Amoxiclav powder for oral suspension 250 mg/5 ml + 62.5 mg/5 ml vial for suspension preparation 100 ml

Instructions Amoxiclav powder for oral suspension 250 mg/5 ml + 62.5 mg/5 ml vial for suspension preparation 100 ml

Composition

active ingredients: amoxicillin, clavulanic acid;

5 ml of oral suspension contains 250.00 mg of amoxicillin, equivalent to 287.03 mg of amoxicillin trihydrate, and 66.88 mg (including an excess of 7%) of clavulanic acid, equivalent to 79.71 mg of potassium clavulanate;

Excipients: colloidal anhydrous silicon dioxide, xanthan gum, strawberry flavor, crospovidone, aspartame, carmellose sodium, anhydrous silicon dioxide.

Dosage form

Powder for oral suspension.

Main physicochemical properties: white to cream powder.

Pharmacotherapeutic group

Antibacterials for systemic use. Beta-lactam antibiotics, penicillins. Combinations of penicillins with beta-lactamase inhibitors. ATX code J01C R02.

Pharmacological properties

Pharmacodynamics.

Mechanism of action

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic metabolism of bacterial peptidoglycan, an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, resulting in cell lysis and death.

Amoxicillin is susceptible to cleavage by beta-lactamases produced by resistant bacteria, therefore the spectrum of activity of amoxicillin as monotherapy does not include organisms that produce these enzymes.

Clavulanic acid is a beta-lactam structurally related to the penicillins. It inactivates some beta-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid as monotherapy does not have a clinically useful antibacterial effect.

FC/FD ratio

The time above the minimum inhibitory concentration (C > MIC) is considered the main factor determining efficacy for amoxicillin.

Resistance mechanisms

There are two mechanisms of resistance to amoxicillin/clavulanic acid:

inactivation by bacterial beta-lactamases that are not inhibited by clavulanic acid themselves, including class B, C and D;

conversion of PZB, which reduces the affinity of the antibacterial drug to the target.

Bacterial impermeability or the reflux pump mechanism can cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

Limit values

MIC breakpoints for amoxicillin/clavulanic acid established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

The prevalence of resistance may vary geographically and over time for individual species, so local susceptibility information is desirable, particularly when treating severe infections. Expert opinion should be sought when the local prevalence of resistance is such that the utility of the agent, at least in some types of infections, is questionable.

Gram-negative aerobes: Acinetobacter sp., Citrobacter freundii, Enterobacter sp., Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas sp., Serratia sp., Stenotrophomonas maltophilia.

Other microorganisms:

Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetti, Mycoplasma pneumoniae

Pharmacokinetics.

Absorption. Amoxicillin and clavulanic acid completely dissociate in aqueous solution at physiological pH. Both components are rapidly and well absorbed after oral administration. The bioavailability of amoxicillin and clavulanic acid is approximately 70% after oral administration. The plasma profiles of both components are identical and the time to maximum plasma concentration (Tmax) for each component is approximately one hour.

Serum concentrations of amoxicillin and clavulanic acid achieved with amoxicillin/clavulanic acid are identical to those achieved with oral administration of equivalent doses of amoxicillin or clavulanic acid alone.

Distribution: Approximately 25% of the total plasma clavulanic acid and 18% of the total plasma amoxicillin are protein bound. The apparent volume of distribution is approximately 0.3–0.4 L/kg for amoxicillin and approximately 0.2 L/kg for clavulanic acid.

After intravenous administration, amoxicillin and clavulanic acid have been found in the gallbladder, abdominal tissue, skin, adipose tissue, muscle tissue, synovial and peritoneal fluids, bile and pus. Amoxicillin does not distribute sufficiently in the cerebrospinal fluid.

Animal studies have not revealed any evidence of significant retention of substances derived from any component of the drug in body tissues. Amoxicillin, like most penicillins, can be found in breast milk. Small amounts of clavulanic acid can also be found in breast milk (see section "Use during pregnancy or lactation").

Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see section “Use during pregnancy or lactation”).

Biotransformation: Amoxicillin is partially excreted in the urine as inactive penicilloic acid in amounts equivalent to 10-25% of the initial dose. Clavulanic acid is extensively metabolized in humans and is excreted in the urine and feces and as carbon dioxide in exhaled air.

Excretion: The primary route of excretion of amoxicillin is the kidney, while clavulanic acid is excreted both renally and by extrarenal mechanisms.

