Augmentin^® (Tablets, Powder) Instructions for Use

ATC Code

J01CR02 (Amoxicillin and beta-lactamase inhibitor)

Active Substances

Amoxicillin (Rec.INN registered by WHO)

Clavulanic acid (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Systemic antibacterial agents; beta-lactam antibacterial agents, penicillins; combinations of penicillins, including combinations with beta-lactamase inhibitors

Pharmacological Action

Mechanism of action

Amoxicillin is a broad-spectrum semisynthetic antibiotic active against many gram-positive and gram-negative microorganisms. However, Amoxicillin is susceptible to degradation by beta-lactamases, and therefore its spectrum of activity does not extend to microorganisms that produce this enzyme.

Clavulanic acid is a beta-lactamase inhibitor structurally related to penicillins, possessing the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is less effective against chromosomal type 1 beta-lactamases, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in Augmentin^® protects Amoxicillin from degradation by beta-lactamase enzymes, thereby extending the antibacterial spectrum of amoxicillin.

The in vitro activity of the amoxicillin/clavulanic acid combination is listed below.

Bacteria usually susceptible to the amoxicillin/clavulanic acid combination

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes^1,2, Streptococcus agalactiae^1,2, Streptococcus spp. (other beta-hemolytic streptococci)^1,2, Staphylococcus aureus (methicillin-susceptible)¹, Staphylococcus saprophyticus (methicillin-susceptible), Staphylococcus spp. (coagulase-negative, methicillin-susceptible).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae¹, Helicobacter pylori, Moraxella catarrhalis¹, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

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

Gram-negative anaerobes Bacteroides fragilis, Bacteroides spp., Capnocytophaga spp., Eikenella corrodens, Fusobacterium nucleatum, Fusobacterium spp., Porphyromonas spp., Prevotella spp.

Other Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Bacteria for which acquired resistance to the amoxicillin/clavulanic acid combination is likely

Gram-negative aerobes Escherichia coli¹, Klebsiella oxytoca, Klebsiella pneumoniae¹, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Proteus spp., Salmonella spp., Shigella spp.

Gram-positive aerobes: Corynebacterium spp., Enterococcus faecium, Streptococcus pneumoniae^1,2, Streptococcus group Viridans².

Bacteria with inherent resistance to the amoxicillin/clavulanic acid combination

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

Other: Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetti, Mycoplasma spp.

¹ For these microorganisms, the clinical efficacy of the amoxicillin/clavulanic acid combination has been demonstrated in clinical studies.

² Strains of these bacterial species do not produce beta-lactamases. Susceptibility to amoxicillin monotherapy suggests similar susceptibility to the amoxicillin/clavulanic acid combination.

Pharmacokinetics

Absorption

Both active components of Augmentin^®, Amoxicillin and Clavulanic acid, are rapidly and completely absorbed from the gastrointestinal tract after oral administration. Absorption of the active substances is optimal when the drug is taken at the start of a meal.

Powder for oral suspension Augmentin^® 125 mg/31.25 mg per 5 ml

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in various studies when healthy volunteers aged 2-12 years took Augmentin^®, powder for oral suspension, 125 mg/31.25 mg in 5 ml (156.25 mg) in three divided doses of 40 mg/10 mg/kg body weight/day on an empty stomach are shown below.

Main pharmacokinetic parameters

Powder for oral suspension Augmentin^® 200 mg/28.5 mg in 5 ml

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in various studies when healthy volunteers aged 2-12 years took Augmentin^®, powder for oral suspension, 200 mg/28.5 mg in 5 ml (228.5 mg) in a dose of 45 mg/6.4 mg/kg/day divided into two doses on an empty stomach are shown below.

Main pharmacokinetic parameters

Powder for oral suspension Augmentin^® 400 mg/57 mg in 5 ml

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in various studies when healthy volunteers took a single dose of Augmentin^®, powder for oral suspension, 400 mg/57 mg in 5 ml (457 mg) are shown below.

Main pharmacokinetic parameters

Distribution

As with intravenous administration of the amoxicillin/clavulanic acid combination, therapeutic concentrations of amoxicillin and clavulanic acid are found in various organs and tissues, interstitial fluid (abdominal organs, adipose, bone and muscle tissues, synovial and peritoneal fluids, skin, bile, purulent discharge).

