Myclov

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

Composition:

Active substances: amoxicilline, clavulanic acid;

5 ml of suspension contain amoxicillin 200 mg (as amoxicillin trihydrate) and clavulanic acid 28.5 mg (as potassium clavulanate);

Excipients: silicon dioxide, xanthan gum, hypromellose, colloidal anhydrous silicon dioxide, succinic acid, aspartame (E 951), orange flavor dry 0471034, raspberry flavor 0473005.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: free-flowing powder, white to almost white.

After reconstitution, a white to almost white suspension is formed.

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

Pharmacological Properties

Pharmacodynamics

Amoxicillin is a semi-synthetic antibiotic with a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative microorganisms. Amoxicillin is susceptible to β-lactamase and undergoes degradation under its influence; therefore, the spectrum of activity of amoxicillin does not include microorganisms producing this enzyme. Clavulanic acid has a β-lactam structure similar to penicillins and possesses the ability to inactivate β-lactamase enzymes produced by microorganisms resistant to penicillins and cephalosporins. In particular, it exhibits pronounced activity against clinically important plasmid-mediated β-lactamases, which are often responsible for the development of cross-resistance to antibiotics. The presence of clavulanic acid in the composition of Mайkлав protects amoxicillin from degradation by β-lactamase enzymes and extends the antibacterial spectrum of amoxicillin to include many microorganisms resistant to amoxicillin and other penicillins and cephalosporins.

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

Sensitive microorganisms

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroids, Streptococcus pyogenes, Streptococcus agalactiae, 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 ictterohaemorrhagiae, Treponema pallidum.

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

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

Strains that may develop resistance

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

Gram-positive aerobes: species of Corynebacterium, Enterococcus faecium, Streptococcus pneumoniae, Streptococcus group viridans.

Insensitive microorganisms

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

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

Pharmacokinetics

Absorption. Both components of Mайkлав (amoxicillin and clavulanic acid) are completely soluble in aqueous solutions at physiological pH values. Both components are rapidly and well absorbed after oral administration. Absorption of the drug is improved when administered at the beginning of a meal.

The serum concentration of amoxicillin achieved after administration of Mайkлав is similar to that achieved after oral administration of equivalent doses of amoxicillin alone.

Concomitant administration of probenecid inhibits the excretion of amoxicillin but does not affect the renal excretion of clavulanic acid.

Distribution. After oral administration, therapeutic concentrations of amoxicillin and clavulanic acid are observed in tissues and interstitial fluid. Therapeutic concentrations of both substances have been found in the gallbladder, abdominal tissues, skin, adipose and muscle tissues, as well as in synovial and peritoneal fluids, bile, and pus. Amoxicillin and clavulanic acid are weakly bound to plasma proteins; studies have shown that protein binding rates are 25% for clavulanic acid and 18% for amoxicillin of their total plasma concentrations.

Amoxicillin, like other penicillins, may be excreted in breast milk. Trace amounts of clavulanic acid may also be detected in breast milk. However, there is no data on impairment of fertility or harmful effects on the fetus.

Elimination. The main route of elimination of amoxicillin, as with other penicillins, is renal excretion, whereas clavulanate is eliminated both via the kidneys and through extrarenal mechanisms. Approximately 60–70% of amoxicillin and 40–65% of clavulanic acid are excreted unchanged in urine within the first 6 hours.

Clinical characteristics.

Indications.

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

• acute bacterial sinusitis (confirmed);
• acute otitis media;
• confirmed 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.

When prescribing antibacterial agents, the principles of their appropriate use should be followed.

Contraindications.

Hypersensitivity to any component of the drug and to any antibacterial agents 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 amoxicillin/clavulanate.

Interaction with other medicinal products and other types of interactions.

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

Penicillins may reduce the elimination of methotrexate, potentially increasing its toxicity.

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

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

There have been 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, and treatment with Mайkлав should be discontinued if necessary.

Mycophenolate mofetil

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 fully reflect changes in total exposure to mycophenolic acid.

Special precautions for use

Before initiating therapy with Mайkлав, it is essential to carefully assess the patient's history for hypersensitivity reactions to penicillins, cephalosporins, or other allergens.

Severe and occasionally fatal hypersensitivity reactions (anaphylactoid reactions) have been reported during penicillin therapy. Such reactions are more likely to occur in patients with a history of penicillin hypersensitivity (see section "Contraindications").

If the infection is proven to be caused by microorganisms sensitive to amoxicillin, consideration should be given to switching from the combination amoxicillin/clavulanic acid to amoxicillin alone, in accordance with official recommendations.

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

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

Development of a polymorphic erythema associated with pustules at the beginning of treatment may be a sign of acute generalized exanthematous pustulosis (AGEP). In such cases, treatment must be discontinued, and subsequent administration of amoxicillin is contraindicated.

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

Mайkлав should be used with caution in patients with hepatic dysfunction. Alterations in liver function tests have been reported in some patients treated with Mайkлав.

There have been isolated reports of cholestatic jaundice, which may be severe but is usually reversible. Symptoms may not appear until up to 6 weeks after completion of treatment.

The 228.5 mg/5 ml Mайkлав suspension is not recommended for patients with impaired renal function (see section "Dosage and administration").

In patients with reduced urine output, crystalluria has been very rarely observed, primarily following parenteral administration of the drug. To reduce the risk of crystalluria during high-dose amoxicillin therapy, adequate fluid intake and urine output should be maintained (see section "Overdose").

