Maiclav

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

Composition:

Active substances: amoxicilline, clavulanic acid;

5 ml of suspension contain amoxicillin 125 mg (as amoxicillin trihydrate) and clavulanic acid 31.25 mg (as potassium clavulanate);

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

Pharmaceutical form. Powder for oral suspension.

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

MaiKlav is a combination of amoxicillin, a broad-spectrum penicillin-class antibiotic, and clavulanic acid, an irreversible inhibitor of β-lactamases that forms an inactive complex with these enzymes and protects amoxicillin from degradation. Potassium clavulanate has weak antibacterial activity and does not interfere with the mechanism of action of amoxicillin. Since clavulanic acid inhibits β-lactamases that normally inactivate amoxicillin, the combination of amoxicillin and clavulanic acid is effective against many microorganisms producing β-lactamases that are resistant to amoxicillin.

The combination is active both in vitro and in clinical infections against Gram-positive and Gram-negative microorganisms, whether or not they produce penicillinase:

• Gram-positive aerobes: penicillin-sensitive strains of Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive strains of Staphylococcus aureus, Listeria spp., Enterococcus faecalis, Enterococcus faecium, Corynebacterium spp.;
• Gram-positive anaerobes: Peptococcus spp., Peptostreptococcus spp., Clostridium perfringens, Actinomyces israelii;
• Gram-negative aerobes: Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Salmonella spp., Shigella spp., Vibrio cholerae, Helicobacter pylori, Bordetella pertussis;
• Gram-negative anaerobes: Bacteroides spp., Fusobacterium spp., Prevotella spp.

Resistant to MaiKlav are Pseudomonas aeruginosa, methicillin-resistant strains of Staphylococcus aureus, Legionella spp., Chlamydia spp., Mycoplasma spp.

Pharmacokinetics

The main pharmacokinetic properties of amoxicillin and clavulanic acid are similar. Both components are well absorbed after oral administration; food does not affect the extent of absorption. Maximum serum concentrations are reached approximately 1–2 hours after administration. Both components are characterized by a high volume of distribution into body fluids and tissues (lungs, middle ear exudate, maxillary sinus secretions, nasal sinus secretions, pleural and peritoneal fluid, prostate gland, tonsils, sputum, bronchial secretions, liver, gallbladder, uterus, ovaries, synovial fluid). Amoxicillin and clavulanic acid do not cross the blood-brain barrier when the meninges are not inflamed.

Both components cross the placental barrier and are present in small amounts in breast milk.

Amoxicillin and clavulanic acid are characterized by low plasma protein binding.

Both components are eliminated by the kidneys; amoxicillin is metabolized by 10–20%, while clavulanic acid is metabolized by nearly 50%. A small amount may be excreted via the intestine and lungs. The elimination half-life of amoxicillin and clavulanic acid is 1–1.5 hours, increasing to 7.5 hours and 4.5 hours, respectively, in patients with severe renal impairment. Both substances are effectively removed by hemodialysis, but only minimally by peritoneal dialysis.

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, 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 hepatic dysfunction associated with the use of amoxicillin/clavulanate.

Interaction with other medicinal products and other types of interactions.

MaiKlav should not be used concomitantly with bacteriostatic chemotherapeutic agents/antibiotics (chloramphenicol, macrolides, tetracyclines, or sulfonamides), as an antagonistic effect has been observed in vitro with such combinations.

Concomitant use with allopurinol increases the risk of skin rashes.

Simultaneous administration of MaiKlav and methotrexate may increase the toxicity of the latter (leukopenia, thrombocytopenia, skin ulceration).

Probenecid reduces tubular secretion of amoxicillin; therefore, concomitant use of probenecid with MaiKlav may lead to increased blood levels of amoxicillin. Elevated amoxicillin levels may persist for a prolonged period. This does not apply to clavulanic acid.

Like other broad-spectrum antibiotics, MaiKlav may reduce the effectiveness of oral contraceptives.

In some cases, concomitant use of MaiKlav with oral anticoagulants may prolong prothrombin time; therefore, such combination requires caution. Amoxicillin may reduce plasma concentrations of sulfasalazine.

Concomitant administration of the drug with digoxin may increase the extent of absorption of the latter.

MaiKlav should not be used concomitantly with disulfiram.

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

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 MaiKlav should be discontinued if necessary.

Myophenolate 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 Myklav, it is essential to determine whether the patient has a history of hypersensitivity reactions to penicillins, cephalosporins, or other allergens. Severe allergic reactions (including anaphylactoid reactions) most commonly occur in patients with a history of hypersensitivity to penicillins. In the event of allergic reactions, therapy with Myklav should be discontinued and appropriate alternative treatment initiated.

If it has been established that the infection is caused by microorganisms sensitive to amoxicillin, it may be possible to switch from the combination amoxicillin/clavulanic acid to amoxicillin alone, in accordance with official recommendations.

Prolonged use of the drug may occasionally lead to overgrowth of microorganisms not susceptible to it. The drug should not be used for the treatment of S. pneumoniae that is penicillin-resistant.

Seizures may occur in patients with impaired renal function or in those receiving high doses of the drug.

The development of generalized erythema at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis. In such cases, Myklav must be discontinued, and subsequent administration of amoxicillin is contraindicated.

Myklav should be discontinued if there is suspicion of infectious mononucleosis or lymphocytic leukemia, as the development of a measles-like rash in these conditions may be associated with amoxicillin intake.

