Peringatan Keamanan

Overdose

Post-marketing reports have been made of overdose cases with piperacillin/tazobactam. Nausea, vomiting, and diarrhea are frequent manifestations of an overdose. Neuromuscular excitability or seizures may also occur with high intravenous doses or renal failure. There is no specific antidote. Provide supportive measures in case of an overdose. Anticonvulsive agents may be indicated when neuromuscular excitability or seizures occur. If anaphylaxis occurs, traditional measures should be taken to manage hypersensitivity (for example, adrenaline, antihistamines, corticosteroids, and oxygen/airway maintenance).L6661 Similar measures should be taken after a ceftolozane-tazobactam overdose.FDA label Hemodialysis can be used to remove the drug from the circulation FDA label,L4417.

A note on nephrotoxicity

Cases of life-threatening nephrotoxicity have been seen in critically ill patients receiving piperacillin-tazobactam. Alternative therapy and/or renal monitoring should be considered in critically ill patients.L6664

Carcinogenesis/Mutagenesis

Tazobactam tested negative for genotoxic effects in the Ames assay, an after in vitro chromosomal aberration and point mutation assay in the Chinese hamster, an various other assays.FDA label

Use in pregnancy

Tazobactam has been found cross the placenta in rats. No data on human studies are available, however, rat studies have shown no teratogenetic effects at doses 6-14 times the equivalent maximum recommended human dose.L4417

Use in lactation

There are no data on the presence of tazobactam in human breastmilk. No data are currently available on the effects of tazobactam on the infant, or how it affects milk production. Use clinical judgement and consider the maternal need for the drug and the benefits of breastfeeding the infant before administration during lactation.L4417 Small concentrations of piperacillin-tazobactam have been found in the breastmilk and can lead to hypersensitivity in a breastfeeding infant. In some cases, breastfeeding may have to be discontinued temporarily.L6661

Tazobactam

DB01606

small molecule approved

Deskripsi

Tazobactam is an antibiotic of the beta-lactamase inhibitor class that prevents the breakdown of other antibiotics by beta-lactamase enzyme producing organisms. It is combined with Piperacillin and Ceftolozane for the treatment of a variety of bacterial infections.

Piperacillin-tazobactam was initially approved by the FDA in 1994, and ceftolozane-tazobactam was approved by the FDA in 2014FDA label, providing wider antibacterial coverage for gram-negative infections. In June 2019, ceftolozane-tazobactam was approved by the FDA for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, which are significant causes of morbidity and mortality in hospitalized patients.L6673

Struktur Molekul 2D

Berat 300.291
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Piperacillin-tazobactam After a single dose in healthy volunteers, the plasma half-life of piperacillin and tazobactam was in the range of 0.7 to 1.2 hours.[L4417] Ceftolozane-tazobactam 0.91-1.03 hours [L41618]
Volume Distribusi 18.2 L when given with piperacillin [L4417] 13.5-18.2 L when given with ceftolozane [L41618] Piperacillin-tazobactam is widely distributed in body tissues and fluids. These may include but are not limited to the intestine, gallbladder, lung, female reproductive organs, and the bile. Meningeal distribution of piperacillin-tazobactam increases with inflammation, but is otherwise low.[L4417]
Klirens (Clearance) Because tazobactam is cleared by the kidneys and is a substrate of the transporters OAT1 and OAT3, inhibitors of these transporters should be avoided to ensure efficacy.[L4417] Dosage adjustments of piperacillin-tazobactam and ceftolozane-tazobactam must be made for patients with impaired renal clearance.[L41618,L4417,L6661] The mean clearance rate of tazobactam was found to be 48.3-83.6 mL/min in patients admitted to the intensive care unit who were given renal replacement therapy and receiving intravenous piperacillin-tazobactam.[A179371] The clearance of tazobactam is dependent on renal function, as determined by renal clearance.[FDA label,A179377]

