Libakcil (Powder) Instructions for Use

Marketing Authorization Holder

Abolmed, LLC (Russia)

ATC Code

J01CR01 (Ampicillin and beta-lactamase inhibitor)

Active Substances

Ampicillin (Rec.INN registered by WHO)

Sulbactam (Rec.INN registered by WHO)

Dosage Forms

	Libakcil	Powder for preparation of solution for intravenous and intramuscular administration 1 g+500 mg: vial 1 pc.
		Powder for preparation of solution for intravenous and intramuscular administration 2 g+1g: vial 1 pc.
		Powder for preparation of solution for intravenous and intramuscular administration 500 mg+250 mg: vial 1 pc.

Dosage Form, Packaging, and Composition

Vials (1) – carton packs.

Vials (1) – carton packs.

Vials (1) – carton packs.

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Antibiotic, semi-synthetic penicillin + beta-lactamase inhibitor

Pharmacological Action

Libakcil is an antibiotic representing a combination of the semi-synthetic aminopenicillin ampicillin and the beta-lactamase inhibitor sulbactam.

Ampicillin is a broad-spectrum bactericidal antibiotic. The bactericidal action of ampicillin is due to irreversible binding to bacterial transpeptidases involved in the biosynthesis of glycopeptides, the main component of the bacterial cell wall. Ampicillin is destroyed by beta-lactamases, enzymes produced by microorganisms, which significantly limits its spectrum of action. Sulbactam is a derivative of the basic penicillin nucleus. Sulbactam does not possess clinically significant antibacterial activity (with the exception of Neisseriaceae, Acinetobacter spp.), but is an irreversible inhibitor of most major bacterial beta-lactamases (including plasmid beta-lactamases) that destroy penicillins and cephalosporins and determine microbial resistance to beta-lactam antibiotics. Therefore, Libakcil acquires the ability to act on strains resistant (producing beta-lactamases) to ampicillin.

Active against gram-positive aerobes Staphylococcus aureus (beta-lactamase producing and non-producing strains), Staphylococcus epidermidis (beta-lactamase producing and non-producing strains), Staphylococcus saprophyticus (beta-lactamase producing and non-producing strains), Enterococcus faecalis, Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes. Streptococcus spp. of the viridans group, Listeria monocytogenes; gram-negative aerobes: Hemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis (beta-lactamase producing and non-producing strains), Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Morganella morganii, Neisseria gonorrhoeae (beta-lactamase producing and non-producing strains); clinically significant anaerobes: Clostridium spp. (except Clostridium difficile), Peptococcus spp., Peptostreptococcus spp., Bacteroides spp., including Bacteroides fragilis.

Resistant methicillin-resistant Staphylococcus spp., most strains of Enterobacter spp., Citrobacter spp., Pseudomonas aeruginosa, Mycobacterium spp., Clostridium difficile, Chlamydia spp. and mycoplasmas.

Pharmacokinetics

C_max of ampicillin and sulbactam after IV administration of 1.5 g and 3.0 g of the drug range from 40 µg/ml to 71 µg/ml and from 109 µg/ml to 150 µg/ml for ampicillin, from 21 µg/ml to 40 µg/ml and from 48 µg/ml to 88 µg/ml for sulbactam, respectively. After IM injection of 1.5 g ampicillin+sulbactam, C_max of ampicillin varies from 8 µg/ml to 37 µg/ml, C_max of sulbactam – from 6 µg/ml to 24 µg/ml. The degree of binding to plasma proteins is 28% for ampicillin and 38% for sulbactam. Both components of the drug penetrate well and are distributed in many organs, tissues and body fluids. Therapeutic concentrations after IV and IM administration are achieved in peritoneal and pleural fluids, interstitial fluid, intestinal wall, pelvic organs, skin and subcutaneous tissue. They penetrate poorly through the blood-brain barrier, the permeability of which increases with inflammation of the meninges. T_1/2 of ampicillin and sulbactam is about 1 hour. Both components of the drug are excreted primarily by the kidneys unchanged. From 75% to 85% of the administered dose of ampicillin and sulbactam are excreted by the kidneys within the first 8 hours. In patients with impaired renal function, T_1/2 of the drug components increases, which requires adjustment of doses and administration regimens.

Indications

Bacterial infections of various locations of moderate and severe severity caused by susceptible microorganisms

• Infections of the ENT organs (including sinusitis, tonsillitis, otitis media);
• Respiratory tract infections (including pneumonia, lung abscess, infected bronchiectasis, acute and exacerbation of chronic bronchitis, pleural empyema);
• Bacterial meningitis;
• Infectious endocarditis;
• Uncomplicated and complicated abdominal infections (cholecystitis, cholangitis, peritonitis, abdominal abscess);
• Urinary tract infections (acute and exacerbation of chronic pyelonephritis, pyelitis);
• Skin and soft tissue infections (erysipelas, phlegmon, wound and postoperative infections);
• Infectious and inflammatory diseases of the pelvic organs (salpingitis, endometritis, tubo-ovarian abscess, pelvic peritonitis);
• Bone and joint infections;
• Sepsis;
• Gonococcal infection.
• Prevention of postoperative complications in operations on the abdominal and pelvic organs.

ICD codes

Dosage Regimen

Libakcil is administered IV and IM. The method of administration depends on the severity of the infection and the chosen dose.

In adults, for treatment of moderate infections, administer 1.5 g every 6 hours IV or IM. For severe infections – 3 g every 6 hours. The maximum daily dose of sulbactam should not exceed 4 g, which corresponds to a daily dose of Libakcil of 12 g.

Typically, treatment is continued for another 48 hours after normalization of body temperature and disappearance of other symptoms of infection. The duration of the course of therapy is from 5 to 14 days, however, in more severe cases it can be extended or Ampicillin can be additionally prescribed.

In children from 1 month to 12 years (or weighing up to 40 kg), Libakcil for mild and moderate infections is administered at a dose of 150 mg/kg/day, divided into 3-4 administrations. For the treatment of severe infections, the dose is increased to 300 mg/kg/day. Usually, the course of treatment with Libakcil should not exceed 14 days.

In premature newborns and children of the first week of life, the daily dose of Libakcil^® is 75 mg/kg, divided into 2 IV administrations.

In children aged from 7 days to 28 days, it is prescribed at a dose of 150 mg/kg/day, divided into 3 IV injections.

For perioperative prophylaxis of surgical infections, Libakcil is administered IV at a dose of 1.5-3 g along with premedication or induction anesthesia; if necessary, additionally administered at the same dose every 6-8 hours for 24 hours after surgery.

In patients with renal failure, due to the slowed elimination of the drug components, it is necessary to increase the intervals between administrations,

In children with renal failure (creatinine clearance less than 30 ml/min/1.73 m²), administer at usual single doses (50-75 mg/kg), increasing the intervals between administrations as indicated for adults.

Rules for preparation of solution and administration

For preparation of solution for IM administration, use sterile water for injections, 0.5% procaine solution, 0.5% or 2% lidocaine solutions as a solvent. Add 2.0 ml to a vial containing 750 mg of the drug, 1.5 g – 4 ml of solvent.

For IV bolus administration: add 10-15 ml of water for injections, 0.9% sodium chloride solution to a vial containing 750 mg or 1.5 mg of Libakcil. Administer IV slowly over 3-5 minutes.

For IV drip administration: dissolve 1.5-3.0 g of the drug in 15 ml of water for injections, then add the resulting solution to 150-250 ml of 0.9% sodium chloride solution or 5% dextrose solution and administer at a rate of 60-80 drops per minute.

Adverse Reactions

From the digestive system nausea, vomiting, decreased appetite, diarrhea, increased activity of hepatic transaminases; rarely – pseudomembranous colitis.

From the hematopoietic system hemolytic anemia, thrombocytopenia, eosinophilia, leukopenia, false-positive Coombs test.

From the nervous system drowsiness, headache.

From laboratory parameters azotemia, increased urea concentration, hypercreatininemia.

Allergic reactions urticaria, skin hyperemia, skin itching, angioedema, rhinitis, conjunctivitis, fever, arthralgia, in rare cases – anaphylactic shock, Stevens-Johnson syndrome, toxic epidermal necrolysis, multiform exudative erythema.

Local reactions with IM administration – pain at the injection site; with IV – phlebitis.

Other malaise, with prolonged treatment – superinfection caused by microorganisms resistant to the drug (candidiasis).

Contraindications

• Infectious mononucleosis;
• Lymphocytic leukemia;
• Hypersensitivity to any component of the drug and other penicillins.

The safety of using ampicillin/sulbactam in patients with end-stage chronic renal failure (creatinine clearance less than 5 ml/min/1.73m²) has not been established.

With caution bronchial asthma, hay fever and other allergic diseases, hypersensitivity to cephalosporin antibiotics and carbapenems, history of chronic gastrointestinal diseases, as well as previously transferred antibiotic-associated colitis, hepatic insufficiency, severe renal impairment.

Use in Pregnancy and Lactation

During pregnancy, it is prescribed in cases where the intended benefit to the mother outweighs the possible risk to the fetus.

Ampicillin and Sulbactam pass into breast milk in low concentrations. If it is necessary to use the drug during lactation, the issue of discontinuing breastfeeding should be decided.

Use in Hepatic Impairment

The drug should be prescribed with caution in hepatic insufficiency.

Use in Renal Impairment

The safety of using ampicillin/sulbactam in patients with end-stage chronic renal failure (creatinine clearance less than 5 ml/min/1.73m²) has not been established, therefore the use of the drug is contraindicated.

With caution: severe renal impairment.

In patients with renal failure, due to the slowed elimination of the drug components, it is necessary to increase the intervals between administrations,

In children with renal failure (creatinine clearance less than 30 ml/min/1.73 m²), administer at usual single doses (50-75 mg/kg), increasing the intervals between administrations as indicated for adults.

Pediatric Use

In children from 1 month to 12 years of age (or with a body weight up to 40 kg), Libakcil is administered at a dose of 150 mg/kg/day for mild to moderate infections, divided into 3-4 administrations. For the treatment of severe infections, the dose is increased to 300 mg/kg/day. Usually, the course of treatment with Libakcil should not exceed 14 days.

In premature newborns and children in the first week of life, the daily dose of Libakcil^® is 75 mg/kg, divided into 2 intravenous administrations.

In children from 7 days to 28 days of age, it is prescribed at a dose of 150 mg/kg/day, divided into 3 intravenous injections.

Special Precautions

Libakcil is a drug for monotherapy of most mixed infections. When a chlamydial and mycoplasma etiology is probable (for example, inflammatory pelvic diseases in women), it is combined with doxycycline or macrolides.

During course treatment, monitoring of the state of the hematopoietic organs, liver, and kidney function is necessary.

If diarrhea occurs during treatment with Libakcil, caution should be exercised due to the possible development of pseudomembranous colitis. If the diagnosis of antibiotic-associated diarrhea or pseudomembranous colitis is established, administration of Libakcil should be discontinued immediately and appropriate treatment should be prescribed.

The development of superinfection due to the growth of microflora insensitive to Libakcil is possible, which requires appropriate correction of antibacterial therapy.

During treatment with Libakcil, a false-positive direct Coombs test is possible; false-positive results may be observed in tests for glucosuria using the Benedict or Fehling method, as well as when using ClinTest. In patients receiving Libakcil, it is desirable to use glucose oxidase tests.

When treating patients with sepsis, a bacteriolysis reaction (Jarisch-Herxheimer reaction) may develop.

Intramuscular injections are painful; therefore, it is preferable to use a solution of a local anesthetic (0.5-2% lidocaine solution) to dissolve Libakcil.

In persons with intolerance to local anesthetics, do not use a lidocaine solution for preparing the solution for intramuscular injection.

Effect on the ability to drive vehicles and mechanisms

There are no data indicating a negative effect of Libakcil on the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

When using a lidocaine solution as a solvent, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities.

Overdose

Symptoms neurological disorders in the form of convulsions.

Treatment anticonvulsant therapy; in severe cases – hemodialysis.

Drug Interactions

When used concomitantly with aminoglycosides, a pronounced synergy of bactericidal action against gram-positive and gram-negative bacteria is observed.

Pharmaceutically incompatible with aminoglycosides. When used concomitantly with aminoglycosides, they should not be mixed in the same syringe or the same infusion medium; when administered intramuscularly, inject into different body sites; when administered intravenously, administer separately, observing a certain sequence with the longest possible time interval between injections (infusions), or use separate intravenous catheters.

Probenecid reduces the tubular secretion of ampicillin and sulbactam, increasing their T_1/2 in the blood.

Concomitant administration of allopurinol and ampicillin increases the risk of skin rash.

When used concomitantly, Ampicillin+Sulbactam potentiates the effect of indirect anticoagulants.

Storage Conditions

List B. Store the drug in a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of the reach of children.

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

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.