Augmentin powder for oral suspension 200 mg/28.5 mg in 5 ml bottle 70 ml

Instructions Augmentin powder for oral suspension 200 mg/28.5 mg in 5 ml bottle 70 ml

Composition

active ingredients: amoxicillin, clavulanic acid;

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

excipients: xanthan gum, aspartame (E 951), succinic acid, colloidal anhydrous silicon dioxide, hydroxypropyl methylcellulose, dry orange flavors (1 and 2), dry raspberry flavor, dry "Light molasses" flavor, silicon dioxide.

Dosage form

Powder for oral suspension.

Main physicochemical properties: white or off-white free-flowing 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 (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 Augmentin, 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;

bone and joint infections, including osteomyelitis.

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

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 beta-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

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics are widely used in clinical practice without any reports of interactions. However, cases of increased international normalization ratio have been described in patients taking acenocoumarol or warfarin who were prescribed a course of amoxicillin. If concomitant use of such drugs is necessary, the prothrombin index or international normalization ratio should be carefully monitored when amoxicillin is added or discontinued. In addition, dose adjustment of oral anticoagulants may be required (see sections 4.4 and 4.8).

Methotrexate

Penicillins may reduce the excretion of methotrexate, causing a potential increase in toxicity.

Probenecid

Concomitant use of probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Concomitant use of probenecid may lead to increased levels and duration of amoxicillin (but not clavulanic acid) in the blood.

Mycophenolate mofetil

In patients treated with mycophenolate mofetil, the overdosage concentration of the active metabolite mycophenolic acid may decrease by approximately 50% after initiation of oral amoxicillin/clavulanic acid. This change in overdosage level may not fully reflect the change in total mycophenolic acid exposure. Therefore, a change in mycophenolate mofetil dosage 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 initiating therapy with amoxicillin/clavulanic acid, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam drugs (see sections 4.3 and 4.8).

Serious and in some cases fatal hypersensitivity reactions (including anaphylactic reactions and severe cutaneous adverse reactions) have been reported in patients treated with penicillin. Such reactions are more likely to occur in patients with a history of hypersensitivity to penicillin and in patients with atopic diseases. If an allergic reaction occurs, amoxicillin/clavulanic acid should be discontinued and appropriate alternative therapy should be initiated.

If the infection is proven to be caused by an organism(s) susceptible to amoxicillin, a switch from amoxicillin/clavulanic acid to amoxicillin should be considered in accordance with generally accepted guidelines.

This formulation of Augmentin is not suitable for use when there is a high risk that the likely causative agents have resistance to beta-lactam drugs that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This formulation should not be used for the treatment of penicillin-resistant S. pneumoniae.

In patients with impaired renal function and in patients taking high doses of the drug, seizures may occur (see section "Adverse reactions").

Amoxicillin/clavulanic acid should be avoided in suspected infectious mononucleosis, as a crust-like rash has been associated with the use of amoxicillin in this case.

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.

The occurrence of febrile generalized erythema associated with pustular eruption at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AGEP) (see section 4.8). Such a reaction requires discontinuation of Augmentin and is a contraindication to further use of amoxicillin.

Hepatic complications have been reported predominantly in men and elderly patients and may be associated with long-term treatment. Such complications have been reported very rarely in children. In all patient groups, symptoms usually occur during or shortly after treatment, but in some cases may not appear until several weeks after the end of treatment. Such events are usually reversible. Hepatic complications can be severe and, in extremely rare cases, fatal. Such events have almost always been observed in patients with severe underlying disease or in those taking concomitant medications with a known potential to cause hepatic complications (see section 4.8).

Antibiotic-associated colitis has been reported with nearly all antibacterial agents, including amoxicillin, and may range in severity from mild to life-threatening (see Adverse Reactions). 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, Augmentin should be discontinued immediately, medical attention should be sought, and appropriate treatment should be initiated. The use of anti-peristaltic agents is contraindicated in such cases.

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

Prolonged prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. Appropriate monitoring should be performed when anticoagulants are administered concomitantly. Dosage adjustment of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see Interactions with other medicinal products and other forms of interaction and Adverse reactions).

In patients with renal impairment, the dose should be adjusted depending on the degree of impairment (see section "Method of administration and dosage").

Crystalluria has been observed very rarely in patients with reduced diuresis, mainly with parenteral therapy. Adequate fluid intake and diuresis should be maintained during high doses of amoxicillin to reduce the likelihood of amoxicillin-associated crystalluria. In patients with bladder catheterization, the patency of the catheters should be checked regularly (see section "Overdose").

