Zinforo - instructions for use, analogs, reviews and release forms (injections in ampoules for injections, infusions) of the antibiotic drug for the treatment of community-acquired pneumonia and other infections in adults, children and in pregnancy

In this article, you can read the instructions for using the drug Zinforo. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Zinforo antibiotic in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Zinforo in the presence of existing structural analogues.Use for the treatment of community-acquired pneumonia, pustular and other infections in adults, children, as well as during pregnancy and lactation.

Zinforo - antibiotic group of 5 generation cephalosporins (anti-MRSA-cefepem).

After intravenous administration, the prodrug of ceftaroline fosamil rapidly turns into active ceftaroline.

Mechanism of action

Ceftarolin is an antibiotic of the class of cephalosporins with activity against gram-positive and gram-negative microorganisms. The bactericidal action of ceftaroline results in inhibition of the biosynthesis of the bacterial cell wall, by binding to penicillin-binding proteins (PSB). Ceftarolin exhibits bactericidal activity against Staphylococcus aureus (staphylococcus) due to its high affinity for PSB2a and against Streptococcus pneumoniae due to its high affinity for PSB2x.

Relationship pharmacokinetics and pharmacodynamics

The antibacterial activity of ceftaroline, as well as of other beta-lactam antibiotics, correlates well with the time period during which the drug concentrations remain above the minimum inhibitory concentration (MIC) for the infecting microorganism (% T over MIC).

The mechanism of resistance

Tseftarolin is not active against Enterobacteriaceae strains producing extended-spectrum beta-lactamase-producing ESBLs of the TEM, SHV or CTX-M families, serine carbapenemases (such as CRS), Class B or class C metal-beta-lactamase (AmpC cephalosporinase).

Cross-resistance

Despite the possible development of cross-resistance, some strains resistant to other cephalosporins may be sensitive to ceftarolin.

Sensitivity

The prevalence of acquired resistance to antibiotics in certain microorganisms may vary depending on the region and time. It is recommended to take into account local data on resistance, especially when treating severe infections. If the local resistance is such that the effectiveness of the drug for some infections becomes questionable, you need to seek the advice of an expert.

Sensitivity to ceftarolin should be determined using standard methods. Interpretation of results should be carried out in accordance with local guidelines.

Typically, sensitive microorganisms: Gram-positive microorganisms - Staphylococcus aureus (methicillin-sensitive and methicillin-resistant), Streptococcus agalactiae (streptococcus), group Streptococcus anginosus (includes S. anginosus, S. intermedius and S.constellatus), Streptococcus dysgalactiae, Streptococcus pneumoniae, Streptococcus pyogenes; Gram-negative microorganisms - Haemophilus influenzae, Haemophilus parainfluenzae; anaerobes - Fusobacterium spp., Peptostreptococcus spp., Prevotella spp., Propionibacterium acnes.

Microorganisms for which the problem of acquired resistance is relevant: Gram-negative microorganisms - Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii.

Microorganisms possessing natural resistance: Chlamydophila spp., Legionella spp. (Legionella), Mycoplasma spp. (mycoplasma), Pseudomonas aeruginosa.

Composition

Tseftarolina fosamyl acetate monohydrate + auxiliary substances.

Pharmacokinetics

The degree of binding of ceftaroline to plasma proteins is low (about 20%), the drug does not penetrate into the red blood cells. In plasma of blood under the influence of phosphatases, the prodrug of ceftaroline fosamil is rapidly converted to active ceftaroline, the concentration of the prodrug is amenable to measurement in plasma, mainly during intravenous infusion. In the hydrolysis of the beta-lactam ring of ceftaroline, a microbiologically inactive metabolite, ceftorolin M-1, is formed. Metabolism ceftarolina occurs without the participation of enzymes of the cytochrome P450 system. Ceftarolin is excreted mainly by the kidneys.

The pharmacokinetics of ceftaroline were similar in men and women. No dosage adjustment is required depending on the patient's sex.

Indications

Treatment for adults of the following infections:

• complicated skin and soft tissue infections caused by susceptible strains of the following Gram-positive and Gram-negative microorganisms: Staphylococcus aureus (including methicillin-sensitive and methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxyloca and Morganella morganii;
• Community-acquired pneumonia caused by susceptible strains of the following Gram-positive and Gram-negative microorganisms: Streptococcus pneumoniae (including cases accompanied by bacteremia), Staphylococcus aureus (methicillin-sensitive strains only), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli.

