Pipzo

Pipzo Mechanism of Action

piperacillin + tazobactam

Manufacturer:

Alkem Lab

Distributor:

Getz Bros
Full Prescribing Info
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Pharmacology: Pharmacodynamics: Pharmacological effect/mode of action: Piperacillin sodium exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. In vitro, piperacillin is active against a variety of gram-positive and gram-negative aerobic and anaerobic bacteria. Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is, however, a ß-lactamase inhibitor of the Richmond-Sykes class III (Bush class 2b & 2b') penicillinases and cephalosporinases. It varies in its ability to inhibit class II and IV (2a & 4) penicillinases. Tazobactam does not induce chromosomally-mediated ß-lactamases at tazobactam concentrations achieved with the recommended dosage regimen.
Peak plasma concentrations of piperacillin and tazobactam are attained immediately after completion of an intravenous infusion piperacillin sodium and Tazobactam sodium injection. Piperacillin plasma concentrations, following a 30-minute infusion of piperacillin sodium and Tazobactam sodium, were similar to those attained when equivalent doses of piperacillin were administered alone, with mean peak plasma concentrations of approximately 134, 242 and 298 μg/mL for the 2.25 g, 3.375 g and 4.5 g piperacillin/tazobactam doses, respectively. The corresponding mean peak plasma concentrations of tazobactam were 15, 24 and 34 μg/mL, respectively.
Following a 30-minute I.V. infusion of 3.375 g piperacillin sodium and Tazobactam sodium for injection every 6 hours, steady-state plasma concentrations of piperacillin and tazobactam were similar to those attained after the first dose. In like manner, steady-state plasma concentrations were not different from those attained after the first dose when 2.25 g or 4.5 g doses of piperacillin sodium and Tazobactam sodium for injection were administered via 30-minute infusions every 6 hours.
Following single or multiple piperacillin sodium and Tazobactam sodium for injection doses to healthy subjects, the plasma half-life of piperacillin and of tazobactam ranged from 0.7 to 1.2 hours and was unaffected by dose or duration of infusion.
Piperacillin is metabolized to a minor microbiologically active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacological and antibacterial activities. Both piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion. Piperacillin is excreted rapidly as unchanged drug with 68% of the administered dose excreted in the urine. Tazobactam and its metabolite are eliminated primarily by renal excretion with 80% of the administered dose excreted as unchanged drug and the remainder as the single metabolite. Piperacillin, tazobactam and desethyl piperacillin are also secreted into the bile.
Both piperacillin and tazobactam are approximately 30% bound to plasma proteins.
The protein binding of either piperacillin or tazobactam is unaffected by the presence of the other compound. Protein binding of the tazobactam metabolite is negligible.
Piperacillin and tazobactam are widely distributed into tissues and body fluids including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary, and fallopian tube), interstitial fluid, and bile. Mean tissue concentrations are generally 50% to 100% of those in plasma. Distribution of piperacillin and tazobactam into cerebrospinal fluid is low in subjects with non-inflamed meninges, as with other penicillins.
Piperacillin/Tazobactam: Piperacillin/tazobactam was negative in microbial mutagenicity assays at concentrations up to 14.84/1.86 µg/mL. Piperacillin/tazobactam was negative in the unscheduled DNA synthesis (UDS) test at concentrations up to 5689/711 µg/mL. Piperacillin/tazobactam was negative in a mammalian point mutation (Chinese hamster ovary cell HPRT) assay at concentrations up to 8000/1000 µg/mL. Piperacillin/tazobactam was negative in a mammalian cell (BALB/c-3T3) transformation assay at concentrations up to 8/1 µg/mL. In vivo, piperacillin/tazobactam did not induce chromosomal aberrations in rats dosed I.V. with 1500/187.5 mg/kg; this dose is similar to the maximum recommended human daily dose on a body-surface-area basis (mg/m2).
Piperacillin: Piperacillin was negative in microbial mutagenicity assays at concentrations up to 50 µg/plate. There was no DNA damage in bacteria (Rec assay) exposed to piperacillin at concentrations up to 200 µg/disk. Piperacillin was negative in the UDS test at concentrations up to 10,000 µg/mL. In a mammalian point mutation (mouse lymphoma cells) assay, piperacillin was positive at concentrations ≥2500 µg/mL. Piperacillin was negative in a cell (BALB/c-3T3) transformation assay at concentrations up to 3000 µg/mL. In vivo, piperacillin did not induce chromosomal aberrations in mice at I.V. doses up to 2000 mg/kg/day or rats at I.V. doses up to 1500 mg/kg/day. These are half (mice) or similar (rats) to the maximum recommended human daily dose based on body-surface on body-surface area (mg/m2). In another in vivo test, there was no dominant lethal effect when piperacillin was administered to rats at I.V. doses up to 2000 mg/kg/day, which is similar to the maximum recommended human daily dose based on body-surface area (mg/m2). When mice were administered piperacillin at I.V. doses up to 2000 mg/kg/day, which is half the maximum recommended human daily dose based on body-surface area (mg/m2), urine from these animals was not mutagenic when tested in a microbial mutagenicity assay. Bacteria injected into the peritoneal cavity of mice administered piperacillin at I.V. doses up to 2000 mg/kg/day did not show increased mutation frequencies.
Tazobactam: Tazobactam was negative in microbial mutagenicity assays at concentrations up to 333 µg/plate. Tazobactam was negative in the UDS test at concentrations up to 2000 µg/mL. Tazobactam was negative in a mammalian point mutation (Chinese hamster ovary cell HPRT) assay at concentrations up to 5000 µg/ml. In another mammalian point mutation (mouse lymphoma cells) assay, tazobactam was positive at concentrations ≥3000 µg/mL. Tazobactam was negative in a cell (BALB/ c-3T3) transformation assay at concentrations up to 900 µg/mL. In an in vitro cytogenetics (Chinese hamster lung cells) assay, tazobactam was negative at concentrations up to 3000 µg/ml. In vivo, tazobactam did not induce chromosomal aberrations in rats at I.V. doses up to 5000 mg/kg, which is 23 times the maximum recommended human daily dose based on body-surface area (mg/m2).
Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility: Long term carcinogenicity studies in animals have not been conducted with piperacillin/tazobactam, piperacillin, or tazobactam.
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