Zinforo
Zinforo: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Zinforo
ATX code: J01DI02
Active ingredient: Ceftaroline fosamil (Ceftaroline fosamil)
Manufacturer: ASTRAZENECA UK Limited (Great Britain)
Description and photo update: 2018-04-07
Zinforo is a cephalosporin antibiotic.
Release form and composition
Dosage form - powder for the preparation of a concentrate for the preparation of a solution for infusion: from yellowish-white to light yellow (600 mg each in transparent glass vials with a volume of 20 ml, 1 or 10 vials are packed in a cardboard box with first opening control).
Active ingredient: ceftaroline fosamil (in the form of acetate monohydrate) - 600 mg.
L-arginine is used as an auxiliary component.
Pharmacological properties
Pharmacodynamics
The prodrug of ceftaroline fosamil, after intravenous (iv) administration, is rapidly converted into active ceftaroline, which is an antibiotic from the group of cephalosporins that is active against gram-positive and gram-negative microorganisms. According to in vitro studies, the bactericidal effect of the substance is due to inhibition of the biosynthesis of the bacterial cell wall due to binding to penicillin-binding proteins (PBPs).
The bactericidal activity of ceftaroline was noted against penicillin-insensitive Streptococcus pneumoniae (PNSP) and methicillin-resistant Staphylococcus aureus (MRSA), which is associated with its high affinity for the altered PSP of these strains.
The antimicrobial property of the active ingredient Zinforo is best correlated with the period of time during which the concentration of ceftaroline remains above the minimum inhibitory concentration of the infecting bacteria.
Ceftaroline is not active against Enterobacteriaceae microorganisms producing extended spectrum beta-lactamases (ESBLs) of the TEM, SHV or CTX-M families, metallo-beta-lactamases of classes B and C (cephalosporinases AmpC), and serine carbapenemases (such as cattle). Resistance can be caused by a violation of the permeability of the bacterial cell wall or efflux (active elimination of the antibiotic). A microorganism can have both one mechanism of resistance, and several.
Despite the potential for cross-resistance, some strains resistant to other cephalosporins can be susceptible to ceftaroline.
Microorganisms that have natural resistance: Mycoplasma spp., Proteus spp., Legionella spp., Chlamydophila spp. and Pseudomonas aeruginosa.
In vitro studies have not revealed antagonism while using ceftaroline in combination with other commonly prescribed antimicrobial agents, such as levofloxacin, aztreonam, meropenem, azithromycin, amikacin, vancomycin, linezolid, daptomycin, tigecycline.
In vitro sensitivity of ceftaroline, like other antibiotics, can change over time and depending on the geographic region, so local resistance information should be taken into account when choosing the optimal antibiotic therapy.
In cases where, taking into account local resistance, the effectiveness of Zinforo against certain microorganisms is assessed as doubtful, it is necessary to consult with the appropriate specialist. Ceftaroline susceptibility is determined using standard methods, and interpretation of results is carried out in accordance with local guidelines.
In clinical studies, the efficacy of ceftaroline has been established against the following pathogenic bacteria: Streptococcus dysgalactiae, Streptococcus pyogenes, Staphylococcus aureus (including methicillin-resistant strains), Streptococcus agalactiae, Streptococcus anginosus group (also includes Streptococcus aginosus (also includes Streptococcus aginosus) susceptible strains), Streptococcus pneumoniae (including infections accompanied by bacteremia), Klebsiella pneumoniae, Escherichia coli, Morganella morganii, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Haemophilus parainfluenzae, microorganisms gram-positive microorganisms, gram-positive microorganisms, gram-positive microorganisms, Haemophilus influenzae and soft tissues.
With regard to the following pathogenic microorganisms, the clinical efficacy of the active substance Zinforo has not been established, however, according to the results of in vitro studies, it was found that they do not have acquired resistance mechanisms, therefore there is reason to assume their sensitivity to ceftaroline: Fusobacterium spp., Peptostreptococcus spp., Gram-positive and gram-negative anaerobes.
Pharmacokinetics
With a single administration of Zinforo in the dose range from 50 to 1000 mg, the maximum concentration (C max) and the area under the concentration-time curve (AUC) of the drug increase almost proportionally to the dose. There was no noticeable cumulation of the active substance after its repeated intravenous administration to healthy volunteers with normal renal function at a dose of 600 mg for 60 minutes at intervals of 12 hours for a course of 14 days.
