Zinforo concentrate powder for infusion solution 600mg vials, 10pcs

Composition

Active ingredient:

ceftaroline fosamil acetate monohydrate 668.4 mg;

Auxiliary substances:

L-arginine – 395 mg

Pharmacological action

Zinforo is an antibiotic of the Fifth generation cephalosporin group (anti-MRSA-Cefepimee).

After intravenous use, the ceftaroline prodrug fosamil is rapidly converted to active ceftaroline.

Mechanism of action

Ceftaroline is an antibiotic of the cephalosporin class with in vitro activity against gram-positive and gram-negative microorganisms. The bactericidal action of ceftaroline leads to inhibition of the biosynthesis of the bacterial cell wall, due to binding to penicillin-binding proteins (PSBs). Ceftaroline exhibits bactericidal activity against Staphylococcus aureus due to its high affinity for PSB 2A and against Streptococcus pneumoniae due to its high affinity for PSB 2 X.

Relationship between pharmacokinetics and Pharmacodynamics

The antibacterial activity of ceftaroline, as well as 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 > MIC).

Mechanism of resistance

Ceftaroline is not active against Enterobacteriaceae strains producing extended-spectrum beta-lactamases (ESBLs) of the TEM, SHV or CTX-M families, serine carbapenemases (such as CATTLE), class B or Class C metallo-beta-lactamases (AmpC cephalosporinases).

Cross-resistance

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

Sensitivity

The prevalence of acquired antibiotic resistance in certain microorganisms may vary depending on the region and time. It is recommended to take into account local information about resistance, especially in the treatment of severe infections. If local resistance is such that the effectiveness of the drug against certain infections becomes questionable, you should consult an expert.

Sensitivity to ceftaroline should be determined using standard methods. The results should be interpreted in accordance with local guidelines.

Indications

Treatment of the following infections in adults:

• complicated infections of skin and soft tissues 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 involving bacteremia), Staphylococcus aureus (only methicillin-susceptible strains), Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli.

Use during pregnancy and lactation

There are no clinical data on the use of ceftaroline fosamil in pregnant women. Experimental animal studies have not shown any adverse effects of ceftaroline fosamil on fertility, pregnancy, childbirth, or postpartum development.

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

There are no data on the penetration of ceftaroline into breast milk. However, due to the fact that many beta-lactam antibiotics are excreted in breast milk, if therapy with Zinforo is necessary, discontinuation of breastfeeding is recommended.

Contraindications

• severe renal insufficiency (creatinine clearance < 30 ml / min) or end-stage renal failure;
• children under 18 years of age;
• hypersensitivity to any antibacterial agent having a beta-lactam structure (for example, cephalosporins, penicillins or carbapenems);
• hypersensitivity to ceftaroline fosamil or L-arginine.

Caution should be exercised when prescribing the drug to patients with a history of convulsive syndrome.

Side effects

of the gastrointestinal tract:  diarrhea, nausea, vomiting, abdominal pain, constipation.

The nervous system:  headache, dizziness, convulsions.

Skin and subcutaneous tissues:  rash, itching, hives.

Liver and biliary tract:  increased transaminase activity, hepatitis.

Cardiovascular system:  phlebitis, bradycardia, palpitation.

Metabolism and nutrition:  hyperglycemia, hypokalemia, hyperkalemia.

General disorders and reactions at the injection site:  fever, infusion site reactions (erythema, phlebitis, pain).

Blood and lymphatic system:  anemia, thrombocytopenia, eosinophilia, neutropenia.

The immune system:  hypersensitivity/ anaphylaxis.

Infections and infestations:  colitis caused by Clostridium difficile.

Kidneys and urinary tract:  impaired renal function (increased blood creatinine).

Interaction

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

In vitro studies, ceftaroline did not inhibit the cytochrome P 450 isoenzymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4, nor did it induce the isoenzymes CYP1A2, CYP2B6, CYP2C8, CYP2C9, or CYP2C19. CYP3A4/5. In this regard, the probability of interaction of ceftaroline with drugs that are metabolized under the action of cytochrome P450 isoenzymes is low. Ceftaroline is not metabolized by cytochrome P450 isoenzymes in vitro, therefore, the effect on the pharmacokinetics of ceftaroline when co-administered with inducers or inhibitors of cytochrome P isoenzymes is unlikely. 450.

