suffering from [18:<10%. 1 Avibactam: 5.7 8.2%. 1 Elimination Metabolism Ceftazidime and avibactam do not undergo clinically important metabolism. 1 Metabolism of avibactam not observed in vitro in human liver preparations (microsomes and hepatocytes). 1 Elimination Route Both ceftazidime and avibactam principally eliminated unchanged in urine. 1 Ceftazidime: Approximately 80 90% of an IV dose excreted unchanged by the kidneys over 24 hours. 1 Avibactam: Average of 97% of an IV dose eliminated in urine; 1 0.2% eliminated in feces. 1 Half-life Ceftazidime: 2.8 hours following multiple IV doses of ceftazidime and avibactam. 1 Avibactam: 2.7 hours following multiple IV doses of ceftazidime and avibactam. 1 Special Populations Renal impairment: Half-life of ceftazidime prolonged. 1 AUC of avibactam increased by 2.6-, 3.8-, or 7-fold in adults with mild, moderate, or severe renal impairment, respectively. 1 Both ceftazidime and avibactam removed by hemodialysis. 1 In patients with end-stage renal disease (ESRD), 55% of a ceftazidime dose or 55% of a avibactam dose recovered in dialysate. 1 Hepatic impairment: Ceftazidime pharmacokinetics not affected. 1 Avibactam pharmacokinetics not established in patients with hepatic impairment; 1 does not appear to undergo clinically important hepatic metabolism and systemic clearance of avibactam not expected to be affected. 1 Stability Storage Parenteral Powder for IV Infusion 25 C (may be exposed to 15 30 C). 1 Protect from light. 1 Reconstituted solution may be stored for up to 30 minutes prior to transfer and dilution. 1 Following reconstitution and dilution, may be stored for up to 12 hours at room temperature. 1 Alternatively, may be stored for up to 24 hours at 2 8 C and then used within 12 hours after removal from refrigeration to room temperature. 1 Compatibility For information on systemic interactions resulting from concomitant use, see Interactions. Parenteral Solution Compatibility Compatible Dextrose 2.5% in sodium chloride 0.45% 1 Dextrose 5% 1 Ringer s injection, lactated 1 Sodium chloride 0.9% 1 Actions and Spectrum Ceftazidime and avibactam is a fixed combination of ceftazidime (a third generation cephalosporin antibiotic) and avibactam (a non-β-lactam β-lactamase inhibitor). 1 2 Like other cephalosporins, antibacterial activity of ceftazidime results from inhibition of mucopeptide synthesis in the bacterial cell wall and is mediated by penicillin-binding proteins (PBPs). 1 Ceftazidime has an expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins, and is distinguished from many other cephalosporins by its activity against Ps. aeruginosa . 2 Avibactam is a non-β-lactam β-lactamase inhibitor; 1 5 6 25 26 27 differs structurally and pharmacologically from β-lactam β-lactamase inhibitors (e.g., sulbactam, clavulanic acid, tazobactam). 5 6 25 26 27 Avibactam inactivates many β-lactamases in Ambler class A (e.g., some extended-spectrum β-lactamases [ESBLs], carbapenemases such as K. pneumoniae carbapenemases [KPCs]), class C (e.g., cephalosporinases such as AmpC), and class D (e.g., some oxacillinases [OXAs]). 1 5 6 10 25 26 27 28 Cannot inactivate Ambler class B metallo-β-lactamases (MBLs) 5 26 28 or certain OXA-type carbapenemases. 5 9 26 Because avibactam inactivates certain β-lactamases, concomitant use with ceftazidime can protect ceftazidime from degradation by these β-lactamases and expand its spectrum of activity to include many β-lactamase-producing bacteria resistant to ceftazidime alone. 1 5 6 10 11 13 16 17 18 19 Avibactam does not decrease antibacterial activity of ceftazidime against ceftazidime-susceptible bacteria. 1 Ceftazidime and avibactam is bactericidal in action. 