Clavulanic acid overdose for children. Amoxicillin Clavulanic acid is a combined antibacterial agent. Amoxiclav intravenously - instructions for use

With the advent of soluble antibiotic preparations in Russia, such as amoxicillin clavulanic acid, we get what we have been waiting for a long time - drugs with a lower likelihood of adverse reactions, with a greater hope for recovery. Meanwhile, if we look at the real picture of prescribing antimicrobial drugs (hereinafter - MP) in our country, it can be noted that, despite the efforts that are being made to exclude certain antimicrobial agents from the arsenal of a practical doctor, the situation is still far from ideal. .

Nevertheless, we note a trend towards expanding the use of drugs with proven efficacy. If we talk about the treatment of respiratory infections, then we can note the main directions in the treatment of our patients - this is the fight against Str.pneumoniae, H.influenzae and Moraxella catarrhbalis.

Such an antimicrobial drug as amoxicillin occupies a leading position in our country. Its high activity against group A beta-hemolytic streptococci, pneumococci, Haemophilus influenzae (not producing beta-lactamase) has been confirmed. Combined drug amoxicillin + clavulanic acid characterized by greater completeness and absorption rate than ampicillin, has a high level of penetration into the tonsils, maxillary sinuses, middle ear cavity, bronchopulmonary system. Compared with ampicillin trihydrate, amoxicillin with clavulanic acid has a great advantage - a smaller molecule size, which facilitates its penetration into the microbial cell, greater bioavailability, which does not depend on food intake, especially characteristic of the soluble dosage form of this drug, manufactured using the Solutab technology. "(Flemoxin Solutab). High bioavailability in the case of antimicrobial drugs is important not only in terms of the effect of the drug, but also in relation to the risk of developing intestinal dysbiosis. After all, the amount of antibiotic that is not absorbed into the systemic circulation will remain in the intestinal lumen, which increases the likelihood of dysbiotic lesions and diarrhea.

The subject of our discussion is the combination of amoxicillin and clavulanic acid in a soluble dosage form (hereinafter referred to as LF). It is worth mentioning that the creation of soluble dosage forms is relevant, including from the point of view of compliance: despite the fact that liquid dosage forms are intended for children, and solid (capsules and tablets) for adults, many adults, due to individual preferences or other reasons (elderly, bedridden patient) would like to use liquid LF. Traditional liquid dosage forms, such as syrups, have limitations in the concentration of the drug associated with the solubility limit of the drug itself, suspensions - the optimal ratio of antibiotic / stabilizer. The solution to this problem was the emergence of the Solutab technology, in which the active substances are placed in microgranules, each of which is covered with a shell that dissolves in the alkaline environment of the small intestine.

Amoxicillin in microgranules remains stable in an acidic environment. When taking regular amoxicillin, some of it dissolves in the stomach, so we lose a certain percentage of the drug. When taken, the dissolution of the drug occurs in the upper part of the small intestine, which leads to faster, most complete absorption and the least negative effect on the stomach. Medicinal technologies "Solutab" allow to achieve an increase in bioavailability, not only amoxicillin, but also clavulanic acid.

According to the data in the following picture, you can see that dispersed dosage forms have significant advantages over conventional ones, not only in terms of pharmacokinetics, but also compliance: the possibility of taking "bed patients" without the risk of "sticking" the capsule or tablet in the folds of the esophagus, one dosage form for an adult and child, the choice is to dissolve the tablet or take it whole. It should also be noted that Flemoclav Solutab has a minimal effect on the intestinal microflora, which is ensured by the minimum residual concentration of the drug in the intestine.

Currently, there is an increase in the detection of strains of pathogenic microorganisms producing beta-lactamase. These enzymes produce topical pathogens of respiratory infections: H.influenzae, Moraxella catarrhbalis, E. coli. The use of inhibitor-protected penicillins is one of the most promising ways to overcome resistance associated with the production of beta-lactamase.

Inhibitors bind irreversibly to beta-lactamases (the so-called suicidal effect) both outside the cell (in gram-positive bacteria) and inside it (in gram-negative bacteria), and enable the antibiotic to carry out an antimicrobial effect. The result of the use of inhibitors is a sharp decrease in the minimum inhibitory concentration (MIC) of the antibiotic and, consequently, a significant increase in the effectiveness of the drug, which is clearly seen in the comparison of the activity of amoxicillin and its combination with clavulanic acid.

Clavulanic acid enhances the action of the antibiotic not only due to the blockade of enzymes, but also due to the anti-inoculation effect (decrease in the concentration of microorganisms per unit volume), as well as post-beta-lactamase-inhibitory action against some pathogens. The meaning of the latter is that under the action of clavulanate, the microbial cell stops producing beta-lactamase for some time, which gives amoxicillin an additional “degree of freedom”. The post-beta-lactamase inhibitory effect persists for at least 5 hours after the acid begins its work, and if the microbial cell does not produce beta-lactamase within 5 hours, the activity of amoxicillin naturally increases.

Amoxicillin in combination with clavulanic acid shows a significant potentiation of the effect. The addition of a beta-lactamase inhibitor also creates anti-anaerobic activity, which is important for the treatment of mixed infections, often encountered, for example, in obstetric and gynecological practice.

Let us return to the pharmacokinetics of the drug in question. There is an objective difference in the absorption of amoxicillin and clavulanic acid due to the difference in the acid-base properties of these substances. Amoxicillin is a weak base and clavulanate is a weak acid. As a result, these drugs have different absorption constants, and conditions are created for incomplete absorption of clavulanate.

Accordingly, there are differences in the time of absorption - absorption occurs not only with a different constant, but also at a different speed. This is the second condition due to which clavulanic acid is "delayed" with absorption and retains a residual concentration in the intestine, which creates the preconditions for an adverse effect of acid on the intestinal mucosa - 20-25% of patients receiving conventional LF of this drug, who respond to diarrhea therapy, causing them to stop taking their medication.

How to level differences in absorption? After all, the more acid is absorbed in the intestine, the less its residual toxic effect on the intestinal mucosa. Adverse reactions associated with incomplete absorption of the beta-lactamase inhibitor are diarrhea, pseudomembranous colitis, nausea, changes in taste sensations. The Solutab technology, due to the use of a microencapsulated form, allows a sharp increase in the absorption constant of the inhibitor, while the absorption constant of the antibiotic increases slightly (only by 5%). When using Flemoclav Solutab, fewer side effects are expected. Now, for example, a study is being conducted in the Russian Federation, the preliminary results of which showed the absence of these undesirable effects, which is observed for the first time in relation to amoxicillin / clavulanate, at the same time, there is evidence of microbiological confirmation of the activity of this drug, clinical improvement and recovery.

