Instructions Amoxiclav 2X film-coated tablets 875 mg + 125 mg No. 14
Composition
active ingredients: amoxicillin, clavulanic acid;
1 tablet contains 875 mg of amoxicillin in the form of trihydrate and 125 mg of clavulanic acid in the form of potassium salt;
excipients: colloidal anhydrous silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, microcrystalline cellulose;
shell: hydroxypropylcellulose, ethylcellulose, polysorbate, triethyl citrate, talc, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white, oblong tablets, film-coated, with beveled edges, a score and embossing "875/125" on one side and embossing "AMS" on the other side.
Pharmacotherapeutic group
Antibacterials for systemic use. ATX code J01C R02.
Pharmacological properties
Pharmacodynamics.
Amoxicillin is a semisynthetic antibiotic with a broad spectrum of antibacterial activity against many gram-positive and gram-negative microorganisms. Amoxicillin is sensitive to β-lactamase and undergoes degradation under its influence, therefore the spectrum of activity of amoxicillin does not include microorganisms that synthesize this enzyme. Clavulanic acid has a β-lactam structure similar to penicillins, as well as the ability to inactivate β-lactamase enzymes inherent in microorganisms that are resistant to penicillins and cephalosporins. In particular, it has pronounced activity against clinically important plasmid β-lactamases, which are often responsible for the emergence of cross-resistance to antibiotics. The presence of clavulanic acid in the composition of the drug protects amoxicillin from degradation by β-lactamase enzymes and expands the spectrum of antibacterial action of amoxicillin, including many microorganisms resistant to amoxicillin and other penicillins and cephalosporins.
The microorganisms listed below are classified according to their susceptibility to amoxicillin/clavulanate in vitro.
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 cholera.
Others: Borrelia burgdorferi, Leptospirosa icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: Clostridium species, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus species.
Gram-negative anaerobes: Bacteroides species (including Bacteroides fragilis), Capnocytophaga species, Eikenella corrodens, Fusobacterium species, Porphyromonas species, Prevotella species.
Strains with possible acquired resistance
Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella species, Proteus mirabilis, Proteus vulgaris, Proteus species, Salmonella species, Shigella species.
Gram-positive aerobes: Corynebacterium species, Enterococcus faecium.
Non-susceptible microorganisms
Gram-negative aerobes: Acinetobacter species, Citrobacter freundii, Enterobacter species, Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia species, Pseudomonas species, Serratia species, Stenotrophomonas maltophilia, Yersinia enterolitica.
Others: Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia species, Coxiella burnetti, Mycoplasma species.
Pharmacokinetics.
The pharmacokinetic parameters of the two components of the drug are closely related. Peak serum concentrations of both components are reached approximately 1 hour after oral administration. Optimal absorption is achieved if the drug is taken at the beginning of a meal.
Doubling the dose increases the serum levels of the drug approximately twofold.
Both components, clavulanate and amoxicillin, have a low level of binding to serum proteins, approximately 70% of them remaining in the serum in an unbound state.
Indication
Treatment of bacterial infections in adults and children caused by microorganisms sensitive to the drug:
– acute bacterial sinusitis;
– 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 widespread cellulitis;
– infections of bones and joints, including osteomyelitis.
Contraindication
Hypersensitivity to any components 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 liver dysfunction associated with the use of amoxicillin/clavulanate.
Interaction with other medicinal products and other types of interactions
Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions. There are no data on the concomitant use of allopurinol and Amoxiclav® 2X.
Like other antibiotics, Amoxiclav® 2X may have an effect on the intestinal flora, leading to reduced reabsorption of estrogens and reduced effectiveness of combined oral contraceptives.
There are isolated reports of increased international normalized ratio (INR) in patients treated with acenocoumarol or warfarin and taking amoxicillin. If such use is necessary, prothrombin time or INR should be closely monitored with the addition or withdrawal of a combination product containing amoxicillin.
In patients treated with mycophenolate mofetil, the overdosage concentration of the active metabolite of mycophenolic acid may decrease by approximately 50% after initiation of oral amoxicillin/clavulanic acid. This change in overdosage level may not accurately reflect the change in total exposure to mycophenolic acid.
Penicillins may reduce the excretion of methotrexate, which may lead to increased toxicity of the latter.
Application features
Before starting therapy with the drug, it is necessary to accurately determine the presence of a history of hypersensitivity reactions to penicillins, cephalosporins or other allergens.
Serious and sometimes fatal cases of hypersensitivity (anaphylactic reactions) have been reported in patients receiving penicillin therapy. These reactions are more likely to occur in individuals with a history of similar reactions to penicillin (see section 4.3). If allergic reactions occur, Amoxiclav® 2X should be discontinued and alternative therapy instituted.
