Peringatan Keamanan

A note on nephrotoxicity

This drug is mainly excreted by the kidneysA179431, and if administered to a patient with a creatinine clearance of less than 50 mL/min, may cause renal damage. Consult official product labeling for dosing adjustments in patients with renal impairment.L41618,A179437

Overdose information

If an overdose occurs, discontinue the drug and follow this with supportive treatment. Dialysis may be used.L41618

Use in pregnancy

Ceftolozane-tazobactam is a pregnancy category B drug, but human studies have not been performed to validate this in humans. At doses equivalent to 4-7 the standard dose administered in humans, no developmental abnormalities were seen. Since animal studies are not always predictive of drug response in humans, it is advisable to exercise caution if this drug is prescribed during pregnancy. The mother's clinical need should be assessed as well as possible risks to the fetus.L41618

Use in lactation

Whether this drug is excreted in human breast milk is unknown. Caution is advised if this drug is administered during lactation, as many other drugs are known to be secreted into breast milk.L41618

Carcinogenesis/mutagenesis

Formal studies have not been conducted in humans to assess mutagenicity or carcinogenicity. Studies in mice and rats did not reveal any mutagenic or carcinogenic potential, however, the potential risks resulting from long-term use have not been studied.L41618

Ceftolozane

DB09050

small molecule approved investigational

Deskripsi

Ceftolozane is a semi-synthetic broad-spectrum fifth generation cephalosporin.L6685 It was approved by the FDA in 2014 for use in combination with Tazobactam for the treatment of serious infections, such as intra-abdominal infections and complicated urinary tract infections. The manufacturer of this drug is Cubist Pharmaceuticals.A179422 Most recently, in June 2019, ceftolozane-tazobactam was approved for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.L41618

Hospital-acquired pneumonia and ventilator-associated pneumonia are major causes of morbidity and mortality in hospitalized patients and the use of ceftolozane-tazobactam offers effective activity against various organisms causing these infections, such as Pseudomonas aeruginosa.L6691

Struktur Molekul 2D

Berat 666.69
Wujud solid

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

Profil Farmakokinetik

Waktu Paruh (Half-Life) 2.77 hours on day 1 of treatment on a dose of 1 g/0.5 g every 8 hours.[L41618,A179431] 3.12 hours on day 10 of treatment on a dose of 1 g/0.5 g every 8 hours.[L41618]
Volume Distribusi 13.5 L.[L41618] Tissue distribution of ceftalozone-tazobactam is rapid and shows good penetration into the lung, rendering it an ideal treatment for bacterial pneumonia.[A179437]
Klirens (Clearance) The renal clearance of was measured to be 3.41 – 6.69 L/h after a single dose of ceftolozane-tazobactam. Dose adjustments of this drug are required in patients with impaired renal function with a creatinine clearance of 50 mL/min or below. Consult official labeling for dosing adjustment guidelines.[L41618,A179437]

Absorpsi

The area under the curve (AUC) of ceftolozane-tazobactam after an injected dose of 1 g/0.5 g every 8 hours for 1 day was 172 mcg•h/mL. The Cmax (peak concentration) and AUC are dose-dependent. The Cmax on day one of the above dose of ceftolozane-tazobactam was 69.1 mcg/mL.L41618

Metabolisme

Certolozane is not metabolized to any significant extent.L41618 The beta-lactam ring of tazobactam, when administered as ceftolozane-tazobactam, is hydrolyzed to form an inactive metabolite.L41618

