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Drug Interactions between ivabradine and st. john's wort

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

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Interactions between your drugs

Major

St. John's wort ivabradine

Applies to: st. john's wort and ivabradine

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 such as St. John's wort may significantly decrease the plasma concentrations of ivabradine and its active N-desmethylated metabolite, both of which are primarily metabolized by the isoenzyme. In 12 healthy volunteers, administration of a single 10 mg dose of ivabradine following pretreatment with St. John's wort 300 mg three times daily for 14 days decreased mean ivabradine peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 53% and 62%, respectively, compared to administration of ivabradine alone. Mean Cmax and AUC of the N-desmethylated metabolite, which is equipotent to ivabradine and circulates at concentrations approximately 40% that of ivabradine, decreased by 25% and 32%, respectively. No significant changes in pharmacodynamic effects of ivabradine were observed in the study. However, reduced therapeutic efficacy may occur based on the magnitude of pharmacokinetic changes.

MANAGEMENT: Concomitant use of ivabradine with St. John's wort should generally be avoided.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Portoles A, Terleira A, Calvo A, Martinez I, Resplandy G "Effects of Hypericum perforatum on ivabradine pharmacokinetics in healthy volunteers: an open-label, pharmacokinetic interaction clinical trial." J Clin Pharmacol 46 (2006): 1188-94
  3. "Product Information. Corlanor (ivabradine)." Amgen USA (2015):

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Drug and food interactions

Major

ivabradine food

Applies to: ivabradine

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of ivabradine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. According to the product labeling, administration with grapefruit juice (quantity unknown) resulted in an approximately twofold increase in ivabradine systemic exposure (AUC). Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

ADJUST DOSING INTERVAL: Food delays the absorption of ivabradine by approximately 1 hour and increases plasma exposure by 20% to 40% compared to fasting conditions.

MANAGEMENT: Patients treated with ivabradine should avoid or limit consumption of grapefruit or grapefruit juice. The manufacturer recommends taking ivabradine with meals to reduce variability in exposure.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Corlanor (ivabradine)." Amgen USA (2015):

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Moderate

St. John's wort food

Applies to: st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8

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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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