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Drug Interactions between Erwinaze and repotrectinib

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

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Interactions between your drugs

Moderate

asparaginase Erwinia chrysanthemi repotrectinib

Applies to: Erwinaze (asparaginase erwinia chrysanthemi) and repotrectinib

Consumer information for this interaction is not currently available.

MONITOR: Concomitant use of asparaginase with other hepatotoxic agents may potentiate the risk of liver injury. Asparaginase-associated hepatotoxicity has been reported more commonly in adults than in children and has been strongly associated with obesity. Hepatomegaly, acute severe hepatotoxicity, and fatal liver failure have been reported with asparaginase treatment in adults. Also, asparaginase may increase the toxicity of drugs bound to plasma proteins or metabolized by the liver.

MANAGEMENT: The risk of additive hepatotoxicity should be considered when asparaginase is used with other hepatotoxic agents (e.g., alcohol, androgens, antituberculosis agents, azole antifungal agents, ACE inhibitors, macrolide antibiotics, nonsteroidal anti-inflammatory agents, nucleoside reverse transcriptase inhibitors, sulfonamides, thiazolidinediones, and statins). Liver function tests should be monitored at regular intervals during asparaginase treatment with or without other hepatotoxic drugs. Patients should be advised to seek medical attention if they experience potential symptoms of hepatotoxicity such as right upper quadrant pain, increasing abdominal size, fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, dark urine, pale stools, and jaundice.

References

  1. "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer PROD (2001):
  2. "Product Information. Elspar (asparaginase)." Merck & Co., Inc PROD (2001):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Australian Product Information." O 0
  5. "Product Information. Erwinaze (asparaginase Erwinia chrysanthemi)." EUSA Pharma PROD
  6. Cerner Multum, Inc "ANVISA Bulário Eletrônico." O 0 (2015):
  7. "Product Information. Asparlas (calaspargase pegol)." Servier (2019):
  8. Al-Nawakil C, Willems L, Mauprivez C, et al. "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4
  9. Christ TN, Stock W, Knoebel RW "Incidence of asparaginase-related hepatotoxicity, pancreatitis, and thrombotic events in adults with acute lymphoblastic leukemia treated with a pediatric-inspired regimen." J Oncol Pharm Pract 24 (2018): 299-308
  10. Jenkins R, Perlin E "Severe hepatotoxicity from Escherichia coli L-asparaginase." J Natl Med Assoc 79 (1987): 775-9
  11. Lu G, Karur V, Herrington JD, Walker MG "Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine" Proc (Bayl Univ Med Cent) 29 (2016): 46-7
  12. Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krahenbuhl S "Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase." Digestion 74 (2006): epub
  13. Burke PW, Aldoss I, Lunning MA, et al. "High-grade PEGylated asparaginase-related hepatotoxicity occurrence in a pediatric-inspired adult acute lymphoblastic leukemia regimen does not necessarily predict recurrent hepatotoxicity in subsequent cycles." Blood 122 (2013): 2671
View all 13 references

Drug and food interactions

Major

repotrectinib food

Applies to: repotrectinib

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations and adverse effects of repotrectinib. According to prescribing information, repotrectinib is primarily metabolized by CYP450 3A4, and is also a substrate of P-gp in vitro. 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 repotrectinib and grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Drug interaction studies have shown that the administration of repotrectinib with itraconazole, a potent CYP450 3A4 and P-gp inhibitor, increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of repotrectinib by 1.7-fold and 5.9-fold, respectively. 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 exposure to repotrectinib may increase the risk of adverse reactions such as dizziness, fatigue, cognitive disorders, ataxia, dysgeusia, peripheral neuropathy, muscular weakness, and dyspnea as well as more serious adverse effects such as interstitial lung disease/pneumonitis, liver transaminase elevations, myalgia with creatinine phosphokinase (CPK) elevation, hyperuricemia, and skeletal fractures.

MANAGEMENT: The manufacturer advises that concomitant use of repotrectinib with grapefruit, grapefruit juice, or supplements that contain grapefruit should be avoided.

References

  1. "Product Information. Augtyro (repotrectinib)." Bristol-Myers Squibb ORIG-1 (2023):

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.

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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