There are also differences in the permeability of different LFs amoxycillini + acidi clavulanici, which have different molecular weights. This graph clearly shows how the permeability differs for conventional LF, having a molecular weight of 600-800 g/mol, from Flemoclav Solutab (200-400 g/mol).

It has been found that the frequency of diarrhea when taken directly depends on the variability of clavulanate absorption. When using conventional tableted LF amoxicillin with clavulanate, including the original drug, it is not possible to achieve uniform and rapid absorption of the acid. In the case of Flemoklav Solutab, we get a much more encouraging result: the differences in the absorption of clavulanate from a tablet taken whole or previously dissolved are not significant. At the same time, we can also observe an increase in the concentration of clavulanate in the blood serum - when using conventional LF, you can achieve a concentration of just over 2 μg / ml, when using Flemoclav - almost 3 μg / ml.

Modern developments in the field of pharmacy that affect the pharmacokinetic properties of antimicrobial agents can improve the therapeutic effect of antibiotic therapy in parallel with a decrease in the number and severity of adverse reactions. The new soluble amoxycillinum/acidum clavulanicum LF - Flemoklav Solutab - is a fundamentally new qualitative breakthrough in drug technology. Increasing the absorption of acidi clavulanici increases the protection and efficacy of amoxycillini and at the same time reduces the likelihood of side effects associated with clavulanic acid, primarily post-antibiotic diarrhea. The unique LF provides an increase in the "pharmacodynamic load" on infectious agents, which contributes to a more complete eradication and, as a result, the prevention of new antibiotic pressure with the risk of developing resistant bacterial strains. At the same time, Solutab LF is extremely convenient both for adult patients who prefer suspensions to tablets, and for pediatric patients.

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Pharmacotherapeutic group

Beta-lactam antibiotics - Penicillins. Penicillins in combination with beta-lactamase inhibitors. Clavulanic acid+

Amoxicillin

ATX code J01CR02

Pharmacological properties

Pharmacokinetics

After intravenous administration of the drug in doses of 1.2 and 0.6 g, the average values ​​​​of the maximum plasma concentration (Cmax) of amoxicillin are 105.4 and 32.2 μg / ml, clavulanic acid - 28.5 and 10.5 μg / ml, respectively. Both components are characterized by a good volume of distribution in body fluids and tissues (lungs, middle ear, pleural and peritoneal fluids, uterus, ovaries). Amoxicillin also penetrates into the synovial fluid, liver, prostate gland, palatine tonsils, muscle tissue, gallbladder, sinus secretion, bronchial secretion. Amoxicillin and clavulanic acid do not cross the blood-brain barrier in non-inflamed meninges.

Active substances penetrate the placental barrier and are excreted in breast milk in trace concentrations.

Plasma protein binding is 17-20% for amoxicillin and 22-30% for clavulanic acid.

Both components are metabolized in the liver. Amoxicillin is partially metabolized - 10% of the administered dose, clavulanic acid is extensively metabolized - 50% of the administered dose.

After intravenous administration of the drug amoxicillin + clavulanic acid in doses of 1.2 and 0.6 g, the half-life (T1 / 2) for amoxicillin is 0.9 and 1.07 hours, for clavulanic acid 0.9 and 1.12 hours.

Amoxicillin is excreted by the kidneys (50-78% of the administered dose) almost unchanged by tubular secretion and glomerular filtration. Clavulanic acid is excreted by the kidneys by glomerular filtration unchanged, partially as metabolites (25-40% of the administered dose) within 6 hours after taking the drug.

Small amounts can be excreted through the intestines and lungs.

Pharmacodynamics

The drug is a combination of semi-synthetic penicillin amoxicillin and beta-lactamase inhibitor - clavulanic acid. It acts bactericidal, inhibits the synthesis of the bacterial wall.

Active against:

aerobic gram-positive bacteria (including beta-lactamase producing strains): Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus spp, Corynebacterium spp., Listeria monocytogenes;

anaerobic gram-positive bacteria: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.;

aerobic Gram-negative bacteria (including beta-lactamase producing strains): Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella spp., Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophilus influenzae, 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 II, III, IV and V types of beta-lactamases, is inactive against type I beta-lactamases produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, due to which it forms a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the influence of beta-lactamases.

Indications for use

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

Infections of the upper respiratory tract (including ENT organs):

acute and chronic sinusitis, acute and chronic otitis media,

retropharyngeal abscess, tonsillitis, pharyngitis

Lower respiratory tract infections: acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia

Genitourinary system infections: pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, chancroid, gonorrhea

Infections in gynecology: cervicitis, salpingitis, salpingoophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion

Skin and soft tissue infections: erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection

Bone and connective tissue infections

Biliary tract infections: cholecystitis, cholangitis

Odontogenic infections, post-surgical infections, prevention of infections caused by susceptible microorganisms in the surgical treatment of pathologies of the gastrointestinal tract

Dosage and administration

The dosage regimen is set individually depending on age, body weight, kidney function, as well as the severity of the infection. Treatment should not be continued for more than 14 days without reassessment of the patient's condition.

Adults and children over 12 years of age: the drug is prescribed at a dose of 1.2 g every 8 hours 3 times a day, in case of severe infection - every 6 hours, 4 times a day. The maximum daily dose is 6 g.

In children weighing less than 40 kg, dosing is applied based on the body weight of the child. It is recommended to maintain a 4-hour interval between injections of Amoxicillin + Clavulanic acid to prevent an overdose of clavulanic acid.

Children under 3 months

Children weighing less than 4 kg: 50/5mg/kg every 12 hours

Children over 4 kg: 50/5mg/kg every 8 hours, depending on the severity of the infection

Children from 3 months to 12 years

50/5mg/kg every 6-8 hours, depending on the severity of the infection

For patients with renal insufficiency, the dose and / or interval between injections of the drug should be adjusted depending on the degree of insufficiency: with a creatinine clearance of more than 30 ml / min, dose reduction is not required; with a creatinine clearance of 10-30 ml / min, treatment begins with the introduction of 1.2 g, then 0.6 g every 12 hours; with creatinine clearance less than 10 ml / min - 1.2 g, then 0.6 g / day.

For children with a creatinine level of less than 30 ml / min, the use of this form of Amoxicillin + Clavulanic acid is not recommended. Since 85% of the drug is removed by hemodialysis, the usual dose of the drug must be administered at the end of each hemodialysis session.

With peritoneal dialysis, dose adjustment is not required.

Preparation and administration of solutions for intravenous injection: dissolve the contents of the vial 0.6 g (0.5 g + 0.1 g) in 10 ml of water for injection or 1.2 g (1.0 g + 0.2 g) in 20 ml of water for injection.