Amoxicillin and Clavulanic acid have a low degree of binding to plasma proteins. Conducted studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin bind to plasma proteins.

Studies in animals have not revealed accumulation of the components of Augmentin^®.

Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid have also been found in breast milk. Apart from the possibility of sensitization, development of diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed infants are known. Reproductive studies in animals have shown that Amoxicillin and Clavulanic acid cross the placental barrier, with no signs of negative effects on the fetus detected.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicilloic acid). Clavulanic acid undergoes extensive metabolism to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted by the kidneys, through the gastrointestinal tract, and also in exhaled air as carbon dioxide.

Excretion

Like other penicillins, Amoxicillin is excreted mainly by the kidneys, whereas Clavulanic acid is excreted by both renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged by the kidneys within the first 6 hours after taking one 250 mg/125 mg tablet or one 500 mg/125 mg tablet.

Indications

Bacterial infections caused by microorganisms susceptible to the drug

• Infections of the upper respiratory tract and ENT organs (e.g., recurrent tonsillitis, sinusitis, otitis media), usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*, Streptococcus pyogenes;
• Infections of the lower respiratory tract: exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*;
• Infections of the genitourinary tract: cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the Enterobacteriaceae family (mainly Escherichia coli*), Staphylococcus saprophyticus and species of the genus Enterococcus;
• Gonorrhea, caused by Neisseria gonorrhoeae*;
• Infections of the skin and soft tissues, usually caused by Staphylococcus aureus*, Streptococcus pyogenes and species of the genus Bacteroides*;
• Infections of bones and joints (e.g., osteomyelitis, usually caused by Staphylococcus aureus*); when long-term therapy is required.

* Some representatives of the specified genus of microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin.

Infections caused by microorganisms susceptible to amoxicillin can be treated with Augmentin^®, since Amoxicillin is one of its active ingredients.

Augmentin^® is also indicated for the treatment of mixed infections caused by microorganisms susceptible to amoxicillin, as well as beta-lactamase-producing microorganisms susceptible to the amoxicillin/clavulanic acid combination.

The susceptibility of bacteria to the amoxicillin/clavulanic acid combination varies by region and over time. Where possible, local susceptibility data should be taken into account. If necessary, microbiological samples should be collected and tested for bacteriological susceptibility.

ICD codes

Dosage Regimen

Powder

The drug is taken orally.

The dosage regimen is set individually depending on the patient’s age, body weight, renal function, and the severity of the infection.

For optimal absorption and to reduce possible side effects from the digestive system, Augmentin^® is recommended to be taken at the start of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without review of the clinical situation.

If necessary, stepwise therapy can be carried out (starting with parenteral administration of the drug followed by a switch to oral administration).

Adults and children over 12 years of age or weighing 40 kg and more

It is recommended to use other dosage forms of Augmentin^® or the suspension with an amoxicillin to clavulanic acid ratio of 7:1 (400 mg/57 mg in 5 ml).

Children aged from 3 months to 12 years weighing less than 40 kg

The dose is calculated depending on age and body weight, indicated in mg/kg body weight/day (calculated based on amoxicillin) or in ml of suspension.

The frequency of administration for the 125 mg/31.25 mg in 5 ml suspension is 3 times/day every 8 hours.

The frequency of administration for the 200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml suspension is 2 times/day every 12 hours.

The recommended dosing regimen and frequency of administration are presented in the table below.

Table of the dosing regimen for Augmentin^® (dose calculation is based on amoxicillin)

Low doses of Augmentin^® are used for the treatment of skin and soft tissue infections, as well as recurrent tonsillitis.

High doses of Augmentin^® are used for the treatment of conditions such as otitis media, sinusitis, lower respiratory tract and urinary tract infections, bone and joint infections .

There are insufficient clinical data to recommend the use of Augmentin^® in doses higher than 40 mg/kg/day in 3 divided doses (suspension 4:1) and 45 mg/kg/day in 2 divided doses (suspension 7:1) in children under 2 years of age.

Children from birth to 3 months

Due to the immaturity of the renal excretory function, the recommended dose of Augmentin^® (calculated based on amoxicillin) is 30 mg/kg/day in 2 divided doses as a 4:1 suspension.

The use of the 7:1 suspension (200 mg/28.5 mg per 5 ml or 400 mg/57 mg per 5 ml) in this population is contraindicated.