Absorpsi

Tazobactam is coadministered with piperacillin or ceftolozane, pharmacokinetic information will be provided for these combinations. Piperacillin-tazobactam Peak plasma concentrations occur immediately after the completion of intravenous infusion. Following several doses of piperacillin-tazobactam infusions every 6 hours, peak concentrations were similar to those that were measured after the initial dose.L4417 Ceftolozane-piperacillin AUC: 24.4-25 mcg•h/mL Peak concentrations are reached on day 1 after the first dose and range from 18 to 18.4 mcg/mL.L41618

Metabolisme

Tazobactam is mainly metabolized to M1, an inactive metabolite.L4417 Hydrolysis occurs on the beta-lactam ring to form M1 (the inactive metabolite).L41618,A179368

Rute Eliminasi

Tazobactam and its metabolite are mainly eliminated by the kidneys with about 80% of the administered dose eliminated as unchanged drug. The remaining drug is excreted as a single metabolite.L4417

Interaksi Obat

281 Data
Aspartame The excretion of Tazobactam can be decreased when combined with Aspartame.
Pravastatin The excretion of Tazobactam can be decreased when combined with Pravastatin.
Pantoprazole The excretion of Tazobactam can be decreased when combined with Pantoprazole.
Cefotiam The excretion of Tazobactam can be decreased when combined with Cefotiam.
Liothyronine The excretion of Tazobactam can be decreased when combined with Liothyronine.
Conjugated estrogens The excretion of Tazobactam can be decreased when combined with Conjugated estrogens.
Indomethacin The excretion of Tazobactam can be decreased when combined with Indomethacin.
Aminohippuric acid The excretion of Tazobactam can be decreased when combined with Aminohippuric acid.
Lansoprazole The excretion of Tazobactam can be decreased when combined with Lansoprazole.
Cefalotin The excretion of Tazobactam can be decreased when combined with Cefalotin.
Tenoxicam The excretion of Tazobactam can be decreased when combined with Tenoxicam.
Cefotaxime The excretion of Tazobactam can be decreased when combined with Cefotaxime.
Zidovudine The excretion of Tazobactam can be decreased when combined with Zidovudine.
Cimetidine The excretion of Tazobactam can be decreased when combined with Cimetidine.
Guanidine The excretion of Tazobactam can be decreased when combined with Guanidine.
Piroxicam The excretion of Tazobactam can be decreased when combined with Piroxicam.
Cephalexin The excretion of Tazobactam can be decreased when combined with Cephalexin.
Enalapril The excretion of Tazobactam can be decreased when combined with Enalapril.
Diclofenac The excretion of Tazobactam can be decreased when combined with Diclofenac.
Oxytetracycline The excretion of Tazobactam can be decreased when combined with Oxytetracycline.
Leucovorin The excretion of Tazobactam can be decreased when combined with Leucovorin.
Furosemide The excretion of Tazobactam can be decreased when combined with Furosemide.
Esomeprazole The excretion of Tazobactam can be decreased when combined with Esomeprazole.
Tetracycline The excretion of Tazobactam can be decreased when combined with Tetracycline.
Acyclovir The excretion of Tazobactam can be decreased when combined with Acyclovir.
Phenylbutazone The excretion of Tazobactam can be decreased when combined with Phenylbutazone.
Cefaclor The excretion of Tazobactam can be decreased when combined with Cefaclor.
Bumetanide The excretion of Tazobactam can be decreased when combined with Bumetanide.
Quinidine The excretion of Tazobactam can be decreased when combined with Quinidine.
Dinoprostone The excretion of Tazobactam can be decreased when combined with Dinoprostone.
Famotidine The excretion of Tazobactam can be decreased when combined with Famotidine.
Salicylic acid The excretion of Tazobactam can be decreased when combined with Salicylic acid.
Ganciclovir The excretion of Tazobactam can be decreased when combined with Ganciclovir.
Ketoprofen The excretion of Tazobactam can be decreased when combined with Ketoprofen.
Minocycline The excretion of Tazobactam can be decreased when combined with Minocycline.
Ibuprofen The excretion of Tazobactam can be decreased when combined with Ibuprofen.
Novobiocin The excretion of Tazobactam can be decreased when combined with Novobiocin.
Benzylpenicillin The excretion of Tazobactam can be decreased when combined with Benzylpenicillin.
Melatonin The excretion of Tazobactam can be decreased when combined with Melatonin.
Ouabain The excretion of Tazobactam can be decreased when combined with Ouabain.
Rosuvastatin The excretion of Tazobactam can be decreased when combined with Rosuvastatin.
Cefadroxil The excretion of Tazobactam can be decreased when combined with Cefadroxil.
Ceftriaxone The excretion of Tazobactam can be decreased when combined with Ceftriaxone.
Cefamandole The excretion of Tazobactam can be decreased when combined with Cefamandole.
Cefazolin The excretion of Tazobactam can be decreased when combined with Cefazolin.
