Maiclav 625

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MYCLAV 625 (MYCLAV 625)

Composition:

Active substances: amoxicillin, clavulanic acid;

One tablet contains amoxicillin (as amoxicillin trihydrate) 500 mg, clavulanic acid (as potassium clavulanate) 125 mg;

Excipients: magnesium stearate, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, microcrystalline cellulose, sodium lauryl sulfate; coating Opadry OY-C-7000A: hypromellose, diethyl phthalate, titanium dioxide (E 171), ethylcellulose.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, oval-shaped, biconvex, film-coated tablets, smooth on both sides.

Pharmacotherapeutic group.

Antibacterials for systemic use. Combinations of amoxicillin and beta-lactamase inhibitor. ATC code J01CR02.

Pharmacological properties.

Pharmacodynamics.

MaiKlav 625 is a combination of amoxicillin, a broad-spectrum antibiotic with antibacterial activity, and clavulanic acid, a β-lactamase inhibitor that forms stable inactive complexes with β-lactamases and protects amoxicillin from degradation. It exerts a bactericidal effect by inhibiting bacterial cell wall synthesis.

MaiKlav 625 has a broad spectrum of antimicrobial activity.

The microorganisms listed below are classified according to their in vitro sensitivity to amoxicillin/clavulanate.

Sensitive microorganisms

Gram-positive aerobes*: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus viridans, other β-hemolytic Streptococcus species, Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus saprophyticus (methicillin-sensitive strains), coagulase-negative staphylococci (methicillin-sensitive strains).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Moraxella catarrhalis, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Others: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Gram-positive anaerobes: Clostridium species, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, and other Peptostreptococcus species.

Gram-negative anaerobes: Bacteroides species (including Bacteroides fragilis), Capnocytophaga species, Eikenella corrodens, Fusobacterium species, Porphyromonas species, Prevotella species.

Strains that may develop resistance

Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, other Klebsiella species, Proteus mirabilis, Proteus vulgaris, other Proteus species, Salmonella species, Shigella species.

Gram-positive aerobes: Corynebacterium species, Enterococcus faecium.

Insensitive microorganisms

Gram-negative aerobes: Acinetobacter species, Citrobacter freundii, other Enterobacter species, Hafnia alvei, Legionella pneumophila, Morganella morganii, other Providencia species, Pseudomonas species, Serratia species, Stenotrophomonas maltophilia, Yersinia enterocolitica.

Others: Chlamydia pneumoniae, Chlamydia psittaci, other Chlamydia species, Coxiella burnetii, Mycoplasma species.

Pharmacokinetics.

After oral administration, both active components of MaiKlav 625 — amoxicillin and clavulanic acid — are rapidly and completely absorbed from the gastrointestinal tract. Absorption is optimal when the drug is taken at the beginning of a meal. Following administration of MaiKlav 625, plasma concentrations of amoxicillin are similar to those achieved after oral administration of equivalent doses of amoxicillin alone. Therapeutic concentrations of amoxicillin and clavulanic acid are achieved in various organs and tissues, including lung interstitial fluid, abdominal organs, adipose, bone and muscle tissues, pleural, synovial and peritoneal fluids, skin, bile, and sputum, after oral administration. Both amoxicillin and clavulanic acid exhibit moderate plasma protein binding, specifically 25% of total clavulanic acid and 18% of amoxicillin. Traces of clavulanic acid and amoxicillin are detected in breast milk (in breastfed infants, there is a risk of sensitization without other adverse effects). Amoxicillin and clavulanic acid cross the placental barrier (no impairment of fertility or adverse effects on the fetus have been observed). Both components are metabolized in the liver: amoxicillin — 10% of the administered dose, clavulanic acid — 50%. They are primarily excreted by the kidneys (glomerular filtration and tubular secretion): 50–78% of amoxicillin and 25–40% of clavulanic acid are excreted unchanged within the first 6 hours after administration.

Clinical characteristics.

Indications.

Treatment of bacterial infections caused by microorganisms sensitive to the drug, such as:

• acute bacterial sinusitis;
• acute otitis media;
• acute exacerbation of chronic bronchitis;
• community-acquired pneumonia;
• cystitis;
• pyelonephritis;
• skin and soft tissue infections, including cellulitis, animal bites, severe dentoalveolar abscesses with spreading cellulitis;
• bone and joint infections, including osteomyelitis.

Contraindications.

Hypersensitivity to any component of the drug, to any antibacterial agent of the penicillin group.

History of severe hypersensitivity reactions (including anaphylaxis) associated with the use of other β-lactam agents (including cephalosporins, carbapenems, or monobactams).

History of jaundice or liver dysfunction associated with the use of the drug.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of probenecid is not recommended. Probenecid reduces renal tubular secretion of amoxicillin. Concurrent administration with Myclav 625 may lead to increased and prolonged blood levels of amoxicillin, but does not affect clavulanic acid levels.

Concomitant use of allopurinol during amoxicillin therapy increases the risk of allergic skin reactions. There are no data on concomitant use of Myclav 625 and allopurinol.