In / in enter slowly (within 3-4 minutes)

Preparation and administration of solutions for intravenous infusions: prepared solutions for intravenous injections containing 0.6 g (0.5 g + 0.1 g) or 1.2 g (1.0 g + 0.2 g) of the drug should be diluted in 50 ml or 100 ml of solution for infusion, respectively. The duration of the infusion is 30-40 minutes.

When using the following infusion solutions in the recommended volumes, they retain the necessary concentrations of the antibiotic.

As a solvent for intravenous infusion, infusion solutions can be used: sodium chloride solution 0.9%, Ringer's solution, potassium chloride solution.

Side effects

Often (≥1/100,<1/10)

Candidiasis

Uncommon (≥1/1000,<1/100)

Dizziness, headache

Nausea, vomiting, dyspepsia

Moderate elevation of liver enzymes

Skin rash, itching, urticaria

Rarely (≥1/10000,<1/1000)

Reversible leukopenia (including neutropenia), thrombocytopenia

Erythema multiforme

Thrombophlebitis at the injection site

Very rarely (<1/10000)

Reversible agranulocytosis and hemolytic anemia, increased bleeding time and prothrombin time index

Angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis

Reversible overactivity and seizures

Pseudomembranous or hemorrhagic colitis

Discoloration of the surface layer of tooth enamel

Hepatitis, cholestatic jaundice

Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous

pustulosis

Interstitial nephritis, crystalluria

Contraindications

Hypersensitivity to penicillins or to any component of the drug

Known hypersensitivity to other beta-lactam antibiotics (cephalosporins, carbapenems, monobactams)

Jaundice or abnormal liver function developed during the use of Amoxicillin + Clavulanic acid or beta-lactam antibiotics

Infectious mononucleosis (including with the appearance of a bark-like rash).

Drug Interactions

Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) have a synergistic effect; bacteriostatic drugs (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) - antagonistic.

The drug increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and the prothrombin index). While taking the drug with anticoagulants, it is necessary to monitor the indicators of blood clotting.

Amoxicillin + clavulanic acid reduces the effectiveness of oral contraceptives. With the simultaneous use of the drug with ethinyl estradiol or with drugs in the process of metabolism of which para-aminobenzoic acid (PABA) is formed, there is a risk of breakthrough bleeding.

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs and other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration). Allopurinol increases the risk of skin rashes.

With the simultaneous use of the drug with methotrexate, the toxicity of the latter increases.

Avoid concomitant use with disulfiram.

Pharmaceutically incompatible with solutions containing blood, proteins, lipids, glucose, dextran, bicarbonate. Do not mix in a syringe or infusion bottle with other drugs. Incompatible with aminoglycosides.

special instructions

Before initiating treatment with Amoxicillin + Clavulanic Acid, a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam antibiotics should be taken.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock) to penicillins have been described. In the event of an allergic reaction, it is necessary to stop treatment and start alternative therapy. With the development of serious hypersensitivity reactions, adrenaline should be administered to the patient immediately. Oxygen therapy, intravenous steroids, and airway management, including intubation, may be required.

Amoxicillin + Clavulanic acid should not be given if infectious mononucleosis is suspected, as in patients with this disease, amoxicillin can cause a skin rash, making it difficult to diagnose the disease.

Long-term treatment with Amoxicillin + Clavulanic acid may be accompanied by overgrowth of microorganisms insensitive to it.

Pregnancy

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

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

As with all medicines, the combination of amoxicillin with clavulanic acid is not recommended during pregnancy unless the expected benefit to the mother outweighs the potential risk to the fetus.

breastfeeding period

The combination of amoxicillin with clavulanic acid can be used during breastfeeding. With the exception of the possibility of developing sensitization, diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects were observed in breast-fed children. In the event of adverse effects in children who are breastfed, it must be discontinued.

Description of the dosage form

Symptoms: Gastrointestinal symptoms and fluid and electrolyte disturbances may occur.

Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure.

Convulsions may occur in patients with impaired renal function, as well as in those receiving high doses of the drug.

Treatment: symptomatic therapy, correction of water and electrolyte balance. Amoxicillin + Clavulanic acid is removed from the blood by hemodialysis.

Component Properties

Tablets - 1 tab.:

• Active ingredients: Amoxicillin 250 mg / 500 mg / 875 mg (as amoxicillin trihydrate 286.70 mg / 573.40 mg / 1003.44 mg); Clavulanic acid 125 mg (as potassium clavulanate 277.77 mg);
• Excipients: microcrystalline cellulose 80.58 mg / 118.83 mg / 110.74 mg, sodium carboxymethyl starch 6.65 mg / 10 mg / 14.35 mg, colloidal silicon dioxide 6.65 mg / 10 mg / 14.35 mg , magnesium stearate 6.65 mg / 10 mg / 14.35 mg, opadry white 06B58855 (hypromellose-5cP 14.62 mg / 21.49 mg / 30.96 mg, hypromellose-15cP 1.36 mg / 1.99 mg / 2.88 mg, macrogol-400 2.18 mg / 3.21 mg / 4.62 mg, titanium dioxide 6.12 mg / 8.99 mg / 12.96 mg).

Film-coated tablets, 500 mg + 125 mg

7 tablets in a 3-layer PA/Aluminum/PVC film and aluminum foil blister

2 blisters with instructions for use in a cardboard box.

Pharmacokinetics

Antibiotic penicillin semi-synthetic + beta-lactamase inhibitor.

Pharmacodynamics

Suction

Both active ingredients of the drug Amoxicillin + Clavulanic acid, amoxicillin and clavulanic acid, are rapidly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. The absorption of the active ingredients of the drug Amoxicillin + Clavulanic acid is optimal if the drug is taken at the beginning of a meal.

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained from different studies are shown below, when fasting healthy volunteers were taken:

• 1 tablet of a drug containing a combination of amoxicillin with clavulanic acid, 250 mg + 125 mg (375 mg); 2 tablets of a drug containing a combination of amoxicillin with clavulanic acid, 250 mg + 125 mg (375 mg); 1 tablet of a drug containing a combination of amoxicillin with clavulanic acid, 500 mg + 125 mg (625 mg); 500 mg amoxicillin; 125 mg clavulanic acid; 2 tablets of a preparation containing a combination of amoxicillin with clavulanic acid, 875 mg + 125 mg (1000 mg)

