Why it is better to buy amoxicillin with clavulanic acid?

The ability of our defense system to fend off an attack by microorganisms depends largely on nutrition. The presence of antibiotics in food to date remains a pressing problem. Prolonged use of animal products containing antibiotics has adverse health effects, contributes to the emergence of antibiotic resistance and the development of resistant forms of microorganisms. And this means that many infectious diseases in humans can no longer be treated with standard antibiotics, as they no longer work on the bacteria. But there is a solution: Amoxicillin + Clavulanic acid.

Amoxicillin was synthesized in 1972 by Beecham, which was considered one of the oldest and best-known companies in the UK, but was later taken over by GlaxoSmithKline Corporation.

Amoxicillin – a broad-spectrum semi-synthetic antibiotic that has activity against many Gram-positive and Gram-negative microorganisms. At the same time, amoxicillin is susceptible to degradation by beta-lactamases, and therefore the spectrum of amoxicillin activity does not extend to microorganisms that produce these enzymes. This beta-lactam antibiotic is the name given to substances that have an unusual «ring» of three carbon atoms and one nitrogen atom. This structure made it vulnerable because some strains of bacteria are able to produce beta-lactamase enzymes that cleave this ring. Then amoxicillin loses its power and can no longer interfere with the binding of peptidoglycans – components of the cell wall, which makes this antibiotic especially vulnerable to Gram-positive (well stained) bacteria, which have a lot of peptidoglycans.

To reduce the chance of bacteria becoming resistant to amoxicillin, the same Beecham company decided to add clavulanic acid, which gets its name from a strain of bacteria Streptomyces clavuligerus, which produces its.

Clavulanic acid Is a beta-lactamase inhibitor structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases commonly found in microorganisms that are resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against the plasmid beta-lactamases that most often cause resistance in bacteria. This substance itself is not very active as an antibiotic, but when added to substances in the penicillin family (to which amoxicillin belongs), clavulanic acid helps them avoid being killed by «hands» beta-lactamase.

The combination of these two components the company called Augmentin. By now the patent has long expired and there are many generics – drugs that are made on the basis of the active substance of drugs with an expired patent, but are produced under a generic name. Here, For example, the names of generics of Augmentin sold in the European Union are listed. Today you can easily buy generic Agumentin online.

Indications for use of amoxicillin + clavulanic acid

Treatment of infectious and inflammatory diseases caused by susceptible pathogens: Lower respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess); ENT organ infections (sinusitis, tonsillitis, otitis media); Infections of the urogenital system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingoophoritis, tuboovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelviperitonitis, soft chancre, gonorrhea); Skin and soft tissue infections (rye, impetigo, secondary infected dermatoses, abscesses, phlegmon, wound infections); osteomyelitis; postoperative infections.

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to the combination of amoxicillin and clavulanic acid:

– Upper respiratory tract infections (including ENT infections), such as recurrent tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae1,2, Haemophilus influenzae1, Moraxella catarrhalis1 and Streptococcus pyogenes1,2;

– Lower respiratory tract infections, such as: exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae1,2, Haemophilus influenzae1 and Moraxella catarrhalis1;

– Infections of the genitourinary tract, such as cystitis, urethritis, pyelonephritis, infections of the female genitalia, usually caused by Enterobacteriaceae (mainly Escherichia coli1), Staphylococcus saprophyticus and Enterococcus species, and gonorrhea caused by Neisseria gonorrhoeae;

– skin and soft tissue infections, usually caused by Staphylococcus aureus1, Streptococcus pyogenes1,2 and Bacteroides species;

– Bone and joint infections, e.g.: osteomyelitis, usually caused by Staphylococcus aureus1, long-term therapy may be necessary;

– odontogenic infections, such as: periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis

– Other mixed infections (e.g.: septic abortion, postpartum sepsis, intra-abdominal sepsis) as part of step therapy.

Certain representatives of these microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin. Infections caused by amoxicillin-sensitive microorganisms can be treated with amoxicillin with clavulanic acid, since amoxicillin is one of its active components. Amoxicillin with clavulanic acid is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as microorganisms producing beta-lactamase, sensitive to the combination of amoxicillin and clavulanic acid.

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

1 – for these types of microorganisms clinical efficacy of amoxicillin and clavulanic acid combination has been demonstrated in clinical trials.

2 – strains of these bacterial species do not produce β-lactamase. Sensitivity in amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin with clavulanic acid.

Pharmacological action

Bactericidal, inhibits bacterial wall synthesis.

Active against aerobic Gram-positive bacteria (including beta-lactamase-producing strains): Staphylococcus aureus; Aerobic Gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis. The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic Clostridium spp., Peptococcus spp., Peptostreptococcus spp.;as well as aerobic gram-negative bacteria (including beta-lactamase-producing strains): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic Gram-negative bacteria (including beta-lactamase producing strains): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV and V beta-lactamases, not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropicity to penicillinases, due to which it forms a stable complex with the enzyme, which prevents enzymatic degradation of amoxicillin under the influence of beta-lactamases.

Use during pregnancy and lactation

Caution should be exercised during pregnancy and lactation (breastfeeding).

In animal reproductive studies, oral and parenteral administration of amoxicillin with clavulanic acid did not cause teratogenic effects.

In a single study in women with premature rupture of fetal membranes, it was found that prophylactic therapy with the drug may be associated with an increased risk of necrotizing enterocolitis in newborns.

The drug is not recommended for use during pregnancy, except in cases where the expected benefit to the mother exceeds the potential risk to the fetus.

