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Interactions between Infliximab and Pegaspargase

1 drug interaction and 19 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

pegaspargase inFLIXimab

Applies to: pegaspargase and infliximab
Monitor closely

The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections and sepsis, including fatalities, have been reported with the use of TNF blockers, particularly in patients on concomitant immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids. Concomitant use of TNF blockers with other immunosuppressants such as azathioprine or mercaptopurine may also increase the risk of a rare and often fatal cancer of white blood cells known as hepatosplenic T-Cell lymphoma (HSTCL), which has primarily been reported in adolescent and young adult males receiving treatment for Crohn's disease or ulcerative colitis. Cases of HSTCL have also occurred during use of these agents alone. Because individuals with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis may be more likely to develop lymphoma than the general population, it is difficult to assess the added risk of TNF blockers, azathioprine, and/or mercaptopurine.

Management

Patients receiving a TNF blocker alone or with other immunosuppressive or myelosuppressive agents should be monitored closely for the development of infections. TNF blocker therapy should be discontinued if a serious infection or sepsis occurs. Close monitoring for signs and symptoms of HSTCL (e.g., splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) is also recommended during use of TNF blockers, particularly in combination with other immunosuppressants such as azathioprine and mercaptopurine.

References (6)
  1. (2001) "Product Information. Remicade (infliximab)." Centocor Inc
  2. (2001) "Product Information. Enbrel (etanercept)." Wyeth-Ayerst Laboratories
  3. (2003) "Product Information. Humira (adalimumab)." Abbott Pharmaceutical
  4. (2008) "Product Information. Cimzia (certolizumab pegol)." UCB Pharma Inc
  5. (2009) "Product Information. Simponi (golimumab)." Centocor Inc
  6. FDA. U.S. Food and Drug Administration (2012) FDA Drug Safety Communication: Drug labels for the Tumor Necrosis Factor-alpha (TNFa) blockers now include warnings about infection with Legionella and Listeria bacteria. http://www.fda.gov/Drugs/DrugSafety/ucm270849.htm

Food/lifestyle interactions

No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

Disease interactions

19 potential interactions Applies to: 18 conditions, including Heart Failure, COPD, Diabetes Mellitus, Thrombotic/Thromboembolic Disorder, and Liver Disease.

Bleeding Disorder

Major:

pegaspargase

Pegaspargase 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.

Bone Marrow Depression/Low Blood Counts

Moderate:

infliximab

inFLIXimab has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients treated with TNF blocking agents. Caution should be exercised when treating patients who have ongoing or a history of significant hematologic abnormalities. Discontinuation of therapy should be considered in patients with confirmed significant hematologic abnormalities.

Central Nervous System Disorders

Major:

infliximab

inFLIXimab has a major potential interaction with Central Nervous System Disorders.

The use of TNF blocking agents has been associated with rare cases of CNS manifestations of systemic vasculitis, seizure and new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and optic neuritis, and peripheral demyelinating disorders, including Guillain-Barré syndrome. Care should be exercised when considering the use of these agents in patients with neurologic disorders and discontinuing the agent is recommended if these disorders develop during therapy.

COPD

Moderate:

infliximab

inFLIXimab has a moderate potential interaction with COPD.

In studies, patients with moderate to severe chronic obstructive pulmonary disease (COPD) treated with infliximab developed more malignancies, the majority of lung or head and neck origin than those treated with placebo. Caution should be exercised when considering the use of infliximab in patients with moderate to severe COPD.

Diabetes Mellitus

Moderate:

pegaspargase

Pegaspargase 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.

Heart Failure

Major:

infliximab

inFLIXimab has a major potential interaction with Heart Failure.

In a study of patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), an increase incidence of death and hospitalization due to worsening of heart failure was observed after treatment with infliximab at 10 mg/kg. Infliximab at doses > 5 mg/kg is contraindicated in patients with moderate to severe heart failure.

History, Skin Cancer

Major:

infliximab

inFLIXimab has a major potential interaction with History, Skin Cancer.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

History, Thrombotic/Thromboembolic Disorder

Major:

pegaspargase

Pegaspargase 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.