1 13 Active in vitro against many Enterobacteriaceae, including C. freundii , 1 8 11 16 18 C. koseri , 1 16 19 E. coli , 1 8 9 11 13 16 18 E. aerogenes , 1 E. cloacae , 1 8 11 16 18 19 K. pneumoniae , 1 8 9 11 16 18 K. oxytoca , 1 18 19 Morganella morganii , 1 11 18 Proteus 1 11 (including P. mirabilis 1 8 11 16 19 and P. vulgaris 19 ), P. rettgeri , 1 11 P. stuartii , 1 and Serratia marcescens . 1 8 18 19 Active in vitro against many strains of Ps. aeruginosa , 1 8 9 10 13 16 18 20 21 including some multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. 10 21 Active in vitro against some Enterobacteriaceae that produce certain TEM, SHV, CTX-M, KPC, AmpC, or OXA β-lactamases and active in vitro against some Ps. aeruginosa that produce certain AmpC β-lactamases. 1 5 6 8 9 10 11 13 16 18 20 21 Has only limited activity in vitro against most anaerobic bacteria. 5 31 Resistance or reduced susceptibility to ceftazidime and avibactam can occur. 1 5 13 16 17 19 26 29 Mechanism of resistance may be multifactorial. 20 Bacteria that produce metallo-β-lactamases are resistant to ceftazidime and avibactam; 5 13 26 bacterial strains producing certain OXA β-lactamases (e.g., Acinetobacter , Ps. aeruginosa ) also resistant to ceftazidime and avibactam. 5 9 13 26 Bacteria resistant to ceftazidime because of altered PBPs may also be resistant to ceftazidime and avibactam. 5 Some strains of gram-negative bacteria (e.g., Ps aeruginosa , S. marcescens ) that over-express efflux pumps or have porin mutations that result in resistance to ceftazidime may also have reduced susceptibility or resistance to ceftazidime and avibactam. 1 5 8 16 20 Cross-resistance between ceftazidime and avibactam and other classes of anti-infectives not reported. 1 Some bacteria resistant to carbapenems, other cephalosporins (including ceftazidime alone), or fluoroquinolones may be susceptible to ceftazidime and avibactam. 1 8 Advice to Patients Advise patients that antibacterials (including ceftazidime and avibactam) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold). 1 Importance of completing full course of therapy, even if feeling better after a few days. 1 Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftazidime and avibactam or other antibacterials in the future. 1 Advise patients that allergic reactions, including serious allergic reactions, requiring immediate treatment could occur. 1 Importance of informing clinicians about any previous hypersensitivity reactions to ceftazidime and avibactam, other β-lactams (including cephalosporins), or other allergens. 1 Advise patients that adverse neurologic reactions can occur while receiving ceftazidime and avibactam. 1 Importance of immediately informing a clinician if any neurologic signs and symptoms, including encephalopathy (disturbance of consciousness such as confusion, hallucinations, stupor, coma), myoclonus, and seizures, occur; 1 immediate treatment, dosage adjustment, or discontinuance of ceftazidime and avibactam may be necessary. 1 Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. 1 Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose. 1 Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses. 1 Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed. 1 Importance of informing patients of other important precautionary information. 1 (See Cautions.) Preparations Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. cefTAZidime and Avibactam Sodium Routes Dosage Forms Strengths Brand Names Manufacturer Parenteral For injection, for IV infusion 2.5 g (2 g of ceftazidime and 0.5 g of avibactam) Avycaz Forest AHFS DI Essentials. Copyright 2017, Selected Revisions October 19, 2015. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. References 1. Forest Pharmaceuticals, Inc. Avycaz (ceftazidime and avibactam sodium) for injection prescribing information. Cincinnati, OH; 2015 Sep. 2. Andes DR, Craig WA. Cephalosporins. In: Bennett JE, Dolin R, Blaser MJ eds. Mandell, Douglas and Bennett s principles and practices of infectious disease. 