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Interactions between Budesonide and Nintedanib

1 drug interaction and 20 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

budesonide nintedanib

Applies to: budesonide and nintedanib
Monitor

Coadministration of corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs) may potentiate the risk of gastrointestinal (GI) perforation that can occasionally occur with the use of nintedanib. Overall, premarketing clinical data reveal no increased risk of GI perforation in nintedanib-treated patients. There were no reports of GI perforation in patients receiving nintedanib in the phase III clinical studies cited by the prescribing information for the treatment of systemic sclerosis-associated interstitial lung disease and chronic fibrosing interstitial lung diseases with a progressive phenotype. GI perforation occurred in 0.3% of patients (2 cases, both serious) receiving nintedanib compared to 0 cases in placebo-treated patients in the clinical studies for idiopathic pulmonary fibrosis. In the phase III LUME-Lung1 study comparing treatment with nintedanib plus docetaxel against placebo plus docetaxel in patients with locally advanced, metastatic, or recurrent non-small cell lung cancer after first-line chemotherapy, the frequency of GI perforation was comparable between the treatment arms. However, cases of GI perforation and ischemic colitis, including some with fatal outcome, have been reported in the postmarketing period. Although a definitive causal relationship to nintedanib has not been established, the association is possible based on nintedanib's mechanism of action. Additional risk factors for GI perforation include recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease.

Management

Caution is recommended when using nintedanib in combination with other drugs associated with an increased risk of GI perforation, such as corticosteroids and NSAIDs, and in patients with other risk factors such as recent abdominal surgery or hollow organ perforation, a prior history of peptic ulceration, or diverticular disease. Nintedanib should only be used if the anticipated benefit outweighs the potential risk. Some authorities recommend waiting at least 4 weeks after abdominal surgery before initiating nintedanib. Patients should be advised to contact their healthcare provider if they experience signs and symptoms of GI perforation such as severe abdominal pain, fever, chills, nausea, or vomiting. Therapy with nintedanib should be permanently discontinued in patients who develop GI perforation.

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

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

budesonide Food/Lifestyle

Applies to: budesonide
Generally avoid

Grapefruit juice may increase the plasma concentrations and systemic effects of orally administered budesonide. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the manufacturer, the systemic exposure of oral budesonide approximately doubles after extensive intake of grapefruit juice.

Management

Patients receiving budesonide should avoid the regular consumption of grapefruits and grapefruit juice to prevent undue increases in plasma budesonide levels and systemic effects.

References (1)
  1. (2001) "Product Information. Entocort (budesonide)." AstraZeneca Pharma Inc
Moderate:

nintedanib Food/Lifestyle

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

Disease interactions

18 potential interactions Applies to: 17 conditions, including Osteoporosis, Lactose Intolerance, Cataract, Gastrointestinal Diverticula, and Thrombotic/Thromboembolic Disorder.

Bleeding Disorder

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Bleeding Disorder.

Nintedanib may increase the risk of bleeding. Nintedanib should only be used in patients with known risk of bleeding if the anticipated benefit outweighs the potential risk. Close monitoring is recommended.

Cataract

Moderate:

budesonide

Budesonide has a moderate potential interaction with Cataract.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Gastrointestinal Diverticula

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Gastrointestinal Diverticula.

Nintedanib may increase the risk of gastrointestinal perforation. Use caution when treating patients who have had recent abdominal surgery or history of diverticular disease. It is recommended to discontinue therapy with nintedanib in patients who develop gastrointestinal perforation. Nintedanib should only be used in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk. Care and close monitoring is recommended.

Gastrointestinal Perforation

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Gastrointestinal Perforation.

Nintedanib may increase the risk of gastrointestinal perforation. Use caution when treating patients who have had recent abdominal surgery or history of diverticular disease. It is recommended to discontinue therapy with nintedanib in patients who develop gastrointestinal perforation. Nintedanib should only be used in patients with known risk of gastrointestinal perforation if the anticipated benefit outweighs the potential risk. Care and close monitoring is recommended.

Glaucoma/Intraocular Hypertension

Moderate:

budesonide

Budesonide has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Herpetic Keratitis

Moderate:

budesonide

Budesonide has a moderate potential interaction with Herpetic Keratitis.

