Clavulanic acid is part of the group of metabolics (enzymes and antienzymes). It is a beta-lactamase inhibitor and has an antimicrobial effect. The structure of the substance is similar to the structure of the core of the core of the penicillin molecule. However, unlike it, instead of a thiazolidine ring, clavulanic acid contains an oxazolidine ring.
After oral administration, clavulanic acid inhibits beta-lactamases formed as a result of the action of gram-negative and some other microorganisms. The mechanism of action of the substance is as follows: clavulanic acid penetrates the membrane of bacterial cells and inactivates enzymes located in these cells and on their borders. The process of beta-lactamase inhibition is often irreversible. As a result, microorganisms become unable to develop resistance to the antibiotic used.
How are medications containing clavulanic acid used?
Clavulanic acid is prescribed simultaneously with Amoxicillin or Ticarcillin for the treatment of infectious and inflammatory diseases caused by microorganisms sensitive to the combination. The dosage of drugs is individual and determined by the doctor depending on the patient’s age, indications and dosage form. Intravenous clavulanic acid preparations are used with caution in patients with severe impairment of the functional state of the liver. If urticaria or an erythematous rash occurs, medication should be discontinued.
Clavulanic acid is contraindicated in case of individual intolerance. During pregnancy, this drug can be used with Amoxicillin or Ticarcillin only for health reasons. It is not recommended to use the medicine during lactation. Side effects of clavulanic acid include: dyspepsia, cholestatic jaundice, impaired liver function, hepatitis, pseudomembranous colitis, candidiasis, allergic reactions (erythema multiforme, Quincke's edema, exfoliative dermatitis, urticaria, anaphylactic shock).
The trade name of the drug with clavulanic acid is “Potassium clavulanate + Microcrystalline cellulose.” Combined medications containing clavulanic acid: “Amovicombe”, “Amoxiclav”, “Amoxiclav Quiktab”, “Arlet”, “Augmentin”, “Bactoclav”, “Verklav”, “Klamosar”, “Liklav”, “Panklav”, “Ranklav” ", "Taromentin", "Flemoclav Solutab", "Ecoclave", "Timentin".
Antibiotics are powerful treatments for bacterial infections. Therapists and infectious disease doctors can no longer do without them. Bacteria are becoming resistant to antibiotics. The most common antibiotics are the penicillin and cephalosporin groups, and bacteria produce beta-lactamases to counteract them (penicillins and cephalosporins are also called beta-lactam antibiotics). In such cases, additional agents are used to fight the infection, such as clavulanic acid.
In Latin, the name of the active substance is written as acidum clavulanicum.
Ath
Release forms and composition
Pills
In tablet form, clavulanate is used together with amoxicillin. This dosage form is most convenient to give to adults, since the patient’s adherence to treatment is higher, the more convenient and less frequent it is to take medications. Dosage - 125 mg of clavulanate in combination with an antibiotic.
Drops
They are used in children under 1 year of age, since this form can be given to a child without fear of choking.
Powder
Available in bags, used to prepare a suspension.
Syrup
This dosage form is used for infants and children under 1 year of age.
Suspension
This dosage form is used for young children. The suspension is available in bottles and is ready for use.
Mechanism of action
Clavulanate has an antimicrobial effect against many microorganisms. Its activity is especially good against bacteria resistant to beta-lactam antibiotics (most often these are staphylococci, a little less often - streptococci). In addition to antimicrobial activity, the drug inactivates bacterial lactamases, preventing them from resisting unprotected antibiotics. Due to this property, clavulanate is often used in combination with another antibiotic, which mutually potentiates the effect of both substances.
Pharmacokinetics
The active substance is quickly absorbed from the gastrointestinal tract. The maximum concentration of the active substance in the blood occurs within 1 hour after administration. The active substance does not bind to blood proteins, remaining unchanged in the plasma. The drug is excreted primarily by the kidneys.
Indications for use
It is used for diseases caused by bacteria, such as:
- Bacterial diseases of the nose and sinuses.