In healthy volunteers, the mean elimination half-life of amoxicillin/clavulanic acid is approximately one hour and the mean total clearance is approximately 25 l/h. Various studies have shown that urinary excretion is 50–85% for amoxicillin and 27–60% for clavulanic acid over a 24-hour period. In the case of clavulanic acid, the largest amount of the substance is excreted within the first 2 hours after administration.

Concomitant use of probenecid slows down the elimination of amoxicillin, but does not delay the renal excretion of clavulanic acid (see section "Interaction with other medicinal products and other types of interactions").

Age. The half-life of amoxicillin is identical for children aged 3 months to 2 years, older children and adults. For children (including premature infants) in the first week of life, the frequency of administration should not exceed twice a day due to the immaturity of the renal excretion pathway. Since elderly patients are more prone to decreased renal function, dosage should be selected with caution, and monitoring of renal function is also recommended.

Renal impairment. The total serum clearance of amoxicillin/clavulanic acid decreases proportionally with decreasing renal function. The decrease in drug clearance is more pronounced for amoxicillin than for clavulanic acid, since a greater proportion of amoxicillin is excreted by the kidneys. In renal insufficiency, the dosage should prevent excessive accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section 4.2).

Hepatic impairment. Patients with hepatic insufficiency are recommended to use the drug with caution and regularly monitor liver function.

Indication

Treatment of bacterial infections in adults and children 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 widespread cellulitis;

infections of bones and joints, including osteomyelitis.

When prescribing antibacterial drugs, one should follow the rules for their proper use.

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 probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin.

Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions. There are no data on the simultaneous use of allopurinol and Amoxiclav®.

Like other antibiotics, Amoxiclav® may have an effect on the intestinal flora, leading to reduced reabsorption of estrogens and reduced efficacy of combined oral contraceptives.

There have been 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.

Amoxiclav® should not be used together with bacteriostatic chemotherapeutic agents/antibiotics (chloramphenicol, macrolides, tetracyclines or sulfonamides), since antagonistic effects have been observed in vitro with such combinations.

Penicillins may reduce the excretion of methotrexate, which may lead to a potential increase in toxicity.

When amoxicillin/clavulanic acid was co-administered with mycophenolate mofetil, a decrease in plasma concentrations of the active metabolite mycophenolic acid by approximately 50% has been reported. This change in the overdosage level may not fully reflect the change in total mycophenolic acid exposure. Therefore, a change in the dosage of mycophenolate mofetil is not usually necessary unless there is clinical evidence of graft dysfunction. However, close monitoring is necessary during concomitant use and for some time after antibiotic therapy.

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 hypersensitivity reactions, some of which were fatal (including anaphylactoid and severe cutaneous adverse reactions), have been reported in patients treated with penicillin. Hypersensitivity reactions may also progress to Kounis syndrome, a serious allergic reaction that may lead to myocardial infarction (see section 4.8). Such reactions are more likely to occur in patients with a history of penicillin hypersensitivity and in patients with atopic diseases. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate alternative therapy should be initiated. If the infection is proven to be caused by amoxicillin-susceptible organisms, consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidelines.

This dosage form of Amoxiclav® should not be used in cases of high risk of pathogens developing resistance to β-lactams, and should not be used to treat pneumonia caused by penicillin-resistant strains of S. pneumoniae. Insufficient efficacy of the drug due to resistance of microorganisms has been reported.

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

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 Amoxiclav® and the development of pseudomembranous colitis of varying severity. In the presence of severe persistent diarrhea after the use of antimicrobial agents, it is important to make sure that it is not associated with the specified pathology. Drugs that inhibit peristalsis are contraindicated. In the event of antibiotic-associated colitis, treatment with the drug should be stopped immediately, consult a doctor and begin appropriate treatment.

With long-term use of the drug, as with other broad-spectrum antibiotics, superinfection with resistant bacteria and fungi (Pseudomonas spp, Candida albicans) may occur, which requires discontinuation of therapy and the use of other drugs.

With prolonged therapy, periodic assessment of organ and organ system functions, including renal, hepatic, and hematopoietic function, is recommended.

Isolated cases of severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis) requiring discontinuation of the drug have been reported during treatment.

The use of the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns (see section "Use during pregnancy or breastfeeding").

Occasionally, patients taking Amoxiclav® and oral anticoagulants may experience an abnormal prolongation of prothrombin time (increased INR). Appropriate monitoring is required when anticoagulants are taken concomitantly. Dose adjustment of oral anticoagulants may be necessary to maintain the required level of anticoagulation.

