Trifamox ibl

INSTRUCTIONS for medical use of the medicinal product Trifamox IBL (Trifamox IBL)

Composition:

Active substances: amoxicillin, sulbactam;

One tablet contains amoxicillin (as amoxicillin trihydrate) 250 mg and sulbactam (as sulbactam pivoxil) 250 mg;

One tablet contains amoxicillin (as amoxicillin trihydrate) 500 mg and sulbactam (as sulbactam pivoxil) 500 mg;

Excipients: colloidal anhydrous silicon dioxide, sodium croscarmellose, magnesium stearate, microcrystalline cellulose, Opadry II YS-30-18056 coating, yellow iron oxide (E 172), purified water.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: oval, biconvex, film-coated tablets of yellow color with a score on both sides.

Pharmacotherapeutic group. Antimicrobial agents for systemic use. Amoxicillin and enzyme inhibitor. ATC code J01CR02.

Pharmacological properties.

Pharmacodynamics.

A combination preparation of amoxicillin (a broad-spectrum semi-synthetic penicillin) and sulbactam, an irreversible inhibitor of beta-lactamases. Amoxicillin exerts a bactericidal effect by inhibiting bacterial cell wall synthesis. It is active against aerobic gram-positive bacteria (including beta-lactamase-producing strains): Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic gram-positive bacteria: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; aerobic gram-negative bacteria (including beta-lactamase-producing strains): Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella spp., Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophilus influenzae, Haemophilus ducreyi, Yersinia multocida, Campylobacter jejuni, Acinetobacter spp.; anaerobic gram-negative bacteria (including beta-lactamase-producing strains): Bacteroides spp., including Bacteroides fragilis.

Sulbactam is a stable, irreversible inhibitor of beta-lactamases produced by microorganisms resistant to beta-lactam antibiotics. Sulbactam extends the spectrum of activity of the preparation against relatively resistant strains, without altering the activity of amoxicillin against susceptible strains. By binding to certain bacterial penicillin-binding proteins, sulbactam exhibits synergy when used concomitantly with beta-lactam antibiotics. Sulbactam has no clinically significant intrinsic antibacterial activity, except against Neisseriaceae and Acinetobacter.

Pharmacokinetics.

After oral administration, both active components of the preparation are rapidly absorbed from the gastrointestinal tract. The bioavailability of amoxicillin after oral administration is 80%; food intake does not affect drug absorption. Time to maximum concentration is 1–2 hours; elimination half-life is 1 hour. Plasma protein binding is 20%. Amoxicillin is distributed into most tissues and body fluids, crosses the placental barrier and is excreted in breast milk. It is primarily eliminated by the kidneys (glomerular filtration and tubular secretion) – 70–80% – and with bile – 5–10%.

Sulbactamum pivoxil is hydrolyzed in the gastrointestinal tract, which enhances sulbactam absorption. Time to maximum concentration is 1–2 hours. Protein binding is 40%. Elimination half-life is 1 hour. Sulbactam does not affect the pharmacokinetics of amoxicillin.

Clinical characteristics.

Indications.

Bacterial infections caused by pathogens sensitive to the drug and resistant to monotherapy with beta-lactam and cephalosporin antibiotics:

• infections of the ear, nose, and throat organs (sinusitis, otitis media);
• respiratory tract infections (pneumonia);
• urinary and genital system infections (acute and chronic pyelonephritis, pyelitis, cystitis, urethritis, gonorrhea);
• intestinal infections (dysentery, salmonellosis, salmonella carriage);
• skin and soft tissue infections (impetigo, secondary infected dermatoses, abscess, phlegmon, wound infection).

Contraindications.

Hypersensitivity to the components of the drug or to other beta-lactam antibiotics, penicillins and/or cephalosporins; infectious mononucleosis; lympholeukemia; ulcerative colitis; regional enteritis or antibiotic-associated colitis; Crohn's disease; jaundice/liver function disorders.

Interaction with other medicinal products and other types of interactions.

When allopurinol and amoxicillin are used simultaneously, the risk of developing skin allergic reactions may increase.

Isolated cases of increased international normalized ratio (INR) have been reported in patients who concurrently received amoxicillin and acenocoumarol or warfarin. If such co-administration is necessary, prothrombin time or INR should be carefully monitored during initiation or discontinuation of amoxicillin therapy. In addition, dose adjustment of oral anticoagulants may be required.

Penicillins may reduce methotrexate excretion, potentially leading to increased toxicity of the latter.

During amoxicillin treatment, non-enzymatic glucose oxidase-based reactions should be used to determine glucose levels in urine, as non-enzymatic methods may yield false-positive results.