  Main pharmacokinetic parameters

  Preparations	Dose (mg)	Сmax (mg/l)	Tmax (h)	AUC (mhh/l)	Т1/2 (h)
  Amoxicillin
  	250	3,7	1,1	10,9	1,0
  	500	5,8	1,5	20,9	1,3
  	500	6,5	1,5	23,2	1,3
  Amoxicillin 500 mg	500	6,5	1,3	19,5	1,1
  	1750	11.64±2.78	1.50(1.0±2.5)	53.52±12.31	1.19±0.21
  clavulanic acid
  amoxicillin + clavulanic acid, 250 mg + 125 mg	125	2,2	1,2	6,2	1,2
  amoxicillin + clavulanic acid, 250 mg + 125 mg, 2 tablets	250	4,1	1,3	11,8	1,0
  Clavulanic acid, 125 mg	125	3,4	0,9	7,8	0,7
  amoxicillin + clavulanic acid, 500 mg + 125 mg	125	2,8	1,3	7,3	0,8
  amoxicillin + clavulanic acid, 875 mg + 125 mg, 2 tablets	250	2.18±0.99	1.25(1.0±2.0)	10.16±3.04	0.96±0.12

  Cmax - maximum plasma concentration

  Tmax - time to reach maximum plasma concentration

  AUC - area under the concentration-time curve

  T1 / 2 - half-life

  When using a drug containing a combination of amoxicillin with clavulanic acid, plasma concentrations of amoxicillin are similar to those with oral administration of equivalent doses of amoxicillin

  Distribution

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

  The combination of amoxicillin with clavulanic acid has a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in blood plasma bind to plasma proteins.

  In animal studies, no accumulation of the components of the combination of amoxicillin with clavulanic acid was found in any organ. Amoxicillin, like most penicillins, passes into breast milk.

  Trace amounts of clavulanic acid can also be found in breast milk. With the exception of the possibility of developing sensitization, diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed children are known.

  Reproductive studies in animals have shown that amoxicillin and clavulanic acid cross the placental barrier. However, there was no negative effect on the fetus

  Metabolism

  10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicillic acid)

  Clavulanic acid is extensively metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and excreted by the kidneys, through the gastrointestinal tract, as well as with exhaled air in the form of carbon dioxide

  breeding

  Like other penicillins, amoxicillin is excreted primarily by the kidneys, while clavulanic acid is eliminated via both renal and extrarenal mechanisms.

  Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged by the kidneys in the first 6 hours after administration of 1 tablet of the drug in the dosage form of film-coated tablets, 250 mg + 125 mg or 500 mg + 125 mg

  The simultaneous administration of probenecid slows down the excretion of amoxicillin, but not clavulanic acid.

Clinical pharmacology

Simultaneous use of the drug Amoxicillin + Clavulanic acid and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Amoxicillin + Clavulanic acid and probenecid can lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid

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

Penicillins can slow down the excretion of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Amoxicillin + Clavulanic acid and methotrexate can increase the toxicity of methotrexate

Like other antibacterial drugs, the drug Amoxicillin + Clavulanic acid can affect the intestinal microflora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives

The literature describes rare cases of an increase in the international normalized ratio (INR) in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe the drug Amoxicillin + Clavulanic acid with anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or canceling the drug Amoxicillin + Clavulanic acid, dose adjustment of oral anticoagulants may be required

In patients receiving mycophenolate mofetnl, after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect overall changes in mycophenolic acid exposure.

Indications for use Amoxicillin + clavulanic acid

• Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins) in history;
• previous episodes of jaundice or abnormal liver function when using a combination of amoxicillin with clavulanic acid in history;
• children under 12 years of age or body weight less than 40 kg;
• severe renal impairment (creatinine clearance (CC)

With caution: in patients with impaired liver function.

Amoxicillin + clavulanic acid Use in pregnancy and children

Mechanism of action

Amoxicillin is a semi-synthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not apply to microorganisms that produce this enzyme.

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has 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 not effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in the drug Amoxicillin + Clavulanic acid protects amoxicillin from destruction by enzymes - beta-lactamases, which allows expanding the antibacterial spectrum of amoxicillin

The following is the activity of the combination of amoxicillin with clavulanic acid in vitro

Bacteria normally sensitive to the combination of amoxicillin with clavulanic acid

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 sensitive)(1); Staphylococcus saprophyticus (methicillin sensitive) Coagulase-negative staphylococci (methicillin sensitive)

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

Gram-negative aerobes: Bordetella pertussis; Haemophilus influenzae(1); Helicobacter pylori; Moraxella catarrhalis(1); Neisseria gonorrhoeae; Pasteurella multocida; Vibrio cholerae

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

Others: Borrelia burgdorferi; Leptospira icterohaemorrhagiae; Treponema pallidum

Bacteria likely to become resistant to the combination of amoxicillin with clavulanic acid

Gram-negative aerobes: Escherichia coli(1); Klebsiella oxytoca; Klebsiella pneumoniae(1); Klebsiella spp.; Proteus mirabilis; Proteus vulgaris; Proteus spp.; Salmonella spp.; Shigella spp.

Gram-positive aerobes: Corynebaclerium spp.; Enterococcus faecium; Streptococcus pneumoniae(1,2); Streptococci of the Viridans group

Bacteria that are naturally resistant to the combination of amoxicillin with clavulanic acid

Gram-negative aerobes: Acinetobacter spp.; Citrobacter freundii; Enterobacter spp.; hafnia alvei; Legionella pneumophila; Morganella morganii; Providence spp.; Pseudomonas spp.; Serratia spp.; Stenotrophomonas maltophilia; Yersinia enterocolitica

Others: Chlamydia pneumoniae; Chlamydia psittaci; Chlamydia spp.; Coxiella burnetii; Mycoplasma spp.

(1) - for these bacteria, the clinical efficacy of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies

(2) - strains of these types of bacteria do not produce beta-lactamase. Sensitivity with amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.

Amoxicillin + clavulanic acid side effects

Infectious and inflammatory diseases caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid:

• ENT infections, such as recurrent tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes.
• Lower respiratory tract infections, such as exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
• Urinary tract infections, such as cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus and species of the genus Enterococcus, as well as 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, such as osteomyelitis, usually caused by Staphylococcus aureus, if necessary, long-term therapy is possible.
• Other mixed infections (eg, septic abortion, puerperal sepsis, intra-abdominal sepsis) as part of stepwise therapy.
• Odontogenic infections, eg periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis.

The 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. Where necessary, microbiological samples should be collected and tested for bacteriological susceptibility.

drug interaction

Before starting treatment with Amoxicillin + Clavulanic Acid, a detailed history should be taken regarding previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause 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. If an allergic reaction occurs, treatment with Amoxicillin + Clavulanic Acid should be discontinued and appropriate alternative therapy initiated.

Serious anaphylactic reactions should promptly administer epinephrine to the patient. Oxygen therapy, intravenous glucocorticosteroids, and airway management, including intubation, may also be required.

If infectious mononucleosis is suspected, Amoxicillin + Clavulanic Acid should not be used because in patients with this disease, amoxicillin can cause a measles-like skin rash, which makes it difficult to diagnose the disease.