The drug should be administered with caution to patients with signs of hepatic insufficiency. 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. These events were generally 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.

For patients with renal impairment, the dose should be adjusted according to the degree of impairment.

In patients with reduced urine output, crystalluria (including acute kidney injury) has been observed very rarely, mainly with parenteral therapy. Adequate fluid intake and diuresis should be maintained during high doses of amoxicillin to reduce the likelihood of amoxicillin crystalluria. In patients with bladder catheterization, the patency of the catheters should be checked regularly (see sections "Adverse Reactions" and "Overdose").

When using high doses, amoxicillin may precipitate in a catheter inserted into the bladder. In such cases, regular monitoring of the condition of the catheter is necessary.

During treatment with amoxicillin, enzymatic reactions with glucose oxidase should be used to determine the level of glucose in the urine, as other methods may give false-positive results.

The presence of clavulanic acid in the drug may cause nonspecific binding of IgG and albumin on erythrocyte membranes, therefore, as a result, a false-positive result is possible when performing the Coombs test.

There have been reports of false-positive Aspergillus test results in patients receiving amoxicillin/clavulanic acid (using the Bio-Rad Laboratories Platelis Aspergillus EIA test) who were subsequently found to have no aspergillosis. Cross-reactions with non-aspergillus polysaccharides and polyfuranoses have been reported in the Aspergillus enzyme immunoassay test. Therefore, such positive results should be interpreted with caution and confirmed by other diagnostic methods.

Concomitant use of allopurinol during treatment with amoxicillin increases the likelihood of allergic skin reactions.

Prolonged use in some cases may lead to excessive reproduction of microorganisms insensitive to the drug.

Antibiotic-associated colitis has been reported with nearly all antibacterial agents, including amoxicillin, and may range in severity from mild to life-threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhea during or after taking any antibiotic. If antibiotic-associated colitis occurs, Amoxiclav should be discontinued immediately, medical advice should be sought, and appropriate treatment should be initiated. The use of anti-peristaltic agents is contraindicated in such cases.

Drug-induced enterocolitis syndrome (DIES) has been reported, mainly in children receiving amoxicillin/clavulanic acid (see section 4.8). Drug-induced enterocolitis syndrome is an allergic reaction with the main symptom being prolonged vomiting (1-4 hours after the drug) in the absence of allergic skin or respiratory symptoms. Additional symptoms may include abdominal pain, diarrhoea, hypotension or leukocytosis with neutrophilia. Serious cases, including progression to shock, have been reported.

Use during pregnancy or breastfeeding

Breastfeeding. Both active components of the drug are excreted in breast milk (there is no information on the effect of clavulanic acid on a breastfed infant). Accordingly, diarrhea and fungal infection of the mucous membranes may occur in a breastfed infant, so breastfeeding should be discontinued. The possibility of allergic reactions should be taken into account. Amoxiclav 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

Doses are given in units of amoxicillin/clavulanic acid.

When selecting the dose of Amoxiclav®, the following should be taken into account:

expected pathogenic microorganisms and their likely sensitivity to active substances;

severity and location of infection;

the patient's age, body weight, and kidney function status.

If necessary, the use of alternative forms of Amoxiclav® (for example, those containing higher doses of amoxicillin and/or a different ratio 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 assessing the patient's condition.

Adults and children weighing ≥ 40 kg: 500 mg/125 mg 3 times a day.

Children weighing < 40 kg: 20 mg/5 mg per kg body weight per day (for mild to moderate infections) to 60 mg/15 mg per kg body weight per day (for severe infections) in three divided doses. The maximum daily dose is 2400 mg/600 mg.

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

There are no clinical data on the use of Amoxiclav® in suspension for the treatment of children under 2 months of age, therefore no dosage recommendations exist.

To measure the suspension, a measuring spoon with graduations of 1.25 / 2.5 / 5 ml is included, or a measuring syringe with a volume of 5 ml with a graduation of 0.1 ml.

The measuring syringe is graduated to ensure accurate and repeatable dosing. The amount of suspension should be calculated according to the child's body weight, not their age. Each

The same doses of the drug should be administered every 8 hours.

Elderly patients: No dose adjustment is required.

Renal impairment: Dose adjustment is based on the maximum recommended dose of amoxicillin and depends on glomerular filtration rate. No dose adjustment is required for patients with creatinine clearance greater than 30 ml/min.

Adults and children weighing ≥ 40 kg

Children weighing < 40 kg

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

Method of administration. For optimal absorption and reduction of possible side effects from the digestive tract, the drug should be taken at the beginning of a meal.