Like other antibiotics, Myclav 625 may affect intestinal flora, leading to reduced reabsorption of estrogens and reduced efficacy of combined oral contraceptives.

There are isolated reports of increased international normalized ratio (INR) in patients receiving acenocoumarol or warfarin and taking amoxicillin. If such concomitant use is necessary, prothrombin time or INR should be closely monitored.

In patients receiving mycophenolate mofetil, initiation of oral amoxicillin with clavulanic acid may reduce the pre-dose concentration of the active metabolite mycophenolic acid by approximately 50%. This change in pre-dose levels may not accurately reflect changes in total exposure to mycophenolic acid.

Penicillins may reduce methotrexate excretion, potentially increasing its toxicity.

Special precautions for use.

Prior to initiating therapy, it is essential to determine accurately whether the patient has a history of hypersensitivity reactions to penicillins, cephalosporins, or other allergens. Severe, and sometimes even fatal, hypersensitivity reactions (including anaphylactic reactions and severe skin adverse reactions) have been reported in patients receiving penicillin therapy. Such reactions are most likely to occur in individuals with a prior history of hypersensitivity to penicillins. If allergic reactions occur, the drug should be discontinued immediately and appropriate alternative therapy should be initiated.

If it has been established that the infection is caused by microorganisms susceptible to amoxicillin, consideration should be given to switching from the combination amoxicillin/clavulanic acid to amoxicillin alone, in accordance with official recommendations.

Mykla 625 should not be used when there is a high risk that pathogens are resistant to β-lactams, and it is not indicated for the treatment of pneumonia caused by penicillin-resistant strains of S. pneumoniae.

Mykla 625 should not be prescribed if infectious mononucleosis is suspected, as amoxicillin use in this condition has been associated with the occurrence of maculopapular rash.

Prolonged use of the drug may occasionally lead to overgrowth of microorganisms not susceptible to Mykla 625.

The development of erythema multiforme with pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AGEP). In such cases, treatment must be discontinued and further use of amoxicillin is contraindicated.

Mykla 625 should be prescribed with caution in patients showing signs of hepatic impairment. Hepatic adverse reactions have occurred mainly in males and elderly patients and were associated with prolonged treatment. Reports in children are very rare. In all patient groups, symptoms usually appeared during or immediately after treatment, although in some cases they occurred several months after treatment cessation. These effects are generally reversible. Hepatic reactions may be severe and very rarely may be fatal. They have always occurred in patients with serious underlying conditions or when concomitant medications with potential hepatotoxic effects were used.

Antibiotic-associated colitis, ranging from mild to life-threatening, has been reported with nearly all antibacterial agents. Therefore, it is important to consider this diagnosis in patients who develop diarrhea during or after antibiotic use. If antibiotic-associated colitis occurs, treatment with Mykla 625 should be discontinued immediately and appropriate therapy initiated.

Rarely, patients receiving amoxicillin and clavulanic acid concomitantly with oral anticoagulants may experience excessive prolongation of prothrombin time (elevated INR). Appropriate laboratory monitoring is required when anticoagulants are used concurrently. Dose adjustment of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Dosage adjustment is required for patients with impaired renal function according to the degree of renal insufficiency.

In patients with reduced urine output, crystalluria may very rarely occur, primarily after parenteral administration of the drug. Therefore, to reduce the risk of crystalluria, adequate fluid intake should be maintained during high-dose amoxicillin therapy.

When monitoring urinary glucose levels during amoxicillin therapy, enzymatic glucose oxidase-based methods should be used, as other methods may yield false-positive results.

The presence of clavulanic acid in Mykla 625 may cause nonspecific binding of IgG and albumin to erythrocyte membranes, potentially leading to a false-positive Coombs' test.

There have been reports of false-positive results in Aspergillus antigen tests (Bio-Rad Laboratories Platelia Aspergillus EIA) in patients receiving amoxicillin/clavulanic acid. Therefore, positive test results in patients treated with amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

Use during pregnancy or breastfeeding.

Prophylactic treatment with amoxicillin combined with clavulanic acid has been reported to increase the risk of necrotizing enterocolitis in newborns. Mykla 625 should be avoided during pregnancy, particularly in the first trimester, unless the expected benefit outweighs the potential risk to the fetus.

Both active components of the drug are excreted in breast milk (there is no information on the effect of clavulanic acid on breastfed infants). Therefore, diarrhea and fungal mucosal infections may occur in breastfed infants, and breastfeeding should be discontinued.

Mykla 625 may be used during breastfeeding only if, in the physician’s opinion, the benefit of treatment outweighs the potential risk.

Ability to influence the speed of reactions when driving or operating machinery.

No studies have been conducted on the ability of the drug to affect reaction speed when driving or operating machinery. However, adverse reactions (e.g., allergic reactions, dizziness, seizures) may occur that could impair the ability to drive or operate machinery.

Dosage and Administration

The drug should be used in accordance with official recommendations on antibiotic therapy and local antibiotic susceptibility data. Susceptibility to amoxicillin/clavulanate varies across different regions and may change over time. When necessary, local susceptibility data should be consulted, and microbiological identification and susceptibility testing should be performed.

