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Interactions between Levacetylleucine and Ripretinib

1 drug interaction and 8 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

ripretinib levacetylleucine

Applies to: ripretinib and levacetylleucine
Monitor

Coadministration with inhibitors of P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) may increase the plasma concentrations of ripretinib and its active metabolite, DP-5439. In vitro studies indicate that ripretinib and DP-5439 are substrates of the P-gp and BCRP plasma membrane efflux transporters. However, pharmacokinetic and clinical data regarding the interaction are currently lacking.

Management

Until more information is available, caution may be advisable when ripretinib is used concomitantly with drugs that are inhibitors of P-gp and/or BCRP. Patients should be monitored for increased adverse effects such as nausea, vomiting, constipation, diarrhea, alopecia, arthralgia, myalgia, hypertension, cardiac dysfunction, and palmar-plantar erythrodysesthesia.

References (4)
  1. (2023) "Product Information. Qinlock (ripretinib)." Deciphera Pharmaceuticals
  2. (2023) "Product Information. Qinlock (ripretinib)." Deciphera Pharmaceuticals (Netherlands) B.V.
  3. (2022) "Product Information. Qinlock (ripretinib)." Deciphera Pharmaceuticals, LLC
  4. (2022) "Product Information. Qinlock (ripretinib)." Specialised Therapeutics Australia Pty Ltd

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

ripretinib Food/Lifestyle

Applies to: ripretinib
Monitor

Grapefruit or 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 (32)
  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
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  32. Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286

Disease interactions

7 potential interactions Applies to: 7 conditions, including High Blood Pressure, Heart Disease, Liver Disease, Bleeding Disorder, and Cardiovascular Conditions and Disorders.

Bleeding Disorder

Moderate:

ripretinib

Ripretinib has a moderate potential interaction with Bleeding Disorder.

Ripretinib has the potential to affect wound healing adversely. Do not administer ripretinib for at least two weeks following major surgery and until adequate wound healing. It is recommended to withhold ripretinib for at least one week before elective surgery. Care should be exercised when using this agent in patients with impaired wound complications. The safety of this agent after the resolution of wound healing complications has not been established.

Cardiovascular Conditions and Disorders

Moderate:

ripretinib

Ripretinib has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Ripretinib may cause cardiac dysfunction. The safety of ripretinib has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or multiple gated acquisition (MUGA) scan prior to initiating treatment with ripretinib and during treatment, as clinically indicated. Permanently discontinue therapy for Grade 3 or 4 left ventricular systolic dysfunction.

Coagulation Defects and Disorders

Moderate:

ripretinib

Ripretinib has a moderate potential interaction with Coagulation Defects and Disorders.

Ripretinib has the potential to affect wound healing adversely. Do not administer ripretinib for at least two weeks following major surgery and until adequate wound healing. It is recommended to withhold ripretinib for at least one week before elective surgery. Care should be exercised when using this agent in patients with impaired wound complications. The safety of this agent after the resolution of wound healing complications has not been established.

Heart Disease

Moderate:

ripretinib

Ripretinib has a moderate potential interaction with Heart Disease.

Ripretinib may cause cardiac dysfunction. The safety of ripretinib has not been assessed in patients with a baseline ejection fraction below 50%. Assess ejection fraction by echocardiogram or multiple gated acquisition (MUGA) scan prior to initiating treatment with ripretinib and during treatment, as clinically indicated. Permanently discontinue therapy for Grade 3 or 4 left ventricular systolic dysfunction.

High Blood Pressure

Moderate:

ripretinib

Ripretinib has a moderate potential interaction with High Blood Pressure.

Ripretinib may cause hypertension. It is recommended to control blood pressure prior to initiating therapy and monitor blood pressure as clinically indicated during treatment. Based on severity, withhold treatment with ripretinib and resume at the same or reduced dose or permanently discontinue. Do not initiate ripretinib in patients with uncontrolled hypertension.

Liver Disease

Moderate:

levacetylleucine

Levacetylleucine has a moderate potential interaction with Liver Disease.

Levacetylleucine has not been studied in patients with liver and renal impairment.

Renal Dysfunction

Moderate:

levacetylleucine

Levacetylleucine has a moderate potential interaction with Renal Dysfunction.

Levacetylleucine has not been studied in patients with liver and renal impairment.

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More resources

levacetylleucine

A total of 88 drugs are known to interact with levacetylleucine.

ripretinib

A total of 356 drugs are known to interact with ripretinib.

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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