In In vitro ceftaroline is not transported by the efflux transporters P-gp or BCRP. Ceftaroline does not inhibit P-gp, so interaction with substrates such as digoxin is not expected. Ceftaroline is a weak inhibitor of BCRP, but this effect is not clinically significant.

In vitro studies have shown that ceftaroline is not a substrate, and does not inhibit transporters of organic cations (OST 2) and anions (OAT1, OAT3) in the kidneys; therefore, interaction with drugs that inhibit active renal secretion (for example, probenecid) or with drugs that are substrates of these transporters is unlikely.

Interaction with other antibacterial drugs

In vitro tests showed no antagonism when ceftaroline was co-administered with other commonly used antibacterial drugs (e. g., amikacin, azithromycin, aztreonam, daptomycin, levofloxacin, linezolid, meropenem, tigecycline, and vancomycin).

How to take, course of use and dosage

of Zinforo™ is administered intravenously as an infusion for 60 minutes.

The duration of therapy should be determined depending on the type and severity of infection, the patient’s response to therapy.

The following dosage 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.

Overdose

Overdose data is limited. Overdose is more likely in patients with impaired renal function. When using the drug at doses higher than recommended, the same adverse reactions were observed as when using the drug at the recommended doses.

Treatment: symptomatic. Ceftaroline is partially eliminated by hemodialysis.

Special instructions

When using the drug, it is necessary to follow the official recommendations for the proper use of antibacterial drugs.

Hypersensitivity reactions

As with all beta-lactam antibiotics, serious hypersensitivity reactions (sometimes fatal) may occur.

Patients with a history of hypersensitivity to cephalosporins, penicillins, or other beta-lactam antibiotics may also develop an allergic reaction to ceftaroline fosamil. Before starting therapy with Zinforo, the patient’s data should be carefully examined for hypersensitivity reactions to beta-lactam antibiotics. The drug is contraindicated in patients with a history of hypersensitivity to cephalosporins. The drug is also contraindicated in patients who have previously experienced severe hypersensitivity reactions of an immediate type (for example, anaphylactic reaction) to any other antibacterial agent with a beta-lactam structure (for example, penicillins or carbapenems).

If a severe allergic reaction develops, it is necessary to stop the use of the drug and take appropriate measures.

Clostridium difficile-associated diarrhea

Antibiotic-associated colitis and pseudomembranous colitis, which can range in severity from mild to life-threatening, have been reported with almost all antibacterial agents, including Zinforo. It is necessary to take into account the possibility of developing colitis if diarrhea occurs against the background of the use of ceftaroline fosamil. In this case, it is necessary to stop therapy with Zinforo, carry out maintenance measures and prescribe specific treatment for Clostridium difficile.

Patients with a history of convulsive syndrome

As with the use of other cephalosporins, studies on the toxicity of ceftaroline showed the development of seizures when taking the drug at doses exceeding the_cmax by 7-25 times. Experience with the use of ceftaroline in patients with a history of convulsive syndrome is limited, and therefore caution should be exercised when using the drug Zinforo in this group of patients.

Kidney failure

Experience with the use of ceftaroline in patients with severe renal insufficiency and end-stage renal failure and in patients undergoing hemodialysis is limited. Therefore, the use of the drug 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 fosamil was 10.7% in the combined phase 3 studies. No patients with positive PAT were found to show signs of hemolysis while using ceftaroline.

Insensitive microorganisms

When using ceftaroline fosamil, as with other antibiotics, superinfection may develop.

Influence on the ability to drive motor vehicles and manage mechanisms

No studies have been conducted to study the effect of the drug Zinforo on the ability to drive vehicles and manage other mechanisms. Dizziness may occur during therapy, so caution should be exercised when driving vehicles and when engaging in other potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions. If dizziness occurs, you should refrain from performing these activities.

Form of production

Powder for preparation of concentrate.

Storage conditions

Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

of Ceftaroline fosamil

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Indications

Pneumonia, Skin Infections