Can Caspofungin cause sepsis?

ADVERSE REACTIONS The following serious adverse reactions are discussed in detail in another section of the labeling: Hypersensitivity [see Warnings and Precautions ( 5.1 )] Hepatic Effects [see Warnings and Precautions ( 5.2 )] Elevated Liver Enzymes During Concomitant Use with Cyclosporine [see Warnings and Precautions ( 5.3 )] Adults: Most common adverse reactions (incidence 10% or greater) are diarrhea, pyrexia, ALT/AST increased, blood alkaline phosphatase increased, and blood potassium decreased. ( 6.1 ) Pediatric Patients: Most common adverse reactions (incidence ≥10%) are pyrexia, diarrhea, rash, ALT/AST increased, blood potassium decreased, hypotension, and chills. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Sagent Pharmaceuticals at 1-866-625-1618 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of caspofungin cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice. Clinical Trials Experience in Adults The overall safety of caspofungin was assessed in 1865 adult individuals who received single or multiple doses of caspofungin: 564 febrile, neutropenic patients (empirical therapy study); 382 patients with candidemia and/or intra-abdominal abscesses, peritonitis, or pleural space infections (including 4 patients with chronic disseminated candidiasis); 297 patients with esophageal and/or oropharyngeal candidiasis; 228 patients with invasive aspergillosis; and 394 individuals in phase I studies. In the empirical therapy study patients had undergone hematopoietic stem-cell transplantation or chemotherapy. In the studies involving patients with documented Candida infections, the majority of the patients had serious underlying medical conditions (e.g., hematologic or other malignancy, recent major surgery, HIV) requiring multiple concomitant medications. Patients in the noncomparative Aspergillus studies often had serious predisposing medical conditions (e.g., bone marrow or peripheral stem cell transplants, hematologic malignancy, solid tumors or organ transplants) requiring multiple concomitant medications. Empirical Therapy for Presumed Fungal Infections in Febrile Neutropenic Patients In the randomized, double-blinded empirical therapy study, patients received either caspofungin 50 mg/day (following a 70 mg loading dose) or AmBisome ® (amphotericin B liposome for injection, 3 mg/kg/day). In this study clinical or laboratory hepatic adverse reactions were reported in 39% and 45% of patients in the caspofungin and AmBisome groups, respectively. Also reported was an isolated, serious adverse reaction of hyperbilirubinemia. Adverse reactions occurring in 7.5% or greater of the patients in either treatment group are presented in Table 2 . Table 2: Adverse Reactions Among Patients with Persistent Fever and Neutropenia Incidence 7.5% or greater for at Least One Treatment Group Within any system organ class, individuals may experience more than 1 adverse reaction. * 70 mg on Day 1, then 50 mg once daily for the remainder of treatment; daily dose was increased to 70 mg for 73 patients. † 3 mg/kg/day; daily dose was increased to 5 mg/kg for 74 patients. Adverse Reactions Caspofungin * N=564 (%) AmBisome † N=547 (%) All Systems, Any Adverse Reaction 95 97 Investigations 58 63 Alanine Aminotransferase Increased 18 20 Blood Alkaline Phosphatase Increased 15 23 Blood Potassium Decreased 15 23 Aspartate Aminotransferase Increased 14 17 Blood Bilirubin Increased 10 14 Blood Magnesium Decreased 7 9 Blood Glucose Increased 6 9 Bilirubin Conjugated Increased 5 9 Blood Urea Increased 4 8 Blood Creatinine Increased 3 11 General Disorders and Administration Site Conditions 57 63 Pyrexia 27 29 Chills 23 31 Edema Peripheral 11 12 Mucosal Inflammation 6 8 Gastrointestinal Disorders 50 55 Diarrhea 20 16 Nausea 11 20 Abdominal Pain 9 11 Vomiting 9 17 Respiratory, Thoracic and Mediastinal Disorders 47 49 Dyspnea 9 10 Skin and Subcutaneous Tissue Disorders 42 37 Rash 16 14 Nervous System Disorders 25 27 Headache 11 12 Metabolism and Nutrition Disorders 21 24 Hypokalemia 6 8 Vascular Disorders 20 23 Hypotension 6 10 Cardiac Disorders 16 19 Tachycardia 7 9 The proportion of patients who experienced an infusion-related adverse reaction (defined as a systemic event, such as pyrexia, chills, flushing, hypotension, hypertension, tachycardia, dyspnea, tachypnea, rash, or anaphylaxis, that developed during the study therapy infusion and one hour following infusion) was significantly lower in the group treated with caspofungin (35%) than in the group treated with AmBisome (52%). To evaluate the effect of caspofungin and AmBisome on renal function, nephrotoxicity was defined as doubling of serum creatinine relative to baseline or an increase of greater than or equal to 1 mg/dL in serum creatinine if baseline serum creatinine was above the upper limit of the normal range. Among patients whose baseline creatinine clearance was greater than 30 mL/min, the incidence of nephrotoxicity was significantly lower in the group treated with caspofungin (3%) than in the group treated with AmBisome (12%). Candidemia and Other Candida Infections In the randomized, double-blinded invasive candidiasis study, patients received either caspofungin 50 mg/day (following a 70 mg loading dose) or amphotericin B 0.6 to 1 mg/kg/day. Adverse reactions occurring in 10% or greater