Long-term treatment with Amoxicillin + Clavulanic Acid may lead to overgrowth of non-susceptible organisms.

In general, the drug Amoxicillin + Clavulanic acid is well tolerated and has a low toxicity characteristic of all penicillins. During long-term therapy with Amoxicillin + Clavulanic acid, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis. Cases of pseudomembranous colitis have been described with antibiotics, the severity of which can vary from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after the use of antibiotics. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

In patients receiving a combination of amoxicillin with clavulanic acid together with indirect (oral) anticoagulants, in rare cases, an increase in prothrombin time (increased INR) was reported. With the joint appointment of indirect (oral) anticoagulants with a combination of amoxicillin with clavulanic acid, it is necessary to control the relevant indicators. To maintain the desired effect of oral anticoagulants, dose adjustment may be required.

In patients with impaired renal function, the dose of Amoxicillin + Clavulanic Acid should be reduced according to the degree of impairment (see section "Method of administration and doses" - Patients with impaired renal function)

In patients with reduced diuresis, crystalluria very rarely occurs, mainly with parenteral therapy. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

When taking the drug Amoxicillin + Clavulanic acid inside, a high content of amoxicillin in the urine is observed, which can lead to false positive results in determining glucose in the urine (for example, Benedict's test, Fehling's test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

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

Abuse and drug dependence

There were no drug dependence, addiction and euphoria reactions associated with the use of the drug Amoxicillin + Clavulanic acid

Influence on the ability to drive vehicles and control mechanisms

Since the combination of amoxicillin with clavulanic acid may cause dizziness, care should be taken when driving or operating machinery.

Dosage Amoxicillin + clavulanic acid

For oral administration

The minimum course of antibiotic therapy is 5 days. Treatment should not be continued for more than 14 days without a review of the clinical situation.

For optimal absorption and to reduce possible side effects on the part of the digestive system, the drug is recommended to be taken at the beginning of a meal.

If necessary, it is possible to carry out stepwise therapy (initially, intravenous administration of a drug containing amoxicillin and clavulanic acid, in the dosage form of a powder for preparing a solution for intravenous administration, followed by a transition to a drug containing amoxicillin and clavulanic acid, in dosage forms for oral administration

It must be remembered that 2 tablets of the drug Amoxicillin + Clavulanic acid 250 mg + 125 mg are not equivalent to one tablet of the drug Amoxicillin + Clavulanic acid 500 mg + 125 mg

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

1 tablet 250 mg + 125 mg 3 times a day for mild to moderate infections

For severe infections (including chronic and recurrent urinary tract infections, chronic and recurrent infections of the lower respiratory tract), a dosage of 250 mg + 125 mg is not recommended

1 tablet 500 mg + 125 mg 3 times a day or 1 tablet 875 mg + 125 mg 2 times a day for moderate and severe infections

Special patient groups

Children under 12 years of age or weighing less than 40 kg

Elderly patients

Dosing regimen correction is not required. In elderly patients with impaired renal function, the dose should be adjusted as indicated below for adults with impaired renal function.

Patients with impaired renal function

Dosage adjustments are based on the maximum recommended dose of amoxicillin and creatinine clearance.

Tablets 875 mg + 125 mg should only be used in patients with a creatinine clearance of more than 30 ml / min, and dosing regimen adjustment is not required. In most cases, if possible, parenteral therapy should be preferred.

Patients on hemodialysis

Dosing adjustments are based on the maximum recommended dose of amoxicillin

2 tablets 250 mg + 125 mg in one dose every 24 hours

1 tablet 500 mg + 125 mg in one dose every 24 hours

During the dialysis session, an additional 1 dose (one tablet) and another tablet at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid)

Patients with impaired liver function

Treatment is carried out with caution; regularly monitor liver function

Overdose

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence.

The frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥ 1/100 and

Frequency of occurrence of undesirable reactions

Blood and lymphatic system disorders: Rarely - reversible leukopenia (including neutropenia), reversible thrombocytopenia; Very rarely - reversible agranulocytosis and reversible hemolytic anemia, prolongation of bleeding time and prothrombin time, anemia, eosinophilia, thrombocytosis

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

Nervous system disorders: Infrequently - dizziness, headache; Very rarely - reversible hyperactivity, convulsions. Seizures may occur in patients with impaired renal function, as well as in those receiving high doses of the drug. Insomnia, agitation, anxiety, behavior change

Gastrointestinal disorders

Adults: Very often - diarrhea; Often - nausea, vomiting

Children: Often - diarrhea, nausea, vomiting

General population: Nausea was most commonly associated with high doses of the drug; Infrequently - indigestion; Very rarely - antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue, gastritis, stomatitis

If adverse reactions from the gastrointestinal tract are observed after the start of taking the drug, they can be eliminated if Amoxicillin + Clavulanic Acid is taken at the beginning of a meal

Liver and biliary tract disorders: Infrequently - a moderate increase in the activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This phenomenon is observed in patients receiving therapy with beta-lactam antibiotics, but its clinical significance is unknown; Very rarely - hepatitis and cholestatic jaundice. These reactions are observed in patients receiving therapy with penicillin antibiotics and cephalosporins.

Increasing the concentration of bilirubin and alkaline phosphatase

Adverse reactions from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse reactions are very rare in children.

The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after the end of therapy. Adverse reactions are usually reversible. Adverse reactions from the liver can be severe, in extremely rare cases there have been reports of death. In almost all cases, these were patients with serious comorbidities or patients receiving concomitantly potentially hepatotoxic drugs.

Skin and subcutaneous tissue disorders: Uncommon: rash, itching, urticaria; Rarely - erythema multiforme; Very rare - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis

In the event of allergic skin reactions, treatment with Amoxicillin + Clavulanic Acid should be discontinued.

Renal and urinary disorders: Very rare - interstitial nephritis, crystalluria, hematuria.

Precautionary measures

Dosage tablets 500 mg +125 mg biconvex, oval-shaped, white or off-white film-coated tablets, debossed with "A" on one side and "64" on the other side

On the transverse section: the core is light yellow in color, surrounded by a filmy membrane of white or almost white color.

The combination "Amoxicillin and Clavulanic acid" (with a similar Latin name) is available in many countries. Such a combined preparation is produced in Russia, Slovenia, Switzerland, India and Serbia. This antibiotic helps with a wide range of diseases, and is available in three forms at once - tablets and two types of powder. One of the advantages of the drug is its low price. The drug under different trade names can be bought for 45 rubles.

