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Drug Interactions between lenvatinib and nintedanib

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

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Interactions between your drugs

Moderate

nintedanib lenvatinib

Applies to: nintedanib and lenvatinib

MONITOR: Lenvatinib use in combination with or after recent use of other medications associated with osteonecrosis of the jaw (ONJ) may increase the risk of this rare side effect. Theories as to how ONJ develops include inhibition of bone remodeling, inflammation or infection, angiogenesis inhibition, innate or acquired immune dysfunction, as well as genetic predisposition; however, the pathophysiology is likely related to multiple factors. Medication-related ONJ (MRONJ) is a rare, but severe and debilitating condition whose exact cause remains unknown. Known risk factors for MRONJ include cancer, duration of antiresorptive therapy, dentoalveolar operations (such as tooth extraction), preexisting inflammatory dental disease, and concurrent use of multiple medications associated with a risk of ONJ (such as bisphosphonates, denosumab, romosozumab, angiogenesis inhibitors, and corticosteroids).

MANAGEMENT: Caution is advised when lenvatinib is used with other agents that are also associated with the development of ONJ. A routine oral examination should be performed prior to initiation of either treatment. Patients should be advised regarding good oral hygiene practices and to have regular preventive dentistry performed throughout treatment. For patients requiring invasive dental procedures, discontinuation of lenvatinib may be recommended. Patients should be advised to seek medical attention if they experience signs and symptoms of ONJ, such as: pain in the mouth, teeth, or jaw; swelling or sores inside the mouth; numbness or a feeling of heaviness in the jaw; loosening of a tooth; or exposure of bone in the jaw. Those who are suspected of having or who develop ONJ during lenvatinib therapy should receive care by a dentist or an oral surgeon. In all circumstances involving MRONJ, clinical judgment and a risk-benefit assessment should guide the management plan of each patient based on their specific clinical circumstances.

References (5)
  1. (2015) "Product Information. Lenvima (lenvatinib)." Eisai Inc
  2. Zhang X, Hamadeh IS, Song S Osteonecrosis of the Jaw in the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.2693
  3. Rosella D, Papi P, Giardino R Medication-related osteonecrosis of the jaw: Clinical and practical guidelines. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820581/
  4. AIDhalaan NA, BaQais A, Al-Omar A Medication-related Osteonecrosis of the Jaw: A Review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067354/
  5. Ruggiero SL, Dodson TB, Aghaloo T Medication-Related Osteonecrosis of the Jaw - 2022 Update https://www.aaoms.org/docs/govt_affairs/advocacy_white_papers/mronj_position_paper.pdf

Drug and food interactions

Moderate

nintedanib food

Applies to: nintedanib

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of nintedanib. After food intake, nintedanib exposure increased by approximately 20% compared to administration under fasted conditions. Absorption was also delayed, as indicated by an increase in the median time to reach maximum plasma concentration (Tmax) from 2 hours in the fasted state to approximately 4 hours under fed conditions, irrespective of the type of food ingested. In an in vitro study, mixing nintedanib capsules with a small amount of apple sauce or chocolate pudding for up to 15 minutes did not have any impact on their pharmaceutical quality, but swelling and deformation of the capsules were observed with longer exposure time due to water uptake of the gelatin capsule shell. Therefore, administration with soft food would not be expected to alter the clinical effect of nintedanib when taken immediately.

GENERALLY AVOID: Grapefruit and grapefruit juice may increase the plasma concentrations of nintedanib, which has been shown to be a substrate of the P-glycoprotein (P-gp) efflux transporter and a minor substrate of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of both P-gp-mediated efflux in the gut wall as well as CYP450 3A4-mediated first-pass metabolism in the intestinal tract by certain compounds present in grapefruit.

MANAGEMENT: Nintedanib should be administered with food to reduce the incidence of gastrointestinal effects. Nintedanib capsules may be taken with water or a small amount (teaspoonful) of cold or room temperature soft food, such as apple sauce or chocolate pudding, and must be swallowed whole (unchewed) immediately, to ensure the capsule stays intact. Food containing grapefruit, grapefruit juice, Seville orange (a citrus relative of the grapefruit), or Seville orange juice should be avoided during treatment with nintedanib.

References (5)
  1. (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim
  2. (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (Canada) Ltd
  3. (2025) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Ltd
  4. (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Pty Ltd, 2
  5. (2024) "Product Information. Vargatef (nintedanib)." Boehringer Ingelheim Ltd

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

Multikinase inhibitors

Therapeutic duplication

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

  • lenvatinib
  • nintedanib

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.

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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