The degree of binding of the drug to plasma proteins is approximately 20%, ceftaroline does not penetrate into erythrocytes. After a single intravenous injection of 600 mg of isotope-labeled ceftaroline fosamil in healthy adult men, the median volume of distribution in the equilibrium state was 20.3 liters, almost the same as the volume of extracellular fluid.
The prodrug of ceftaroline fosamil under the action of phosphatases in the blood plasma is rapidly converted to active ceftaroline. Ceftaroline fosamil concentrations can be measured in plasma primarily at the time of intravenous administration.
The hydrolysis of the beta-lactam ring of ceftaroline produces ceftaroline M-1, a microbiologically inactive metabolite. After a single intravenous injection of ceftaroline fosamil to healthy volunteers at a dose of 600 mg, the ratio of the mean AUC values of ceftaroline M-1 to ceftaroline in blood plasma is about 20-30%.
Ceftaroline is metabolized without the participation of cytochrome P 450 isoenzymes.
The substance is excreted mainly by the kidneys. Its renal clearance is equal to or slightly lower than the glomerular filtration rate in the kidneys. According to in vitro studies of transporters, active secretion does not enhance renal excretion of ceftaroline.
The half-life of a substance in healthy adults averages 2.5 hours. After a single intravenous injection of isotope-labeled ceftaroline fosamil in adult men at a dose of 600 mg, about 88% of radioactivity is found in urine, about 6% in feces.
Special patient groups
After a single intravenous injection of the drug at a dose of 600 mg for 60 minutes in patients with normal renal function, mild renal failure and moderate renal failure C maxCeftaroline in plasma is reached approximately 60 minutes after the start of the infusion and is 28.4 ± 6.9 μg / ml, 28.2 ± 5.4 μg / ml and 30.8 ± 4.9 μg / ml, respectively. AUC increases in proportion to the degree of renal failure and is 75.6 ± 9.7 μg * h / ml, 92.3 ± 25.3 μg * h / ml and 114.8 ± 14.1 μg * h / ml, respectively. Patients with moderate renal failure [creatinine clearance (CC) 30–50 ml / min] require dose adjustment of Zinforo. There are insufficient data for recommendations for the correction of the dosage regimen in severe renal failure (CC <30 ml / min) and end-stage renal failure, including in hemodialysis.
Pharmacokinetic studies of ceftaroline in patients with hepatic insufficiency have not been conducted. Considering the fact that the substance is not significantly hepatic metabolized, it is assumed that hepatic impairment does not significantly affect the systemic clearance of ceftaroline. In this regard, there is no need to adjust the dose for this category of patients.
The pharmacokinetic parameters of the drug after a single intravenous injection at a dose of 600 mg in healthy elderly people (over the age of 65) and healthy young people (at the age of 18–45) are similar. In elderly patients, there is a slight (33%) increase in AUC o -∞, which is primarily due to age-related changes in the kidneys. No dose adjustment is required in patients with CC> 50 ml / min.
The pharmacokinetic parameters of ceftaroline are similar in women and men, and there are also no significant differences in patients belonging to different ethnic groups. In this regard, dose adjustment depending on gender and race is not required.
Indications for use
- complicated infections of the skin and soft tissues caused by susceptible strains of gram-positive and gram-negative microorganisms such as Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Morganella morganii, Streptococcus anginosus, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus dysgalactia;
- community-acquired pneumonia caused by susceptible strains of gram-positive and gram-negative microorganisms, such as Klebsiella pneumoniae, Haemophilus parainfluenzae, Haemophilus influenzae, Escherichia coli, methicillin-susceptible strains of Staphylococcus aureus, Streptococcus pneumoniae (including infections, Streptococcus pneumonia)
Contraindications
- severe renal failure (CC <30 ml / min), end-stage renal failure; also the drug is contraindicated in patients on hemodialysis;
- severe immediate hypersensitivity reactions (for example, anaphylaxis) to any other antibiotic with a beta-lactam structure (for example, carbapenems, penicillins);
- age up to 18 years;
- hypersensitivity to ceftaroline fosamil, L-arginine or other cephalosporins.