Composition and form of release

The drug is available in various forms. Three medicinal types can be distinguished:

• Oval biconvex film-coated tablets. The surface is white, but there may be a different color of a light shade. There are different engravings on both sides, the specific image depends on the mass and proportion. In the form of 250 + 125 mg, these are "A" and "63", 500 + 125 mg - "A" and "64", 875 + 125 mg - "A" and "6 | 5" (the second engraving has a division by risk). Through the transverse section, you can see the core of a soft yellow color, it is surrounded by a white or very light shell. One carton contains two blisters, each containing seven tablets.
• Powder for suspension preparation which is taken orally. Has a strawberry taste. The granules are very light or white, the dosage and proportion of substances differ, as in tablets, but the product is always placed in an almost transparent 150 ml bottle.
• Mass for restoring the solution which is administered intravenously. The 10 ml vials contain white contents, which may have a yellowish tint. A carton pack for one patient contains either one or ten vials, hospitals purchase packages that can contain up to 50 ampoules.

The composition also depends on the form of release. One tablet contains the following active ingredients and auxiliary components:

• amoxicillin 250, 500 or 875 mg;
• clavulanic acid (125 mg);
• sodium carboxymethyl starch;
• cellulose;
• magnesium stearate;
• titanium dioxide;
• macrogol.

The content of the reconstituted mass for oral administration is somewhat different. The composition includes:

• amoxicillin (125 or 250 mg);
• potassium clavulanate (31.25 or 62.5 mg);
• xanthan gum;
• silica;
• hypromellose;
• aspartame;
• succinic acid;
• silicon dioxide in colloidal form;
• strawberry flavour.

Injections differ in that they do not require additional substances. The powder consists of amoxicillin (500 or 1000 mg) and potassium clavulanate (100 or 200 mg).

Amoxicillin is a semi-synthetic antibiotic. It is active against many bacteria. Does not affect organisms that produce beta-lactamase enzymes - their effect is detrimental to amoxicillin. The substance is used to treat a large list of diseases.

Clavulanic acid is a beta-lactamase inhibitor similar in structure to penicillin. It makes inactive the vast majority of beta-lactamases, so it can affect microorganisms that are not affected by cephalosporins and penicillins - they most often have resistance. The substance is not active against chromosomal beta-lactamases of the first type.

Potassium clavulanate in combination protects Amoxicillin from the effects of beta-lactamase, thereby increasing its spectrum of action. This combination allows the drug to affect bacteria that are resistant to pure Amoxicillin.

After oral administration of a tablet or suspension, the active substances enter the stomach and are completely absorbed. This happens quite quickly - the highest concentration is observed after one to two hours. To achieve optimal absorption, the drug should be taken right before a meal.

The active elements bind to plasma proteins with moderate intensity both when taken orally and when administered intravenously. For amoxicillin, this is 17–20%, and for clavulanic acid, 22–30%.

Both substances are well distributed throughout the body, reach the liquid in the cavity of the organs, as well as their tissues. Like most antibiotics from the penicillin group, amoxicillin easily passes into breast milk, in which clavulanic acid is sometimes also found.

The components are able to pass through the barrier of the placenta. If the lining of the brain is not inflamed, then they do not have the ability to penetrate the blood-brain barrier.

In the liver, the active components are metabolized:

1. About 10% of the total dose of amoxicillin.
2. Almost half of the total amount of clavulanic acid.

Most of the first substance is excreted by glomerular filtration and tubular secretion, almost unchanged (50−78%). A little more than a quarter of the second component is also excreted by the kidneys - a small part is metabolites, and the rest is unchanged. Both substances are eliminated in the first six hours, with small amounts excreted through the intestines and lungs. The half-life increases if the patient suffers from severe renal insufficiency up to 7.5 and 4.5 hours for the first and second components, respectively. They are also removed during peritoneal dialysis and hemodialysis procedures.

Indications and contraindications

This drug is usually prescribed for diseases of an infectious and inflammatory nature. At the same time, provoking microorganisms are sensitive to active substances:

• sinusitis in acute and chronic forms;
• exacerbation of chronic bronchitis;
• infection of the connective or bone tissue;
• cholangitis;
• pyelitis;
• dermatosis with re-infection;
• meningitis;
• odontogenic infections;
• intra-abdominal infections;
• recurrent tonsillitis;
• acute form of bronchitis;
• osteomyelitis;
• pyelonephritis;
• phlegmon;
• peritonitis;
• sepsis after childbirth or abortion;
• abscess;
• endocarditis;
• impetigo;
• otitis media in acute or chronic form;
• bronchopneumonia;
• urethritis;
• pharyngitis;
• pneumonia.

An antibiotic is also used in surgery to reduce the risk of post-operative infection in a patient.

But in some cases, its reception is not possible. First of all, this applies to patients who correspond to one of these parameters:

• mononucleosis of an infectious nature, which is sometimes accompanied by a rash;
• age under 12 years (primarily for tablets);
• individual intolerance to antibiotics of this type;
• cholestatic jaundice and other disorders of the liver that have arisen due to the intake of one of the active substances;
• phenylketonuria (the ban applies to the suspension).

For tablets in a combination of 875 and 125 mg, there is another limitation - they are not prescribed to patients with too low creatinine clearance. Caution should be exercised in relation to those people who suffer from such diseases:

• liver failure in severe form;
• problems with the gastrointestinal tract;
• malfunction of the kidneys.

It can also be used during pregnancy and lactation, but only if the potential therapeutic effect exceeds the effect on the child.

Instructions for use

The method of use directly depends on the dosage form. It also affects the dosage and duration of administration. It should be borne in mind that there are different ratios of the substances amoxicillin and clavulanic acid, the instructions for use also change because of this.

Tablets are taken orally, it is better to do this at the beginning of a meal. This way you can achieve optimal absorption and minimize the risk of side effects from the gastrointestinal tract.

The dosage regimen can only be chosen by a doctor, while he is guided by the severity of the infection, the body weight and age of the patient, as well as the state of his kidneys.

Sometimes stepwise therapy is prescribed, it begins with intravenous administration, which is gradually replaced by oral administration. Adults and children over 12 years of age weighing more than 40 kg should not take more than 6000 mg of amoxicillin and 600 mg of clavulanic acid daily.

The duration of treatment varies from five to 14 days. After the maximum period has elapsed, the doctor re-examines the patient, prolonging the course if necessary. Patients with acute otitis media recover without complications in five to seven days.

The dose of the drug must be adjusted if the patient has impaired kidney function. First of all, pay attention to the value of creatinine clearance. Adjustment is also necessary for patients scheduled for dialysis sessions.

oral suspension

Children under the age of 12 are prescribed a suspension powder, which is taken orally. To do this, a bottle with granules is poured into 2/3 parts with chilled drinking boiled water at room temperature, after shaking, fill the vessel to the mark and shake again. You need to shake it before each dose, otherwise a lot of powder may remain after this.

Each package should contain a measuring cap with 2.5 ml marks, which is necessary for accurate dosage compliance. After use, just wash it in clean water.