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

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

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

The medicinal product contains aspartame (E 951), a source of phenylalanine. Therefore, the product should be administered with caution to patients with phenylketonuria.

Use during pregnancy or breastfeeding

One study in women with premature rupture of fetal membranes reported that prophylactic use of amoxicillin with clavulanic acid may be associated with an increased risk of necrotizing enterocolitis in newborns. Use of amoxicillin/clavulanic acid during pregnancy should be avoided unless considered essential by the physician.

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

Effect on ability to drive and use machines

No negative effects on the ability to drive or operate machinery have been observed. However, the possibility of adverse effects such as dizziness should be taken into account.

Method of Administration and Dosage

The drug should be used in accordance with official recommendations on antibiotic therapy and local antibiotic susceptibility data (if available). Susceptibility to amoxicillin/clavulanate varies across different regions and may change over time. If necessary, microbial susceptibility to the antibiotic should be determined.

The dosage of the drug is determined by a physician depending on the expected microorganisms and their susceptibility to antibacterial agents, severity of the disease and site of infection, patient's age, body weight, and renal function.

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

If higher doses of amoxicillin are needed for treatment, other formulations of Myclav should be used to avoid unnecessary high doses of clavulanic acid.

Adults and children with body weight ≥ 40 kg: use another pharmaceutical form of the amoxicillin/clavulanic acid combination.

Children with body weight < 40 kg

Recommended daily doses: from 25/3.6 mg/kg body weight to 45/6.4 mg/kg body weight, divided into two doses.

For children with body weight < 40 kg, the drug is prescribed at a daily dose of 1000–2800 mg amoxicillin/143–400 mg clavulanic acid, as specified below.

Approximate calculation of Myclav suspension (mL per day (based on amoxicillin))

For the treatment of certain infections such as otitis media and sinusitis, lower respiratory tract infections, children aged 2 years and older may be given daily doses up to 70/10 mg/kg body weight, divided into two doses.

If higher doses of amoxicillin are required for treatment, other formulations of Augmentin should be used to avoid excessive high doses of clavulanic acid.

Renal impairment.

In children with glomerular filtration rate (GFR) greater than 30 mL/min, no dose adjustment is necessary. The use of Augmentin 228.5 mg/5 mL suspension is not recommended for treatment of children with GFR less than 30 mL/min.

Hepatic impairment.

Use with caution; liver function should be monitored regularly. There is insufficient data available to provide dosing recommendations.

For optimal absorption and to minimize gastrointestinal side effects, the medication should be taken at the beginning of a meal.

Treatment should not be continued for more than 14 days without medical consultation.

Treatment may be initiated with parenteral administration of the drug and continued with an oral formulation.

Preparation of suspension.

The powder contained in the bottle should be reconstituted into a suspension as described below.

1. Check the bottle cap for evidence of prior opening.
2. Invert and shake the bottle to loosen the powder.
3. Add boiled water to the powder in the bottle up to the level indicated by the red line with an arrow.
4. Close with the cap and shake the bottle until a suspension is formed.
5. Then add the remaining water up to the upper level indicated by the black line with an arrow, and shake again.
6. Allow the suspension to stand for 5 minutes to ensure complete dispersion of the powder.
7. Shake the suspension well before each use.

For accurate dosing, the measuring cap provided should be used and rinsed with water after each use.

Children.

The drug is indicated for children aged 2 months and older.

Overdose.

Overdose may be associated with gastrointestinal symptoms and disturbances in fluid and electrolyte balance. These effects should be treated symptomatically, with attention paid to correction of fluid and electrolyte balance. Cases of crystalluria have been reported, which occasionally led to renal failure (see section "Special precautions"). Augmentin can be removed from the bloodstream by hemodialysis.

Adverse reactions.

Infections and infestations: candidiasis of the skin and mucous membranes.

Blood and lymphatic system disorders: reversible leukopenia (including neutropenia), thrombocytopenia, reversible agranulocytosis, 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, seizures. Seizures may occur in patients with impaired renal function or in those receiving high doses of the drug.

Gastrointestinal disorders: adults: diarrhea, nausea, vomiting; children: diarrhea, nausea, vomiting, digestive disturbances, antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue.

Nausea is more commonly associated with high doses of the drug. The above gastrointestinal symptoms may be minimized by administering the drug at the beginning of a meal.

Very rarely, superficial discoloration of teeth has been observed in children. Proper oral hygiene may prevent this effect. Discoloration can be removed by tooth brushing.

Hepatobiliary disorders: mild elevations in aspartate aminotransferase and/or alanine aminotransferase levels have been observed in patients treated with β-lactam antibiotics, although the clinical significance of this is not established; hepatitis and cholestatic jaundice. These events have been reported with other penicillins and cephalosporins.

Hepatitis has occurred mainly in men and elderly patients, and its occurrence may be related to prolonged treatment with the drug.

Such events are very rare in children.

Symptoms may occur during or immediately after treatment, but in some cases may appear several weeks after completion of therapy. These events are usually reversible. Liver function abnormalities can be severe and very rarely may be fatal. This almost always occurs in patients with severe underlying disease or in patients concurrently receiving medications with hepatotoxic potential.

Skin and subcutaneous tissue disorders: skin rashes, pruritus, urticaria, polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

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.

The reconstituted suspension should be stored at 2–8 °C for up to 7 days; do not freeze.

Packaging.

Powder for the preparation of 70 ml of suspension in a bottle; 1 bottle with a measuring cap in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Unicem Laboratories Limited.

Manufacturer's address and location of business activity.

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