- Acute purulent inflammation of the middle ear.
- Follicular and lacunar tonsillitis, which are accompanied by the discharge of pus from the tonsils.
- Acute and chronic purulent bronchitis.
- Acute and chronic lung abscesses.
- Pneumonia of various localizations, the causative agents of which are pneumococci, staphylococci, streptococci.
- Acute and chronic pyelonephritis.
- Acute cystitis, which is accompanied by the accumulation of pus.
- Acute hematogenous osteomyelitis (more common in children than in adults).
- Acute peritonitis resulting from breakthroughs of abscesses from internal organs into the abdominal cavity.
- Septic conditions such as septicemia, septicopyemia.
Contraindications
There are no absolute contraindications for the use of medications containing clavulanate. It is not recommended to take it only if an individual intolerance to the components of the drug is detected.
If you have impaired renal or liver function, the drug should not be used.
How to take clavulanic acid
Preparations containing clavulanate must be taken for 7 to 14 days, depending on the symptoms of the disease. Use for less than 7 days is not recommended as pathogenic microorganisms may survive and develop resistance to the active substance. Dosage for adults - 125 mg of potassium clavulanate and 875 mg of amoxicillin trihydrate (in combination). For mild disease, the dosage is 500 mg amoxicillin and 125 mg clavulanate.
Dosage for children is 30 mg of amoxicillin and 15 mg of clavulanate per 1 kg of body weight per day. The tablet is best taken with food, as absorption and bioavailability of the drug will be higher.
Taking the drug for diabetes mellitus
Diabetes mellitus may be accompanied by diabetic nephropathy, resulting in impaired renal function. Since the drug is excreted primarily by the kidneys, this must be taken into account when treating patients with diabetes.
Side effects of clavulanic acid
Side effects are divided depending on the body system.
Gastrointestinal tract
Clavulanate can cause various types of undesirable dyspeptic reactions. This is mainly due to increased peristalsis, which can manifest as diarrhea. This condition must be distinguished from antibiotic-associated diarrhea, which occurs due to the death of microflora and the proliferation of pathogenic microorganisms in the intestine.
During treatment with the drug, cholestatic jaundice may occur, which is manifested by yellowing of the skin and pain in the right hypochondrium. In addition, there is a risk of drug-induced hepatitis, which is more common in older men and occurs as a result of long-term use of this medication.
Blood-forming organs
This drug affects the white sprout of the red bone marrow, causing a reversible (the level is restored after stopping the drug) decrease in the level of leukocytes and neutrophils. Along with white blood cells, the level of platelets decreases during use, which can weaken blood clotting.
central nervous system
Dizziness or headache may occur during clavulanate therapy. In rare cases, seizures of central origin may occur. Convulsions are associated with impaired elimination of the drug from the body or the use of high doses.
Allergies
When treated with clavulanate, various types of allergic reactions may occur, such as urticaria, Stevens-Johnson syndrome, and atopic dermatitis. They occur extremely rarely due to individual intolerance to the drug. To avoid the occurrence of these conditions, a drug sensitivity test should be performed.
Impact on the ability to operate machinery
Side effects include dizziness, which may affect mental clarity. Therefore, during therapy with this drug, it is necessary to refrain from driving a vehicle or using machinery that requires increased concentration.
special instructions
In addition to the mandatory test for individual sensitivity to the drug, you need to make sure that the patient has not previously had reactions to antibiotics of the penicillin group, cephalosporins or other beta-lactam antibiotics.
If you have a history of allergies to amoxicillin (a group of semisynthetic penicillins), ceftazidime (or another antibiotic from the cephalosporin group), ticarcillin or penicillin, do not use the drug. In such cases, treatment with a macrolide (eg, azithromycin) that will not cause cross-allergy should be considered.
If the patient has renal failure with creatinine clearance below 30 mg per minute, then the use of the drug is not recommended, since it may be difficult to eliminate the drug by the kidneys and accumulation of the drug in tissues and organs. In the case when the clearance of endogenous creatinine is above 30 mg per minute, there is no need to adjust the dosage of the drug.