Probenecid, phenylbutazone, oxphenbutazone, and to a lesser extent acetylsalicylic acid and sulfinpyrazone, inhibit tubular secretion of penicillin-class drugs, resulting in prolonged elimination half-life and increased plasma concentration of amoxicillin. Concomitant use with probenecid is contraindicated.

Like other antibiotics, amoxicillin may affect intestinal flora, leading to reduced reabsorption of estrogens and decreased effectiveness of combined oral contraceptives.

Bacteriostatic agents (tetracycline-class antibiotics, macrolides, chloramphenicol) may neutralize the bactericidal effect of amoxicillin. Concomitant use of aminoglycosides is possible (synergistic effect).

Special precautions for use.

Hypersensitivity

Prior to initiating treatment with amoxicillin, it is necessary to carefully assess the patient's history for hypersensitivity reactions to penicillins, cephalosporins, other beta-lactam antibacterial agents, or to other allergens.

Severe and occasionally fatal (anaphylactic) hypersensitivity reactions have been reported in patients receiving penicillin therapy.

Such reactions are more likely to occur in patients with a history of penicillin hypersensitivity or multiple allergen sensitivities. If any allergic reaction occurs, the drug should be discontinued immediately and appropriate therapy initiated.

Severe anaphylactic reactions require immediate emergency treatment with epinephrine, along with administration of oxygen and intravenous corticosteroids, as well as airway management including intubation if necessary.

Pseudomembranous colitis

Cases of pseudomembranous colitis associated with the use of antibacterial agents, including antibiotic/beta-lactamase inhibitor combinations, have been reported. The severity of these cases varies, and in some patients this condition may be severe. Therefore, pseudomembranous colitis should be considered in the differential diagnosis of patients who develop diarrhea following antibacterial therapy.

Infectious mononucleosis

Exanthematous rash has been reported in patients with infectious mononucleosis or lymphatic-type leukemoid reactions. Penicillins should not be administered to such patients.

Renal impairment

The drug should be used with caution in patients with renal impairment due to reduced amoxicillin clearance. Dose adjustment may be necessary based on creatinine clearance. Renal function should be monitored during prolonged therapy.

Crystalluria

The risk of crystalluria increases when high doses of the drug are administered. Therefore, adequate fluid intake is recommended to prevent crystalluria.

Resistance

Prolonged use of the drug may lead to the development of microflora resistant to amoxicillin and increase the risk of superinfection. The drug should be discontinued if superinfection caused by Pseudomonas or Candida occurs.

Cross-resistance

There is a risk of cross-resistance between penicillins and cephalosporins.

Hepatic impairment

The drug should be used with caution in patients with severe hepatic impairment. Liver function should be monitored during prolonged therapy.

When using the drug Trifamox IBL, increased levels of liver transaminases, predominantly glutamic-oxaloacetic transaminase, may occur.

Seizures

Seizures may occur in patients receiving high doses of the drug, as well as in patients with impaired renal function.

Jarisch-Herxheimer reaction

The Jarisch-Herxheimer reaction may occur during amoxicillin treatment of Lyme disease.

Contraceptives

A transient decrease in serum levels of conjugated estriol and estrone, as well as estradiol concentration, may occur. Therefore, alternative or additional contraceptive methods are recommended for patients receiving estrogen or progestin therapy.

Use during pregnancy or breastfeeding.

Adequate and well-controlled studies on the use of the drug in pregnant women have not been conducted. Limited data on amoxicillin use during pregnancy suggest no adverse effects on the fetus/newborn. The drug may be prescribed during pregnancy only after careful assessment of the benefit-risk ratio.

Amoxicillin crosses the placental barrier, and its concentration in fetal plasma is approximately 25–30% of the maternal plasma concentration.

Amoxicillin is excreted in small amounts in breast milk; therefore, the risk of hypersensitivity reactions in the nursing infant cannot be excluded. The use of the drug during lactation is possible only if the expected benefit to the mother outweighs the potential risk to the infant. Breastfeeding should be discontinued if gastrointestinal disturbances (diarrhea, candidiasis, or skin rash) occur in the newborn.

Ability to affect reaction speed when driving or operating machinery.

Until individual response to the drug is established (dizziness, allergic reactions, seizures may occur), caution is recommended when driving or operating complex machinery.

Dosage and administration.

The dosage of amoxicillin is determined by the physician depending on the patient's age, body weight, and renal function, as well as on the susceptibility of microorganisms and the localization of the infectious process.

The tablet should be swallowed whole or divided into parts, not chewed, and taken with one glass of water.

The drug can be taken independently of food intake.

Dosages are given in terms of amoxicillin.