The dosage depends on the expected pathogens and their susceptibility to antibacterial agents, severity of the disease, site of infection, patient's age, body weight, and renal function.

For adults and children with body weight ≥ 40 kg, the daily dose is 1500 mg of amoxicillin/375 mg of clavulanic acid (3 tablets), administered as described below.

For children aged 6 years and older with body weight between 25 and 40 kg, the maximum daily dose is 2400 mg of amoxicillin/600 mg of clavulanic acid (4 tablets), administered as described below.

If higher doses of amoxicillin are required for treatment, other formulations of the combination drug (amoxicillin/clavulanic acid) should be used to avoid administering unnecessarily high doses of clavulanic acid.

The duration of treatment is determined based on the patient's clinical response. Some infections (e.g., osteomyelitis) require prolonged treatment.

Adults and children with body weight ≥ 40 kg: 1 tablet three times daily.

Children aged 6 years and older with body weight between 25 and 40 kg: dose from 20 mg/5 mg/kg to 60 mg/15 mg/kg body weight per day, divided into three doses.

Since the tablet cannot be split, this formulation, Myclav 625, should not be administered to children weighing less than 25 kg.

Elderly patients

Dosage adjustment is not required in elderly patients. If necessary, dosage should be adjusted according to renal function.

Dosing in Renal Impairment

Dosing is based on the maximum concentration of amoxicillin. There is no need to adjust the dose in patients with creatinine clearance > 30 mL/min.

Adults and children with body weight ≥ 40 kg

Children aged 6 years and older with body weight between 25 and 40 kg

If a lower dose of the medicinal product is required for children aged 6 years with body weight between 25 and 40 kg, with creatinine clearance less than 30 mL/min, or for children undergoing hemodialysis, other dosage forms of the drug Augmentin should be used.

Dosage in hepatic impairment

Use with caution; liver function should be monitored regularly.

The tablet should be swallowed whole without chewing. If necessary, the tablet may be split in half and the halves swallowed without chewing.

For optimal absorption and to reduce the risk of gastrointestinal adverse effects, the drug should be taken at the beginning of a meal.

The duration of treatment should be determined individually. Treatment should not be continued for more than 14 days without reassessment of the patient's condition.

Treatment may be initiated parenterally and then continued orally.

Children.

This dosage form of Augmentin 625 may be used in children aged 6 years and older with body weight of at least 25 kg, as specified in the section "Method of administration and dosage."

Overdose.

Overdose may be associated with gastrointestinal symptoms (nausea, vomiting, diarrhea) and disturbances of fluid and electrolyte balance. Nervous system symptoms such as agitation, insomnia, dizziness, and occasionally seizures may occur. These symptoms should be treated symptomatically, with special attention given to correction of fluid and electrolyte imbalances.

Amoxicillin crystalluria may occur, which in some cases may lead to renal failure. There have been reports of amoxicillin precipitation in urinary catheters following intravenous administration of high-dose amoxicillin with clavulanic acid. Catheter patency should therefore be monitored regularly.

Treatment is symptomatic. Augmentin 625 can be removed from the bloodstream by hemodialysis.

Side effects.

Infections and infestations: candidiasis of the skin and mucous membranes, overgrowth of non-susceptible microorganisms.

Blood system disorders: reversible leukopenia (including neutropenia) and thrombocytopenia, reversible agranulocytosis and hemolytic anemia, prolonged bleeding time and prothrombin index.

Immune system disorders: angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis.

Nervous system disorders: dizziness, headache, reversible hyperactivity, aseptic meningitis, seizures. Seizures may occur in patients with impaired renal function or in those receiving high doses of the drug.

Gastrointestinal disorders: diarrhea, nausea (more commonly associated with high doses of the drug), vomiting (the above gastrointestinal symptoms may be reduced if the drug is taken at the beginning of a meal), dyspepsia, antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis – see section "Special precautions"), black "hairy" tongue.

Hepatobiliary disorders: mild elevations in serum transaminases (aspartate aminotransferase and/or alanine aminotransferase), hepatitis, and cholestatic jaundice. These reactions have been reported with other penicillins and cephalosporins.

Hepatitis occurs mainly in males and elderly patients, and may be associated with prolonged treatment with the drug.

Such events are very rare in children.

Symptoms may appear during or immediately after treatment, but in some cases may occur several weeks after completion of therapy. These events are usually reversible. Fatal outcomes have been reported extremely rarely, mainly in patients with severe underlying diseases or in patients who were concurrently treated with drugs known to have hepatotoxic potential.

Skin and subcutaneous tissue disorders: skin rash, pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative bullous dermatitis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS).

If any allergic dermatitis occurs, treatment should be discontinued.

Renal and urinary disorders: interstitial nephritis, crystalluria.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging.

6 tablets per strip, 1 strip per cardboard box, 10 boxes per cardboard package.

Prescription status. Prescription only.

Manufacturer.

Unique Laboratories Limited.

Manufacturer's address and place of business.

Village Bhattauli Kalan, Himachal Pradesh IN – 173205, India.