If the infection is proven to be caused by microorganisms susceptible to amoxicillin, consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official recommendations.
This dosage form of Amoxiclav® 2X should not be used in cases of high risk of pathogens being resistant to β-lactams, and is not used to treat pneumonia caused by penicillin-resistant strains of S. pneumoniae.
The drug should not be prescribed if infectious mononucleosis is suspected, since cases of choreoid rashes have been observed when amoxicillin was used for this pathology.
Prolonged use of the drug can sometimes cause excessive growth of microflora insensitive to it.
The development of erythema multiforme associated with pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (see section "Adverse reactions"). In such cases, treatment should be discontinued and further use of amoxicillin is contraindicated.
The drug should be administered with caution to patients with signs of hepatic insufficiency (see sections "Method of administration and dosage", "Contraindications", "Adverse reactions"). Adverse reactions from the liver occurred mainly in men and elderly patients and were associated with long-term treatment. Such events have been reported very rarely in children. In all patient groups, symptoms and signs usually occurred during or immediately after treatment, but in some cases they appeared several months after discontinuation of treatment. In general, these events were reversible. Adverse reactions from the liver can be severe and very rarely fatal. They always occurred in patients with severe concomitant diseases or with concomitant use of drugs known to have a potential negative effect on the liver (see section "Adverse reactions").
Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life-threatening (see section 4.8). Therefore, it is important to keep this in mind when patients develop diarrhoea during or after antibiotic therapy. If antibiotic-associated colitis occurs, treatment with the drug should be discontinued immediately, a doctor should be consulted and appropriate treatment should be initiated.
With prolonged therapy, periodic assessment of organ and organ system functions, including renal, hepatic, and hematopoietic function, is recommended.
Rarely, patients taking Amoxiclav® 2X and oral anticoagulants may experience prolongation of prothrombin time (increased INR). When anticoagulants are taken concomitantly, appropriate monitoring of laboratory parameters is necessary. Dose adjustment of oral anticoagulants may be necessary to maintain the required level of coagulation.
For patients with renal impairment, the dose should be adjusted according to the degree of renal impairment (see section "Method of administration and dosage").
In patients with reduced urine output, crystalluria may occur very rarely, mainly with parenteral administration of the drug. Therefore, to reduce the risk of crystalluria, it is recommended to maintain a balance between fluid intake and urine output during treatment with high doses of amoxicillin (see section "Overdose").
The presence of clavulanic acid in the drug may cause nonspecific binding of IgG and albumin on erythrocyte membranes, resulting in a false-positive result when performing the Coombs test.
False-positive Aspergillus test results have been reported in patients receiving amoxicillin/clavulanic acid (using the Bio-Rad Laboratories Platelis Aspergillus EIA test). Therefore, such positive results in patients receiving amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.
Use during pregnancy or breastfeeding
Animal reproduction studies (at doses 10 times the human dose) of oral and parenteral forms of Amoxiclav® 2X did not reveal any teratogenic effects. In one study involving women with premature rupture of membranes, it was reported that prophylactic use of the drug may be associated with an increased risk of necrotizing enterocolitis in newborns. As with other drugs, the use of the drug should be avoided during pregnancy, especially in the first trimester, unless the benefit of the drug outweighs the potential risk.
Both active components of the drug are excreted in breast milk (there is no information on the effects of clavulanic acid on breast-fed infants). Accordingly, diarrhea and fungal infection of the mucous membranes may occur in breast-fed infants, so breastfeeding should be discontinued.
The drug can be used during breastfeeding only if, in the opinion of the doctor, the benefit of use outweighs the risk.
Ability to influence reaction speed when driving vehicles or other mechanisms
No studies have been conducted to study the ability of the drug to affect the reaction speed when driving or using other mechanisms. However, adverse reactions (e.g. allergic reactions, dizziness, convulsions) may occur that may affect the ability to drive or use other mechanisms.
Method of administration and doses
The product should be used in accordance with official antibiotic treatment guidelines and local antibiotic susceptibility data. Susceptibility to amoxicillin/clavulanate varies between regions and may change over time. Local susceptibility data should be consulted if available and microbiological determination and susceptibility testing should be performed as appropriate.
The suggested dose range depends on the expected pathogens and their susceptibility to antibacterial drugs, the severity of the disease and the location of the infection, the age, body weight and renal function of the patient.
For adults and children weighing ≥ 40 kg, the daily dose is 1750 mg amoxicillin/250 mg clavulanic acid (2 tablets), the daily dose should be divided into 2 doses.
