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Drug Interactions between neratinib and trastuzumab

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

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Interactions between your drugs

No interactions were found between neratinib and trastuzumab. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

neratinib

A total of 183 drugs are known to interact with neratinib.

trastuzumab

A total of 177 drugs are known to interact with trastuzumab.

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." O 0
  2. Abbas R, Hug BA, Leister C, Burns J, Sonnichsen D "Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects." Br J Clin Pharmacol 71 (2011): 522-7
  3. "Product Information. Nerlynx (neratinib)." Puma Biotechnology, Inc. (2017):

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Her2 inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'HER2 inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'HER2 inhibitors' category:

  • neratinib
  • trastuzumab

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.