clindamycin phosphate

WARNING: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD) and COLITIS Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clindamycin Phosphate in Sodium Chloride Injection and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. Because Clindamycin Phosphate in Sodium Chloride Injection therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate [ see Indications and Usage ( 1 ) ] . It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause 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 antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated [ see Warnings and Precautions ( 5.1 ) ]. WARNING: CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD) and COLITIS See full prescribing information for complete boxed warning. Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clindamycin Phosphate in Sodium Chloride Injection and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile ( 5.1 ). Because Clindamycin Phosphate in Sodium Chloride Injection therapy has been associated with severe colitis which may end fatally, it should be reserved for serious infections where less toxic antimicrobial agents are inappropriate (1). It should not be used in patients with nonbacterial infections such as most upper respiratory tract infections. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy ( 5.1 ).

5 WARNINGS AND PRECAUTIONS • Anaphylactic shock, anaphylactic reactions and severe hypersensitivity reactions have been reported. Discontinue treatment if such reactions occur. ( 5.2 ) • Cases with acute kidney injury (AKI) have been reported during treatment with clindamycin. Consider renal function monitoring, particularly in certain patients (e.g., those with pre-existing renal dysfunction). Discontinue treatment, if AKI occurs and no other etiology is identified. ( 5.3 ) • Elderly patients with associated severe illness may have a greater risk of developing adverse reactions from diarrhea. Monitor these patients carefully for change in bowel frequency. ( 5.4 ) • Avoid use of Clindamycin Phosphate in Sodium Chloride Injection in individuals with a history of gastrointestinal disease, particularly colitis. ( 5.5 ) • Avoid use of Clindamycin Phosphate in Sodium Chloride Injection in atopic individuals. ( 5.6 ) • During prolonged therapy, perform periodic liver and kidney function tests and blood counts. ( 5.7 ) • The use of Clindamycin Phosphate in Sodium Chloride Injection may result in overgrowth of nonsusceptible organisms-particularly yeasts. Take appropriate measures, if this occurs. ( 5.8 ) 5.1 Clostridioides difficile -Associated Diarrhea Clostridioides difficile- associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Clindamycin Phosphate in Sodium Chloride Injection, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing isolates of C. difficile cause 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 antibacterial use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated [see Boxed Warning ]. 5.2 Anaphylactic and Severe Hypersensitivity Reactions Anaphylactic shock and anaphylactic reactions have been reported [see Adverse Reactions (6) ]. Severe hypersensitivity reactions, including acute myocardial ischemia with or without myocardial infarction, and severe skin reactions such as toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), some with fatal outcome, have been reported [see Adverse Reactions (6) ]. In case of such an anaphylactic or severe hypersensitivity reaction, discontinue treatment permanently and institute appropriate therapy. A careful inquiry should be made concerning previous sensitivities to drugs and other allergens. 5.3 Nephrotoxicity Clindamycin is potentially nephrotoxic and cases with acute kidney injury have been reported. Consider monitoring of renal function particularly in patients with pre-existing renal dysfunction or those taking concomitant nephrotoxic drugs. In case of acute kidney injury, discontinue Clindamycin Phosphate in Sodium Chloride Injection when no other etiology is identified [see Adverse Reactions (6) ]. 5.4 Diarrhea in Elderly Patients with Associated Severe Illness Elderly patients with associated severe illness may have a greater risk of developing adverse reactions from diarrhea. When clindamycin is indicated in these patients, they should be carefully monitored for change in bowel frequency [see Use in Specific Populations (8.5) ] . 5.5 Use in Patients with Gastrointestinal Disease Clindamycin Phosphate in Sodium Chloride Injection products should be avoided in individuals with a history of gastrointestinal disease, particularly colitis. 5.6 Use in Atopic Individuals Clindamycin Phosphate in Sodium Chloride Injection should be avoided in atopic individuals. 5.7 Laboratory Tests: Monitoring to Assess Safety During prolonged therapy periodic liver and kidney function tests and blood counts should be performed. Clindamycin dosage modification is not necessary in patients with renal disease. In patients with moderate to severe liver disease, prolongation of clindamycin half-life has been found. However, it was postulated from studies that when given every eight hours, accumulation should rarely occur. Therefore, dosage modification in patients with liver disease may not be necessary. However, periodic liver enzyme determinations should be made when treating patients with severe liver disease. 5.8 Overgrowth of Nonsusceptible Organisms The use of Clindamycin Phosphate in Sodium Chloride Injection may result in overgrowth of nonsusceptible organisms-particularly yeasts. If such infections occur, appropriate measures should be taken as indicated by the clinical situation. 5.9 Development of Drug-Resistant Bacteria Prescribing Clindamycin Phosphate in Sodium Chloride Injection in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

6 ADVERSE REACTIONS The following serious adverse reactions to clindamycin are described below and elsewhere in the labeling: • Clostridioides difficile- Associated Diarrhea [see Warnings and Precautions (5.1) ] • Anaphylactic and Severe Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] • Nephrotoxicity [see Warnings and Precautions (5.3) ] The following adverse reactions associated with the use of clindamycin were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably, or to establish a causal relationship to drug exposure. Infections and Infestations Clostridioides difficile colitis Gastrointestinal Antibacterial drug-associated colitis [see Warnings and Precautions (5.1) ] , pseudomembranous colitis, abdominal pain, nausea, and vomiting. The onset of pseudomembranous colitis symptoms may occur during or after antibacterial treatment [see Warnings and Precautions (5.1) ] . An unpleasant or metallic taste has been reported after intravenous administration of the higher doses of clindamycin phosphate. Hypersensitivity Reactions Maculopapular rash and urticaria have been observed during drug therapy. Generalized mild to moderate morbilliform-like skin rashes are the most frequently reported of all adverse reactions. Severe skin reactions such as toxic epidermal necrolysis, some with fatal outcome, have been reported [see Warnings and Precautions (5.2) ] . Cases of acute generalized exanthematous pustulosis (AGEP), erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin. Anaphylactic shock, anaphylactic reaction, hypersensitivity, and acute myocardial ischemia with or without myocardial infarction occurring as part of an allergic reaction have also been reported [see Warnings and Precautions (5.2) ]. Cutaneous vasculitis and symmetrical drug-related intertriginous and flexural exanthema have also been reported. Skin and Mucous Membranes Pruritus, vaginitis, angioedema and rare instances of exfoliative dermatitis have been reported [see Warnings and Precautions (5.2) ]. Liver Jaundice and abnormalities in liver function tests have been observed during clindamycin therapy. Renal Acute kidney injury [see Warnings and Precautions (5.3) ]. Hematopoietic Transient neutropenia (leukopenia) and eosinophilia have been reported. Reports of agranulocytosis and thrombocytopenia have been made. Immune System Drug reaction with eosinophilia and systemic symptoms (DRESS) cases have been reported. Local Reactions Thrombophlebitis has been reported after intravenous infusion. Avoid prolonged use of indwelling intravenous catheters. Musculoskeletal Polyarthritis cases have been reported. Cardiovascular Cardiopulmonary arrest and hypotension have been reported following too rapid intravenous administration [see Dosage and Administration (2) ] . Most common adverse reactions: gastrointestinal (abdominal pain, nausea, vomiting) and hypersensitivity reactions (anaphylaxis, urticaria, skin rash). ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare at 1-866-888-2472 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.