For children weighing < 40 kg, the maximum daily dose is 1000-2800 mg amoxicillin/143-400 mg clavulanic acid when administered as indicated below.
If higher doses of amoxicillin are required for treatment, other forms of the combination drug should be used to avoid prescribing unnecessarily high doses of clavulanic acid.
The duration of treatment should be determined by the patient's clinical response to treatment. Some infections (e.g. osteomyelitis) require longer treatment.
Children weighing < 40 kg
Recommended doses range from 25 mg/3.6 mg/kg body weight/day to 45 mg/6.4 mg/kg body weight/day, divided into 2 doses.
Elderly patients
No dose adjustment is required for elderly patients. If necessary, the dose should be adjusted based on renal function.
Dosage in hepatic impairment
Use with caution, monitor liver function at regular intervals. Data are insufficient to make dosage recommendations.
Dosage in renal impairment
The drug should only be prescribed for the treatment of patients with creatinine clearance greater than 30 ml/min. In renal failure with creatinine clearance less than 30 ml/min, the drug should not be used.
The tablet should be swallowed whole without chewing. If necessary, the tablet can be broken in half and swallowed whole without chewing.
For optimal absorption and reduction of possible side effects from the digestive tract, 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 assessing the patient's condition.
Treatment can be initiated with parenteral administration and then continued with oral administration.
Children.
The drug in this dosage is not recommended for the treatment of children under 12 years of age.
Overdose
Overdose may be accompanied by gastrointestinal symptoms and disturbances of water and electrolyte balance. These phenomena should be treated symptomatically, paying attention to the correction of water and electrolyte balance. Cases of crystalluria have been reported, sometimes leading to renal failure (see section "Special instructions"). The drug can be removed from the bloodstream by hemodialysis.
Adverse reactions
Adverse reactions have been classified according to their frequency of occurrence - from very common to very rare. The following classification of the frequency of occurrence of adverse reactions is used: very common ≥ 1/10; common ≥ 1/100 and < 1/10; uncommon ≥ 1/1000 and < 1/100; rare ≥ 1/10000 and < 1/1000; very rare < 1/10000.
Infections and infestations: Common: candidiasis of the skin and mucous membranes; very rare: overgrowth of non-susceptible microorganisms.
Hematopoietic and lymphatic system disorders: Rarely - reversible leukopenia (including neutropenia) and thrombocytopenia; very rarely - reversible agranulocytosis and hemolytic anemia. Increased bleeding time and prothrombin index.
Allergic reactions: Very rare: angioedema, anaphylaxis, serum sickness syndrome, allergic vasculitis.
Nervous system: Uncommon: dizziness, headache; very rare: reversible hyperactivity, aseptic meningitis and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses of the drug.
Gastrointestinal tract. Adults. Very common: diarrhea; common: nausea, vomiting.
Children: Often – diarrhea, nausea, vomiting.
Nausea is more commonly associated with high doses of the drug. The above gastrointestinal symptoms may be reduced by taking the drug at the beginning of a meal.
Uncommon: indigestion.
Very rare: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis - see section "Special warnings and precautions for use"), black "hairy" tongue.
Hepatobiliary reactions. Uncommon: Moderate elevations of AST and/or ALT have been reported in patients treated with β-lactam antibiotics; very rare: hepatitis and cholestatic jaundice. These events have been reported with other penicillins and cephalosporins. Hepatitis occurs predominantly in men and the elderly and may be associated with prolonged treatment. In children, such events have been reported very rarely. Signs and symptoms of the disease occur during or immediately after treatment, but in some cases may occur several weeks after the end of treatment. These events are usually reversible. Fatalities have been extremely rare and always occur in patients with severe underlying disease or in patients receiving concomitant medications that have a negative effect on the liver.
Skin and subcutaneous tissue disorders: Uncommon: skin rash, pruritus, urticaria; rare: erythema multiforme; very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. If any allergic dermatitis occurs, treatment should be discontinued.
Kidneys and urinary system.
Very rare: interstitial nephritis, crystalluria (see section "Overdose").
Expiration date
2 years.
Storage conditions
Store at a temperature not exceeding 25 °C in the original packaging.
Keep out of reach of children.
Packaging
7 tablets in a blister; 2 (7 × 2) blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Lek Pharmaceuticals dd, Slovenia.
Location of the manufacturer and its business address.
Personali 47, 2391 Prevalje, Slovenia/Perzonali 47, Prevalje 2391, Slovenia (full cycle production).
Verovskova 57, 1526 Ljubljana, Slovenia (series release).
