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Drug Interactions between neratinib and ranitidine

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

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Interactions between your drugs

Major

raNITIdine neratinib

Applies to: ranitidine and neratinib

GENERALLY AVOID: Coadministration with proton pump inhibitors or H2-receptor antagonists may significantly decrease the oral bioavailability of neratinib. The solubility of neratinib is pH-dependent and increases as neratinib becomes protonated at acidic pH, thus an increase in pH may interfere with its absorption. According to the product labeling, neratinib is sparingly soluble at pH 1.2 (32.90 mg/mL) and insoluble at approximate pH 5.0 and above (0.08 mg/mL or less). When a single 240 mg dose of neratinib was administered to 15 healthy adult subjects on day 5 of treatment with lansoprazole 30 mg orally once daily for 7 days, mean neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 65%, respectively, compared to neratinib administered alone. In addition, the Cmax and AUC of neratinib were reduced by 55% and 47%, respectively, when neratinib was administered 2 hours after a 300 mg dose of ranitidine.

MANAGEMENT: Concomitant use of neratinib with proton pump inhibitors and H2-receptor antagonists should generally be avoided. According to some authorities, if H2-receptor antagonist therapy is required, neratinib should be administered at least 2 hours before or 10 hours after the H2-receptor antagonist. In addition, short-acting antacids could be considered if acid-suppression therapy is required, with neratinib dosing separated by at least three hours after antacid administration. If coadministered with a gastric acid reducing agent, increasing the dose of neratinib is unlikely to compensate for the loss of bioavailability.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. (2017) "Product Information. Nerlynx (neratinib)." Puma Biotechnology, Inc.

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Drug and food interactions

Major

neratinib food

Applies to: neratinib

GENERALLY AVOID: Grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges may increase the plasma concentrations of neratinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in these fruits. Inhibition of hepatic CYP450 3A4 may also contribute. In a study consisting of 24 healthy subjects, neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 3.2- and 4.8-fold, respectively, when a single 240 mg oral dose of neratinib was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily for 5 days). Also, mean apparent oral clearance of neratinib decreased by approximately 75% and mean elimination half-life increased by 54%. The interaction has not been studied with these fruits. In general, for example, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to neratinib may increase adverse effects such as diarrhea, nausea, vomiting, abdominal pain, stomatitis, anorexia, and hepatotoxicity.

Food with a high fat content enhances the oral bioavailability of neratinib. In healthy volunteers, administration of neratinib 240 mg with a high-fat meal (approximately 55% fat; 31% carbohydrate; 14% protein) increased neratinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 1.7- and 2.2-fold, respectively, compared to administration under fasting conditions. By contrast, a standard breakfast (approximately 50% carbohydrate; 35% fat; 15% protein) increased the Cmax and AUC of neratinib by 1.2- and 1.1-fold, respectively.

MANAGEMENT: The manufacturer recommends administering neratinib with food at approximately the same time every day. Patients should avoid consumption of grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges during treatment with neratinib.

References

  1. Cerner Multum, Inc. "Australian Product Information."
  2. Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D (2011) "Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects." Br J Clin Pharmacol, 71, p. 522-7
  3. (2017) "Product Information. Nerlynx (neratinib)." Puma Biotechnology, Inc.

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Minor

raNITIdine food

Applies to: ranitidine

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 (1990) "Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans." Eur J Clin Pharmacol, 38, p. 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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