Biotechnology Healthcare - July/August 2008 - (Page 12)

RISK OF INFECTIONS Tuberculosis (TB) (frequently disseminated or extrapulmonary at clinical presentation), bacterial infections including sepsis, invasive fungal infections, and other opportunistic infections have been observed in patients receiving REMICADE. Some of these infections have led to hospitalizations and death. Patients should be evaluated for TB risk factors and tested for latent TB.3,4 Treatment of latent TB infection should be initiated prior to therapy with REMICADE. Some patients who received treatment for latent or active TB or who tested negative for latent TB prior to receiving REMICADE have developed active TB. In consultation with a physician with expertise in the treatment of TB, consider anti-TB treatment prior to REMICADE therapy in patients with a history of latent or active TB, when adequate treatment cannot be confirmed, or in patients who have a negative test for latent TB, but have several or highly significant risk factors.5 Monitor all patients receiving REMICADE for signs and symptoms of active TB. Serious infections have occurred in patients on REMICADE alone or on concomitant immunosuppressive therapy that, in addition to their disease, could predispose them to infections. Cases of pneumonia, histoplasmosis, coccidioidomycosis, listeriosis, and pneumocystosis have been reported. For patients who have resided in regions where histoplasmosis or coccidioidomycosis is endemic, the benefits and risks of REMICADE should be considered before initiation of therapy. REMICADE should not be given to patients with a clinically important, active infection. Use with caution in patients with a history of infection. Monitor and educate patients for infection during or after treatment. Discontinue REMICADE if a patient develops a serious infection. MALIGNANCIES 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. In clinical trials of all TNF inhibitors, more cases of lymphoma were observed compared with controls and the expected rate in the general population. However, patients with Crohn’s disease, rheumatoid arthritis, or plaque psoriasis may be at higher risk for developing lymphoma. In clinical trials of some TNF inhibitors, including REMICADE, more cases of other malignancies were observed compared with controls. The rate of these malignancies among REMICADE-treated patients was similar to that expected in the general population whereas the rate in control patients was lower than expected. As the potential role of TNF inhibitors in the development of malignancies is not known, caution should be exercised when considering treatment of patients with a current or a past history of malignancy or other risk factors such as chronic obstructive pulmonary disease (COPD). CONTRAINDICATIONS REMICADE is contraindicated in patients with moderate to severe (NYHA Class III/IV) congestive heart failure (CHF) at doses greater than 5 mg/kg. Higher mortality rates at the 10 mg/kg dose and higher rates of cardiovascular events at the 5 mg/kg dose have been observed in these patients. REMICADE should be used with caution and only after consideration of other treatment options. Patients should be monitored closely. Discontinue REMICADE if new or worsening CHF symptoms appear. REMICADE should not be (re)administered to patients who have experienced a severe hypersensitivity reaction or to patients with hypersensitivity to murine proteins or other components of the product. HEPATITIS B REACTIVATION TNF inhibitors, including REMICADE, have been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases were fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating REMICADE. Exercise caution when prescribing REMICADE for patients identified as carriers of HBV and monitor closely for active HBV infection during and following termination of therapy with REMICADE. Discontinue REMICADE in patients who develop HBV reactivation and initiate antiviral therapy with appropriate supportive treatment. Exercise caution when considering resumption of REMICADE and monitor patients closely. HEPATOTOXICITY Severe hepatic reactions, including acute liver failure, jaundice, hepatitis, and cholestasis have been reported rarely in patients receiving REMICADE postmarketing. Some cases were fatal or required liver transplant. Aminotransferase elevations were not noted prior to discovery of liver injury in many cases. 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) develop, REMICADE should be discontinued, and a thorough investigation of the abnormality should be undertaken. HEMATOLOGIC EVENTS Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some fatal, have been reported. The causal relationship to REMICADE therapy remains unclear. Exercise caution in patients who have ongoing or a history of significant hematologic abnormalities. Advise patients to seek immediate medical attention if they develop signs and symptoms of blood dyscrasias or infection. Consider discontinuation of REMICADE in patients who develop significant hematologic abnormalities. HYPERSENSITIVITY REMICADE has been associated with hypersensitivity reactions that differ in their time of onset. Acute urticaria, dyspnea, and hypotension have occurred in association with REMICADE infusions. Serious infusion reactions including anaphylaxis were infrequent. Medications for the treatment of hypersensitivity reactions should be available. NEUROLOGIC EVENTS TNF inhibitors, including REMICADE, have been associated with rare cases of new or exacerbated symptoms of demyelinating disorders including multiple sclerosis and optic neuritis, seizure, and CNS manifestations of systemic vasculitis. Exercise caution when considering REMICADE in all patients with these disorders. Consider discontinuation for significant CNS adverse reactions.

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Biotechnology Healthcare - July/August 2008 Openers Contents Editorial/David B. Nash, MD, MBA Drug Track Health Plan Confidential Rheumatoid Arthritis A Decade of Trial, Error, False Starts, and Hope What Path Will Comparative Effectiveness Research Take? RA Therapies in Development: A New Generation of Relief Assessing the Full Impact of RA on Employers and Payers Stem Cells: Health Insurance You Can Bank On Specialty Pharmacy Employer to Employer Personalized Medicine Trends Clinical Briefs

Biotechnology Healthcare - July/August 2008

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