Cefoperazone The excretion of Tazobactam can be decreased when combined with Cefoperazone.
Ceftizoxime The excretion of Tazobactam can be decreased when combined with Ceftizoxime.
Cefacetrile The excretion of Tazobactam can be decreased when combined with Cefacetrile.
Ceftibuten The excretion of Tazobactam can be decreased when combined with Ceftibuten.
Liotrix The excretion of Tazobactam can be decreased when combined with Liotrix.
Cilastatin The excretion of Tazobactam can be decreased when combined with Cilastatin.
Succinic acid The excretion of Succinic acid can be decreased when combined with Tazobactam.
Citrulline The excretion of Citrulline can be decreased when combined with Tazobactam.
Oseltamivir The excretion of Oseltamivir can be decreased when combined with Tazobactam.
Tenofovir disoproxil The excretion of Tenofovir disoproxil can be decreased when combined with Tazobactam.
Trifluridine The excretion of Trifluridine can be decreased when combined with Tazobactam.
Allopurinol The excretion of Allopurinol can be decreased when combined with Tazobactam.
Cefdinir The excretion of Cefdinir can be decreased when combined with Tazobactam.
Valaciclovir The excretion of Valaciclovir can be decreased when combined with Tazobactam.
Levocarnitine The excretion of Levocarnitine can be decreased when combined with Tazobactam.
Fluorescein The excretion of Fluorescein can be decreased when combined with Tazobactam.
Hydrocortisone The excretion of Hydrocortisone can be decreased when combined with Tazobactam.
Estradiol The excretion of Estradiol can be decreased when combined with Tazobactam.
Ranitidine The excretion of Ranitidine can be decreased when combined with Tazobactam.
Quinapril The excretion of Quinapril can be decreased when combined with Tazobactam.
Fexofenadine The excretion of Fexofenadine can be decreased when combined with Tazobactam.
Captopril The excretion of Captopril can be decreased when combined with Tazobactam.
Sitagliptin The excretion of Sitagliptin can be decreased when combined with Tazobactam.
Cyclic adenosine monophosphate The excretion of Cyclic adenosine monophosphate can be decreased when combined with Tazobactam.
Cholic Acid The excretion of Cholic Acid can be decreased when combined with Tazobactam.
Glutaric Acid The excretion of Glutaric Acid can be decreased when combined with Tazobactam.
Oxalic Acid The excretion of Oxalic Acid can be decreased when combined with Tazobactam.
Taurocholic acid The excretion of Taurocholic acid can be decreased when combined with Tazobactam.
Doripenem The excretion of Doripenem can be decreased when combined with Tazobactam.
Saxagliptin The excretion of Saxagliptin can be decreased when combined with Tazobactam.
Ellagic acid The excretion of Ellagic acid can be decreased when combined with Tazobactam.
Cefaloridine The excretion of Cefaloridine can be decreased when combined with Tazobactam.
Avibactam The excretion of Avibactam can be decreased when combined with Tazobactam.
Eluxadoline The excretion of Eluxadoline can be decreased when combined with Tazobactam.
Silibinin The excretion of Silibinin can be decreased when combined with Tazobactam.
Tenofovir alafenamide The excretion of Tenofovir alafenamide can be decreased when combined with Tazobactam.
Baricitinib The serum concentration of Baricitinib can be increased when it is combined with Tazobactam.
Relebactam The excretion of Relebactam can be decreased when combined with Tazobactam.
Tenofovir The excretion of Tenofovir can be decreased when combined with Tazobactam.
trans-2-hydroxycinnamic acid The excretion of Tazobactam can be decreased when combined with trans-2-hydroxycinnamic acid.
Topiroxostat The excretion of Tazobactam can be decreased when combined with Topiroxostat.
Benzoic acid The excretion of Tazobactam can be decreased when combined with Benzoic acid.
Caprylic acid The excretion of Tazobactam can be decreased when combined with Caprylic acid.
Ataluren The excretion of Tazobactam can be decreased when combined with Ataluren.
Teriflunomide The excretion of Tazobactam can be decreased when combined with Teriflunomide.
Dabrafenib The excretion of Tazobactam can be decreased when combined with Dabrafenib.
Dolutegravir The excretion of Tazobactam can be decreased when combined with Dolutegravir.
Lenvatinib The excretion of Tazobactam can be decreased when combined with Lenvatinib.
Cabotegravir The excretion of Tazobactam can be decreased when combined with Cabotegravir.
Apalutamide The excretion of Tazobactam can be decreased when combined with Apalutamide.
Pradigastat The excretion of Tazobactam can be decreased when combined with Pradigastat.
Enasidenib The excretion of Tazobactam can be decreased when combined with Enasidenib.
Hydrochlorothiazide The excretion of Hydrochlorothiazide can be decreased when combined with Tazobactam.
Gemfibrozil The excretion of Tazobactam can be decreased when combined with Gemfibrozil.
Dronedarone The excretion of Tazobactam can be decreased when combined with Dronedarone.