The average duration of treatment is the same as for tablets. It is better to take at the beginning of a meal. The dosage regimen is determined by the doctor.

For children under three months old, a particularly low daily dose is used, which is divided into two doses. Premature birth does not require adjustment, but it is required for kidney problems and hemodialysis.

Powder for solution preparation

A solution is made from such a powder, which is then administered intravenously. To do this, the granules in the vial are dissolved with injection water. The drug should come slowly, it is administered within three to four minutes.

It is allowed to use droppers, but for this, the mixture prepared for injections is additionally diluted with an infusion solution. Potassium chloride, Ringer's liquid and sodium chloride will do. The infusion lasts even longer - from 30 to 40 minutes.

Adjustment of the duration of treatment and dosage can only be handled by the attending physician. Childhood and kidney problems are a reason for additional adjustments.

Side effects

Admission may be accompanied by unpleasant consequences. Often there are such side effects:

• headache;
• diarrhea;
• thrombocytopenia (reversible);
• hives;
• hematuria;
• an increase in the concentration of bilirubin;
• candidiasis of the mucous membranes;
• dizziness;
• nausea and vomiting;
• reversible leukopenia;
• skin rash and itching;
• crystalluria;
• impaired hepatic function;
• staining of teeth in yellow, gray or brown;
• excited anxiety;
• glossitis;
• anemia;
• allergic vasculitis;
• interstitial nephritis;
• cholestatic jaundice;
• confusion;
• stomatitis;
• reversible agranulocytosis;
• anaphylactic shock;
• hepatitis;
• angioedema;
• gastritis;
• convulsions.

Usually, patients suffer only from diarrhea and hematuria, more serious effects occur with the wrong choice of dosage or time of administration. The detrimental effect on the liver is mostly reversible, the organ recovers at the end of treatment. However, in patients with severe pre-existing illness who have been treated with hepatoxic drugs, this may be life threatening.

Overdose

An overdose usually threatens with problems with the gastrointestinal tract. Diarrhea, abdominal pain, vomiting and other disorders may occur, and water imbalance may occur. Insomnia, anxiety and agitation, dizziness are predictable effects from the nervous system. At high doses or impaired renal function, there is a possibility convulsive seizures.

For patients with renal or hepatic insufficiency, an overdose is life threatening. To neutralize, normalize the water-electrolyte balance, and also prescribe hemodialysis.

Special instructions and price

Clavulanic acid in combination is released only by prescription. It must be stored in a dry place, protected from light and children. Temperatures below 25 degrees are optimal for tablets and powder (oral mixture). Ampoules for reconstitution of intravenous solution should be kept at a temperature below 15 degrees.

Under these conditions, tablets and ampoules for reconstitution of the injection solution are stored for two years, and powder for the preparation of oral suspension - for a year and a half. The diluted dry mass should be stored at about six degrees (in the refrigerator) for no more than seven days, while avoiding freezing.

The average price for tablets in Russian pharmacies is 45 rubles.

The antibacterial agent Amoxicillin + Clavulanic acid belongs to the combined extended spectrum penicillins. Activity is provided by the presence in the composition of the combined preparation of the antibiotic amoxicillin and the compound clavulanic acid, which inhibits bacterial beta-lactamase enzymes.

Produce Amoxicillin + Clavulanic acid in the form of:

• coated tablets with different dosage;
• clavulanic acid is always 0.125 g;
• amoxicillin;
  • 250;
• powder for suspension - 156 mg / 5 ml, 312 mg / 5 ml;
• powder for injection with a dose of 600 mg / 1200 mg.

As part of the complex preparation, clavulanic acid is found as a potassium salt - potassium clavulanate.

Amoxicillin + Clavulanate tablets have an oblong biconvex shape, white with a transverse risk. In addition to the active ingredients, the composition of the tablets includes:

• fillers - silicon dioxide, magnesium stearate, microcrystalline cellulose;
• in the shell - polyethylene glycol, hypromelose, titanium dioxide.

Spectrum of antimicrobial activity

Amoxicillin/Clavulanic acid has bactericidal activity, is effective against bacteria and protozoa sensitive to amoxicillin, including beta-lactamase producing strains.

Bactericidal activity is achieved by a violation of the synthesis of bacterial peptidoglycan, which is necessary for the bacterial cell wall.

The extended spectrum inhibitor-protected antibiotic amoxicillin with clavulanic acid includes:

• Gram-positive aerobes:
  • Staphylococcus sp., including mecitillin-sensitive strains of Staphylococcus aureus;
  • streptococci, pneumococci, hemolytic streptococcus;
  • enterococci;
  • listeria;
• gram-negative aerobes - Escherichia, Haemophilus influenzae, Enterobacter, Klebsiella, Moxarella, Neisseria, Helicobacter pylori;
• gram-positive anaerobes - clastridia, peptococci;
• gram-negative anaerobes - bacteroids, fusobacteria.

Many strains of bacteria have developed resistance to semi-synthetic penicillins, the properties of which can be found on the Penicillin Series page.

Acquired resistance to the semi-synthetic penicillin amoxicillin is observed in some strains of Escherichia coli, Klebsiella, Proteus, Salmonella, Shigella, Enterococcus, Corynebacter. Not sensitive to Amoxicillin / Clavulanate chlamydia and mycoplasma.

Clavulanic acid does not act on beta-lactamases, which are produced by:

• Pseudomonas aeruginosa, which has a "quorum sense" that allows you to quickly adapt to antibiotics, producing strains resistant to them;
• serrations - bacteria that cause infections of the intestines, urinary system, skin;
• Acinetobacter (Acinetobacter) - the culprit of septicemia, meningitis, included in 2017 by the WHO in the list of the most dangerous infections.

pharmachologic effect

The active components of the drug are quickly absorbed both when taken orally and when the drug is administered in intravenous injections. The concentration of the combined drug Amoxicillin / Clavulanate necessary for the therapeutic effect in the blood is created after 45 minutes.

The components of the drug bind little to blood proteins, and 70-80% of the drug that enters the blood is in a free form.

Metabolize active substances in the liver:

• amoxicillin - 10% of the incoming antibiotic is transformed;
• clavulanic acid - 50% of the incoming compound is cleaved.

Amoxicillin is excreted by the urinary system. The half-life of the combined drug, depending on the dose, is 1.3 hours.

The drug is excreted when taking the drug in compliance with the instructions, on average within 6 hours.

Indications

Amoxicillin + Clavulanic acid is prescribed to children and adults in the form of tablets, suspensions, intravenous injections at the dosage indicated in the instructions for use.