Rarely, prolonged prothrombin time may occur in patients taking Myklav. Appropriate monitoring is required when anticoagulants are used concomitantly.

Myklav should be administered with caution in patients with hepatic dysfunction. Adverse reactions affecting the liver occur predominantly in men and elderly patients, and may also be associated with prolonged use of the drug. Symptoms arise during or immediately after treatment, but in some cases may appear several weeks after completion of therapy. These effects are usually reversible. Fatal cases have been reported extremely rarely – in patients with severe underlying disease or those receiving concomitant medications with hepatotoxic potential.

Antibiotic use may lead to the development of pseudomembranous colitis of varying severity. In cases of severe persistent diarrhea following antimicrobial therapy, it is important to rule out this condition. Medications that inhibit peristalsis are contraindicated.

In cases of prolonged treatment, regular monitoring of renal and liver function and hematological tests are recommended.

Dosage adjustment is required for patients with impaired renal function, depending on the degree of impairment. Crystalluria may very rarely occur in patients with reduced urine output, primarily following parenteral administration of the drug.

When monitoring blood glucose levels during amoxicillin therapy, enzymatic methods using glucose oxidase are recommended, as other methods may yield false-positive results.

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

There have been reports of false-positive test results for Aspergillus in patients receiving amoxicillin/clavulanic acid.

The medicinal product contains aspartame (E 951), a source of phenylalanine; therefore, the drug should be used with caution in patients with phenylketonuria.

Use during pregnancy or breastfeeding.

There is no evidence of teratogenic effects of the drug.

In one study, use of the drug in women with premature rupture of fetal membranes was associated with an increased risk of necrotizing enterocolitis in newborns. Amoxicillin/clavulanic acid should be avoided during pregnancy unless the potential benefit justifies the potential risk.

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

Ability to affect reaction speed while driving or operating machinery.

No negative effect on reaction speed during driving or operating machinery has been observed; however, the possibility of dizziness as a potential adverse effect should be taken into account.

Dosage and Administration.

Dosages are specified in units of amoxicillin/clavulanic acid.

When selecting the dose of Mайkлав (Mайkлав is a brand name for amoxicillin/clavulanic acid), the following factors should be considered:

• The likely pathogenic microorganisms and their probable susceptibility to the active ingredients;
• The severity and site of infection;
• The patient's age, body weight, and renal function.

If necessary, the appropriateness of using alternative formulations of Mайkлав (e.g., those containing higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered.

The duration of therapy depends on the course of the disease. Treatment should not be continued for more than 14 days without re-evaluation of the patient's condition.

Adults and children with body weight ≥ 40 kg: Another pharmaceutical form of the amoxicillin/clavulanic acid combination should be used.

Children with body weight < 40 kg: From 20 mg/5 mg to 60 mg/15 mg per 1 kg of body weight per day, depending on the severity of infection (lower dose for mild to moderate infections, higher dose for severe infections), administered in three divided doses. The maximum daily dose of the drug is 2400 mg/600 mg.

Children under 2 years of age should receive no more than 40 mg/10 mg per kg of body weight per day.

There are no clinical data on the use of Mайkлав oral suspension for the treatment of children under 2 months of age; therefore, dosage recommendations are not available.

The volume of suspension must be calculated according to the child's body weight, not age. Equal doses should be administered every 8 hours.

Renal impairment. Dose adjustment is based on the maximum recommended doses of amoxicillin and depends on the glomerular filtration rate. For patients with creatinine clearance above 30 mL/min, dose adjustment is not required.

Children with body weight < 40 kg

Hepatic impairment. Use the drug with caution. Liver function should be monitored regularly.

Route of administration

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

Treatment may be initiated with parenteral administration of the drug, followed by continuation with the oral formulation.

Preparation of the suspension

The powder contained in the vial should be reconstituted to form a suspension as described below.

1. Check the vial cap for any signs of prior opening.
2. Invert and shake the vial to loosen the powder.
3. Add boiled water to the vial containing the powder up to the level indicated by the line.
4. Close with the cap and shake the vial until a suspension is formed.
5. Then add the remaining water up to the upper level indicated by the line and shake again.
6. Allow the suspension to stand for 5 minutes to ensure complete dispersion of the powder.
7. Shake the suspension thoroughly before each use.

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

Children.

The suspension formulation of 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 conditions should be treated symptomatically, with attention to correction of fluid and electrolyte imbalances. Cases of crystalluria have been reported, which occasionally led to renal failure. Seizures may occur in patients with impaired renal function or in those receiving high doses of the drug. Hemodialysis is effective.

Adverse Reactions.

Infections and infestations: skin and mucosal candidiasis, development of superinfection.

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

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

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

Gastrointestinal disorders: diarrhea, nausea, vomiting, anal pruritus, digestive disturbances, abdominal pain, stomatitis, antibiotic-associated colitis (including hemorrhagic and pseudomembranous colitis), black hairy tongue, tooth discoloration which can be removed by tooth brushing.

Hepatobiliary disorders: mild elevations in AST, ALT, lactate dehydrogenase, alkaline phosphatase, hepatitis, cholestatic jaundice.

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, hematuria.

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

Packaging.

Powder for the preparation of 100 ml of suspension in a bottle; 1 bottle with a measuring cap in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Unique Laboratories Limited.

Manufacturer's address and place of business.

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