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Drug Interactions between dronedarone and pegaspargase

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

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Interactions between your drugs

Moderate

pegaspargase dronedarone

Applies to: pegaspargase and dronedarone

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 (13)
  1. (2001) "Product Information. Oncaspar (pegaspargase)." Rhone Poulenc Rorer
  2. (2001) "Product Information. Elspar (asparaginase)." Merck & Co., Inc
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
  5. "Product Information. Erwinaze (asparaginase Erwinia chrysanthemi)." EUSA Pharma
  6. Cerner Multum, Inc (2015) "ANVISA Bulário Eletrônico."
  7. (2019) "Product Information. Asparlas (calaspargase pegol)." Servier
  8. Al-Nawakil C, Willems L, Mauprivez C, et al. (2014) "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma, 55, p. 1670-4
  9. Christ TN, Stock W, Knoebel RW (2018) "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, p. 299-308
  10. Jenkins R, Perlin E (1987) "Severe hepatotoxicity from Escherichia coli L-asparaginase." J Natl Med Assoc, 79, p. 775-9
  11. Lu G, Karur V, Herrington JD, Walker MG (2016) "Successful treatment of pegaspargase-induced acute hepatotoxicity with vitamin B complex and L-carnitine" Proc (Bayl Univ Med Cent), 29, p. 46-7
  12. Bodmer M, Sulz M, Stadlmann S, Droll A, Terracciano L, Krahenbuhl S (2006) "Fatal liver failure in an adult patient with acute lymphoblastic leukemia following treatment with L-asparaginase." Digestion, 74, epub
  13. Burke PW, Aldoss I, Lunning MA, et al. (2013) "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, p. 2671

Drug and food interactions

Major

dronedarone food

Applies to: dronedarone

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.

MANAGEMENT: Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.

References (1)
  1. (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis

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.

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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

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