Forms of release

Powder for the preparation of concentrate for the preparation of solution for infusions (injections in ampoules, vials for injections).

Instructions for use and dosing regimen

Zinforo is administered intravenously in the form of infusion for 60 minutes.

The duration of therapy should be determined depending on the type and severity of the infection, the patient's response to therapy. The following dosing regimen is recommended:

• complicated skin and soft tissue infections - 600 mg every 12 hours for 5-14 days;
• Community-acquired pneumonia - 600 mg every 12 hours for 5-7 days.

Rules for the preparation of a solution for infusion

When preparing and administering the drug, you must follow the standard rules of asepsis. Each bottle is for single use only. Zinforo powder for the preparation of a concentrate for the preparation of a solution for infusion should be dissolved in 20 ml of sterile water for injection. 1 ml of concentrate contains 30 mg of ceftaroline fosamil. The resulting concentrate should be immediately used, not stored (the time from the beginning of the dissolution of the powder to the complete preparation of the solution for intravenous infusion should not exceed 30 minutes). To prepare the infusion solution, the resulting concentrate is shaken and transferred to an infusion bottle containing one of the following compatible infusion liquids: 9 mg / ml sodium chloride solution (0.9%) for injection, Dextrose solution 50 mg / ml (5%) for injection, solution of sodium chloride 4.5 mg / ml and a solution of dextrose 25 mg / ml for injection (0.45% sodium chloride solution and 2.5% dextrose solution), Ringer's lactate solution.

When using a dose of 600 mg in a bottle with a compatible infusion fluid, transfer the entire concentrate (20 ml), with a dose of 400 mg - 14 ml of concentrate.

The infusion solution can be prepared by adding the concentrate to a vial of an infusion fluid of 50 ml, 100 ml or 250 ml.

After preparing the solution for infusion, it should be used within 6 hours from the moment of preparation. The prepared infusion solution remains stable for 24 hours when stored in a refrigerator (2-8 ° C). After removal from the refrigerator, the infusion solution should be used for 6 hours at room temperature.

Unused product or waste must be disposed of in accordance with local regulations.

Side effect

• diarrhea, constipation;
• nausea, vomiting;
• abdominal pain;
• headache;
• dizziness;
• convulsions;
• rash;
• itching;
• hives;
• hepatitis;
• phlebitis;
• bradycardia;
• a feeling of palpitations;
• hyperglycemia;
• hypokalemia;
• fever;
• reactions at the site of infusion (erythema, phlebitis, pain);
• anemia, thrombocytopenia, eosinophilia, neutropenia;
• anaphylaxis;
• Colitis caused by Clostridium difficile;
• impaired renal function (increased concentration of blood creatinine).

Contraindications

• severe renal failure (QC less than 30 ml / min) or terminal stage of renal failure;
• children's age till 18 years;
• hypersensitivity to any antibacterial agent having a beta-lactam structure (eg, cephalosporins, penicillins or carbapenems);
• hypersensitivity to ceftaroline fosamyl or L-arginine.

Application in pregnancy and lactation

There are no clinical data on the use of ceftaroline in pregnant women. Animal studies did not reveal the adverse effects of ceftaroline fosamil on fertility, pregnancy, childbirth or post-natal development.

Zinforo should not be used during pregnancy, unless the potential benefit to the mother exceeds the possible risk to the fetus.

Data on the penetration of ceftaroline into breast milk are not available. However, due to the fact that many beta-lactam antibiotics are excreted in breast milk, if necessary, Zinforo therapy, it is recommended to stop breastfeeding.

Use in children

Safety and effectiveness of Zinforo in children under the age of 18 years are not established.

Application in elderly patients

There is no need to adjust the dose of the drug in elderly patients with CC greater than 50 ml / min.

special instructions

When using the drug should be guided by official recommendations for the proper use of antibacterial drugs.

Hypersensitivity reactions

As with all beta-lactam antibiotics, it is possible to develop serious hypersensitivity reactions (sometimes with a fatal outcome).

In patients with hypersensitivity to cephalosporins, penicillins or other beta-lactam antibiotics in an anamnesis, an allergic reaction to ceftarolin may also develop. Before starting therapy with Zinforo, a thorough examination of the patient should be conducted to identify hypersensitivity reactions to beta-lactam antibiotics.