Pharmacologic dosages of corticosteroids may increase the risk of corneal perforation in patients with ocular herpes simplex. Therapy with inhaled and nasal corticosteroids should be administered cautiously in such patients.

History, Thrombotic/Thromboembolic Disorder

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

Arterial thromboembolic events, including myocardial infarction have been reported in patients taking nintedanib. It is recommended to exercise caution when treating patients at higher cardiovascular risk, including known coronary artery disease and to consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Hyperadrenocorticism

Moderate:

budesonide

Budesonide has a moderate potential interaction with Hyperadrenocorticism.

The use of corticosteroids may rarely precipitate or aggravate conditions of hyperadrenocorticism. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used. The development of symptoms such as menstrual irregularities, acneiform lesions, cataracts and cushingoid features during inhaled or nasal corticosteroid therapy may indicate excessive use.

Infection

Moderate:

budesonide

Budesonide has a moderate potential interaction with Infection.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Ischemic Heart Disease

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Ischemic Heart Disease.

Arterial thromboembolic events, including myocardial infarction have been reported in patients taking nintedanib. It is recommended to exercise caution when treating patients at higher cardiovascular risk, including known coronary artery disease and to consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Lactose Intolerance

Moderate:

budesonide

Budesonide has a moderate potential interaction with Lactose Intolerance.

Some inhaled corticosteroid formulations contain lactose and may cause adverse reactions including cough, wheezing and bronchospasm in patients with severe milk protein allergy or intolerance. Caution is advised.

Liver Disease

Moderate:

budesonide

Budesonide has a moderate potential interaction with Liver Disease.

Corticosteroids are predominantly cleared by hepatic metabolism and impairment of the liver function may lead to their accumulation. Patients with hepatic disease should be closely monitored.

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Liver Disease.

The use of nintedanib is associated with elevations of liver enzymes. Treatment with nintedanib is not recommended in patients with moderate or severe hepatic impairment. Patients with mild hepatic impairment can be treated with a reduced dose of nintedanib. It is recommended to conduct liver function tests prior to treatment with nintedanib and periodically thereafter as clinically indicated. Dosage modifications or interruption may be necessary for liver enzyme elevations as clinically indicated and according to medical practices.

Osteoporosis

Moderate:

budesonide

Budesonide has a moderate potential interaction with Osteoporosis.

Prolonged use of inhaled corticosteroids may be associated with a reduction in bone density. This effect appears to be dose-related and has been reported primarily with high dosages (800 mcg/day or more of beclomethasone or equivalent for 1 year or greater). Reduced levels of total body calcium have also been demonstrated in patients receiving lower dosages. Long-term therapy with inhaled and nasal corticosteroids should be administered cautiously in patients with osteoporosis. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Renal Dysfunction

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Renal Dysfunction.

Based on a population pharmacokinetics analysis of nintedanib, exposure to nintedanib is not influenced by mild or moderate renal impairment. No dose adjustment is required in patients with mild to moderate renal impairment. Care and close monitoring is recommended when using this agent in patients with severe renal impairment and end-stage renal disease as the safety, efficacy, and, pharmacokinetics of nintedanib have not been studied these patients.

Smoking

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Smoking.

Smoking is associated with decreased exposure to nintedanib. Patients that are smokers might alter the efficacy profile of nintedanib. Encourage patients that are smokers to stop smoking prior to treatment because it might alter the efficacy profile of nintedanib and to avoid smoking while on therapy.

Thrombotic/Thromboembolic Disorder

Moderate:

nintedanib

Nintedanib has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

Arterial thromboembolic events, including myocardial infarction have been reported in patients taking nintedanib. It is recommended to exercise caution when treating patients at higher cardiovascular risk, including known coronary artery disease and to consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.

Tuberculosis, Latent

Moderate:

budesonide

Budesonide has a moderate potential interaction with Tuberculosis, Latent.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

More resources

budesonide

A total of 621 drugs are known to interact with budesonide.

nintedanib

A total of 263 drugs are known to interact with nintedanib.

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.