PIPERACILLIN AND TAZOBACTAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PIPERACILLIN AND TAZOBACTAM (PIPERACILLIN AND TAZOBACTAM).
Piperacillin inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), while tazobactam is a beta-lactamase inhibitor that protects piperacillin from degradation by beta-lactamases.
| Metabolism | Piperacillin is partially metabolized to desethyl piperacillin; tazobactam is metabolized to an inactive metabolite. Both are primarily excreted renally. |
| Excretion | Primarily renal: piperacillin ~68% unchanged, tazobactam ~80% unchanged; biliary excretion <10%; fecal <1%. |
| Half-life | Piperacillin ~0.7–1.2 h, tazobactam ~0.7–1.5 h; prolonged in renal impairment (piperacillin up to 3.3 h, tazobactam up to 5.6 h in severe impairment). |
| Protein binding | Piperacillin: ~30% bound to albumin; tazobactam: ~30% bound to albumin. |
| Volume of Distribution | Piperacillin: ~0.27–0.31 L/kg; tazobactam: ~0.21–0.27 L/kg; distributes well into tissues, including lung, bile, and peritoneal fluid. |
| Bioavailability | Oral: not available; IM: >80% absolute bioavailability; IV: 100%. |
| Onset of Action | IV: immediate upon completion of infusion; IM: within 30 minutes. |
| Duration of Action | Bactericidal levels persist for 4–6 h after IV dose; requires frequent dosing (q6h or q8h) due to short half-life and time-dependent killing. |
3.375 g (piperacillin 3 g + tazobactam 0.375 g) IV every 6 hours, or 4.5 g (piperacillin 4 g + tazobactam 0.5 g) IV every 8 hours for nosocomial pneumonia.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 20-40 mL/min: 3.375 g IV every 8 hours; CrCl <20 mL/min: 2.25 g IV every 8 hours; Hemodialysis: 2.25 g IV every 12 hours, plus 0.75 g after dialysis. |
| Liver impairment | No dose adjustment required for hepatic impairment; pharmacokinetics not significantly altered in Child-Pugh class A, B, or C cirrhosis. |
| Pediatric use | Neonates <1 week: 100 mg piperacillin component/kg/dose IV every 12 hours; Infants 1-4 weeks: 100 mg/kg/dose IV every 8 hours; Children ≥2 months: 100 mg piperacillin component/kg/dose IV every 8 hours; Maximum 16 g piperacillin/day. |
| Geriatric use | Start at lower end of dosing based on renal function; elderly patients more likely to have decreased renal function, adjust dose according to CrCl; monitor for bleeding risk and nephrotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PIPERACILLIN AND TAZOBACTAM (PIPERACILLIN AND TAZOBACTAM).
| Breastfeeding | PIPERACILLIN AND TAZOBACTAM ARE EXCRETED INTO BREAST MILK IN LOW CONCENTRATIONS. THE MILK-TO-PLASMA RATIO (M/P) IS APPROXIMATELY 0.15 FOR PIPERACILLIN AND 0.05 FOR TAZOBACTAM. ORAL BIOAVAILABILITY OF BOTH IS POOR, MAKING SIGNIFICANT INFANT EXPOSURE UNLIKELY. THE AMERICAN ACADEMY OF PEDIATRICS CONSIDERS PIPERACILLIN COMPATIBLE WITH BREASTFEEDING. USE WITH CAUTION IN NURSING MOTHERS DUE TO POTENTIAL FOR GASTROINTESTINAL DISTURBANCE OR SENSITIZATION IN THE INFANT. |
| Teratogenic Risk | PIPERACILLIN/TAZOBACTAM IS FDA PREGNANCY CATEGORY B. ANIMAL STUDIES SHOW NO FETAL HARM, BUT ADEQUATE HUMAN STUDIES ARE LACKING. INTRAPARTUM USE HAS NOT BEEN ASSOCIATED WITH CONGENITAL DEFECTS. THEORETICAL RISK OF BILIRUBIN DISPLACEMENT IN NEONATES EXISTS, BUT CLINICAL SIGNIFICANCE UNLIKELY AT USUAL DOSES. NO SPECIFIC TRIMESTER-SPECIFIC RISKS IDENTIFIED. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to piperacillin, tazobactam, or any beta-lactam antibiotic","History of severe allergic reaction to any penicillin"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis)","Clostridioides difficile-associated diarrhea","Renal impairment (dosage adjustment required)","Hematologic effects (leukopenia, neutropenia)","Electrolyte disturbances (hypokalemia)","Neurologic events (seizures, especially with high doses or renal failure)"] |
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| Fetal Monitoring | MONITOR MATERNAL RENAL FUNCTION, HEPATIC FUNCTION, AND COMPLETE BLOOD COUNT (CBC) WITH DIFFERENTIAL DURING PROLONGED THERAPY. ASSESS FOR SIGNS OF HYPERSENSITIVITY OR NEUROTOXICITY. FETAL MONITORING IS NOT ROUTINELY REQUIRED, BUT ULTRASOUND MAY BE CONSIDERED IF MATERNAL INFECTION POSES FETAL RISK. |
| Fertility Effects | NO STUDIES HAVE EVALUATED THE EFFECTS OF PIPERACILLIN/TAZOBACTAM ON HUMAN FERTILITY. ANIMAL STUDIES DID NOT DEMONSTRATE IMPAIRED FERTILITY. UNLIKELY TO CAUSE CLINICALLY SIGNIFICANT REPRODUCTIVE IMPAIRMENT. |