Dosage. In cases of mild to moderate infectious-inflammatory diseases, adults and children aged 12 years and older (with body weight over 40 kg) are recommended to take 500–750 mg twice daily or 500 mg three times daily. The dosage for children should be up to 30 mg/kg/day.

For treatment of chronic diseases, relapses, and severe infections, the dose may be increased and should be divided into three doses: adults should be given 750–1000 mg three times daily; children aged 12 years and older—up to 60 mg/kg/day, divided into three doses.

Duration of treatment. In cases of mild to moderate infections, the drug should be taken for 5–7 days. However, in infections caused by streptococcus, the duration of treatment should be at least 10 days.

For treatment of chronic diseases, localized infectious lesions, and severe infections, the duration of treatment should be determined based on the clinical presentation of the disease.

The drug should be continued for 48 hours after disappearance of symptoms of the disease.

Dosage reduction in patients with impaired renal function:

In case of hemodialysis, 500 mg of amoxicillin should be administered at the end of the procedure.

Patients with hepatic impairment.

Dosage adjustment is not required in patients with impaired liver function.

Treatment of uncomplicated gonorrhea – 3 g of the drug as a single dose in combination with 1 g of probenecid.

Children.

To be used in children aged 12 years and older. For children under 12 years of age, another dosage form of the drug should be used.

Overdose.

Symptoms: cases of crystalluria have been reported, which sometimes led to renal failure; gastrointestinal disturbances (nausea, vomiting, diarrhea) and fluid-electrolyte imbalances.

Treatment: induce vomiting or perform gastric lavage, followed by administration of activated charcoal and an osmotic laxative. Fluid and electrolyte balance should be maintained. Hemodialysis may be used.

Adverse Reactions

The drug is generally well tolerated when used at recommended doses. However, in some patients, adverse reactions of various types and severities may develop.

Adverse reactions that may occur during treatment with amoxicillin are listed below according to their frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); frequency not known (cannot be estimated based on available data).

Infections and infestations. Uncommon: prolonged use of the drug may lead to development of superinfection and resistance.

Blood and lymphatic system disorders. Rare: eosinophilia, hemolytic anemia; very rare: leukopenia, severe neutropenia, agranulocytosis, thrombocytopenia, pancytopenia, myelosuppression, granulocytopenia, prolonged bleeding time and prothrombin index. These effects are reversible upon discontinuation of therapy.

Immune system disorders. Rare: laryngeal edema, severe allergic reactions including anaphylactic shock, angioneurotic edema, anaphylaxis, serum sickness, allergic vasculitis; frequency not known: Jarisch-Herxheimer reaction.

Gastrointestinal disorders. Common: diarrhea, nausea, vomiting, flatulence, stomach pain, soft stools, perianal pruritus, loss of appetite, enanthema (especially in the oral area), dry mouth, taste disturbances; rare: black hairy tongue, tooth discoloration (especially in children taking the suspension). Proper oral hygiene procedures may prevent tooth discoloration, as such deposits are usually removed by tooth brushing; very rare: antibiotic-associated colitis (including pseudomembranous and hemorrhagic colitis), intestinal candidiasis. These adverse effects are generally mild and resolve either during or immediately after completion of therapy. The occurrence of such events may be prevented by taking amoxicillin with food.

Nervous system disorders. Very rare: hyperkinesia, hyperactivity, dizziness, seizures, aseptic meningitis.

Hepatobiliary disorders. Very rare: hepatitis, cholestatic jaundice, mild and transient increase in liver enzymes (AST, ALT).

Skin and subcutaneous tissue disorders. Common: skin rashes, urticaria, pruritus; very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative bullous dermatitis, acute generalized exanthematous pustulosis, Lyell's syndrome. Sudden onset of urticaria indicates an allergic reaction to amoxicillin and requires immediate discontinuation of therapy.

Renal and urinary disorders. Rare: acute interstitial nephritis, crystalluria.

Other. Rare: fever.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging, in a dry place out of reach of children.

Packaging.

8 tablets per blister pack, 1 or 2 blister packs per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Laboratorios Bago S.A. /
Laboratorios Bago S.A.

Manufacturer's address and location of operations.

Legal address:
Bernardo de Irigoyen, 248, City of Buenos Aires (C.P.: C1072AAF), Argentine Republic /
Bernardo de Irigoyen 248, City of Buenos Aires (C.P.: C1072AAF), Argentine Republic

Manufacturing site:
St. Ciudad de Necochea between st. Ciudad de Mar del Plata and Av. Matienzo;
Industrial Park, Province of La Rioja (C.P.: F5302CTA), Argentine Republic /
St. Ciudad de Necochea between st. Ciudad de Mar del Plata and Av. Matienzo; Industrial Park, Province of La Rioja (C.P.: F5302CTA), Argentine Republic.