Children born prematurely

There are no recommendations regarding the dosing regimen.

Elderly patients

No dose adjustment of the drug is required. In elderly patients with renal impairment, the dose should be adjusted as indicated below for adults with renal impairment.

Patients with renal impairment

Dose adjustment is based on the maximum recommended dose of amoxicillin and is carried out taking into account CrCl values.

The 7:1 suspension (200 mg/28.5 mg per 5 ml or 400 mg/57 mg per 5 ml) should be used only in patients with CrCl >30 ml/min, and no dose adjustment is required.

In most cases, parenteral therapy should be preferred whenever possible.

Patients on hemodialysis

The recommended dosing regimen is 15 mg/3.75 mg/kg once daily.

One additional dose of 15 mg/3.75 mg/kg should be administered before the hemodialysis session. To restore blood concentrations of the active components of Augmentin^®, a second additional dose of 15 mg/3.75 mg/kg should be administered after the hemodialysis session.

Patients with hepatic impairment

Treatment should be carried out with caution; liver function should be regularly monitored. There is insufficient data to adjust the dosing regimen in this category of patients.

Instructions for suspension preparation

The suspension is prepared immediately before first use.

Suspension (125 mg/31.25 mg per 5 ml): add approximately 60 ml of boiled water cooled to room temperature to the vial with powder, then close the vial with the cap and shake until the powder is completely dissolved, let the vial stand for 5 minutes to ensure complete dissolution. Then add water up to the mark on the vial and shake the vial again. In total, about 92 ml of water is required to prepare the suspension.

Suspension (200 mg/28.5 mg per 5 ml or 400 mg/57 mg per 5 ml): add approximately 40 ml of boiled water cooled to room temperature to the vial with powder, then close the vial with the cap and shake until the powder is completely dissolved, let the vial stand for 5 minutes to ensure complete dissolution. Then add water up to the mark on the vial and shake the vial again. In total, about 64 ml of water is required to prepare the suspension.

For children under 2 years of age, the measured single dose of Augmentin^® suspension can be diluted with water in a 1:1 ratio.

The vial should be shaken well before each use. A measuring cap should be used for accurate dosing of the drug, which must be rinsed well with water after each use. After preparation, the suspension should be stored for no more than 7 days in a refrigerator, but not frozen.

Tablets

The drug is taken orally.

The dosing regimen is set individually depending on the patient’s age, body weight, renal function, and the severity of the infection.

For optimal absorption and to reduce possible side effects from the digestive system, Augmentin^® is recommended to be taken at the start of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without review of the clinical situation.

If necessary, step-down therapy is possible (starting with intravenous administration of Augmentin^® in the powder for solution for intravenous injection form, followed by a switch to Augmentin^® in oral dosage forms).

It must be remembered that 2 tablets of 250 mg/125 mg are not equivalent to 1 tablet of 500 mg/125 mg.

Adults and children over 12 years of age or weighing 40 kg and more

1 tab. 250 mg/125 mg 3 times/day for mild to moderate infections.

For severe infections (including chronic and recurrent urinary tract infections, chronic and recurrent lower respiratory tract infections), other dosages of Augmentin^® are recommended – 1 tab. 500 mg/125 mg 3 times/day or 1 tab. 875 mg/125 mg 2 times/day.

Special patient groups

Children under 12 years of age weighing less than 40 kg

It is recommended to use other dosage forms of Augmentin^®.

Elderly patients

No dose adjustment of the drug is required. In elderly patients with renal impairment, the dose should be adjusted as indicated below for adults with renal impairment.

Patients with renal impairment

Dose adjustment is based on the maximum recommended dose of amoxicillin and is carried out taking into account CrCl values.

In most cases, parenteral therapy should be preferred whenever possible.

875 mg+125 mg tablets should be used only in patients with CrCl >30 ml/min, and no dose adjustment is required.

Patients on hemodialysis

Dose adjustment is based on the maximum recommended dose of amoxicillin: 2 tabs. 250 mg/125 mg or 1 tab. 500 mg/125 mg in a single dose every 24 hours. During the hemodialysis session, an additional 1 dose (1 tab.) and another 1 dose (1 tab.) at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patients with hepatic impairment

Treatment should be carried out with caution; liver function should be regularly monitored. There is insufficient data to adjust the dosing regimen in this category of patients.