If the patient has liver dysfunction (for example, with hepatitis or cholestatic jaundice), clavulanate is prescribed with caution, assessing the risks and the expected positive result.
Preparations containing clavulanate should be used only if pathogenic microorganisms are resistant to an unprotected antibiotic. If there is a possibility that microorganisms do not produce factors that destroy an unprotected antibiotic, then preference should be given to therapy with only an antibiotic without the addition of clavulanate.
Clavulanate may cause nonspecific conjugation of immunoglobulin G and albumins on red blood cell membranes, which may give a false positive result in the laboratory Coombs test. This must be taken into account when treating with this drug.
Use during pregnancy and lactation
There is insufficient data on the use of the drug in pregnant women, and it is impossible to talk about complete safety for the health of the mother and fetus. If it is necessary to take clavulanate, the doctor must compare the possible risks with the expected results of treatment and only then decide on prescribing the drug.
Prescription of clavulanic acid for children
Children can be prescribed medications containing clavulanate from the first days of life. For infants and young children, dosage forms in the form of a suspension or syrup are used because they are easier to dose and are easier to give to children.
Use in old age
In the elderly, clavulanate is prescribed with caution only in the presence of renal or hepatic pathology. In the absence of violations in these systems, the drug does not need to be limited in use.
Overdose of clavulanic acid
Taking high doses of drugs is accompanied by increased side effects from the gastrointestinal tract. This may include severe nausea, vomiting, and diarrhea. There is also a violation of the water-electrolyte balance, which must be corrected primarily with water-salt infusion solutions. An overdose is characterized by euphoria, insomnia, dizziness, convulsions (in rare cases with severe water and electrolyte disturbances).
Interaction with other drugs
Since clavulanate affects the composition of the intestinal microflora (especially with long-term use), it can reduce the absorption of estrogens and thereby reduce the contraceptive effect of oral combined hormonal contraceptives.
The effect on the microflora is also manifested in increased activity of indirect anticoagulants, because small intestinal bacteria are responsible for the synthesis of vitamin K (one of the coagulation factors, a target for indirect anticoagulants) and the absorption of vitamin E (antioxidant system).
One of the frequent and striking side effects of the drug is loosening of the stool and, as a result, the occurrence of diarrhea. Therefore, the combined use of clavulanate and laxatives may cause profuse diarrhea. This combination of drugs should be avoided as it will worsen fluid and electrolyte disturbances and increase the risk of seizures. Laxatives reduce the absorption of the drug, thereby reducing its antimicrobial activity.
Ascorbic acid may increase the absorption of this drug, thereby enhancing its antimicrobial effect.
During treatment, it is necessary to periodically check kidney function with laboratory tests.
Alcohol compatibility
There are no biochemical reactions where alcohol and clavulanate intersect, so we cannot talk about their incompatibility. But you should still refrain from drinking alcohol during treatment to reduce the load on the liver.
Analogues
The following analogues are available on the market - Panklav, Ecoclave, Augmentin, Amoxiclav, Flemoxin Solutab.
Conditions for dispensing from a pharmacy
Can I buy it without a prescription?
This medicine can be bought without a prescription, but before use you must consult your doctor and take it according to the instructions.
Price for clavulanic acid
The price varies from 150 to 300 rubles depending on the manufacturer.
Storage conditions of the drug
Store the drug in its original packaging at room temperature. Keep out of reach of children.
Best before date
3 years from the date of manufacture, which is indicated on the cardboard packaging.
Clavulanic acid was first discovered in 1974-1975 in the UK. It is produced by bacteria Streptomyces clavuligerus. Chemically, it is a bicyclic beta-lactam containing neither a penicillin nor a cephalosporin core. Clavulanic acid is active against some bacteria, including chlamydia, neisseria, streptococci,. However, it is not used as a stand-alone antibiotic. The most important property of clavulanic acid is its ability to inhibit beta-lactamases. These are enzymes that protect bacteria from the action of. They destroy beta-lactams before they can damage the bacterial cell wall. It is beta-lactamases that provide bacterial resistance to penicillins and cephalosporins. They are produced by both gram-positive and gram-negative bacteria.