Rute Eliminasi

Ceftolozane is mainly excreted in the urine.L41618,A179431

Interaksi Obat

837 Data
Probenecid The serum concentration of Ceftolozane can be increased when it is combined with Probenecid.
BCG vaccine The therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ceftolozane.
Typhoid vaccine The therapeutic efficacy of Typhoid vaccine can be decreased when used in combination with Ceftolozane.
Cyclosporine Cyclosporine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Icosapent Icosapent may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefotiam Cefotiam may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Mesalazine Mesalazine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefmenoxime Cefmenoxime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefmetazole Cefmetazole may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Pamidronic acid Pamidronic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Tenofovir disoproxil Tenofovir disoproxil may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Indomethacin Indomethacin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cidofovir Cidofovir may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefpiramide Cefpiramide may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceftazidime Ceftazidime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Loracarbef Loracarbef may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefalotin Cefalotin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Nabumetone Nabumetone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ketorolac Ketorolac may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Tenoxicam Tenoxicam may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Celecoxib Celecoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefotaxime Cefotaxime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Tolmetin Tolmetin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Foscarnet Foscarnet may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Rofecoxib Rofecoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Piroxicam Piroxicam may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Methotrexate Methotrexate may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cephalexin Cephalexin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Fenoprofen Fenoprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Valaciclovir Valaciclovir may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Valdecoxib Valdecoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Diclofenac Diclofenac may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Sulindac Sulindac may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Bacitracin Bacitracin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Amphotericin B Amphotericin B may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cephaloglycin Cephaloglycin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Flurbiprofen Flurbiprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Adefovir dipivoxil Adefovir dipivoxil may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Pentamidine Pentamidine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Etodolac Etodolac may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Mefenamic acid Mefenamic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Acyclovir Acyclovir may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Naproxen Naproxen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Sulfasalazine Sulfasalazine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Phenylbutazone Phenylbutazone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Meloxicam The risk or severity of methemoglobinemia can be increased when Ceftolozane is combined with Meloxicam.
Carprofen Carprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefaclor Cefaclor may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Diflunisal Diflunisal may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Tacrolimus Tacrolimus may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceforanide Ceforanide may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Salicylic acid Salicylic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Meclofenamic acid Meclofenamic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Carboplatin Carboplatin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Oxaprozin Oxaprozin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ketoprofen Ketoprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Balsalazide Balsalazide may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ibuprofen Ibuprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefditoren Cefditoren may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Atazanavir Atazanavir may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Colistimethate Colistimethate may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefuroxime Cefuroxime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefapirin Cefapirin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefadroxil Cefadroxil may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefprozil Cefprozil may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceftriaxone Ceftriaxone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Olsalazine Olsalazine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Lumiracoxib Lumiracoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefamandole Cefamandole may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefazolin Cefazolin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefonicid Cefonicid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefoperazone Cefoperazone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefotetan Cefotetan may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefoxitin Cefoxitin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceftizoxime Ceftizoxime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefradine Cefradine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Magnesium salicylate Magnesium salicylate may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Salsalate Salsalate may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Choline magnesium trisalicylate Choline magnesium trisalicylate may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefepime Cefepime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefacetrile Cefacetrile may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceftibuten Ceftibuten may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cefpodoxime Cefpodoxime may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Antrafenine Antrafenine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Aminophenazone Aminophenazone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Antipyrine Antipyrine may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Tiaprofenic acid Tiaprofenic acid may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Lopinavir Lopinavir may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Etoricoxib Etoricoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Hydrolyzed Cephalothin Hydrolyzed Cephalothin may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cephalothin Group Cephalothin Group may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Oxyphenbutazone Oxyphenbutazone may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Latamoxef Latamoxef may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Nimesulide Nimesulide may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Benoxaprofen Benoxaprofen may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Metamizole Metamizole may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Zomepirac Zomepirac may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Ceftobiprole Ceftobiprole may decrease the excretion rate of Ceftolozane which could result in a higher serum level.
Cimicoxib Cimicoxib may decrease the excretion rate of Ceftolozane which could result in a higher serum level.

Target Protein

Penicillin-binding protein 1B ponB
Cell division protein pbpB
Penicillin-binding protein 1C pbpC
Penicillin-binding protein 2 mrdA
Penicillin-binding protein dacA

Referensi & Sumber

Artikel (PubMed)
  • PMID: 25516692
    Sorbera M, Chung E, Ho CW, Marzella N: Ceftolozane/Tazobactam: a new option in the treatment of complicated gram-negative infections. P T. 2014 Dec;39(12):825-32.
  • 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: 26637512
    Cluck D, Lewis P, Stayer B, Spivey J, Moorman J: Ceftolozane-tazobactam: A new-generation cephalosporin. Am J Health Syst Pharm. 2015 Dec 15;72(24):2135-46. doi: 10.2146/ajhp150049.
  • PMID: 29493397
    Giacobbe DR, Bassetti M, De Rosa FG, Del Bono V, Grossi PA, Menichetti F, Pea F, Rossolini GM, Tumbarello M, Viale P, Viscoli C: Ceftolozane/tazobactam: place in therapy. Expert Rev Anti Infect Ther. 2018 Apr;16(4):307-320. doi: 10.1080/14787210.2018.1447381. Epub 2018 Mar 9.
  • PMID: 29039729
    Shortridge D, Pfaller MA, Castanheira M, Flamm RK: Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Enterobacteriaceae and Pseudomonas aeruginosa with Various Resistance Patterns Isolated in U.S. Hospitals (2013-2016) as Part of the Surveillance Program: Program to Assess Ceftolozane-Tazobactam Susceptibility. Microb Drug Resist. 2018 Jun;24(5):563-577. doi: 10.1089/mdr.2017.0266. Epub 2017 Oct 17.
  • PMID: 22450972
    Miller B, Hershberger E, Benziger D, Trinh M, Friedland I: Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Antimicrob Agents Chemother. 2012 Jun;56(6):3086-91. doi: 10.1128/AAC.06349-11. Epub 2012 Mar 26.
  • PMID: 24348053
    Hong MC, Hsu DI, Bounthavong M: Ceftolozane/tazobactam: a novel antipseudomonal cephalosporin and beta-lactamase-inhibitor combination. Infect Drug Resist. 2013 Nov 29;6:215-23. doi: 10.2147/IDR.S36140.
  • PMID: 20547785
    Moya B, Zamorano L, Juan C, Ge Y, Oliver A: Affinity of the new cephalosporin CXA-101 to penicillin-binding proteins of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2010 Sep;54(9):3933-7. doi: 10.1128/AAC.00296-10. Epub 2010 Jun 14.
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