During treatment with amoxicillin, enzymatic methods for determining glucose oxidase should be used when testing for the presence of glucose in urine, since there is a possibility of obtaining false-positive results when using non-enzymatic methods.

The presence of clavulanic acid in Augmentin may lead to nonspecific binding of IgG and albumin to erythrocyte membranes, which may lead to false-positive Coombs test results.

Positive results have been reported with the Bio-Rad Laboratories Platelia Aspergillus enzyme immunoassay in patients receiving amoxicillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses have been reported with the Bio-Rad Laboratories Platelia Aspergillus enzyme immunoassay. Therefore, positive results in patients receiving amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

Augmentin 228.5 mg/5 ml suspension contains aspartame (E951) 2.5 mg/ml - a source of phenylalanine, therefore the drug should be prescribed with caution to patients with phenylketonuria.

The medicinal product contains maltodextrin (glucose). Do not use the medicinal product in patients with rare glucose-galactose malabsorption syndrome.

Use during pregnancy or breastfeeding

Pregnancy. Animal reproduction studies with oral and parenteral forms of Augmentin have not revealed any teratogenic effects. In one study involving women with premature rupture of membranes, it was reported that prophylactic use of Augmentin may be associated with an increased risk of necrotizing enterocolitis in the newborn. As with other drugs, use of the drug should be avoided during pregnancy, especially during the first trimester, unless considered essential by the physician.

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. Augmentin can be used during breastfeeding only if, in the opinion of the doctor, the benefit of use outweighs the risk.

The ability to influence the reaction speed when driving or working with other mechanisms

Studies on the ability of the drug to affect the speed of reactions when driving vehicles and working with other mechanisms have not been conducted. However, undesirable effects (such as allergic reactions, dizziness, convulsions) may occur, which may affect the ability to drive a car and work with other mechanisms (see the section "Adverse reactions").

Method of administration and doses

The drug should be used in accordance with official recommendations for antibiotic therapy and local antibiotic susceptibility data, if available. Susceptibility to amoxicillin/clavulanate varies between regions and may change over time. If necessary, antibiotic susceptibility testing should be performed.

The dosage of the drug is prescribed by the doctor depending on the expected microorganisms and their sensitivity to antibacterial drugs, the severity of the disease and the location of the infection, the patient's age, body weight, and kidney function.

If necessary, alternative formulations of Augmentin (i.e. those providing higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) should be considered (see sections 4.4 and 5.1).

For children weighing <40 kg, this Augmentin formulation provides a maximum daily dose of 1000-2800 mg amoxicillin/143-400 mg clavulanic acid when administered as recommended below. If an increased dose of amoxicillin is considered necessary, it is recommended that another Augmentin formulation be chosen to avoid excessively high daily doses of clavulanic acid (see sections 4.4 and 5.1).

The duration of treatment is determined by the patient's clinical response to treatment. Some infections (e.g. osteomyelitis) require longer treatment. Treatment should not exceed 14 days without review (see section 4.4 for long-term therapy).

Adults and children weighing ≥ 40 kg: other forms of Augmentin should be used.

Children weighing < 40 kg

Recommended daily doses: from 25/3.6 mg/kg body weight to 45/6.4 mg/kg body weight, divided into 2 doses.

For children weighing < 40 kg, the drug is prescribed at a maximum daily dose of 1000–2800 mg amoxicillin/143–400 mg clavulanic acid when used as indicated below.

Approximate calculation of Augmentin suspension (ml) per day (based on amoxicillin)

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

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

Kidney dysfunction.

For children with creatinine clearance (CrCl) greater than 30 ml/min, no dose adjustment is required. Augmentin 228.5 mg/5 ml suspension is not recommended for the treatment of children with creatinine clearance (CrCl) less than 30 ml/min.

Hepatic impairment: Use with caution, monitor liver function regularly. There are insufficient data to make dosage recommendations.

Method of application

Augmentin is intended for oral use.

The drug should be taken with meals to minimize potential gastrointestinal intolerance.

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

Instructions for preparing the suspension.