Clavulanic acid is used in combination with beta-lactams. With their help, meningitis, endocarditis, sepsis, bronchitis and pneumonia, peritonitis, bacterial diseases of the kidneys, urinary tract and reproductive system, and skin infections are treated. In addition, combined agents are also used for the prevention of diseases, for example, before surgery. Of these, the most famous is “Amoxiclav” (“Panklav”, “Augmentin”, “Verklav”, “Amovikombe”), containing amoxicillin. In veterinary medicine, Amoxiclav is used to treat infections in dogs and cats, as well as pigs, sheep, cows and poultry. It should not be used on rabbits, hamsters, guinea pigs and laying hens, whose eggs are intended for food.
In addition to reducing the activity of beta-lactamases, clavulanic acid enhances the immune response to infection, which increases the effectiveness of combination drugs. Thus, in studies of penicillin-resistant Staphylococcus aureus, amoxicillin reduced the degree of its phagocytosis - the absorption and digestion of bacteria by cells of the immune system. The addition of clavulanic acid, on the contrary, stimulated this process. However, this is only true for bacteria resistant to beta-lactams: studies on strains that do not produce beta-lactamase have not revealed significant differences in the intensity of phagocytosis under the influence of amoxicillin alone and its combination with clavulanic acid.
When taken orally, clavulanic acid is absorbed in the digestive tract and then quickly excreted in the urine. It is also removed from tissues quickly, including after injections. Clavulanic acid is excreted in small amounts in milk.
Clavulanic acid is used in combination with other drugs. Therefore, side effects are usually considered for the drug as a whole, rather than for individual substances. Combination therapy with beta-lactams and clavulanic acid is associated with an increased risk of cholestasis and drug-induced hepatitis occurring during or shortly after treatment. These conditions are usually not life-threatening. There are known cases of allergic reactions caused by clavulanic acid.
The LD50 of clavulanic acid for rats and mice exceeds 2000 mg/kg body weight, which means it is slightly toxic to mammals. Poisoning with this substance causes nausea, diarrhea and abdominal pain. In rare cases, in addition to these symptoms, rash, hyperactivity, or drowsiness were noted. Clavulanic acid does not exhibit genotoxic or carcinogenic properties. However, experiments on rats and mice showed its reproductive toxicity.
In the European Union, the maximum permissible levels of clavulanic acid in food products of animal origin are limited by law. Thus, pork, beef and the fat of these animals should not contain more than 100 mcg/kg of this substance. The content of clavulanic acid in pork and beef liver should not exceed 200 mcg/kg, in kidneys - 400 mcg/kg, in cow's milk - 200 mcg/kg. In the Russian Federation and the EAEU countries, maximum permissible levels of clavulanic acid in food products have not been established.
Literature
- Amoxicillin + Clavulanic acid. Register of medicines of the Russian Federation.
- Clavulanic acid. PubChem.
- Clavulanic Acid. Summary Report (2). Committee For Veterinary Medical Products. EMEA/MRL/776/01-FINAL. February 2001
- Finlay J, Miller L, Poupard JA. A review of the antimicrobial activity of clavulanate. J Antimicrobial Chemother. 2003 Jul;52(1):18-23. Epub 2003 May 29.
- Dufour V, Millon L, Faucher JF, Bard E, Robinet E, Piarroux R, Vuitton DA, Meillet D. Effects of a short-course of amoxicillin/clavulanic acid on systemic and mucosal immunity in healthy adult humans. Int Immunopharmacol. 2005 May;5(5):917-28.
- Tortajada Girbés M, Ferrer Franco A, Gracia Antequera M, Clement Paredes A, García Muñoz E, Tallón Guerola M (2008). Hypersensitivity to clavulanic acid in children. Allergol Immunopathol (Madr). 36 (5): 308-10.
