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Interactions between Nilotinib and Oncaspar

1 drug interaction and 16 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

pegaspargase nilotinib

Applies to: Oncaspar (pegaspargase) and nilotinib
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

Food/lifestyle interactions

Major food/lifestyle interactions

Major:

nilotinib Food/Lifestyle

Applies to: nilotinib
Generally avoid

Grapefruit juice may increase the plasma concentrations of nilotinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Because nilotinib 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 nilotinib. The mechanism of interaction is unknown. Compared to the fast state, nilotinib systemic exposure (AUC) increased by 82% when the dose was given 30 minutes after a high-fat meal. Because nilotinib 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.

Management

Patients treated with nilotinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. In addition, no food should be consumed for at least 2 hours before and 1 hour after a nilotinib dose.

References (1)
  1. (2007) "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals

Disease interactions

15 potential interactions Applies to: 13 conditions, including Hypokalemia, Lactose Intolerance, Diabetes Mellitus, Thrombotic/Thromboembolic Disorder, and Liver Disease.

Bleeding Disorder

Major:

Oncaspar

The pegaspargase in Oncaspar has a major potential interaction with Bleeding Disorder.

The use of pegaspargase is contraindicated in patients who developed significant bleeding with previous L-asparaginase therapy. Pegaspargase interferes with coagulation factors, and both thrombosis and hemorrhage have been observed. Therapy with pegaspargase should be administered with extreme caution to patients with or predisposed to coagulopathies. Patients should be instructed to immediately report any signs or symptoms of thrombosis or bleeding. Close clinical monitoring of hematopoetic function and coagulation profiles is recommended.

Cardiovascular Conditions and Disorders

Moderate:

nilotinib

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

Cardiovascular events (including arterial vascular occlusive events, peripheral arterial occlusive disease, and ischemic cerebrovascular events) have been reported in patients receiving BCR-ABL tyrosine kinase inhibitors. Patients should seek immediate medical attention if acute signs or symptoms of cardiovascular events occur. Cardiovascular status should be evaluated, and cardiovascular risk factors should be monitored and actively managed during treatment.

Diabetes Mellitus

Moderate:

Oncaspar

The pegaspargase in Oncaspar has a moderate potential interaction with Diabetes Mellitus.

Hyperglycemia requiring insulin therapy has been reported during pegaspargase therapy. Therapy with pegaspargase should be administered cautiously to patients with diabetes mellitus.

Electrolyte Abnormalities

Moderate:

nilotinib

Nilotinib has a moderate potential interaction with Electrolyte Abnormalities.

Nilotinib can cause hypophosphatemia, hypokalemia, hyperkalemia, hypocalcemia, and hyponatremia. Electrolyte abnormalities should be corrected prior to initiating nilotinib and during therapy; these electrolytes should be monitored periodically during therapy.

History, Thrombotic/Thromboembolic Disorder

Major:

Oncaspar

The pegaspargase in Oncaspar has a major potential interaction with History, Thrombotic/Thromboembolic Disorder.

The use of pegaspargase is contraindicated in patients who developed significant bleeding with previous L-asparaginase therapy. Pegaspargase interferes with coagulation factors, and both thrombosis and hemorrhage have been observed. Therapy with pegaspargase should be administered with extreme caution to patients with or predisposed to coagulopathies. Patients should be instructed to immediately report any signs or symptoms of thrombosis or bleeding. Close clinical monitoring of hematopoetic function and coagulation profiles is recommended.

Hypokalemia

Major:

nilotinib

Nilotinib has a major potential interaction with Hypokalemia.

The use of nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Nilotinib prolongs the QT interval in a concentration-dependent manner; QT prolongation may lead to torsade de pointes, which can result in syncope, seizures, and/or death. Before initiating nilotinib and periodically, electrolyte, calcium, and magnesium blood levels should be tested. Hypokalemia or hypomagnesemia must be corrected before starting treatment and these electrolytes should be monitored periodically. ECGs should be obtained at baseline, 7 days after starting nilotinib, following dose adjustments, and periodically as clinically indicated.

Intestinal Anastomoses

Moderate:

nilotinib

Nilotinib has a moderate potential interaction with Intestinal Anastomoses.

Nilotinib exposure is reduced in patients with total gastrectomy. More frequent monitoring of these patients is recommended; a dose increase or alternative therapy should be considered.

