibitors or angiotensin II receptor antagonists. Particular caution is warranted in patients with renal impairment, diabetes, old age, severe or worsening heart failure, or dehydration. Patients should be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Perazella MA (2000) "Drug-induced hyperkalemia: old culprits and new offenders." Am J Med, 109, p. 307-14

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Drug and food interactions

Moderate

tacrolimus food

Applies to: Envarsus XR (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References

  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11

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Moderate

losartan food

Applies to: Cozaar (losartan)

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.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

References

  1. (2001) "Product Information. Cozaar (losartan)." Merck & Co., Inc
  2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  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

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

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