8th ed. Philadelphia, PA: Saunders, Elsevier; 2015:278-91. 3. Lucasti C, Popescu I, Ramesh MK et al. Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother . 2013; 68:1183-92. [PubMed 23391714] 4. Vazquez JA, González Patzán LD, Stricklin D et al. Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin . 2012; 28:1921-31. [PubMed 23145859] 5. Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: an evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core Evid . 2014; 9:13-25. [PubMed 24493994] 6. Lahiri SD, Johnstone MR, Ross PL et al. Avibactam and class C β-lactamases: mechanism of inhibition, conservation of the binding pocket, and implications for resistance. Antimicrob Agents Chemother . 2014; 58:5704-13. [PubMed 25022578] 7. Dallow J, Otterson LG, Huband MD et al. Microbiological interaction studies between ceftazidime-avibactam and pulmonary surfactant and between ceftazidime-avibactam and antibacterial agents of other classes. Int J Antimicrob Agents . 2014; 44:552-6. [PubMed 25293578] 8. Pitart C, Marco F, Keating TA et al. Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother . 2015; 59:3059-65. [PubMed 25753646] 9. Aktas Z, Kayacan C, Oncul O. In vitro activity of avibactam (NXL104) in combination with β-lactams against Gram-negative bacteria, including OXA-48 β-lactamase-producing Klebsiella pneumoniae. Int J Antimicrob Agents . 2012; 39:86-9. [PubMed 22041508] 10. Berkhout J, Melchers MJ, van Mil AC et al. In vitro activity of ceftazidime-avibactam combination in in vitro checkerboard assays. Antimicrob Agents Chemother . 2015; 59:1138-44. [PubMed 25487794] 11. Levasseur P, Girard AM, Miossec C et al. In vitro antibacterial activity of the ceftazidime-avibactam combination against enterobacteriaceae, including strains with well-characterized β-lactamases. Antimicrob Agents Chemother . 2015; 59:1931-4. [PubMed 25583732] 12. Cohen SH, Gerding DN, Johnson S et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol . 2010; 31:431-55. [PubMed 20307191] 13. Keepers TR, Gomez M, Celeri C et al. Bactericidal activity, absence of serum effect, and time-kill kinetics of ceftazidime-avibactam against β-lactamase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Antimicrob Agents Chemother . 2014; 58:5297-305. [PubMed 24957838] 14. Fekety R for the American College of Gastroenterology Practice Parameters Committee. Guidelines for the diagnosis and management of Clostridium difficile -associated diarrhea and colitis. Am J Gastroenterol . 1997; 92:739-50. [PubMed 9149180] 15. American Society of Health-System Pharmacists Commission on Therapeutics. ASHP therapeutic position statement on the preferential use of metronidazole for the treatment of Clostridium difficile -associated disease. Am J Health-Syst Pharm . 1998; 55:1407-11. [PubMed 9659970] 16. Yoshizumi A, Ishii Y, Aoki K et al. In vitro susceptibility of characterized β-lactamase-producing Gram-negative bacteria isolated in Japan to ceftazidime-, ceftaroline-, and aztreonam-avibactam combinations. J Infect Chemother . 2015; 21:148-51. [PubMed 25444674] 17. Winkler ML, Papp-Wallace KM, Bonomo RA. Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop. J Antimicrob Chemother . 2015; 70(8):2279-86. [PubMed 25957381] 18. Li H, Estabrook M, Jacoby GA et al. In vitro susceptibility of characterized β-lactamase-producing strains tested with avibactam combinations. Antimicrob Agents Chemother . 2015; 59:1789-93. [PubMed 25534728] 19. Castanheira M, Mills JC, Costello SE et al. Ceftazidime-Avibactam Activity Tested against Enterobacteriaceae Isolates from U.S. Hospitals (2011 to 2013) and Characterization of β-Lactamase-Producing Strains. Antimicrob Agents Chemother . 