Adverse Reactions

The adverse events listed below are presented according to the affected organs and organ systems and frequency of occurrence. Frequency is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000, including isolated cases).

Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance.

Infections and infestations common – candidiasis of skin and mucous membranes.

Blood and lymphatic system disorders: rare – reversible leukopenia (including neutropenia) and reversible thrombocytopenia; very rare – reversible agranulocytosis and reversible hemolytic anemia, prolongation of prothrombin time and bleeding time, anemia, eosinophilia, thrombocytosis.

Immune system disorders: very rare – angioedema, anaphylactic reactions, serum sickness-like syndrome, allergic vasculitis.

Nervous system disorders: uncommon – dizziness, headache; very rare – reversible hyperactivity, convulsions (convulsions may occur in patients with impaired renal function and in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior change.

Gastrointestinal disordersadults: very common – diarrhea, common – nausea, vomiting; children – common – diarrhea, nausea, vomiting; entire population nausea is most often observed when taking high doses of the drug. If gastrointestinal adverse reactions occur after starting the drug, they may be eliminated by taking the drug at the start of a meal. Uncommon – indigestion; very rare – antibiotic-associated colitis induced by antibiotic use (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue, gastritis, stomatitis. In children using the suspension, discoloration of the surface layer of tooth enamel has been very rarely reported.

Hepatobiliary disorders: uncommon – moderate increase in AST and/or ALT activity (observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown); very rare – hepatitis and cholestatic jaundice (these phenomena have been noted during therapy with other penicillins and cephalosporins), increased bilirubin and alkaline phosphatase concentrations. Hepatic adverse events were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse events are very rare in children.

The listed signs and symptoms usually occur during or immediately after therapy, but in some cases may not appear until several weeks after completion of therapy. Adverse events are generally reversible. Hepatic adverse events can be severe, and in extremely rare cases, fatalities have been reported. In almost all cases, these were individuals with serious concomitant pathology or individuals receiving potentially hepatotoxic drugs simultaneously.

Skin and subcutaneous tissue disorders: uncommon – rash, pruritus, urticaria; rare – erythema multiforme; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Renal and urinary disorders: very rare – interstitial nephritis, crystalluria, hematuria.

Contraindications

• Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (e.g., penicillins, cephalosporins) in history;
• Previous episodes of jaundice or impaired liver function when using the combination of amoxicillin with clavulanic acid in history;
• Children under 3 months of age (for powder for oral suspension 200 mg/28.5 mg per 5 ml and 400 mg/57 mg per 5 ml);
• Renal impairment (CrCl less than 30 ml/min) – for powder for oral suspension 200 mg/28.5 mg per 5 ml and 400 mg/57 mg per 5 ml;
• Phenylketonuria.

With caution: hepatic impairment.

Use in Pregnancy and Lactation

In studies of reproductive function in animals, oral and parenteral administration of Augmentin^® did not cause teratogenic effects.

In a single study in women with premature rupture of membranes, it was found that prophylactic therapy with the drug may be associated with an increased risk of necrotizing enterocolitis in newborns. Like all medicines, Augmentin^® is not recommended during pregnancy, except in cases where the expected benefit of use for the mother outweighs the potential risk to the fetus.

Augmentin^® can be used during breastfeeding. Except for the possibility of developing diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active substances of the drug into breast milk, no other adverse effects have been observed in breastfed infants. If adverse effects occur in breastfed infants, breastfeeding should be discontinued.

Use in Hepatic Impairment

The drug should be prescribed with caution in case of hepatic impairment.

Contraindicated in case of previous episodes of jaundice or impaired liver function when using the combination of amoxicillin with clavulanic acid in history.

Use in Renal Impairment

The use of the drug is contraindicated in case of renal impairment (CrCl less than 30 ml/min) – for powder for oral suspension 200 mg/28.5 mg per 5 ml and 400 mg/57 mg per 5 ml.

Pediatric Use

The use of the drug is contraindicated in children under 3 months of age (for powder for oral suspension 200 mg/28.5 mg per 5 ml and 400 mg/57 mg per 5 ml).

Geriatric Use

Elderly patients do not require a reduction in the dose of Augmentin^®; doses are the same as for adults.

In elderly patients with renal impairment, the dose should be adjusted as for adults with renal impairment.

Special Precautions

Before starting treatment with Augmentin^®, a detailed history should be taken regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other substances causing an allergic reaction in the patient.

