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Drug Interactions between Erwinaze and etrasimod

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

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Interactions between your drugs

Moderate

asparaginase Erwinia chrysanthemi etrasimod

Applies to: Erwinaze (asparaginase erwinia chrysanthemi) and etrasimod

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

Moderate

etrasimod food

Applies to: etrasimod

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of etrasimod in patients that are poor CYP450 2C9 metabolizers (e.g., *2/*3, *3/*3). Etrasimod is primarily metabolized by the CYP450 3A4, CYP450 2C8, and CYP450 2C9 isoenzymes. Pharmacokinetic studies reported that no single enzyme appears to dominate etrasimod elimination and that the involvement of multiple CYP450 isoforms reduces the likelihood of drug-drug interactions when only a single CYP450 isoform is strongly or moderately inhibited by a coadministered drug. In clinical drug interaction studies, when etrasimod was administered with the dual moderate CYP450 2C9 and 3A4 inhibitor fluconazole at steady-state levels, etrasimod systemic exposure (AUC) increased by 84%. However, concomitant use with the potent CYP450 3A4 inhibitor itraconazole increased the AUC of etrasimod by 32%, which was not considered by the manufacturer to be clinically significant. The effect on etrasimod systemic exposure in CYP450 2C9 intermediate metabolizers (e.g., *1/*2, *1/*3, *2/*2) treated with less potent CYP450 3A4 inhibitors is not known. Increased plasma concentrations of etrasimod may increase the risk of infection, bradyarrhythmia, AV conduction delays, elevated transaminase levels, and macular edema.

MANAGEMENT: Until further information is available, the consumption of grapefruit and grapefruit juice in combination with moderate to potent CYP450 2C8 inhibitors such as gemfibrozil should be avoided or limited during treatment with etrasimod in patients who are poor CYP450 2C9 metabolizers. Caution is recommended with grapefruit products consumption in patients who are intermediate CYP450 2C9 metabolizers. Patients should be advised to notify their physician if they experience potential adverse effects of etrasimod.

References

  1. "Product Information. Velsipity (etrasimod)." Pfizer U.S. Pharmaceuticals Group (2023):
  2. Lee C, Taylor C, Tang Y, Caballero LV, shan k, Randle A, Grundy JS "Effects of fluconazole, gemfibrozil, and rifampin on the pharmacokinetics, safety, and tolerability of etrasimod https://gut.bmj.com/content/71/Suppl_1/A142.1" (2022):

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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