Target Protein

Beta-lactamase blaZ
Beta-lactamase TEM bla
Beta-lactamase Ohio-1
Beta-lactamase SHV-1 bla

Referensi & Sumber

Synthesis reference: Georg Trickes, "Crystalline tazobactam, and its production and use." U.S. Patent US5763603, issued March, 1988.
Artikel (PubMed)
  • PMID: 17547502
    Gin A, Dilay L, Karlowsky JA, Walkty A, Rubinstein E, Zhanel GG: Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther. 2007 Jun;5(3):365-83. doi: 10.1586/14787210.5.3.365.
  • PMID: 24352909
    Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagace-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP 3rd, Karlowsky JA: Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs. 2014 Jan;74(1):31-51. doi: 10.1007/s40265-013-0168-2.
  • PMID: 1656853
    Wise R, Logan M, Cooper M, Andrews JM: Pharmacokinetics and tissue penetration of tazobactam administered alone and with piperacillin. Antimicrob Agents Chemother. 1991 Jun;35(6):1081-4. doi: 10.1128/aac.35.6.1081.
  • PMID: 10526867
    Williams JD: Beta-lactamases and beta-lactamase inhibitors. Int J Antimicrob Agents. 1999 Aug;12 Suppl 1:S3-7; discussion S26-7.
  • PMID: 8937930
    Derendorf H, Dalla Costa T: Pharmacokinetics of piperacillin, tazobactam and its metabolite in renal impairment. Int J Clin Pharmacol Ther. 1996 Nov;34(11):482-8.
  • PMID: 22282479
    Bauer SR, Salem C, Connor MJ Jr, Groszek J, Taylor ME, Wei P, Tolwani AJ, Fissell WH: Pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in 42 patients treated with concomitant CRRT. Clin J Am Soc Nephrol. 2012 Mar;7(3):452-7. doi: 10.2215/CJN.10741011. Epub 2012 Jan 26.
  • PMID: 24492369
    Wooley M, Miller B, Krishna G, Hershberger E, Chandorkar G: Impact of renal function on the pharmacokinetics and safety of ceftolozane-tazobactam. Antimicrob Agents Chemother. 2014;58(4):2249-55. doi: 10.1128/AAC.02151-13. Epub 2014 Feb 3.
  • PMID: 9066111
    Bonomo RA, Rudin SA, Shlaes DM: Tazobactam is a potent inactivator of selected inhibitor-resistant class A beta-lactamases. FEMS Microbiol Lett. 1997 Mar 1;148(1):59-62. doi: 10.1111/j.1574-6968.1997.tb10267.x.
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