Skip to main content

Drug Interactions between Delyla and fedratinib

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

ethinyl estradiol fedratinib

Applies to: Delyla (ethinyl estradiol / levonorgestrel) and fedratinib

MONITOR CLOSELY: Coadministration of Janus kinase (JAK) inhibitors and combined hormonal contraceptives, hormone replacement therapy (HRT), or estrogen receptor modulators may potentiate the risk of venous thromboembolism (VTE). Serious and sometimes fatal VTE events including pulmonary embolism (PE) and deep vein thrombosis (DVT) have been observed in patients taking JAK inhibitors. In a randomized safety study of patients with rheumatoid arthritis with at least one cardiovascular risk factor (e.g., prior VTE, body mass index greater than or equal to 35 kg/m2, older age, history of chronic lung disease), an increased risk for VTE was observed with tofacitinib compared to tumor necrosis factor (TNF) inhibitors. Similarly, in a meta-analysis evaluating 16 randomized controlled trials for the incidence of venous thromboembolism with JAK inhibitor use (including tofacitinib, upadacitinib, filgotinib, and baricitinib), a potential increase in the risk of VTE, although not clinically significant, was observed compared to placebo or TNF inhibitors. Subgroup analyses showed higher VTE events with tofacitinib compared to TNF inhibitors and with higher doses of JAK inhibitors. Data surrounding the use of JAK inhibitors with hormonal contraceptives, HRT and or estrogen receptor modulators are not available.

MANAGEMENT: Caution and close clinical monitoring are advised when JAK inhibitors are administered in patients with an increased risk for venous thromboembolism (VTE), such as those taking combined hormonal contraceptives, hormone replacement therapy (HRT) and/or estrogen receptor modulators. While not discussed in US product labeling, international labeling for some JAK inhibitors recommends avoiding concomitant use due to their potential to increase the risk of VTE. Other international labeling suggests JAK inhibitors may be administered if necessary, but with additional monitoring. Patients and their caregivers should be advised to seek medical attention if they experience signs and symptoms of VTE. Individual product labeling should be consulted for further guidance.

References

  1. (2011) "Product Information. Jakafi (ruxolitinib)." Incyte Corporation
  2. (2019) "Product Information. Rinvoq (upadacitinib)." AbbVie US LLC
  3. (2022) "Product Information. Cibinqo (abrocitinib)." Pfizer U.S. Pharmaceuticals Group
  4. (2022) "Product Information. Vonjo (pacritinib)." CTI BioPharma Corp.
  5. (2021) "Product Information. Xeljanz (tofacitinib)." Pfizer U.S. Pharmaceuticals Group, SUPPL-28
  6. (2021) "Product Information. Xeljanz (tOFACitinib)." Pfizer Australia Pty Ltd, pfpxeljt11021
  7. (2022) "Product Information. Xeljanz (tofacitinib)." Pfizer Ltd, XJ 5mg 26_0 GB
  8. (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
  9. (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals Ltd
  10. (2022) "Product Information. Olumiant (baricitinib)." Lilly, Eli and Company, SUPPL-7
  11. (2023) "Product Information. Litfulo (ritlecitinib)." Pfizer U.S. Pharmaceuticals Group
  12. (2023) "Product Information. Ojjaara (momelotinib)." GlaxoSmithKline
  13. (2023) "Product Information. Olumiant (bARICITinib)." Eli Lilly Australia Pty Ltd, vA9.0_May2023
  14. (2024) "Product Information. Olumiant (baricitinib)." Eli Lilly and Company Ltd
View all 14 references

