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Drug Interactions between Imbruvica and Lanoxicaps

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

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Interactions between your drugs

Moderate

digoxin ibrutinib

Applies to: Lanoxicaps (digoxin) and Imbruvica (ibrutinib)

MONITOR: Coadministration with ibrutinib may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. In vitro studies indicate that ibrutinib is not a substrate for P-gp, and systemic ibrutinib is unlikely to be an inhibitor of P-gp at clinical doses. However, it may have an effect on P-gp substrates in the gastrointestinal tract due to higher local concentrations after an oral dose.

MANAGEMENT: Caution is advised if ibrutinib is prescribed in combination with orally administered P-gp substrates, particularly those with a narrow therapeutic range. Dosage reduction and/or dosage interval adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever ibrutinib is added to or withdrawn from therapy. Some authorities recommend that narrow therapeutic range P-gp substrates, such as digoxin, should be administered at least 6 hours before or after ibrutinib.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics Inc

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Drug and food interactions

Major

ibrutinib food

Applies to: Imbruvica (ibrutinib)

GENERALLY AVOID: Coadministration with grapefruit, grapefruit juice, or Seville oranges may significantly increase the plasma concentrations of ibrutinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Pharmacokinetic modeling suggests that other moderate CYP450 3A4 inhibitors such as diltiazem and erythromycin may increase ibrutinib systemic exposure (AUC) by 6- to 9-fold under fasting condition. The safety and efficacy of these exposures are unknown. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 to 1400 mg) given for 28 days, which yielded single dose AUC values that were approximately 50% greater than steady-state exposures seen at the highest indicated dose of 560 mg.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ibrutinib. The mechanism of interaction is unknown. According to the product labeling, administration with food increases ibrutinib exposure approximately 2-fold compared to administration after overnight fasting.

MANAGEMENT: Patients treated with ibrutinib should avoid consumption of Seville oranges, grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ibrutinib should be taken once daily at approximately the same time each day.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Imbruvica (ibrutinib)." Pharmacyclics Inc

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Minor

digoxin food

Applies to: Lanoxicaps (digoxin)

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References

  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6

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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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