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

1. Check the bottle cap for previous opening.

2. Invert and shake the bottle to loosen the powder in it.

3. Pour boiled water into the bottle with the powder to the lower level, marked by the red line with an arrow.

4. Close the cap and shake the bottle until a suspension is formed.

5. Then add the rest of the water to the top level marked by the black line with the arrow and shake again.

6. The suspension should be allowed to stand for 5 minutes until the powder is completely dispersed.

7. Shake the suspension thoroughly before each use.

To accurately measure the dose of the drug, a measuring cap or a measuring spoon or a measuring syringe should be used, which should be rinsed with water after each use.

Children

It is used in children from 2 months of age. Children weighing more than 40 kg are prescribed the drug in a different dosage form.

Overdose

Gastrointestinal symptoms and fluid and electrolyte imbalance may occur. Amoxicillin-associated crystalluria has been reported, leading in isolated 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).

Treatment

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 most frequently reported adverse drug reactions (ADRs) were diarrhea, nausea, and vomiting.

The list of adverse drug reactions known from clinical studies of Augmentin and post-marketing surveillance and classified by MedDRA system organ class is provided below.

The following classification of the frequency of side effects is used:

very often ≥ 1/10;

often ≥ 1/100 and < 1/10;

uncommon ≥ 1/1000 and < 1/100;

rare ≥ 1/10,000 and < 1/1,000;

very rare < 1/10,000;

not known (frequency cannot be estimated from the available data).

Infections and invasions.

Common: candidiasis of the skin and mucous membranes.

Not known: overgrowth of microorganisms insensitive to the drug.

Disorders of the hematopoietic and lymphatic systems.

Rare: reversible leukopenia (including neutropenia) and thrombocytopenia.

Not known: reversible agranulocytosis and haemolytic anaemia; increased bleeding time and prothrombin time1.

Immune system disorders10

Not known: angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis.

Nervous system disorders.

Uncommon: dizziness, headache.

Not known: reversible hyperactivity and convulsions2.

Not known: aseptic meningitis.

Gastrointestinal disorders.

Common: diarrhea, nausea3, vomiting.

Uncommon: stomach upset.

Not known: antibiotic-associated colitis 4, "black hairy tongue", tooth enamel discoloration 11.

Hepatobiliary disorders.

Uncommon: increased AST and/or ALT5.

Not known: hepatitis6 and cholestatic jaundice6.

Skin and subcutaneous tissue disorders7

Uncommon: skin rash, itching, urticaria.

Rare: erythema multiforme.

Not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis9, drug reaction with eosinophilia and systemic symptoms (DRESS).

Kidney and urinary tract disorders.

Very rare: interstitial nephritis, crystalluria8.

1 See section "Application features".

2 See section "Application features".

3 Nausea is more commonly associated with higher oral doses of the drug. If gastrointestinal reactions occur, their severity may be reduced by taking Augmentin with food.

4 Including pseudomembranous colitis and hemorrhagic colitis (see section "Special warnings and precautions for use").

5 Moderate elevations in AST and/or ALT levels were more frequently observed in patients treated with beta-lactam antibiotics, but the significance of these findings is unknown.

6 These phenomena have been observed with other penicillin and cephalosporin antibiotics (see section "Special warnings and precautions for use").

7 If hypersensitivity reactions (dermatitis) occur, the use of the drug should be discontinued (see section "Special instructions").

8 See section “Overdose”

9 See section "Application features".

10 See section “Contraindications” and “Special instructions for use”.

11 Discoloration of tooth enamel has been reported very rarely in children. Careful oral hygiene can prevent such discoloration, as it is removed by brushing.

Expiration date

2 years.

Storage conditions

Store original packaging closed at a temperature below 25 °C in a dry place.

Store the prepared suspension in a refrigerator at a temperature of 2 to 8 ° C for 7 days. Keep out of the reach of children.

Packaging

Powder for the preparation of 70 ml of suspension in clear glass bottles with a metal screw cap (with first-time opening control and a polymer film inside) together with a measuring cap or a dosing syringe or a measuring spoon, placed in a cardboard box or with a child-resistant cap together with a dosing syringe or a measuring spoon, placed in a cardboard box.

Vacation category

According to the recipe.

Producer

SmithKline Beecham Pharmaceuticals, United Kingdom.

SmithKline Beecham Pharmaceuticals, United Kingdom.

Location of the manufacturer and its business address

SmithKline Beecham Pharmaceuticals, Clarendon Road, Worthing, BN14 8QH, United Kingdom.

SmithKline Beecham Pharmaceuticals, Clarendon Road, Worthing, BN14 8QH, United Kingdom.