Serious, and sometimes fatal, hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. In the event of an allergic reaction, treatment with Augmentin^® should be discontinued and appropriate alternative therapy initiated. For serious hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous corticosteroids, and airway management, including intubation, may also be required.

If infectious mononucleosis is suspected, Augmentin^® should not be used, since in patients with this disease, Amoxicillin can cause a measles-like skin rash, which complicates the diagnosis of the disease.

Long-term treatment with Augmentin^® sometimes leads to overgrowth of non-susceptible microorganisms.

In general, Augmentin^® is well tolerated and has the low toxicity characteristic of all penicillins.

During long-term therapy with Augmentin^®, it is recommended to periodically evaluate renal, hepatic, and hematopoietic function.

Cases of pseudomembranous colitis have been described with antibiotic use, the severity of which can range from mild to life-threatening. Therefore, it is important to consider the possibility of pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient should be examined.

In patients receiving the combination of amoxicillin with clavulanic acid concomitantly with indirect (oral) anticoagulants, cases of increased prothrombin time (increased INR) have been rarely reported. When prescribing indirect (oral) anticoagulants concomitantly with the combination of amoxicillin with clavulanic acid, appropriate parameters should be monitored. Adjustment of the dose of oral anticoagulants may be required to maintain the desired effect.

In patients with impaired renal function, the dose of Augmentin^® should be reduced according to the degree of impairment.

In patients with reduced diuresis, crystalluria occurs very rarely, mainly during parenteral therapy. When administering amoxicillin in high doses, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

When taking Augmentin^® orally, there is a high content of amoxicillin in the urine, which can lead to false-positive results when determining glucose in the urine (e.g., Benedict’s test, Fehling’s test). In this case, it is recommended to use the glucose oxidase method for determining urine glucose concentration.

Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to erythrocyte membranes, leading to false-positive Coombs test results.

Oral care helps prevent drug-associated tooth discoloration, as brushing teeth is sufficient for this.

Drug abuse and dependence

No drug dependence, addiction, or euphoric reactions associated with the use of Augmentin^® have been observed.

Effect on ability to drive and operate machinery

Since the drug may cause dizziness, patients should be cautioned about precautions when driving a vehicle or operating machinery.

Overdose

Symptoms may include gastrointestinal symptoms and disturbances in water and electrolyte balance. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. Convulsions may occur in patients with impaired renal function and in those receiving high doses of the drug.

Treatment gastrointestinal symptoms – symptomatic therapy, with particular attention to normalization of water and electrolyte balance. In case of overdose, Amoxicillin and Clavulanic acid can be removed from the bloodstream by hemodialysis.

Results of a prospective study involving 51 children in a poison control center showed that administration of amoxicillin at a dose of less than 250 mg/kg did not lead to significant clinical symptoms and did not require gastric lavage.

Drug Interactions

Concomitant use of Augmentin^® and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore concomitant use of Augmentin^® and probenecid may lead to an increase and persistence of the concentration of amoxicillin in the blood, but not clavulanic acid.

Concomitant use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there are no data in the literature on the concomitant use of the combination of amoxicillin with clavulanic acid and allopurinol.

Penicillins can slow the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, concomitant use of Augmentin^® and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, Augmentin^® may affect the intestinal microflora, leading to reduced absorption of estrogens from the gastrointestinal tract and reduced effectiveness of combined oral contraceptives.

The literature describes rare cases of increased INR in patients with concomitant use of acenocoumarol or warfarin and amoxicillin. If concomitant administration of Augmentin^® with anticoagulants is necessary, prothrombin time or INR should be carefully monitored when prescribing or discontinuing Augmentin^®, and adjustment of the dose of oral anticoagulants may be required.

In patients receiving mycophenolate mofetil, a reduction in the concentration of the active metabolite, mycophenolic acid, of approximately 50% was observed after starting the combination of amoxicillin with clavulanic acid, prior to the next dose of the drug. Changes in this concentration may not accurately reflect the overall changes in mycophenolic acid exposure.

Storage Conditions

The drug should be stored in a dry place, out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life of the powder for oral suspension in an unopened bottle is 2 years. Do not take the drug after the expiration date printed on the packaging.

The prepared suspension should be stored in a refrigerator at a temperature from 2°C (35.6°F) to 8°C (46.4°F) for 7 days.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.