Switch to consumer interaction data

Major

levonorgestrel fedratinib

Applies to: Delyla (ethinyl estradiol / levonorgestrel) and fedratinib

MONITOR CLOSELY: Coadministration of Janus kinase (JAK) inhibitors and combined hormonal contraceptives, hormone replacement therapy (HRT), or estrogen receptor modulators may potentiate the risk of venous thromboembolism (VTE). Serious and sometimes fatal VTE events including pulmonary embolism (PE) and deep vein thrombosis (DVT) have been observed in patients taking JAK inhibitors. In a randomized safety study of patients with rheumatoid arthritis with at least one cardiovascular risk factor (e.g., prior VTE, body mass index greater than or equal to 35 kg/m2, older age, history of chronic lung disease), an increased risk for VTE was observed with tofacitinib compared to tumor necrosis factor (TNF) inhibitors. Similarly, in a meta-analysis evaluating 16 randomized controlled trials for the incidence of venous thromboembolism with JAK inhibitor use (including tofacitinib, upadacitinib, filgotinib, and baricitinib), a potential increase in the risk of VTE, although not clinically significant, was observed compared to placebo or TNF inhibitors. Subgroup analyses showed higher VTE events with tofacitinib compared to TNF inhibitors and with higher doses of JAK inhibitors. Data surrounding the use of JAK inhibitors with hormonal contraceptives, HRT and or estrogen receptor modulators are not available.

MANAGEMENT: Caution and close clinical monitoring are advised when JAK inhibitors are administered in patients with an increased risk for venous thromboembolism (VTE), such as those taking combined hormonal contraceptives, hormone replacement therapy (HRT) and/or estrogen receptor modulators. While not discussed in US product labeling, international labeling for some JAK inhibitors recommends avoiding concomitant use due to their potential to increase the risk of VTE. Other international labeling suggests JAK inhibitors may be administered if necessary, but with additional monitoring. Patients and their caregivers should be advised to seek medical attention if they experience signs and symptoms of VTE. Individual product labeling should be consulted for further guidance.

References

  1. (2011) "Product Information. Jakafi (ruxolitinib)." Incyte Corporation
  2. (2019) "Product Information. Rinvoq (upadacitinib)." AbbVie US LLC
  3. (2022) "Product Information. Cibinqo (abrocitinib)." Pfizer U.S. Pharmaceuticals Group
  4. (2022) "Product Information. Vonjo (pacritinib)." CTI BioPharma Corp.
  5. (2021) "Product Information. Xeljanz (tofacitinib)." Pfizer U.S. Pharmaceuticals Group, SUPPL-28
  6. (2021) "Product Information. Xeljanz (tOFACitinib)." Pfizer Australia Pty Ltd, pfpxeljt11021
  7. (2022) "Product Information. Xeljanz (tofacitinib)." Pfizer Ltd, XJ 5mg 26_0 GB
  8. (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
  9. (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals Ltd
  10. (2022) "Product Information. Olumiant (baricitinib)." Lilly, Eli and Company, SUPPL-7
  11. (2023) "Product Information. Litfulo (ritlecitinib)." Pfizer U.S. Pharmaceuticals Group
  12. (2023) "Product Information. Ojjaara (momelotinib)." GlaxoSmithKline
  13. (2023) "Product Information. Olumiant (bARICITinib)." Eli Lilly Australia Pty Ltd, vA9.0_May2023
  14. (2024) "Product Information. Olumiant (baricitinib)." Eli Lilly and Company Ltd
View all 14 references

Switch to consumer interaction data

Drug and food interactions

Moderate

levonorgestrel food

Applies to: Delyla (ethinyl estradiol / levonorgestrel)

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
  4. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
  8. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  9. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  10. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  11. Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
  12. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
  13. Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
  14. Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
  15. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
  16. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  17. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
  19. Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
  20. Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
  21. Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
  22. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  23. Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
  24. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
  25. Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
  26. Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
  27. Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
  28. Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
  29. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  30. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
  31. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
View all 32 references

Switch to consumer interaction data

Moderate

fedratinib food

Applies to: 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

  1. 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
  2. (2022) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb
  3. (2021) "Product Information. Inrebic (fedratinib)." Bristol-Myers Squibb Pharmaceuticals Ltd

Switch to consumer interaction data

Minor

ethinyl estradiol food

Applies to: Delyla (ethinyl estradiol / levonorgestrel)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24

Switch to consumer interaction data

Minor

ethinyl estradiol food

Applies to: Delyla (ethinyl estradiol / levonorgestrel)

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

Switch to consumer interaction data

Minor

levonorgestrel food

Applies to: Delyla (ethinyl estradiol / levonorgestrel)

The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.

References

  1. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

Switch to consumer interaction data

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.


Report options

Loading...
QR code containing a link to this page

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.