Drug Interactions between Inrebic and nintedanib
This report displays the potential drug interactions for the following 2 drugs:
- Inrebic (fedratinib)
- nintedanib
Interactions between your drugs
nintedanib fedratinib
Applies to: nintedanib and Inrebic (fedratinib)
MONITOR: Coadministration of nintedanib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Vascular endothelial growth factor receptor (VEGFR) inhibitors like nintedanib can cause bleeding. In clinical trials, bleeding events were reported in 10% of patients treated with nintedanib versus 7% of patients treated with placebo.
MANAGEMENT: Concomitant use of nintedanib and medications that interfere with platelet function or coagulation should be approached cautiously. Close clinical and laboratory observation for bleeding complications is recommended for patients on full anticoagulation therapy, and the anticoagulant dose adjusted as necessary. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.
References
- (2022) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim
- (2021) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (Canada) Ltd
- (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Pty Ltd
- (2023) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Ltd
- (2023) "Product Information. Vargatef (nintedanib)." Boehringer Ingelheim Ltd
Drug and food interactions
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 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, or Seville oranges should be avoided during treatment with nintedanib.
References
- (2022) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim
- (2021) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim (Canada) Ltd
- (2024) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Pty Ltd
- (2023) "Product Information. Ofev (nintedanib)." Boehringer Ingelheim Ltd
- (2023) "Product Information. Vargatef (nintedanib)." Boehringer Ingelheim Ltd
fedratinib food
Applies to: Inrebic (fedratinib)
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of fedratinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. When a single 300 mg oral dose of fedratinib (0.75 times the recommended dose) was coadministered with 200 mg twice daily ketoconazole, a potent CYP450 3A4 inhibitor, fedratinib total systemic exposure (AUC(inf)) increased by approximately 3-fold. Using physiologically based pharmacokinetic (PBPK) simulations, coadministration of fedratinib 400 mg once daily and ketoconazole 400 mg once daily is predicted to increase fedratinib AUC at steady state by 2-fold. Coadministration with the moderate CYP450 3A4 inhibitors, erythromycin (500 mg three times daily) or diltiazem (120 mg twice daily), is predicted to increase fedratinib AUC by approximately 1.5- to 2-fold following single-dose administration and by approximately 1.2-fold at steady state. In general, 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 fedratinib exposure may potentiate the risk of adverse reactions such as nausea, vomiting, diarrhea, anemia, thrombocytopenia, neutropenia, encephalopathy (including Wernicke's), liver (ALT, AST) and pancreatic (amylase, lipase) enzyme elevations, increased blood creatinine, and secondary malignancies.
Food does not affect the oral bioavailability of fedratinib to a clinically significant extent. Administration of a single 500 mg dose (1.25 times the recommended dose) with a low-fat, low-calorie meal (162 calories; 6% from fat, 78% from carbohydrate, 16% from protein) or a high-fat, high-calorie meal (815 calories; 52% from fat, 33% from carbohydrate, 15% from protein) increased fedratinib peak plasma concentration (Cmax) and systemic exposure (AUC) by up to 14% and 24%, respectively.
MANAGEMENT: Fedratinib may be taken with or without food. However, administration with a high-fat meal may help reduce the incidence of nausea and vomiting. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with fedratinib.
References
- Wu F, Krishna G, Surapaneni S (2020) "Physiologically based pharmacokinetic modeling to assess metabolic drug-drug interaction risks and inform the drug label for fedratinib." Cancer Chemother Pharmacol, 86, p. 461-73
- (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
- (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals 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.
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:
- Inrebic (fedratinib)
- 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
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| 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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