Cefilavancin (Lyophilisate) Instructions for Use

Marketing Authorization Holder

R-Pharm JSC (Russia)

Manufactured By

Deko Company, LLC (Russia)

ATC Code

J01XX (Other antibacterial drugs)

Active Substance

Cefilavancin (Rec.INN registered by WHO)

Dosage Form

Cefilavancin

Lyophilizate for solution for infusion 100 mg

Dosage Form, Packaging, and Composition

Lyophilizate for the preparation of a concentrate for the preparation of a solution for infusion

100 mg – vials – cardboard packs – By prescription

Clinical-Pharmacological Group

Antibacterial drug

Pharmacotherapeutic Group

Systemic antibacterial agents; other antibacterial agents

Pharmacological Action

Cefilavancin is a bactericidal multivalent antibiotic, a selective inhibitor of bacterial cell wall biosynthesis.

It is a heterodimer of a glycopeptide and a cephalosporin, in which vancomycin is attached to the cephalosporin core via a chemically stable linker.

Each of its subunits has its own target in the synthesis of the bacterial cell membrane, namely D-Ala-D-Ala-containing peptidoglycan precursors and the activity centers of transpeptidases in penicillin-binding proteins, which leads to a potent effect against gram-positive bacteria, including polyresistant strains.

Cefilavancin has a broad spectrum of in vitro activity against gram-positive pathogens.

The in vitro activity of cefilavancin is due to a unique multivalent mechanism of action, which contributes to increased activity and a low potential for the selection of resistant mutants of gram-positive bacteria.

The antibacterial activity of cefilavancin is largely independent of coexisting resistance mechanisms, including methicillin/oxacillin resistance in staphylococci, penicillin resistance in pneumococci, fluoroquinolone resistance in streptococci, and quinupristin/dalfopristin resistance in several tested species.

Cefilavancin exhibits bactericidal activity at low MICs against staphylococci in vitro.

It has a long post-antibiotic effect ranging from 2.2 to 2.7 hours against Staphylococcus aureus.

The following are sensitive to cefilavancin: oxacillin-sensitive Staphylococcus aureus, oxacillin-resistant Staphylococcus aureus, oxacillin-sensitive coagulase-negative Staphylococcus spp., oxacillin-sensitive coagulase-positive Staphylococcus spp., vancomycin-sensitive Enterococcus faecalis.

Clinical studies have demonstrated eradication of the following microorganisms: Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, Finegoldia magna, Peptococcus spp., Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus, Streptococcus dysgalactiae, Streptococcus intermedius, Streptococcus mitis, Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus viridans.

Pharmacokinetics

Cefilavancin is moderately bound to plasma proteins (44-57%).

The pharmacokinetics of cefilavancin after multiple intravenous administrations to healthy volunteers were dose-independent.

The data obtained indicated no accumulation of cefilavancin in the body: the ratio of mean AUC_0-24 on Day 14 to AUC_0-24 on Day 1 ranged from 1.10 to 1.17.

When comparing (for each individual dose) the pharmacokinetic profiles obtained on Day 1 with the profiles obtained on Day 14, no significant changes in C_max and AUC were found with repeated use of cefilavancin at doses of 0.5, 1.0, 2.0 and 3.0 mg/kg.

At a concentration of 30 µM (60 µg/ml), Cefilavancin was resistant to metabolic effects by plasma, liver microsomes, and hepatocytes of rats, dogs, and humans.

The main route of elimination of cefilavancin after intravenous administration is expected to be renal excretion.

However, the mean amount of cefilavancin excreted in urine, as a percentage of the dose, ranged from 30.1 to 49.4% in the single-dose study and from 26.2 to 51.8% in the single- and multiple-dose study.

Cefilavancin plasma exposure increases linearly with increasing dose.

Indications

Treatment of complicated skin and soft tissue infections caused by Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, Finegoldia magna, Peptococcus spp, Staphylococcus aureus (including MRSA), Staphylococcus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus anginosus, Streptococcus dysgalactiae, Streptococcus intermedius, Streptococcus mitis, Streptococcus pyogenes, Streptococcus sanguinis, Streptococcus viridans, susceptible to cefilavancin.

ICD codes

Dosage Regimen

Treatment with cefilavancin should be carried out under the direct supervision of a physician experienced in the treatment of complicated skin and soft tissue infections.

Intravenously as an infusion. Infusion duration – 2 hours.

The recommended dose for adults is 1 mg/kg once daily.