2015; 59:3509-17. [PubMed 25845862] 20. Levasseur P, Girard AM, Claudon M et al. In vitro antibacterial activity of the ceftazidime-avibactam (NXL104) combination against Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother . 2012; 56:1606-8. [PubMed 22214778] 21. Sader HS, Castanheira M, Mendes RE et al. Ceftazidime-Avibactam Activity against Multidrug-Resistant Pseudomonas aeruginosa Isolated in U.S. Medical Centers in 2012 and 2013. Antimicrob Agents Chemother . 2015; 59:3656-9. [PubMed 25845861] 22. US Food and Drug Administration. FDA drug safety communication: FDA cautions about dose confusion and medication errors with antibacterial drug Avycaz (ceftazidime and avibactam). 2015 Sept 22. From FDA website. 23. Merdjan H, Rangaraju M, Tarral A. Safety and pharmacokinetics of single and multiple ascending doses of avibactam alone and in combination with ceftazidime in healthy male volunteers: results of two randomized, placebo-controlled studies. Clin Drug Investig . 2015; 35:307-17. [PubMed 25813217] 24. Tarral A, Merdjan H. Effect of age and sex on the pharmacokinetics and safety of avibactam in healthy volunteers. Clin Ther . 2015; 37:877-86. [PubMed 25769615] 25. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 206494Orig1s000. Summary review. From FDA website. 26. Drawz SM, Papp-Wallace KM, Bonomo RA. New β-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother . 2014; 58:1835-46. [PubMed 24379206] 27. Stachyra T, Péchereau MC, Bruneau JM et al. Mechanistic studies of the inactivation of TEM-1 and P99 by NXL104, a novel non-beta-lactam beta-lactamase inhibitor. Antimicrob Agents Chemother . 2010; 54:5132-8. [PubMed 20921316] 28. Drawz SM, Bonomo RA. Three decades of beta-lactamase inhibitors. Clin Microbiol Rev . 2010; 23:160-201. [PubMed 20065329] 29. Livermore DM, Warner M, Jamrozy D et al. In-vitro selection of ceftazidime-avibactam resistance in Enterobacteriaceae with KPC-3 carbapenemase. Antimicrob Agents Chemother . 2015; :. [PubMed 26100712] 30. US Food and Drug Administration. Center for Drug Evaluation and Research. Application number 206494Orig1s000. Clinical pharmacology and biopharmaceutics review(s). From FDA website. 31. Citron DM, Tyrrell KL, Merriam V et al. In vitro activity of ceftazidime-NXL104 against 396 strains of beta-lactamase-producing anaerobes. Antimicrob Agents Chemother . 2011; 55:3616-20. [PubMed 21537015] 217. Hospira Inc. Tazicef (ceftazidime) powder for injection prescribing information. Lake Forest, IL; 2014 Oct. Next Interactions Print this page Add to My Med List More about avibactam/ceftazidime Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: cephalosporins/beta-lactamase inhibitors Consumer resources Avibactam and cefTAZidime Ceftazidime and Avibactam Ceftazidime and avibactam Intravenous (Advanced Reading) Professional resources Ceftazidime and Avibactam (Wolters Kluwer) Other brands: Avycaz Related treatment guides Intraabdominal Infection Kidney Infections Urinary Tract Infection> ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only B Pregnancy Category No proven risk in humans N/A CSA Schedule Not a controlled drug Approval History Drug history at FDA Drug Class Cephalosporins / beta-lactamase inhibitors Related Drugs Kidney Infections ciprofloxacin , cephalexin , Augmentin , Levaquin , Keflex , levofloxacin , Bactrim , More... Urinary Tract Infection ciprofloxacin , amoxicillin , doxycycline , Augmentin , Levaquin , levofloxacin , Bactrim , More... Intraabdominal Infection ciprofloxacin , metronidazole , clindamycin , ceftriaxone , Flagyl , Rocephin , gentamicin , More... Avibactam / ceftazidime Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } mostly
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