And potassium clavulanate.
Release form
The drug Amoxicillin + Clavulanate is produced in the form of a lyophilisate intended for the preparation of an injection solution, drops for internal use or suspension.
pharmachologic effect
This drug is characterized by antibacterial And bactericidal action.
Pharmacodynamics and pharmacokinetics
The combination drug amoxicillin and clavulanate is a beta-lactamase inhibitor. Due to its bactericidal effect, the drug is able to inhibit the synthesis of the bacterial wall. Its activity is manifested against the main aerobic gram-positive bacteria and their strains that produce beta-lactamases, for example: Staphylococcus aureus, Streptococcus pyogenes, Staphylococcus epidermidis, Streptococcus anthracis, Streptococcus viridans, Streptococcus pneumoniae, Enterococcus faecalis and others, as well as some anaerobic gram-positive bacteria , aerobic gram-negative bacteria, anaerobic gram-negative bacteria and so on.
At the same time, clavulanate has an inhibitory effect on types II, III, IV and V beta-lactamases, but is inactive against type I beta-lactamases, which are synthesized by Enterobacter spp., Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp. This substance is characterized by high tropism towards the main penicillinases, forming a stable complex with the enzyme, preventing the enzymatic degradation of amoxicillin under the influence of beta-lactamases.
Indications for use
The main indication for the use of Amoxicillin + Clavulanate is the treatment of bacterial infections:
- ENT organs – , ;
- lower respiratory tract – pneumonia, pleural empyema, lung abscess;
- soft and integumentary tissues – impetigo, abscess, secondary infected dermatoses, phlegmon;
- genitourinary system - , pyelitis, salpingitis, and so on ;
- and also as a prevention of infections during surgical interventions, and other disorders.
Contraindications for use
The use of the drug is contraindicated in:
- infectious mononucleosis ;
- hypersensitivity;
- jaundice or disturbances in liver function during treatment.
The medicine is prescribed with extreme caution when , , severe liver failure, gastrointestinal diseases and other abnormalities.
Side effects
When treated with Amoxicillin + Clavulanate, disturbances in the functioning of the digestive and nervous systems, hematopoietic organs, allergic and local reactions, and other disorders may develop.
Therefore, treatment may be accompanied by: nausea, vomiting, hyperactivity, anxiety, convulsions, hematopoietic disorders, thrombocytopenia, thrombocytosis, eosinophilia and so on.
For locals and allergic reactions characteristic: development phlebitis at the injection site, urticaria, erythematous rashes, etc. In addition, it is possible that candidiasis, superinfections, interstitial nephritis, crystalluria And hematuria .
Amoxicillin + Clavulanate, instructions for use (Method and dosage)
It should be noted that this drug can be used for oral administration and injection. In this case, the therapeutic regimen, dosage and duration of use are determined individually. According to the instructions for use of the drug, it depends on the severity of the disease, the location of the infection and the characteristics of the patient.
For adult patients and children over 12 years of age, a daily dosage of 250 mg is prescribed for 3 doses. Severe infections allow increasing the dosage to 500 mg or 1 g for 2 times a day. Children under 12 years of age are recommended to take the drug in the form of syrup, suspension or drops. A single dosage is set depending on the age of the child: for 9 months-2 years - 62.5 mg, 2-7 years - 125 mg, 7-12 years - 250 mg for 3 doses. Severe cases of disease allow an increase in dosage.
The average duration of treatment is 10-14 days.
Overdose
In cases of overdose, the development of such undesirable symptoms as disruption of the gastrointestinal tract and water-electrolyte balance cannot be ruled out.
In this case, symptomatic treatment is performed, possibly with hemodialysis.
Interaction
Combined treatment with this drug and antacids, laxatives, aminoglycosides – often leads to slower and decreased absorption. Simultaneous use with ascorbic acid – increases absorption.