The maximum single dose for adults is 1 mg/kg, including patients with excess body weight.

Duration of treatment from 5 to 14 days.

Adverse Reactions

Psychiatric disorders Common – insomnia.

Nervous system disorders Very common – headache; Common – dysgeusia; Uncommon – dizziness, paresthesia.

Ear and labyrinth disorders Uncommon – vertigo, tinnitus, hypoacusis.

Cardiac and vascular disorders Common – tachycardia, arterial hypertension, phlebitis.

Respiratory, thoracic and mediastinal disorders Common – cough.

Gastrointestinal disorders Common – nausea, diarrhea, vomiting; Uncommon – abdominal pain, dyspepsia, flatulence, oral hypoesthesia.

Skin and subcutaneous tissue disorders Common – pruritus; Uncommon – rash, red neck syndrome ("red man" syndrome).

Musculoskeletal and connective tissue disorders Common – limb pain.

General disorders and administration site conditions Very common – infusion site reactions; Common – infusion site phlebitis, feeling hot; Uncommon – pyrexia, chills.

Investigations Common – increased blood ALT, increased blood AST, increased blood potassium; Uncommon – increased blood alkaline phosphatase, increased blood LDH.

Contraindications

Hypersensitivity to cefilavancin; pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Studies of cefilavancin in patients with impaired liver function have not been conducted.

Caution should be exercised in patients with pre-existing liver function impairment.

Such patients are recommended to undergo careful monitoring of liver function parameters during cefilavancin use.

Use in Renal Impairment

In mild renal impairment (GFR >60 ml/min/1.73 m²), no dose adjustment is required.

In moderate (GFR 30-60 ml/min/1.73 m²) and severe impairment (GFR 15-29 ml/min/1.73 m²), a 30% dose reduction is recommended.

Pediatric Use

The safety and efficacy of cefilavancin in children aged 0 to 18 years have not been established to date. Data are not available.

Geriatric Use

There are no data on the use of cefilavancin in elderly patients.

Special Precautions

Caution should be exercised during the first infusions of cefilavancin.

Before starting treatment, a detailed history of previous hypersensitivity reactions to cephalosporins, penicillins, vancomycin, teicoplanin and other drugs should be collected.

Particular attention should be paid to patients with a previous non-severe allergic reaction to beta-lactam antibiotics or glycopeptides.

If an allergic reaction develops during treatment, the drug should be discontinued immediately; in severe cases, the use of epinephrine, hydrocortisone, antihistamines or other emergency measures may be required.

Administration of cefilavancin should be performed in the presence of drugs and equipment to provide treatment for anaphylactic and anaphylactoid reactions.

During clinical studies of cefilavancin, cases of mild increases in transaminase activity were recorded.

Studies of cefilavancin in patients with impaired liver function have not been conducted.

Caution should be exercised in patients with pre-existing liver function impairment.

Such patients are recommended to undergo careful monitoring of liver function parameters during cefilavancin use.

The use of cefilavancin should be avoided in patients with pre-existing hearing loss, as well as the concomitant use of cefilavancin with other drugs that have ototoxic effects (such as aminoglycosides).

To reduce the risk of ototoxicity, periodic hearing examination is recommended.

Elderly people are particularly susceptible to hearing damage.

Monitoring of vestibular and auditory function in the elderly is recommended during and after treatment.

Rapid bolus administration of antibacterial drugs of the glycopeptide class may be associated with severe arterial hypotension, shock and, in rare cases, cardiac arrest.

Cefilavancin should be administered slowly in a diluted solution, observing the recommended infusion duration of 2 hours to avoid infusion reactions.

Discontinuation of glycopeptide administration usually leads to rapid resolution of these reactions.

The frequency of infusion reactions increases with increasing doses of glycopeptides and with simultaneous administration of anesthetics.

If anesthesia is necessary, it is recommended to complete the cefilavancin infusion at least 60 minutes before the induction of anesthesia.

Caution should be exercised when using cefilavancin in patients with pre-existing renal impairment and renal function should be monitored during therapy.

As with treatment with other broad-spectrum antibiotics, resistance may develop in some initially susceptible strains of microorganisms when using cefilavancin, therefore it is recommended to periodically test for antibiotic susceptibility during treatment.

Long-term use of antibiotics may lead to an increase in the growth of non-susceptible microorganisms and the development of superinfection.

Drug Interactions

Possible interaction with antiarrhythmic drugs should be considered.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.