Indications for the appointment of amoxicillin / clavulanate are diseases:

• organs of the respiratory system:
  • community-acquired pneumonia, pulmonary abscess;
  • pleurisy;
  • bronchitis;
• ENT diseases:
  • sinusitis;
  • tonsillitis, tonsillitis;
  • otitis;
• urinary organs:
  • pyelonephritis, cystitis;
  • inflammation of the fallopian tubes, endometritis, cervicitis, prostatitis;
  • chancre, gonorrhea;
• skin:
  • erysipelas;
  • phlegmon;
  • impetigo;
  • cellulite;
  • animal bites;
• osteomyelitis;
• for the prevention and treatment of postoperative infections.

Instructions for use

The duration of taking drugs with amoxicillin and clavulanic acid should not be more than 2 weeks. Treatment of otitis media should last 10 days.

The drug in tablets is washed down with water when taken with food. Powder for suspension is diluted with boiled water, in the amount of at least half a glass.

The dosage of drugs is calculated according to amoxicillin.

The doctor draws up a treatment regimen individually, depending on age, weight, functionality of the urinary system, and localization of the lesion.

It should be borne in mind that 0.5 g of amoxicillin / 125 mg of clavulanic acid cannot be replaced with 2 doses of 250 mg / 125 mg.

The total amount of clavulanate in the latter case will be higher, which will lower the relative concentration of the antibiotic in the preparation.

The daily dose should not be more than:

• amoxicillin:
  • after 12 l. - 6 g;
  • under 12 y.o. – no more than 45 mg/kg;
• clavulanic acid:
  • over 12 y.o. - 600 mg;
  • younger than 12 years old – 10 mg/kg.

Tablets for adults, instructions

Adults, children over 40 kg are prescribed Amoxicillin / Clavulanate in accordance with the instructions for use:

• with a mild form of the course of the disease:
  • three times / d. 0.25 g;
  • twice/day 500 mg;
• with pulmonary infections, severe forms of infection:
  • thrice/day 0.5 g;
  • twice/day by 0.875 g

Powder for making a suspension for children

The main criterion for calculating the dose of the drug according to the instructions is weight and age. Amoxicillin / Clavulanic acid is prescribed in a daily dose:

• from birth to 3 months – drink 30 mg/kg in the morning/evening;
• 3 months up to 12 liters:
  • with a mild course of the disease:
    • treated with 25 mg/kg twice/day;
    • use 20 mg/kg 3 times a day in 24 hours;
  • complicated inflammation:
    • drink 45 mg / kg 2 rubles / 24 hours;
    • take 40 mg / kg 3 r. / 24 hours.

A child under 12 years of age - give the suspension three times / day. A single dose of the finished suspension is:

• 9 months - 2 years - 62.5 mg of amoxicillin;
• from 2 l. up to 7 l. — 125;
• 7 l. up to 12 l. - 250 mg.

The pediatrician may increase or decrease the dosage of the drug, depending on the weight, age of the child and the severity of the infection.

IV injections, instructions for adults

Intravenous amoxicillin / clavulanic acid is prescribed after 12 years three times a day or 4 rubles / day at a dosage of:

• with a mild course of the disease - 1 g;
• in case of severe illness - 1200 mg.

IV injections for children, instruction

A child under the age of 12 is given an antibiotic:

• for 3 months, premature babies from 22 weeks - twice a day. 25 mg/kg;
• 3 months up to 12 liters:
  • mild leakage - three times a day 25 mg / kg;
  • with severe illness - 4 times / day. 25 mg/kg.

Correction is carried out with low creatinine clearance, which is measured in ml / min .:

• less than 30 but more than 10:
  • the dosage is in tablets 0.25 g - 0.5 g after 12 hours;
  • in / in - twice a day, first 1 g, after - 0.5 g;
• less than 10:
  • orally - 0.25 g or 0.5 g;
  • in / in - 1 g, after 0.5 g.

Only a doctor can adjust the dosage based on the results of a study of excretory activity.

Amoxicillin/Clavulanic acid is approved for the treatment of patients on hemodialysis. Dosage after 12 liters:

• tablets - 250 mg / 0.5 g;
• injections in / in - 0.5 g - 1 time.

During the hemodialysis procedure at the beginning and at the end of the session, the drug is additionally applied in a single dose.

Contraindications

The use of the drug is contraindicated in case of:

• allergies to penicillins, cephalosporins;
• liver failure;
• phenylketonuria;
• infectious mononucleosis;
• previous episodes of jaundice.

Side effects, overdose

Violation of the instructions for amoxicillin / clavulanic acid, the individual characteristics of the body leads to side effects from:

• nervous system - there are:
  • dizziness;
  • headache;
  • anxious;
  • convulsions;
• digestive tract - the appearance of:
  • nausea, vomiting;
  • gastritis;
  • stomatitis;
  • glossitis;
  • diarrhea;
• immunity:
  • hives;
  • skin rashes;
• hematopoietic system - violation of the blood formula:
  • decrease in platelets;
  • thrombocytosis;
  • hemolytic anemia;
  • increase in eosinophils;
• urinary system - are noted:
  • blood in the urine;
  • interstitial nephritis;
  • the appearance in the urine of salt crystals, sand;
• local reactions - phlebitis at the injection site of the drug into the vein.

In case of violation of the instructions, treatment with amoxicillin / clavulanate can cause an overdose phenomenon. Exceeding the dose is accompanied by symptoms:

• nausea;
• diarrhea;
• dizziness;
• convulsions.

Drug Interactions

The absorption of Amoxicillin / Clavulanate worsens when taken simultaneously with drugs:

• antacids - drugs that neutralize the acidity of the stomach;
• aminoglycoside antibiotics;
• laxatives;
• glucosamine.

Increase the absorption of the combined vitamin C, and the simultaneous use of allopurinol, NSAIDs, calcium channel blockers increases its concentration in the blood, reducing the glomerular filtration rate in the kidneys.

Amoxicillin / Clavulanate is not prescribed simultaneously with antibiotics with a bacteriostatic effect - macrolides, lincosamines, tetracyclines, chloramphenicol.

In the treatment of Amoxicillin + Clavulanic acid, the effectiveness of the action changes:

• anticoagulants - increases, which requires control over blood clotting;
• oral contraceptives - reduced.

Application during pregnancy

Amoxicilldin/Clavulanate is teratogenic in class B. This means that although no negative effects on the developing fetus have been found in studies of the drug, there is not enough clinical data on the complete safety of the drug.

It is necessary to use Amoxillin + Clavulanate strictly according to the instructions for use and the scheme prescribed by the doctor. The appointment of Amoxicillin + Clavulanic acid treatment for pregnant women is possible only according to indications, taking into account the beneficial effect of the drug and its effect on the fetus.

Analogues

Arlet, Amoxiclav, Panklav, Ranklav, Augmentin, Flemoklav Solutab, Kviktab, Klavotsin, Moksiklav.