The drug should be used with caution in patients with a history of convulsive symptoms.
Instructions for use of Zinforo: method and dosage
According to the instructions, Zinforo is administered at 600 mg intravenously as a long (60 minutes) infusion 2 times a day at intervals of 12 hours.
The duration of treatment is determined individually, depending on the indications, the severity of the course of the infection and the patient's response to the therapy. As a rule, the treatment of complicated infections of the skin and soft tissues takes 5-14 days, community-acquired pneumonia - 5-7 days.
With a CC of 30-50 ml / min, Zinforo is administered at 400 mg IV as a 60-minute infusion every 12 hours.
Preparation of solution for infusion
Each vial of Zinforo is to be used for single use only.
When preparing and administering the solution, the standard aseptic rules are followed.
To obtain a concentrate, the powder is dissolved in 20 ml of sterile injection water. Externally, the concentrate is a solution free from visible particles, pale yellow in color. 1 ml of the resulting concentrate contains 30 mg of ceftaroline fosamil. It cannot be stored and must be used immediately: the time from the beginning of the dissolution of the powder to the complete preparation of the solution for infusion should not exceed 30 minutes. To prepare the infusion solution, the resulting concentrate must be shaken and transferred to an infusion bottle with one of the following liquids: Ringer's lactate solution, 5% dextrose solution, 0.9% sodium chloride solution, 0.45% sodium chloride solution with 2.5% dextrose solution … The volume of the infusion solution is 50 ml, 100 ml or 250 ml.
When prescribing ceftaroline at a dose of 600 mg, the entire concentrate (20 ml) is transferred into the vial, when a dose of 400 mg is prescribed, 14 ml of the concentrate is transferred.
The ready-to-administer infusion solution should be used within 6 hours after preparation. It must be stored for 24 hours in the refrigerator (temperature - 2-8 ° C). Once removed from the refrigerator, the solution can be used within 6 hours if stored at room temperature.
Unused product or residues must be disposed of in accordance with local regulations.
Side effects
Side effects are presented in accordance with the following gradation: very often -> 1/10, often - from> 1/100 to <1/10, infrequently - from> 1/1000 to 1/10 000 to <1/1000.
Possible adverse reactions:
- laboratory indicators: very often - positive direct Coombs' test; infrequently - an increase in the international normalized ratio, lengthening of the activated partial thromboplastin time, lengthening of the prothrombin time;
- gastrointestinal tract: often - abdominal pain, nausea, diarrhea, constipation, vomiting;
- nervous system: often - dizziness, headache; infrequently - convulsions;
- cardiovascular system: often - bradycardia, phlebitis; infrequently - palpitations;
- liver and biliary tract: often - increased activity of transaminases; infrequently - hepatitis;
- blood and lymphatic system: infrequently - leukopenia, anemia, thrombocytopenia; rarely - eosinophilia, neutropenia;
- skin and subcutaneous tissues: often - rash, itching; infrequently - urticaria;
- kidneys and urinary tract: infrequently - increased blood creatinine concentration;
- metabolism and nutrition: often - hypokalemia, hyperglycemia; infrequently - hyperkalemia;
- immune system: infrequently - hypersensitivity reactions, anaphylaxis;
- infections and infestations: infrequently - colitis caused by Clostridium difficile.
Overdose
Data on cases of ceftaroline overdose are limited. The likelihood of overdose is higher in patients with impaired renal function. At the same time, in the case of using Zinforo in doses exceeding the recommended ones, the development of similar adverse reactions was observed, as with the use of the drug in the recommended doses. Overdose treatment is symptomatic. Ceftaroline can be partially removed by hemodialysis.
special instructions
Like other beta-lactam antibiotics, ceftaroline can cause severe, sometimes fatal hypersensitivity reactions. In patients with a history of hypersensitivity to penicillins, cephalosporins or other beta-lactam antibiotics, an allergic reaction to ceftaroline fosamil may develop. For this reason, before prescribing Zinforo, it is necessary to carefully study the patient's history in order to identify adverse reactions of hypersensitivity, in case of their presence, it is contraindicated to prescribe the drug. Also, the drug should not be prescribed to patients who have experienced severe allergic reactions of an immediate type (for example, anaphylactic) to any other antibiotic with a beta-lactam structure (for example, a drug of the penicillin or carbapenem group).
