Ceftaroline warnings and precautions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
Hypersensitivity Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterials. Before therapy with Teflaro is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. If this product is to be given to a penicillin- or other beta-lactam-allergic patient, caution should be exercised because cross sensitivity among beta-lactam antibacterial agents has been clearly established.
If an allergic reaction to Teflaro occurs, the drug should be discontinued. Serious acute hypersensitivity (anaphylactic) reactions require emergency treatment with epinephrine and other emergency measures, that may include airway management, oxygen, intravenous fluids, antihistamines, corticosteroids, and vasopressors as clinically indicated.
Clostridium difficile-associated Diarrhea
Clostridium difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial agents, including Teflaro, and may range in severity from mild diarrhea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth ofC. difficile.
C. difficileproduces toxins A and B which contribute to the development of CDAD. Hypertoxin-producing strains ofC. difficilecause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, antibacterials not directed againstC. difficileshould be discontinued, if possible. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment ofC. difficile, and surgical evaluation should be instituted as clinically indicated[see Adverse Reactions (6.3)].
Direct Coombs' Test Seroconversion
Seroconversion from a negative to a positive direct Coombs' test result occurred in 120/1114 (10.8%) of patients receiving Teflaro and 49/1116 (4.4%) of patients receiving comparator drugs in the four pooled Phase 3 trials.
In the pooled Phase 3 CABP trials, 51/520 (9.8%) of Teflaro-treated patients compared to 24/534 (4.5%) of ceftriaxone-treated patients seroconverted from a negative to a positive direct Coombs' test result. No adverse reactions representing hemolytic anemia were reported in any treatment group.
If anemia develops during or after treatment with Teflaro, drug-induced hemolytic anemia should be considered. Diagnostic studies including a direct Coombs' test, should be performed. If drug-induced hemolytic anemia is suspected, discontinuation of Teflaro should be considered and supportive care should be administered to the patient (i.e. transfusion) if clinically indicated.
Development of Drug-Resistant Bacteria
Prescribing Teflaro in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
References
http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/200327s001lbl.pdf