Zavicefta concentrate powder for infusion solution 2000mg+500mg, vials 10pcs

Composition

Active ingredients:  avibactam sodium 543.5 mg, which corresponds to the content of avibactam 500 mg; ceftazidime pentahydrate 2329.6 mg, which corresponds to the content of ceftazidime 2000 mg;

Auxiliary substances:  sodium carbonate anhydrous – 233 mg

Pharmacological action

Combined drug, the active ingredients of which are avibactam and ceftazidime.

Mechanism of action

Avibactam is a non-beta-lactam beta-lactamase inhibitor. Avibactam forms a covalent bond with the enzyme, which does not undergo hydrolysis. It inhibits Class A and C beta-lactamases and some Ambler Class D beta-lactamases, including extended-spectrum beta-lactamases (BLRS), KRS and OX-48 carbapenemases, and AMRs enzymes. Avibactam does not inhibit Class B beta-lactamases (metallo-beta-lactamases) and is unable to inhibit many Class D beta-lactamases. Avibactam has no clinically significant antibacterial activity in vitro. Avibactam does not induce blaAmpC transcription in Enterobacter cloacae, Citrobacter freundii, or Pseudomonas aeruginosa in vitro at the concentrations used to treat patients.

Ceftazidime is a broad-spectrum antibiotic of the cephalosporin class, whose activity against many significant gram-negative and gram-positive pathogenic bacteria has been shown in vitro. Ceftazidime disrupts bacterial cell wall peptidoglycan synthesis by interacting with penicillin-binding proteins (PSPs), which leads to cell wall destruction and bacterial death.

Resistance

The mechanism of resistance. The drug is not active against bacteria that produce metallo-β-lactamases. Mechanisms of bacterial resistance that may potentially affect drug activity include mutant or acquired PSBs, decreased outer membrane permeability to avibactam or ceftazidime, active elimination (efflux) of avibactam or ceftazidime, and beta-lactamases that are resistant to avibactam inhibition and can hydrolyze ceftazidime.

Cross-resistance. The absence of cross-resistance between the drug and fluoroquinolones or aminoglycosides was demonstrated in vitro using clinical isolates described at the molecular level. Some isolates that are resistant to ceftazidime (or other cephalosporins) or carbapenems are sensitive to the ceftazidime/avibactam combination. Cross-resistance with antibacterial drugs from the beta-lactam group, including carbapenems, was noted, when the mechanism of resistance is the production of metallo-beta-lactamases, such as VIM-2.

Interaction with other antibacterial drugs

No synergism or antagonism was observed in in vitro studies when the drug was co-administered with metronidazole, tobramycin, levofloxacin, vancomycin, linezolid, colistin, and tigecycline.

Sensitivity

The prevalence of acquired resistance to certain microbial species may vary from region to region and over time. It is advisable to obtain local information about resistance, especially in the treatment of severe infections. Drug sensitivity for specific clinical isolates should be determined using standard methods. Interpretation of the results of microbiological studies should be carried out in accordance with local guidelines.

Indications

• Treatment of the following infections in adult patients: complicated intra-abdominal infections; complicated urinary tract infections, including pyelonephritis; hospital-acquired pneumonia, including ventilator-associated pneumonia;
• infections caused by aerobic gram-negative microorganisms in patients with limited choice of antibacterial therapy.

Contraindications

Children and adolescents under 18 years of age (efficacy and safety have not been established); hypersensitivity to avibactam, ceftazidime or sodium carbonate (an auxiliary substance included in the drug); hypersensitivity to cephalosporins; severe hypersensitivity reactions of an immediate type (for example, anaphylactic reaction) to any other antibacterial agent with a beta-lactam structure (for example, penicillins, monobactams or carbapenems).

Side effects

Infections and infestations:  often-candidiasis (including vulvovaginal candidiasis and oral candidiasis); infrequently-colitis associated with Clostridium difficile, pseudomembranous colitis.

From the hematopoietic system:  very often-positive direct Coombs test; often-eosinophilia, thrombocytosis; infrequently-neutropenia, leukopenia, thrombocytopenia, lymphocytosis; unspecified frequency-agranulocytosis, hemolytic anemia.

From the immune system:  unspecified frequency – anaphylactic reaction.

Nervous system disorders:  often – headache, dizziness; infrequently-paresthesia.

From the digestive system:  often – diarrhea, abdominal pain, nausea, vomiting, increased ALT activity, increased AST activity, increased ALP activity, increased GGT activity, increased LDH activity; infrequently-taste distortion; unspecified frequency-jaundice.

Skin and subcutaneous fat disorders:  often-macular-papular rash, urticaria; infrequently-pruritus; unspecified frequency-toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, drug rash with eosinophilia and systemic symptoms.

From the urinary system:  infrequently-increased creatinine concentration in the blood, increased urea concentration in the blood, acute renal failure; very rarely – tubulointerstitial nephritis.

Other services:  often-thrombosis at the infusion site, phlebitis at the infusion site, fever.

Interaction

Avibactam did not significantly inhibit cytochrome P 450 isoenzymes. Avibactam and ceftazidime did not induce cytochrome P 450 isoenzymes in vitro in the clinically significant exposure range. Avibactam and ceftazidime do not inhibit major transporters in the kidney and liver in the clinically significant exposure range, so the likelihood of drug interaction through these mechanisms is considered low.

In vitro, avibactam is a substrate of the OAT 1 and OAT 3 transporters, which can promote its active uptake from the bloodstream, and thus its excretion. Probenecid (a potent OAT inhibitor) suppresses this uptake by 56% -70% in vitro, and therefore, when combined with avibactam, can affect the elimination of the latter. Clinical studies of the interaction of avibactam and probenecid have not been conducted, so it is not recommended to use avibactam in combination with probenecid.

Clinical data confirm the absence of interaction between ceftazidime and avibactam, as well as ceftazidime-avibactam and metronidazole.

The use of high-dose cephalosporins in combination with nephrotoxic medications, such as aminoglycosides or powerful diuretics (for example, furosemide), can lead to impaired renal function.

Chloramphenicol is an antagonist of ceftazidime and other cephalosporins in vitro. The clinical significance of these data is unknown, but due to the possibility of antagonism in vivo, the combined use of these drugs should be avoided.

How to take, course of use and dosage

The contents of one vial of the drug (2000 mg ceftazidime+500 mg avibactam) are administered intravenously as a 100 ml infusion at a constant rate for 120 minutes every 8 hours, if the creatinine clearance is ≥51 ml/min.

The following duration of therapy is recommended:

• complicated intra-abdominal infections – 5-14 days;
• complicated urinary tract infections, including pyelonephritis – 5-10 days;
• hospital-acquired pneumonia, including pneumonia associated with ventilation – 7-14 days;
• infections caused by aerobic gram-negative organisms in patients with a limited choice of antibiotic therapy, the duration of therapy depends on severity of the infection, the causative agent, the clinical and bacteriological response to treatment.

Active ingredient

Ceftazidime, [Avibactam]

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution