Fibell (Powder) Instructions for Use

ATC Code

J01CR02 (Amoxicillin and beta-lactamase inhibitor)

Active Substances

Clavulanic acid (Rec.INN registered by WHO)

Amoxicillin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Antibiotic, semi-synthetic penicillin + beta-lactamase inhibitor

Pharmacological Action

A combined preparation of amoxicillin and clavulanic acid, a beta-lactamase inhibitor. It acts bactericidally by inhibiting the synthesis of the bacterial cell wall.

Active against aerobic gram-positive bacteria (including beta-lactamase-producing strains): Staphylococcus aureus; aerobic gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis.

The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic bacteria Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; and also aerobic gram-negative bacteria (including beta-lactamase-producing strains): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic gram-negative bacteria (including beta-lactamase-producing strains): Bacteroides spp., including Bacteroides fragilis.

Pharmacokinetics

After intravenous administration in doses of 1000/200 mg and 500/100 mg, the C_max of amoxicillin is 105.4 and 32.2 mcg/ml, respectively, and of clavulanic acid is 28.5 and 10.5 mcg/ml.

The time to reach a maximum inhibitory concentration of 1 mcg/ml for amoxicillin is similar when administered every 12 hours and 8 hours in both adults and children.

Plasma protein binding: Amoxicillin – 17-20%, Clavulanic acid – 22-30%.

Both components are metabolized in the liver: Amoxicillin – 10% of the administered dose, Clavulanic acid – 50%.

T_1/2 after intravenous administration of a dose of 1200 and 600 mg is 0.9 and 1.07 hours for amoxicillin, and 0.9 and 1.12 hours for clavulanic acid, respectively.

It is excreted mainly by the kidneys (glomerular filtration and tubular secretion): 50-78% and 25-40% of the administered dose of amoxicillin and clavulanic acid, respectively, is excreted unchanged within the first 6 hours after administration.

Indications

Treatment of infectious and inflammatory diseases caused by susceptible pathogens: lower respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess); ENT infections (sinusitis, tonsillitis, otitis media); urinary tract and pelvic organ infections (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingo-oophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelvic peritonitis, chancroid, gonorrhea); skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection); osteomyelitis; postoperative infections.

Prophylaxis of infections in surgery.

ICD codes

Dosage Regimen

Powder

Administered intravenously as injections or infusions.

Doses are given in terms of Amoxicillin. The dosage regimen is established individually depending on the patient’s age, severity and location of the infection, and the sensitivity of the pathogen.

Adults and adolescents over 12 years of age are administered 1 g (based on amoxicillin) 3 times/day, if necessary – 4 times/day. The maximum daily dose is 6 g. For children 3 months to 12 years – 25 mg/kg 3 times/day; in severe cases – 4 times/day; for children under 3 months: preterm and in the perinatal period – 25 mg/kg 2 times/day, in the postperinatal period – 25 mg/kg 3 times/day.

Duration of treatment is 5-14 days, for acute otitis media – up to 10 days.

For the prevention of postoperative infections in operations lasting less than 1 hour, 1 g is administered intravenously during induction anesthesia. For longer operations – 1 g every 6 hours for 24 hours. If the risk of infection is high, administration may be continued for several days.

In case of renal failure, the dose and frequency of administration are adjusted depending on the creatinine clearance.

Adverse Reactions

From the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of hepatic transaminases, in isolated cases – cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (may also develop after therapy), enterocolitis, black “hairy” tongue, darkening of tooth enamel.

From the hematopoietic organs: reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

From the nervous system: dizziness, headache, hyperactivity, anxiety, behavior change, convulsions.

From the urinary system: interstitial nephritis, crystalluria, hematuria.

Local reactions: in some cases – phlebitis at the site of intravenous administration.

Allergic reactions: urticaria, erythematous rashes, rarely – multiform exudative erythema, anaphylactic shock, angioedema, extremely rarely – exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), allergic vasculitis, serum sickness-like syndrome, acute generalized exanthematous pustulosis.

Other: candidiasis, development of superinfection.

Contraindications

Hypersensitivity to amoxicillin and other penicillins, clavulanic acid, to other beta-lactam antibiotics (cephalosporins, carbapenems, monobactams); cholestatic jaundice and/or other liver function disorders caused by the use of amoxicillin/clavulanic acid in history.

With caution

History of pseudomembranous colitis, hepatic insufficiency, severe renal impairment (creatinine clearance <30 ml/min), gastrointestinal diseases (including history of colitis associated with the use of penicillins), simultaneous use with anticoagulants, pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Should be used with caution during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in episodes of jaundice or impaired liver function as a result of previous use of amoxicillin/clavulanic acid.

With caution: severe hepatic insufficiency.

Use in Renal Impairment

In case of renal failure, the dose and frequency of administration are adjusted depending on the creatinine clearance.

Pediatric Use

Used in children according to indications and in appropriate dosage forms.

Special Precautions

Use of this combination is not recommended if infectious mononucleosis is suspected.

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

To reduce the risk of gastrointestinal side effects, the drug should be taken with meals.

Development of superinfection due to the growth of flora insensitive to it is possible, which requires an appropriate change in antibacterial therapy.

May give false-positive results when determining glucose in urine. In this case, it is recommended to use the glucose-oxidase method for determining the concentration of glucose in urine.

In patients with hypersensitivity to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.

Drug Interactions

Bacteriostatic antibiotics (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect.

When combined with rifampicin, a mutual weakening of the antibacterial effect is observed.

Increases the effectiveness of indirect anticoagulants (by suppressing intestinal flora, reduces the synthesis of vitamin K and the prothrombin index). When taking anticoagulants simultaneously, blood clotting parameters should be monitored.

Reduces the effectiveness of oral contraceptives, drugs metabolized to form PABA, ethinylestradiol – risk of “breakthrough” bleeding.

Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion increase the concentration of amoxicillin (Clavulanic acid is excreted mainly by glomerular filtration).

Concomitant use with methotrexate increases the toxicity of methotrexate.

Allopurinol increases the risk of skin rash.

Simultaneous use with probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin. With simultaneous use, an increase and prolongation of the concentration of amoxicillin in the blood is possible, but not clavulanic acid.

Simultaneous use with disulfiram should be avoided.

Concomitant use of amoxicillin and digoxin may lead to an increase in the concentration of digoxin in the blood plasma.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.