With the development of a severe allergic reaction, it is necessary to stop the administration of the drug and take appropriate measures.

Diarrhea associated with Clostridium difficile

When using almost all antibacterial drugs, incl. drug Zinforo, reported the development of antibiotic-associated colitis and pseudomembranous colitis, which can vary in severity from the lungs to life-threatening forms.It should be taken into account the possibility of developing colitis in the occurrence of diarrhea against the background of the use of ceftaroline fosamil. In this case, it is necessary to stop Zinforo therapy, to carry out supportive measures and to prescribe a specific treatment for Clostridium difficile.

Patients with a history of convulsive syndrome

As with the use of other cephalosporins, the development of seizures was observed in studies of toxicity of ceftaroline when the drug was administered at doses exceeding Cmax 7-25 times. Experience in the use of ceftaroline in patients with convulsive syndrome in history is limited, and therefore caution should be used when using Zinforo in this group of patients.

Renal insufficiency

The experience with ceftaroline in patients with severe renal insufficiency and terminal stage of renal failure is limited. Therefore, the use of Zinforo in this population of patients is contraindicated.

Direct antiglobulin test (Coombs test)

A positive direct antiglobulin test (PAT) can be obtained against the background of the use of cephalosporins. The incidence of positive PAT in patients treated with ceftaroline was 10.7% in pooled Phase 3 studies.None of the patients with positive PAT on the background of the use of ceftaroline showed signs of hemolysis.

Impact on the ability to drive vehicles and manage mechanisms

There have been no studies to study the effect of Zinforo on the ability to drive vehicles and manage other mechanisms. During therapy, dizziness may occur, therefore, care should be taken when driving vehicles and when engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Drug Interactions

Clinical studies on the study of drug interaction with ceftaroline have not been conducted.

In in vitro studies, ceftaroline did not inhibit cytochrome P450 isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 and did not induce isoenzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP3A4 / 5. In this regard, the probability of interaction of ceftaroline with drugs that are metabolized by isoenzymes of the cytochrome P450 system is low. Zinforo is not metabolized by cytochrome P450 isoenzymes in vitro,therefore, it is unlikely that the parameters of the pharmacokinetics of ceftaroline will be influenced when combined with inducers or inhibitors of cytochrome P450 isoenzymes.

Tseftarolin is not tolerated by the efflux conveyors P-gp or BCRP. Tseftarolin does not inhibit P-gp, hence interaction with substrates such as Digoxin is not expected. Tseftorolin is a weak inhibitor of BCRP, but this effect has no clinical significance.

Studies have shown that ceftaroline is not a substrate, and does not inhibit the transport of organic cations (OCT2) and anions (OAT1, OAT3) in the kidneys; therefore, interaction with drugs that inhibit active renal secretion (eg, probenecid) or with preparations that are substrates of these transports is unlikely.

Interaction with other antibacterial drugs

The tests did not reveal antagonism in the joint use of ceftaroline and other commonly used antibacterial drugs (for example, amikacin, azithromycin, aztreonama, daptomycin, levofloxacin, linezolid, meropenem, tigecycline and vancomycin).

Analogues of the drug Zinforo

Structural analogues of the active substance antibiotic Zinforo does not. The active substance of the drug is unique at the time of the description in the reference book.

Analogues for the pharmacological group (cephalosporins):

• Azaran;
• Anceph;
• Biotrakson;
• Witsef;
• Duracif;
• Zinnat;
• Zolin;
• Iphietz;
• Ksorim;
• Ladef;
• Longacef;
• Mandol;
• Megion;
• Medaxone;
• Nacef;
• Ortaxime;
• Oframax;
• Panzef;
• Rocefin;
• Sephril;
• Soleksin;
• Spirozin;
• Sulperazone;
• Sulceph;
• Supraks;
• Tazyceph;
• Tertsef;
• Felaxin;
• Forcef;
• Tzedek;
• Cetax;
• Cefazolin;
• Cefaxon;
• Cephalexin;
• Cefamabol;
• Cefatrine;
• Cefepime;
• Ceforal Solutab;
• Cefotaxime;
• Ceftazidime;
• Ceftriabal;
• Ceftriaxone;
• Cefurabol;
• Cefuroxime;
• Epocelin;
• Etipim.

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