Infection

Major:

infliximab

inFLIXimab has a major potential interaction with Infection.

There have been reports of serious infections, including sepsis and opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis with TNF blockers. Treatment with these agents should not be initiated in patients with an active infection, including clinically important localized infections. Caution and close monitoring is recommended when considering their use in patients with a history of recurrent infections, underlying conditions which may predispose them to infections, or chronic, latent, or localized infections. Administration of these agents should be discontinued if a patient develops a serious infection or sepsis.

Infectious Hepatitis

Moderate:

infliximab

inFLIXimab has a moderate potential interaction with Infectious Hepatitis.

The use of TNF blockers has been associated with reactivation of hepatitis B, in some cases fatal, in patients who were previously infected with the hepatitis B virus (HBV). Therefore, screening for viral hepatitis should be performed in accordance with published guidelines before starting therapy with these agents. Monitor patients at risk or with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation. Prescribers should exercise caution in prescribing TNF blockers in patients previously infected with HBV. It is recommended to monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following therapy. In patients who develop HBV reactivation, therapy should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming these agents after HBV reactivation is controlled is not known. Therefore, prescribers should weigh the risks and benefits when considering resumption of therapy.

Liver Disease

Major:

infliximab

inFLIXimab has a major potential interaction with Liver Disease.

Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis, have been reported with the use of infliximab. Infliximab should be discontinued if jaundice and/or marked liver enzyme elevations (e.g., greater than or equal to 5 times the upper limit of normal) develop and a thorough investigation of the abnormality should be undertaken.

Moderate:

pegaspargase

Pegaspargase 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.

Lymphoma

Major:

infliximab

inFLIXimab has a major potential interaction with Lymphoma.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

Pancreatitis

Major:

pegaspargase

Pegaspargase 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.

Pancytopenia

Moderate:

infliximab

inFLIXimab has a moderate potential interaction with Pancytopenia.

Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fatal outcome, have been reported in patients treated with TNF blocking agents. Caution should be exercised when treating patients who have ongoing or a history of significant hematologic abnormalities. Discontinuation of therapy should be considered in patients with confirmed significant hematologic abnormalities.

Skin Cancer

Major:

infliximab

inFLIXimab has a major potential interaction with Skin Cancer.

In clinical trials malignancies have been observed in patients receiving TNF-blockers agents. Patients with psoriasis should be monitored for non-melanoma skin cancers (NMSCs), particularly those patients who have had prior prolonged phototherapy treatment. Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF blocker therapy. Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer. Postmarketing cases of fatal hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with TNF blockers. Caution should be exercised when considering these agents in the treatment of patients with a history of malignancies or in continuing treatment in patients who develop malignancies while receiving these agents.

Thrombotic/Thromboembolic Disorder

Major:

pegaspargase

Pegaspargase 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.

Tuberculosis, Active

Major:

infliximab

inFLIXimab has a major potential interaction with Tuberculosis, Active.

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blocking agents, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with these agents during treatment for latent tuberculosis. Prior to initiating TNF blocking agents, patients should be screened for latent tuberculosis infection with a tuberculin skin test and periodically during therapy. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with TNF blocking agents. Anti-tuberculosis therapy should also be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Tuberculosis should be strongly considered in patients who develop a new infection during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

Tuberculosis, Latent

Major:

infliximab

inFLIXimab has a major potential interaction with Tuberculosis, Latent.

Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients receiving TNF blocking agents, including patients who have previously received treatment for latent or active tuberculosis. Cases of active tuberculosis have also occurred in patients being treated with these agents during treatment for latent tuberculosis. Prior to initiating TNF blocking agents, patients should be screened for latent tuberculosis infection with a tuberculin skin test and periodically during therapy. Patients testing positive in tuberculosis screening should be treated by standard medical practice prior to therapy with TNF blocking agents. Anti-tuberculosis therapy should also be considered prior to initiation of therapy in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Tuberculosis should be strongly considered in patients who develop a new infection during treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis.

More resources

infliximab

A total of 590 drugs are known to interact with infliximab.

pegaspargase

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

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.