For bactericidal antibiotics – aminoglycosides, cephalosporins, and is characterized by a synergistic effect. Some bacteriostatic agents, e.g. macrolides, lincosamides And sulfonamides exhibit an antagonistic effect. There is also an increase in the effectiveness of indirect anticoagulants, leading to suppression of intestinal microflora, a decrease in the synthesis of vitamin K or the prothrombin index.
Simultaneous treatment with anticoagulants requires monitoring of blood clotting parameters. The effect of oral contraceptives is reduced, , which increases the risk of severe bleeding. , diuretics, Phenylbutazone – can increase the concentration of amoxicillin. In addition, allopurinol may cause a rash and skin irritation.
special instructions
During antibiotic therapy, careful monitoring of the state of the functions of the hematopoietic organs, kidneys and liver is necessary. Taking the drug with food will help reduce the risk of developing undesirable effects associated with the gastrointestinal tract. It is also possible that a superinfection may develop due to the growth of microflora insensitive to the drug, requiring a change in the treatment regimen. Increased sensitivity to leads to cross allergic reactions with cephalosporin antibiotics.
Terms of sale
Antibiotics are available in pharmacies by prescription.
Storage conditions
The optimal place to store the medicine is dry, cool, protected from children and light.
Best before date
Analogues
The main analogues include the following drugs: Amoklavin, Clavocin, Ticarcillin Clavulanate, Medoclav, Moxiclav, Ranclave, Rapiclav and.
Alcohol
When treating with antibiotics, it is necessary to refrain from drinking alcohol, as this reduces the effectiveness of therapy and increases the likelihood of side effects.
INN: Amoxicillin, Clavulanic acid
Manufacturer: Kraspharma OJSC
Anatomical-therapeutic-chemical classification: Amoxicillin in combination with beta-lactamase inhibitors
Registration number in the Republic of Kazakhstan: No. RK-LS-5No. 020148
Registration period: 30.09.2013 - 30.09.2018
Instructions
Tradename
Amoxicillin+Clavulanic acid
International nonproprietary name
Dosage form
Powder for the preparation of solution for intravenous administration 0.5 g+0.1 g; 1.0 g +0.2 g.
Compound
One bottle contains
active substances: amoxicillin sodium in terms of amoxicillin - 0.5 g; 1.0 g
potassium clavulanate in terms of clavulanic acid - 0.1 g; 0.2 g
Description
Powder from white to white with a yellowish tint.
Pharmacotherapeutic group
Beta-lactam antibacterial drugs - 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 concentration in blood plasma (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, tonsils, muscle tissue, gall bladder, paranasal sinus secretions, and bronchial secretions. Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier when the meninges are not inflamed.
The 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 undergoes intensive metabolism - 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 in the form of metabolites (25-40% of the administered dose) within 6 hours after taking the drug.
Small amounts may be excreted through the intestines and lungs.
Pharmacodynamics
The drug is a combination of the semisynthetic penicillin amoxicillin and the beta-lactamase inhibitor clavulanic acid. It has a bactericidal effect and inhibits the synthesis of the bacterial wall.
Active regarding:
aerobic gram-positive bacteria(including strains producing beta-lactamases): 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 strains producing beta-lactamases) : 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 multoc ida (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, and 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
Infections of the genitourinary system: 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, secondary infected dermatoses, abscess, cellulitis, wound infection
Bone and connective tissue infections
Biliary tract infections: cholecystitis, cholangitis
Odontogenic infections, post-surgical infections, prevention of infections caused by sensitive microorganisms during surgical treatment of gastrointestinal pathologies
Directions for use and doses
The dosage regimen is set individually depending on age, body weight, kidney function, and the severity of the infection. Treatment should not be continued for more than 14 days without re-evaluating the patient's condition.
For 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.
Children
In children weighing less than 40 kg, dosage is used based on the child’s body weight. It is recommended to maintain a 4-hour interval between administrations of Amoxicillin + Clavulanic acid to prevent an overdose of clavulanic acid.