Amoxicillin with Clavulanic acid can be used during breastfeeding. Except for possible sensitization, diarrhea or oral candidiasis associated with penetration into breast milk of trace amounts of active ingredients of this drug, no other adverse effects have been observed in breastfed infants.

In case of adverse effects in breastfed children, breastfeeding should be stopped.

Use in patients with liver dysfunction

It is contraindicated in case of episodes of jaundice or liver dysfunction due to the use of amoxicillin/clavulanic acid in the anamnesis.

Caution: severe hepatic insufficiency

Use in patients with impaired renal function

When Chronic renal failure Dose and frequency of administration should be adjusted depending on CK.

Use for children

Used in children over 3 months of age by indication and in age-appropriate dosage forms.

Contraindications

– Hypersensitivity to amoxicillin, clavulanic acid, other penicillins, or any other component of the drug;

– History of severe immediate-type hypersensitivity reactions (e.g., anaphylaxis) to other beta-lactam antibiotics (e.g., cephalosporins, carbapenems or monobactams)

– History of jaundice or liver failure due to amoxicillin/clavulanic acid;

– Children under 1 year of age and/or up to 10 kg of body weight (due to the impossibility of dosing the dosage form in this category of patients).

The drug is contraindicated at a dose of 875 mg + 125 mg for children under 12 years of age with CK≤30 ml/min.

Caution

Severe hepatic insufficiency, gastrointestinal diseases (incl.ч. Colitis in anamnesis associated with penicillin use), chronic renal insufficiency.

Side effects

Digestive system disorders: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased liver transaminase activity, in single cases – cholestatic jaundice, hepatitis, liver failure (more often in elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (can also develop after therapy), enterocolitis, black “hairy” Tongue, darkening of tooth enamel.

Blood forming organs: Reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

Nervous system disorders: Dizziness, headache, hyperactivity, anxiety, behavioral changes, seizures.

Urinary system side: interstitial nephritis, crystalluria, hematuria.

Allergic reactions: urticaria, erythematous rashes, rarely – erythema multiforme, anaphylactic shock, angioedema, very rarely – exfoliative dermatitis, erythema malignant exudative (Stevens-Johnson syndrome), allergic vasculitis, syndrome similar to serum sickness, acute generalized exanthematous pustulosis.

Others: Candidiasis, development of superinfection.

How to take, course of treatment and dosage

For oral administration.

The dosage regimen is adjusted individually depending on the patient’s age, body weight, kidney function, and the severity of the infection. To reduce the potential for gastrointestinal disorders and to optimize absorption, the drug should be taken at the beginning of meals. The tablet should be swallowed as a whole with a glass of water, or dissolved in about half a glass of water (30 ml minimum) and stirred thoroughly before drinking.

The minimum course of antibacterial therapy is 5 days.

Treatment should not be continued for more than 14 days without revision of the clinical situation. If necessary, a step therapy (parenteral administration of amoxicillin + clavulanic acid first, followed by conversion to oral administration) may be carried out.

Adults and children over 12 years of age with body weight ≥ 40 kg drug is administered at 500 mg/125 mg 3 times/day or 875 mg/125 mg 2 times/day.

The maximum daily dose should not exceed 2400 mg/600 mg/day.

For children aged 1 to 12 years with body weight from 10 to 40 kg the dosing regimen is established individually, based on the clinical situation and the severity of infection.

The recommended daily dose ranges from 20 mg/5mg/kg per day to 60 mg/15mg/kg per day and is divided into 2-3 doses. Clinical data on the use of amoxicillin/clavulanic acid in a 4:1 ratio in doses > 40 mg/10mg/kg/day in children under two years of age no. Maximum daily dose for children is 60 mg/15 mg/kg per day.

Low doses of the drug are recommended for treatment of skin and soft tissue infections and recurrent tonsillitis; high doses are recommended for treatment of conditions such as otitis media, sinusitis, lower respiratory and urinary tract infections, bone and joint infections.

There is insufficient clinical evidence to recommend the use of the drug at a dose greater than 40 mg/10 mg/kg/day in 3 doses (4:1 ratio) in children younger than 2 years.

Use of high doses of the drug:

10-12 1-2 years old 2 times a day, 1 tablet of 125 mg/ 31.25 mg 3 times a day, 1 tablet of 125 mg/ 31.25 mg

12-15 2-4 years 3 times daily 1 tablet 125 mg/ 31.25 mg 3 times daily 1 tablet 250 mg/62.5 mg

15-20 4-6 years old 3 times daily 1 tablet 250 mg/62.5 mg 3 times daily 1 tablet 250 mg/62.5 mg or 2 times daily 500 mg/125 mg

20-30 6-10 years old 3 times daily 1 tablet 250 mg/62.5 mg 2 times daily 1 tablet 500 mg/125 mg

30-40 10-12 years 2 times daily 1 tablet 500 mg/125 mg 3 times daily 1 tablet 500 mg/125 mg

≥40 ≥12 years old 1 tablet 500 mg/125 mg 3 times daily 1 tablet 500 mg/125 mg

*There is insufficient clinical evidence to recommend using the drug in a dose greater than 40 mg/10 mg/kg/day in 3 doses (4:1 ratio) in children under 2 years of age.

In children aged ≤ 6 years of age preferably take the drug in a diluted form.

Storage conditions

In the original container at a temperature no higher than 25˚C.

Keep out of reach of children.

Shelf life

3 years. Look at the blister.