of the patients in either treatment group are presented in Table 3 . Table 3: Adverse Reactions Among Patients with Candidemia or Other Candida Infections* Incidence 10% or Greater for at Least One Treatment Group Within any system organ class, individuals may experience more than 1 adverse reaction. * Intra-abdominal abscesses, peritonitis and pleural space infections. † Patients received caspofungin 70 mg on Day 1, then 50 mg once daily for the remainder of their treatment. Adverse Reactions Caspofungin 50 mg † N=114 (%) Amphotericin B N=125 (%) All Systems, Any Adverse Reaction 96 99 Investigations 67 82 Blood Potassium Decreased 23 32 Blood Alkaline Phosphatase Increased 21 32 Hemoglobin Decreased 18 23 Alanine Aminotransferase Increased 16 15 Aspartate Aminotransferase Increased 16 14 Blood Bilirubin Increased 13 17 Hematocrit Decreased 13 18 Blood Creatinine Increased 11 28 Red Blood Cells Urine Positive 10 10 Blood Urea Increased 9 23 Bilirubin Conjugated Increased 8 14 Gastrointestinal Disorders 49 53 Vomiting 17 16 Diarrhea 14 10 Nausea 9 17 General Disorders and Administration Site Conditions 47 63 Pyrexia 13 33 Edema Peripheral 11 12 Chills 9 30 Respiratory, Thoracic and Mediastinal Disorders 40 54 Tachypnea 1 11 Cardiac Disorders 26 34 Tachycardia 8 12 Skin and Subcutaneous Tissue Disorders 25 28 Rash 4 10 Vascular Disorders 25 38 Hypotension 10 16 Blood and Lymphatic System Disorders 15 13 Anemia 11 9 The proportion of patients who experienced an infusion-related adverse reaction (defined as a systemic event, such as pyrexia, chills, flushing, hypotension, hypertension, tachycardia, dyspnea, tachypnea, rash, or anaphylaxis, that developed during the study therapy infusion and one hour following infusion) was significantly lower in the group treated with caspofungin (20%) than in the group treated with amphotericin B (49%). To evaluate the effect of caspofungin and amphotericin B on renal function, nephrotoxicity was defined as doubling of serum creatinine relative to baseline or an increase of greater than or equal to 1 mg/dL in serum creatinine if baseline serum creatinine was above the upper limit of the normal range. In a subgroup of patients whose baseline creatinine clearance was greater than 30 mL/min, the incidence of nephrotoxicity was significantly lower in the group treated with caspofungin than in the group treated with amphotericin B. In a second randomized, double-blinded invas

WARNINGS AND PRECAUTIONS Hypersensitivity: Anaphylaxis, possible histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth or bronchospasm, and cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with use of caspofungin acetate for injection. Discontinue caspofungin acetate for injection at the first sign or symptom of a hypersensitivity reaction and administer appropriate treatment. ( 5.1 ) Hepatic Effects: Can cause abnormalities in liver enzymes. Isolated cases of hepatic dysfunction, hepatitis, or hepatic failure have been reported. Monitor patients who develop abnormal liver enzymes for evidence of worsening hepatic function, and evaluate risk/benefit of continuing caspofungin acetate for injection. ( 5.2 ) Elevated Liver Enzymes During Concomitant Use with Cyclosporine: Limit use to patients for whom potential benefit outweighs potential risk. Monitor patients who develop abnormal liver function tests (LFTs) during concomitant use with caspofungin acetate for injection. ( 5.3 ) 5.1 Hypersensitivity Anaphylaxis and other hypersensitivity reactions have been reported during administration of caspofungin acetate for injection. Possible histamine-mediated adverse reactions, including rash, facial swelling, angioedema, pruritus, sensation of warmth or bronchospasm have been reported. Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), some with a fatal outcome, have been reported with use of caspofungin acetate for injection [see Adverse Reactions (6.2) ] . Discontinue caspofungin acetate for injection at the first sign or symptom of a hypersensitivity reaction and administer appropriate treatment. 5.2 Hepatic Effects Laboratory abnormalities in liver function tests have been seen in healthy volunteers and in adult and pediatric patients treated with caspofungin acetate for injection. In some adult and pediatric patients with serious underlying conditions who were receiving multiple concomitant medications with caspofungin acetate for injection, isolated cases of clinically significant hepatic dysfunction, hepatitis, and hepatic failure have been reported; a causal relationship to caspofungin acetate for injection has not been established. Monitor patients who develop abnormal liver function tests during caspofungin acetate for injection therapy for evidence of worsening hepatic function and evaluated for risk/benefit of continuing caspofungin acetate for injection therapy. 5.3 Elevated Liver Enzymes During Concomitant Use With Cyclosporine Elevated liver enzymes have occurred in patients receiving caspofungin acetate for injection and cyclosporine concomitantly. Only use caspofungin acetate for injection and cyclosporine in those patients for whom the potential benefit outweighs the potential risk. Patients who develop abnormal liver enzymes during concomitant therapy should be monitored and the risk/benefit of continuing therapy should be evaluated.