Children under 3 months
Children weighing less than 4 kg: 50/5 mg/kg every 12 hours
Children weighing more than 4 kg: 50/5 mg/kg every 8 hours, depending on severity of infection
Children from 3 months to 12 years
50/5 mg/kg every 6-8 hours, depending on the severity of the infection
For patients with renal insufficiency, the dose and/or interval between doses of the drug should be adjusted depending on the degree of insufficiency: if creatinine clearance is more than 30 ml/min, no dose reduction is required; when creatinine clearance is 10-30 ml/min, treatment begins with the introduction of 1.2 g, then 0.6 g every 12 hours; when creatinine clearance is less than 10 ml/min - 1.2 g, then 0.6 g/day.
For children with creatinine levels 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 procedure.
For peritoneal dialysis, no dose adjustment is required.
Preparation and administration of solutions for intravenous injection: dissolve the contents of the bottle 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.
Inject intravenously slowly (over 3-4 minutes)
Preparation and administration of solutions for intravenous infusion: prepared solutions for intravenous injection 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. Duration of infusion is 30-40 minutes.
When using the infusion solutions listed below in the recommended volumes, they retain the required concentrations of the antibiotic.
Infusion solutions can be used as a solvent for intravenous infusions: 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 hyperactivity and seizures
Pseudomembranous or hemorrhagic colitis
Change in color 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 impaired liver function that developed during the use of Amoxicillin + Clavulanic acid or beta-lactam antibiotics
Infectious mononucleosis (including when a bark-like rash appears).
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 (by suppressing intestinal microflora, reducing the synthesis of vitamin K and the prothrombin index). When taking the drug simultaneously with anticoagulants, it is necessary to monitor blood clotting indicators.
Amoxicillin + clavulanic acid reduces the effectiveness of oral contraceptives. When using the drug simultaneously with ethinyl estradiol or with drugs during the metabolism of which para-aminobenzoic acid (PABA) is formed, there is a risk of developing 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 developing skin rashes.
When used simultaneously with methotrexate, the toxicity of the latter increases.
Concomitant use with disulfiram should be avoided.
Pharmaceutically incompatible with solutions containing blood, proteins, lipids, glucose, dextran, bicarbonate. Do not mix in a syringe or infusion bottle with other medications. Incompatible with aminoglycosides.
special instructions
Before starting treatment with Amoxicillin + Clavulanic acid, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics.
Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock) to penicillins have been described. If an allergic reaction occurs, discontinue treatment and initiate alternative therapy. If serious hypersensitivity reactions develop, the patient should be given adrenaline immediately. Oxygen therapy, intravenous steroids, and airway management including intubation may be required.
Amoxicillin + Clavulanic acid should not be prescribed if infectious mononucleosis is suspected, since in patients with this disease, amoxicillin can cause a skin rash, which makes diagnosing the disease difficult.
Long-term treatment with Amoxicillin + Clavulanic acid may be accompanied by excessive growth of microorganisms insensitive to it.
Carefully Amoxicillin + Clavulanic acid should be used in patients with impaired liver function.
In patients receiving Amoxicillin + Clavulanic acid, an increase in prothrombin time is occasionally observed, therefore, appropriate monitoring should be carried out when using Amoxicillin + Clavulanic acid and anticoagulants simultaneously.
In rare cases, crystalluria may occur in patients with reduced diuresis. During administration of high doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.
Lab tests: High concentrations of amoxicillin give a false-positive reaction to urine glucose when using Benedict's reagent or Fehling's solution. It is recommended to use enzymatic reactions with glucosidase.
Pregnancy and lactation
Amoxicillin + Clavulanic acid passes into breast milk, which can cause diarrhea and fungal infections of the mucous membranes in breastfed infants. The decision to stop breastfeeding is made after a careful assessment of the benefit-risk ratio by the attending physician.
Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms
Unknown.
Overdose
Symptoms: Gastrointestinal disorders and disturbances in water and electrolyte balance are possible. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure.
Treatment: carrying out symptomatic therapy, correction of water and electrolyte balance. Amoxicillin + clavulanic acid is removed from the blood using hemodialysis.
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