Lactose Intolerance

Moderate:

nilotinib

Nilotinib has a moderate potential interaction with Lactose Intolerance.

Nilotinib capsule formulations contain lactose and are not recommended for patients with rare hereditary problems of galactose intolerance, severe lactase deficiency with a severe degree of intolerance to lactose-containing products, or glucose-galactose malabsorption.

Liver Disease

Moderate:

nilotinib

Nilotinib has a moderate potential interaction with Liver Disease.

Nilotinib exposure is increased in patients with hepatic impairment. If possible, alternative therapies should be considered; if nilotinib use is necessary, the dosage should be reduced and the QT interval should be monitored closely. Nilotinib may cause hepatotoxicity as measured by elevations in bilirubin, AST, ALT, and alkaline phosphatase; liver function tests should be monitored monthly or as clinically indicated and after dosage adjustments.

Moderate:

Oncaspar

The pegaspargase in Oncaspar has a moderate potential interaction with Liver Disease.

Reversible liver abnormalities such as elevated liver transaminase and bilirubin levels and decreased albumin synthesis have been reported during pegaspargase therapy. Fatty changes and liver failure have occurred. Patients should be instructed to immediately report any sign or symptoms of hepatic dysfunction such as jaundice, dark urine, right upper quadrant pain, or anorexia. Therapy with pegaspargase should be administered cautiously to patients with or predisposed to compromised hepatic function. Clinical monitoring of hepatic function is recommended.

Long QT Syndrome

Major:

nilotinib

Nilotinib has a major potential interaction with Long QT Syndrome.

The use of nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Nilotinib prolongs the QT interval in a concentration-dependent manner; QT prolongation may lead to torsade de pointes, which can result in syncope, seizures, and/or death. Before initiating nilotinib and periodically, electrolyte, calcium, and magnesium blood levels should be tested. Hypokalemia or hypomagnesemia must be corrected before starting treatment and these electrolytes should be monitored periodically. ECGs should be obtained at baseline, 7 days after starting nilotinib, following dose adjustments, and periodically as clinically indicated.

Magnesium Imbalance

Major:

nilotinib

Nilotinib has a major potential interaction with Magnesium Imbalance.

The use of nilotinib is contraindicated in patients with hypokalemia, hypomagnesemia, or long QT syndrome. Nilotinib prolongs the QT interval in a concentration-dependent manner; QT prolongation may lead to torsade de pointes, which can result in syncope, seizures, and/or death. Before initiating nilotinib and periodically, electrolyte, calcium, and magnesium blood levels should be tested. Hypokalemia or hypomagnesemia must be corrected before starting treatment and these electrolytes should be monitored periodically. ECGs should be obtained at baseline, 7 days after starting nilotinib, following dose adjustments, and periodically as clinically indicated.

Pancreatitis

Major:

Oncaspar

The pegaspargase in Oncaspar has a major potential interaction with Pancreatitis.

The use of pegaspargase is contraindicated in patients with or a history of pancreatitis. Pegaspargase can cause decreased insulin synthesis or inflammation and/or necrosis of cells of the pancreas. Fulminant and fatal pancreatitis has occurred. Clinical monitoring of pancreatic function, including serum amylase levels, is recommended.

Moderate:

nilotinib

Nilotinib has a moderate potential interaction with Pancreatitis.

Nilotinib can increase serum lipase. Patients with a history of pancreatitis may be at greater risk of elevated serum lipase. Serum lipase should be monitored monthly or as clinically indicated. If lipase elevations occur with abdominal symptoms, treatment should be interrupted and appropriate diagnostic evaluation should be considered to exclude pancreatitis.

Thrombotic/Thromboembolic Disorder

Major:

Oncaspar

The pegaspargase in Oncaspar has a major potential interaction with Thrombotic/Thromboembolic Disorder.

The use of pegaspargase is contraindicated in patients who developed significant bleeding with previous L-asparaginase therapy. Pegaspargase interferes with coagulation factors, and both thrombosis and hemorrhage have been observed. Therapy with pegaspargase should be administered with extreme caution to patients with or predisposed to coagulopathies. Patients should be instructed to immediately report any signs or symptoms of thrombosis or bleeding. Close clinical monitoring of hematopoetic function and coagulation profiles is recommended.

More resources

nilotinib

A total of 888 drugs are known to interact with nilotinib.

Oncaspar

A total of 556 drugs are known to interact with Oncaspar.

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.