Zavicefta, 2000 mg+500 mg 10 pcs

A combination drug whose active ingredients are avibactam and ceftazidime.

The mechanism of action

Avibactam is an inhibitor of β-lactamases of non-beta-lactam structure. Avibactam forms a covalent bond with the enzyme that is not subject to hydrolysis. It inhibits β-lactamases of classes A and C and some β-lactamases of class D according to Ambler, including extended spectrum β-lactamases (ALRS), CRC and OXA-48 carbapenemases, as well as AmpC enzymes. Avibactam does not inhibit class B β-lactamases (metal-β-lactamases) and is unable to inhibit many class D β-lactamases. Avibactam has no clinically significant antibacterial activity in vitro. Avibactam does not induce blaAmrC transcription in Enterobacter cloacae, Citrobacter freundii or Pseudomonas aeruginosa in vitro at 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 synthesis of bacterial cell wall peptidoglycan as a result of interaction with penicillin-binding proteins (PBP), which leads to destruction of cell wall and death of bacteria.

Resistance

The mechanism of resistance. The drug is not active against bacteria producing metallo-β-lactamases. Mechanisms of bacterial resistance that could potentially affect drug activity include mutant or acquired BPS, decreased outer membrane permeability to avibactam or ceftazidime, active excretion (efflux) of avibactam or ceftazidime, and β-lactamases that are resistant to inhibition by avibactam and capable of hydrolyzing ceftazidime.

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

In interaction with other antibacterial agents

In in vitro studies, neither synergism nor antagonism was noted with metronidazole, tobramycin, levofloxacin, vancomycin, linezolid, colistin and tigecycline when the drug was used together.

Sensitivity

The prevalence of acquired resistance of certain microbial species may vary in different regions and over time. Local information on resistance is desirable, especially when treating severe infections. Drug sensitivity for specific clinical isolates should be determined using standard methods. Interpretation of microbiological results should be done according to local guidelines.

Indications

Active ingredient

Composition

Active ingredients:

Avibactam sodium 543.5 mg, which corresponds to avibactam 500 mg;

ceftazidime pentahydrate 2329.6 mg, which corresponds to ceftazidime 2000 mg;

Excipients: sodium carbonate anhydrous – 233 mg.

How to take, the dosage

The contents of one vial of the drug (2000 mg ceftazidime+500 mg avibactam) are administered by IV infusion of 100 mL at a constant rate of 120 min every 8 h if the CK is ≥51 mL/min.

The following duration of therapy is recommended:

Interaction

Avibactam did not significantly inhibit cytochrome P450 isoenzymes. Avibactam and ceftazidime in the clinically relevant range of exposure did not induce cytochrome P450 isoenzymes in vitro. Avibactam and ceftazidime in the clinically relevant exposure range do not inhibit major transporters in the kidney and liver, so the likelihood of drug interactions through these mechanisms is considered low.

In vitro, avibactam is a substrate of the OAT1 and OAT3 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 excretion of the latter. Clinical studies of interaction between avibactam and probenecid have not been conducted, so it is not recommended to use avibactam in combination with probenecid.

The clinical data confirm the absence of interaction of ceftazidime and avibactam and ceftazidime-avibactam and metronidazole.

The use of cephalosporins in high doses in combination with nephrotoxic drugs such as aminoglycosides or powerful diuretics (e.g., furosemide) may lead to impaired renal function.

Chloramphenicol is an in vitro antagonist of ceftazidime and other cephalosporins. The clinical relevance of these data is unknown, but because of the possibility of in vivo antagonism, coadministration of these drugs should be avoided.

Contraindications

Side effects

Infections and invasions: often – candidiasis (including vulvovaginal candidiasis and oral candidiasis); infrequent – colitis associated with Clostridium difficile, pseudomembranous colitis.

Hematopoietic system: very common – positive Coombs’ test; common – eosinophilia, thrombocytosis; infrequent – neutropenia, leukopenia, thrombocytopenia, lymphocytosis; unspecified frequency – agranulocytosis, hemolytic anemia.

Immune system disorders: unspecified frequency – anaphylactic reaction.

Nervous system disorders: frequent – headache, dizziness; infrequent – paresthesia.

The digestive system: frequently – diarrhea, abdominal pain, nausea, vomiting, increased ALT activity, increased AST activity, increased ALP activity, increased GGT activity, increased LDH activity; infrequent – perversion of taste; unspecified frequency – jaundice.

Skin and subcutaneous fat: frequently – maculopapular rash, urticaria; infrequently – itching; unspecified frequency – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, drug rash with eosinophilia and systemic symptoms.

Urinary system disorders: infrequent – increase of creatinine concentration in blood, increased concentration of urea in blood, acute renal failure; very rarely – tubulointerstitial nephritis.

Others: often – thrombosis in the place of infusion, phlebitis in the place of infusion, increased body temperature.