Managed Care - December 2008 - (Page 37)

REMICADE® (infliximab) for IV Injection Brief Summary See package insert for Full Prescribing Information. WARNINGS RISK OF INFECTIONS Patients treated with REMICADE are at increased risk for infections, including progression to serious infections leading to hospitalization or death (see WARNINGS and ADVERSE REACTIONS). These infections have included bacterial sepsis, tuberculosis, invasive fungal and other opportunistic infections. Patients should be educated about the symptoms of infection, closely monitored for signs and symptoms of infection during and after treatment with REMICADE, and should have access to appropriate medical care. Patients who develop an infection should be evaluated for appropriate antimicrobial therapy and for serious infections REMICADE should be discontinued. Tuberculosis (frequently disseminated or extrapulmonary at clinical presentation) has been observed in patients receiving REMICADE. Patients should be evaluated for tuberculosis risk factors and be tested for latent tuberculosis infection1, 2 prior to initiating REMICADE and during therapy. Treatment of latent tuberculosis infection should be initiated prior to therapy with REMICADE. Treatment of latent tuberculosis in patients with a reactive tuberculin test reduces the risk of tuberculosis reactivation in patients receiving REMICADE. Some patients who tested negative for latent tuberculosis prior to receiving REMICADE have developed active tuberculosis. Physicians should monitor patients receiving REMICADE for signs and symptoms of active tuberculosis, including patients who tested negative for latent tuberculosis infection. HEPATOSPLENIC T-CELL LYMPHOMAS Rare postmarketing cases of hepatosplenic T-cell lymphoma have been reported in adolescent and young adult patients with Crohn’s disease treated with REMICADE. This rare type of T-cell lymphoma has a very aggressive disease course and is usually fatal. All of these hepatosplenic T-cell lymphomas with REMICADE have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine. CONTRAINDICATIONS: REMICADE at doses >5 mg/kg should not be administered to patients with moderate to severe heart failure. In a randomized study evaluating REMICADE in patients with moderate to severe heart failure (New York Heart Association [NYHA] Functional Class III/IV), REMICADE treatment at 10 mg/kg was associated with an increased incidence of death and hospitalization due to worsening heart failure (see WARNINGS and ADVERSE REACTIONS, Patients with Heart Failure). REMICADE should not be re-administered to patients who have experienced a severe hypersensitivity reaction to REMICADE. Additionally, REMICADE should not be administered to patients with known hypersensitivity to inactive components of the product or to any murine proteins. WARNINGS: RISK OF INFECTIONS (See Boxed WARNINGS) Serious infections, including sepsis and pneumonia, have been reported in patients receiving TNF-blocking agents. Some of these infections have been fatal. Although some of the serious infections in patients treated with REMICADE have occurred in patients on concomitant immunosuppressive therapy, which in addition to their underlying disease could further predispose them to infections, some patients who were hospitalized or had a fatal outcome from infection were treated with REMICADE alone. REMICADE should not be given to patients with a clinically important, active infection. Caution should be exercised when considering the use of REMICADE in patients with a chronic infection or a history of recurrent infection. Patients should be monitored for signs and symptoms of infection while on or after treatment with REMICADE. New infections should be closely monitored. If a patient develops a serious infection, REMICADE therapy should be discontinued (see ADVERSE REACTIONS, Infections). Cases of tuberculosis, histoplasmosis, coccidioidomycosis, listeriosis, pneumocystosis, other bacterial, mycobacterial and fungal infections have been observed in patients receiving REMICADE. Patients should be evaluated for tuberculosis risk factors and be tested for latent tuberculosis infection. Treatment of latent tuberculosis infections should be initiated prior to therapy with REMICADE. When tuberculin skin testing is performed for latent tuberculosis infection an induration size of 5 mm or greater should be considered positive, even if vaccinated previously with Bacille Calmette-Guerin (BCG). Patients receiving REMICADE should be monitored closely for signs and symptoms of active tuberculosis, particularly since tests for latent tuberculosis infection may be falsely negative. The possibility of undetected latent tuberculosis should be considered, especially in patients who have immigrated from or traveled to countries with a high prevalence of tuberculosis or had close contact with a person with active tuberculosis. All patients treated with REMICADE should have a thorough history taken prior to initiating therapy. Some patients who have previously received treatment for latent or active tuberculosis have developed active tuberculosis while being treated with REMICADE. Anti-tuberculosis therapy should be considered prior to initiation of REMICADE in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Anti-tuberculosis therapy prior to initiating REMICADE should also be considered in patients who have several or highly significant risk factors for tuberculosis infection3 and have a negative test for latent tuberculosis. The decision to initiate antituberculosis therapy in these patients should only be made following consultation with a physician with expertise in the treatment of tuberculosis and taking into account both the risk for latent tuberculosis infection and the risks of anti-tuberculosis therapy. For patients who have resided in regions where histoplasmosis or coccidioidomycosis is endemic, the benefits and risks of REMICADE treatment should be carefully considered before initiation of REMICADE therapy. Serious infections were seen in clinical studies with concurrent use of anakinra and another TNFα-blocking agent, etanercept, with no added clinical benefit compared to etanercept alone. Because of the nature of the adverse events seen with combination of etanercept and anakinra therapy, similar toxicities may also result from the combination of anakinra and other TNFα-blocking agents. Therefore, the combination of REMICADE and anakinra is not recommended. HEPATOSPLENIC T-CELL LYMPHOMAS (See Boxed WARNINGS) Rare postmarketing cases of hepatosplenic T-cell lymphomas have been reported in adolescent and young adult patients with Crohn’s disease treated with REMICADE. All of these reports have occurred in patients on concomitant treatment with azathioprine or 6-mercaptopurine. The clinical course of this disease is very aggressive with a fatal outcome in most patients within 2 years of diagnosis.4 The causal relationship of hepatosplenic T-cell lymphoma to REMICADE therapy remains unclear. Hepatitis B Virus Reactivation Use of TNF blockers, including REMICADE has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating TNF blocker therapy. Prescribers should exercise caution in prescribing TNF blockers, including REMICADE, for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. Patients who are carriers of HBV and require treatment with TNF blockers should be closely monitored for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, TNF blockers should be stopped and antiviral therapy with appropriate supportive treatment should be initiated. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, prescribers should exercise caution when considering resumption of TNF blocker therapy in this situation and monitor patients closely. Hepatotoxicity Severe hepatic reactions, including acute liver failure, jaundice, hepatitis and cholestasis have been reported rarely in postmarketing data in patients receiving REMICADE. Autoimmune hepatitis has been diagnosed in some of these cases. Severe hepatic reactions occurred between two weeks to more than a year after initiation of REMICADE; elevations in hepatic aminotransferase levels were not noted prior to discovery of the liver injury in many of these cases. Some of these cases were fatal or necessitated liver transplantation. Patients with symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or marked liver enzyme elevations (e.g., ≥5 times the upper limit of normal) develops, REMICADE should be discontinued, and a thorough investigation of the abnormality should be undertaken. In clinical trials, mild or moderate elevations of ALT and AST have been observed in patients receiving REMICADE without progression to severe hepatic injury (see ADVERSE REACTIONS, Hepatotoxicity). Patients with Heart Failure REMICADE has been associated with adverse outcomes in patients with heart failure, and should be used in patients with heart failure only after consideration of other treatment options. The results of a randomized study evaluating the use of REMICADE in patients

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Managed Care - December 2008 Editor's Memo Contents Legislation & Regulation News and Commentary Medication Management Compensation Monitor ICD-10 Offers Huge Opportunity, Challenge Part D at a Crossroads Plans Can Weather the Financial Crisis DM vs. Medical Home? Tackle Prediabetes Reasonable Approach to Morning Sickness Formulary Files Tomorrow's Medicine Outlook

Managed Care - December 2008

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