Treatment can be started with parenteral administration of the drug, and then continued with the oral form of the drug.

Preparation of the suspension. After opening the screw cap, ensure that the seal of the bottle cap is intact and firmly attached to the bottle rim.

Shake the bottle to separate the powder from the walls and bottom. Add drinking water in two portions (first to 2/3 of the bottle, and then to the circular mark on the label), shaking the bottle each time. SHAKE WELL BEFORE EACH USE.

Do not use this medicine if lumps of powder are visible in the bottle before reconstitution.

After reconstitution, the suspension should be white to cream in color.

Do not use the reconstituted suspension if its color does not match that specified above.

Children.

The drug in suspension form should be prescribed to children aged 2 months and older.

Overdose

Symptoms

Gastrointestinal symptoms and fluid and electrolyte imbalance may occur. Amoxicillin crystalluria has been reported, leading in some cases to renal failure (see section 4.4).

In patients with impaired renal function and in patients taking high doses of the drug, seizures may occur.

Amoxicillin has been reported to settle in bladder catheters, mainly after intravenous administration at high doses. Catheter patency should be checked regularly (see section 4.4).

Gastrointestinal disturbances can be treated symptomatically, with attention to fluid/electrolyte balance.

Amoxicillin/clavulanic acid can be removed from the bloodstream by hemodialysis.

Side effects

The side effects have been classified according to their frequency of occurrence - from very common to very rare. The following classification of the frequency of occurrence of side effects is used:

very often ≥ 1/10; often ≥ 1/100 and < 1/10; infrequently ≥ 1/1000 and < 1/100; rarely ≥ 1/10000 and < 1/1000; very rarely < 1/10000.

Infections and infestations: Common: candidiasis of the skin and mucous membranes. Very rare: overgrowth of non-susceptible microflora.

From the side of the hematopoietic and lymphatic system. Rarely - reversible leukopenia (including neutropenia) and thrombocytopenia. Very rarely - reversible agranulocytosis and hemolytic anemia. Increased bleeding time and prothrombin index.

Immune system disorders: Very rare: angioedema, anaphylaxis, serum sickness syndrome, allergic vasculitis.

Nervous system disorders: 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. Not known: aseptic meningitis.

Cardiac system: Unknown – Kounis syndrome.

From the digestive tract. Adults: Very common - diarrhea. Common - nausea, vomiting.

Children: Common: Diarrhea, nausea, vomiting. Isolated reports of tooth discoloration, which can be resolved by brushing.

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), black hairy tongue. Very rarely, superficial tooth discoloration has been observed in children. Proper oral care can prevent this phenomenon. The discoloration can be eliminated by brushing the teeth.

In one study in women with premature rupture of membranes, it was reported that the use of the drug may be associated with an increased risk of necrotizing enterocolitis in newborns. Not known - drug-induced enterocolitis syndrome (DIES), acute pancreatitis.

On the part of the hepatobiliary system. Infrequently - a moderate increase in AST and/or ALT levels is noted in patients treated with β-lactam antibiotics. Very rarely - hepatitis and cholestatic jaundice. These phenomena occur when using other penicillins and cephalosporins. Hepatitis occurs mainly in men and elderly patients, their occurrence may be associated with long-term treatment with the drug.

Such phenomena occurred very rarely in children.

Symptoms of the disease occur during or immediately after treatment, but in some cases may occur several weeks after the end of treatment. These phenomena are usually reversible. Fatal cases have been observed extremely rarely (less than 1 report per approximately 4 million prescriptions), which always occurred in patients with severe underlying disease or in patients who are simultaneously treated with drugs 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, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome).

If any allergic dermatitis occurs, treatment should be discontinued. Unknown - linear immunoglobulin A (IgA) disease.

Renal and urinary disorders: Very rare: interstitial nephritis, Not known: crystalluria (including acute kidney injury).

Expiration date

36 months.

Storage conditions

Store at a temperature not exceeding 30 °C.

Keep out of reach of children.

Store the vial with the ready-to-use suspension at 2-8°C for no more than 7 days.

Packaging

15.8 g of powder in a bottle; 1 bottle together with a measuring spoon or measuring syringe in a cardboard box.

Vacation category

According to the recipe.

Producer

Sandoz GmbH – Production site Anti-infectives and Chemical Operations Kundl (AIHO Kundl).

Location of the manufacturer and address of its place of business.

Biochemiststrasse 10, 6250 Kundl, Austria