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Drug Interactions between ivabradine and rifapentine

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

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Interactions between your drugs

Major

rifapentine ivabradine

Applies to: rifapentine and ivabradine

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 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 the potent CYP450 3A4 inducer 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 potent CYP450 3A4 inducers should generally be avoided. If coadministration is required, the possibility of diminished therapeutic response to ivabradine should be considered. Pharmacologic response to ivabradine should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.

References

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

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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."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2015) "Product Information. Corlanor (ivabradine)." Amgen USA

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Moderate

rifapentine food

Applies to: rifapentine

ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.

References

  1. (2021) "Product Information. Isoniazid/Rifapentine 300 mg/300 mg (Macleods) (isoniazid-rifapentine)." Imported (India), 2
  2. (2021) "Product Information. Priftin (rifapentine)." sanofi-aventis

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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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