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Drug Interactions between cimetidine and ivabradine

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

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Interactions between your drugs

Moderate

cimetidine ivabradine

Applies to: cimetidine and ivabradine

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of ivabradine, which is primarily metabolized by the isoenzyme. According to the product labeling, potent CYP450 3A4 inhibitors such as ketoconazole and josamycin have been shown to increase ivabradine systemic exposure (AUC) by approximately 7- to 8-fold, and moderate CYP450 3A4 inhibitors such as diltiazem, verapamil and grapefruit juice have been shown to increase ivabradine systemic AUC by approximately 2- to 3-fold. Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

MANAGEMENT: Caution is advised when ivabradine is prescribed with CYP450 3A4 inhibitors. Patients should be monitored for adverse effects such as bradycardia and atrial fibrillation, and the dosage of ivabradine adjusted as necessary in accordance with the product labeling.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "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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Minor

cimetidine food

Applies to: cimetidine

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

References

  1. Feely J, Wood AJ "Effects of cimetidine on the elimination and actions of ethanol." JAMA 247 (1982): 2819-21
  2. Hansten PD "Effects of H2-receptor antagonists on blood alcohol levels." JAMA 267 (1992): 2469

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Minor

cimetidine food

Applies to: cimetidine

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

References

  1. "Product Information. Tagamet (cimetidine)." SmithKline Beecham PROD (2001):
  2. Broughton LJ, Rodgers HJ "Decreased systenuc clearance of caffeine due to cimetidine." Br J Clin Pharmacol 12 (1981): 155-9

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Minor

cimetidine food

Applies to: cimetidine

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.

References

  1. Bendayan R, Sullivan JT, Shaw C, Frecker RC, Sellers EM "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol 38 (1990): 165-9

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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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