In case of severe allergic reactions during the infusion, the drug should be stopped immediately and appropriate measures taken.
Zinforo, like almost all antibacterial drugs, can cause the development of pseudomembranous colitis and colitis associated with antibiotic therapy, which can range in severity from mild to life-threatening forms. In case of diarrhea while using the drug, the likelihood of developing colitis must be taken into account. In this case, it is necessary to stop the administration of the drug, prescribe a specific treatment for Clostridium difficile and carry out supportive measures.
Against the background of the use of cephalosporins, it is possible to obtain a positive direct antiglobulin test (PAT). In patients treated with ceftaroline, the rate of positive PAT was 10.7%, but none of the patients showed signs of hemolysis.
When using Zinforo, the development of superinfection is possible.
Influence on the ability to drive vehicles and complex mechanisms
Studies on the effect of ceftaroline fosamil on the ability to concentrate and reaction rate have not been conducted. Given the likelihood of dizziness during therapy, it is recommended to be careful when driving and engaging in any other activities that require speed of psychophysical reactions and increased attention. If this side effect occurs, you must refrain from these activities.
Application during pregnancy and lactation
There are no clinical data on the use of ceftaroline in pregnant women. Animal studies have shown adverse effects of the drug on fertility, pregnancy, delivery and postpartum development. In this regard, Zinforo is contraindicated during pregnancy, except in cases of urgent need, when the benefits to the woman significantly outweigh the possible risks to the fetus.
It is not known whether ceftaroline passes into breast milk, but many other beta-lactam antibiotics have been found to be excreted in milk. For this reason, if it is necessary to carry out therapy during lactation, it is recommended to stop breastfeeding.
Pediatric use
Due to the fact that the efficacy and safety of Zinforo in children and adolescents under the age of 18 have not been established, the drug is not prescribed for this age category.
With impaired renal function
The drug is contraindicated in people with severe renal failure (CC ≤ 30 ml / min), in patients with end-stage renal failure and in patients on hemodialysis.
For patients with CC 30-50 ml / min, the dose of Zinforo is reduced to 400 mg, the drug is administered for 60 minutes every 12 hours.
For violations of liver function
There is no need to adjust the dose for liver failure.
Use in the elderly
Elderly people (over 65 years old), provided CC> 50 ml / min, do not adjust the dose.
Drug interactions
Clinical studies to study drug interactions of ceftaroline with other drugs have not been conducted.
According to in vitro studies, ceftaroline does not inhibit cytochrome P450 isoenzymes CYP3A4, CYP2C8, CYP2B6, CYP2C9, CYP2A6, CYP2C19, CYP2E1, CYP1A2, CYP1A1, CYP2D6, does not induce CYPC8 isoenzymes, CYP2B2, CYP2D6, CYPA5 For this reason, the likelihood of Zinforo interaction with drugs that are metabolized with the participation of isoenzymes of the cytochrome P 450 system is low.
The effect on the parameters of the pharmacokinetics of ceftaroline of simultaneously used inducers or inhibitors of cytochrome P 450 isoenzymes is unlikely, since ceftaroline is not metabolized by their action in vitro.
Ceftaroline is a weak BCRP inhibitor, but this effect is not clinically relevant.
In vitro, ceftaroline has been shown not to be transported by the efflux transporters P-gp or BCRP. It does not inhibit P-gp, so its interaction with substrates such as digoxin is not expected.
According to in vitro studies, ceftaroline is not a substrate; it does not inhibit transporters of organic cations (OCT2) and anions (OAT1, OATZ) in the kidneys. In this regard, the interaction of Zinforo with drugs that inhibit active renal secretion (for example, probenecid), or drugs that are substrates of these transporters, seems unlikely.
In vitro tests did not reveal antagonism in the combined use of ceftaroline with other commonly used antibacterial agents, such as aztreonam, levofloxacin, amikacin, daptomycin, meropenem, vancomycin, tigecycline, linezolid, azithromycin.
Analogs
There is no information about Zinforo analogues.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° С out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Zinforo
There are no reviews about Zinforo.
Price for Zinforo in pharmacies
The price for Zinforo varies from 27,640 to 31,000 rubles for a pack of 10 bottles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
