CC Pharm | Piperacillin/ Tazo [Zosyn]

Zosyn (Piperacillin/Tazobactam) 80/20 Clinical Summary Core Classification & Mechanism Drug Class: Zosyn is an injectable combination of piperacillin (extended-spectrum penicillin) and tazobactam (beta-lactamase inhibitor). Bactericidal Action: Piperacillin binds to penicillin-binding proteins (PBPs), inhibiting cell wall synthesis and causing autolysin-mediated lysis. Beta-Lactamase Protection: Tazobactam is an irreversible inhibitor of beta-lactamases (Sykes types II–V, staphylococcal penicillinase, and ESBLs), shielding piperacillin. Pharmacodynamics: Exhibits time-dependent (concentration-independent) killing, relying on time free drug levels remain above the pathogen's MIC. Pharmacokinetics & Delivery Administration: Given via IV infusion over at least 30 minutes or via extended (4-hour) / continuous (24-hour) infusions. It is not FDA-approved for IV push. Distribution: Widely distributed in tissues (50–100% of plasma); both drugs are ~30% protein-bound. Elimination: Cleared unchanged in urine (68% piperacillin, 80% tazobactam) via tubular secretion/glomerular filtration. Half-life is 0.7–1.5 hours in normal renal function. High-Yield Indications & Adult Dosing Skin/Skin Structure: 3.375 g IV every 6 to 8 hours (for 5 to 14 days). Intra-abdominal: 3.375 g IV every 4 to 6 hours or 4.5 g IV every 6 hours. Nosocomial Pneumonia: 4.5 g IV every 6 hours (for 7 to 14 days). Sepsis/Bacteremia & Febrile Neutropenia: 4.5 g IV every 6 hours. Renal & Hepatic Adjustments Hepatic Impairment: No dose adjustment needed. Renal Impairment (Conventional Adult Dosing): CrCl > 40 mL/min: No adjustment. CrCl 20 to 40 mL/min: Nosocomial pneumonia reduced to 3.375 g every 6 hours; other indications reduced to 2.25 g every 6 hours. CrCl < 20 mL/min: Nosocomial pneumonia reduced to 2.25 g every 6 hours; other indications reduced to 2.25 g every 8 hours. Hemodialysis: Max 2.25 g every 8 hours (pneumonia) or 12 hours (others); give a 0.75 g to 1.125 g supplemental dose post-dialysis as 30–40% is cleared. Key Safety & Adverse Reactions Common: Diarrhea (11.3–20.0%), headache, nausea (5.8–6.9%), and constipation (7.7–8.4%). Severe Risks: Anaphylactic shock, acute renal failure, seizures, and C. difficile-associated diarrhea. Hematologic Warnings: Leukopenia, thrombocytopenia, platelet dysfunction, and prolonged bleeding times. Cutaneous Reactions: Stevens-Johnson syndrome, TEN, and DRESS.