ab; elevations inhepatic aminotransferase levels were not noted prior to discovery of the liver injury in manyof these cases. Some of these cases were fatal or necessitated liver transplantation.
Patientswith symptoms or signs of liver dysfunction should be eva luated for evidence of liver injury.
If jaundice and/or marked liver enzyme elevations (e.g., ≥ 5 times the upper limit of normal)develop, RENFLEXIS should be discontinued, and a thorough investigation of theabnormality should be undertaken. In clinical trials, mild or moderate elevations of ALT andAST have been observed in patients receiving infliximab products without progression tosevere hepatic injury [see Adverse Reactions (6.1)].
5.5 Patients with Heart Failure
Infliximab products have been associated with adverse outcomes in patients with heart failure,and should be used in patients with heart failure only after consideration of other treatmentoptions. The results of a randomized study eva luating the use of infliximab in patients withheart failure (NYHA Functional Class III/IV) suggested higher mortality in patients whoreceived 10 mg/kg infliximab, and higher rates of cardiovascular adverse events at doses of5 mg/kg and 10 mg/kg. There have been post-marketing reports of worsening heart failure,
with and without identifiable precipitating factors, in patients taking infliximab. There havealso been rare post-marketing reports of new onset heart failure, including heart failure inpatients without known pre-existing cardiovascular disease. Some of these patients have beenunder 50 years of age. If a decision is made to administer RENFLEXIS to patients with heartfailure, they should be closely monitored during therapy, and RENFLEXIS should bediscontinued if new or worsening symptoms of heart failure appear [see Contraindications (4)and Adverse Reactions (6.1)].
5.6 Hematologic Reactions
Cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia, some with a fataloutcome, have been reported in patients receiving infliximab products. The causalrelationship to infliximab product therapy remains unclear. Although no high-risk group(s) has been identified, caution should be exercised in patients being treated with RENFLEXIS
who have ongoing or a history of significant hematologic abnormalities. All patients shouldbe advised to seek immediate medical attention if they develop signs and symptomssuggestive of blood dyscrasias or infection (e.g., persistent fever) while on RENFLEXIS.
Discontinuation of RENFLEXIS therapy should be considered in patients who developsignificant hematologic abnormalities.
5.7 Hypersensitivity
Infliximab products have been associated with hypersensitivity reactions that vary in theirtime of onset and required hospitalization in some cases. Most hypersensitivity reactions,which include anaphylaxis, urticaria, dyspnea, and/or hypotension, have occurred during orwithin 2 hours of infusion.
However, in some cases, serum sickness-like reactions have been observed in patients afterinitial therapy with infliximab products (i.e., as early as after the second dose), and whentherapy with infliximab products was reinstituted following an extended period withouttreatment. Symptoms associated with these reactions include fever, rash, headache, sorethroat, myalgias, polyarthralgias, hand and facial edema and/or dysphagia. These reactionswere associated with a marked increase in antibodies to inflix |
