Symptoms: there may be symptoms from the gastrointestinal tract and violations of the water-electrolyte balance. Amoxicillin crystalluria is described, which in some cases led to the development of renal failure (see "Special instructions").
Treatment: symptoms from the gastrointestinal tract-symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.
hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins) in the anamnesis,
previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis.
With caution: liver function disorders.
Simultaneous use of the drug Augmentin® CP and probenecid are not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Augmentin® CP 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 skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.
Penicillins are able to slow the elimination of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Augmentin® CP and methotrexate may increase the toxicity of methotrexate.
Like other antibacterial drugs, the drug Augmentin® CP 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 increased MHO in patients with the combined use of acenocumarol or warfarin and amoxicillin. If necessary, simultaneous administration or withdrawal of the drug Augmentin® CP with PV or MHO anticoagulants should be carefully monitored, and the dose of anticoagulants for oral administration may need to be adjusted.
Pills: covered with a white film shell, capsule-shaped, on one side is engraved "AC 1000/62. 5", on the other-a dividing groove.
The adverse events presented below are listed according to the lesion of 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 <1/10, infrequently - ≥1/1000 and <1/100, rarely - ≥1/10000 and <1/1000, very rarely - <1/10000, including individual cases. Frequency categories were formed based on clinical trials of the drug and post-registration follow-up.
Infectious and parasitic diseases: often-genital moniliasis, cutaneous-mucosal candidiasis.
From the blood and lymphatic system: rarely-reversible leukopenia (including neutropenia) and thrombocytopenia, very rarely-reversible agranulocytosis and hemolytic anemia, increased bleeding time and PV.
On the part of the immune system: very rarely-angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.
From the nervous system: infrequently-dizziness, headache, very rarely-reversible hyperactivity, convulsions.
From the gastrointestinal tract: very often-diarrhea, often-nausea, abdominal pain, infrequently-vomiting, digestive disorders, very rarely-colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue.
From the liver and biliary tract: infrequently-moderate increase in the activity of ACT and / or ALT. This phenomenon is observed in patients receiving beta-lactam antibiotics, but its clinical significance is unknown, very rarely — hepatitis and cholestatic jaundice. This phenomenon is observed in patients receiving therapy with penicillin-type antibiotics and cephalosporins.
Adverse events from the liver are observed mainly in men and elderly patients and may be associated with long-term therapy.
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 events are usually reversible. Adverse events from the liver can be severe, in extremely rare cases, there have been reports of fatal outcomes. In almost all cases, these were patients with serious comorbidities or patients receiving potentially hepatotoxic drugs at the same time.
From the skin and subcutaneous tissues: infrequently-rash, itching, urticaria, rarely-erythema multiforme, very rarely — Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. In case of any allergic reactions, treatment with Augmentin® The CP must be stopped.
From the kidneys and urinary tract: very rarely — interstitial nephritis, crystalluria.
According to the recipe.
Before starting treatment with Augmentin® SR it is necessary to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins.
Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. In the event of an allergic reaction, it is necessary to stop treatment with Augmentin® CP and start appropriate alternative therapy.
In case of serious anaphylactic reactions, epinephrine should be administered immediately to the patient. Oxygen therapy, intravenous administration of corticosteroids, and airway patency, including intubation, may also be required.
In case of suspected infectious mononucleosis, the drug Augmentin® CP should not be used, because in patients with this disease, amoxicillin can cause a bark-like skin rash, which makes it difficult to diagnose the disease.
Long-term treatment with Augmentin® CP sometimes leads to an excessive multiplication of insensitive microorganisms.
In order to reduce the risk of side effects from the gastrointestinal tract, you should take the drug at the beginning of a meal.
In patients treated with a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in PV (an increase in MHO) was rarely reported. When co-prescribing indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of the corresponding indicators is necessary. To maintain the desired effect of oral anticoagulants, it may be necessary to adjust their dose.
No dose adjustment is required for Augmentin® CP for patients with creatinine Cl ≥30 ml/min. It is not recommended to prescribe the drug to patients with creatinine Cl <30 ml/min. In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. When taking high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystals forming (see "Overdose").
Taking the drug Augmentin® Oral CP leads to a high content of amoxicillin in the urine, which can lead to false positive results when determining glucose in the urine (for example, the Benedict test, the Fehling test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.
Abuse and drug addiction. Drug dependence, addiction, and euphoric reactions associated with the use of the drug Augmentin were not observed® WED.
Influence on the ability to drive vehicles and work with mechanisms. Since the drug can cause dizziness, it is necessary to warn patients about precautions when driving a vehicle or working with moving mechanisms.
The drug Augmentin® CP is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid:
respiratory tract infections, such as community-acquired pneumonia, exacerbation of chronic bronchitis, acute bacterial sinusitis, usually caused by Streptococcus pneumoniae (including penicillin-resistant strains), Haemophilus influenzae1, Moraxella catarrhalis1 and Streptococcus pyogenes,
prevention of local infections after surgery in dentistry.
1 Some strains of these bacteria produce beta-lactamases, which makes them insensitive to amoxicillin monotherapy.
Infections caused by amoxicillin-sensitive microorganisms can be treated with Augmentin® CP, since amoxicillin is one of its active ingredients. The drug Augmentin® CP is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as beta-lactamase-producing microorganisms sensitive to the combination of amoxicillin with clavulanic acid.
The drug Augmentin® CP demonstrated efficacy against strains S. pneumoniae, resistant to penicillin (strains with MPC ≥2 mg/l).
Drugs containing a combination of amoxicillin with clavulanic acid should be used in accordance with the Russian guidelines for antibiotic therapy and regional data on the sensitivity of pathogens to the combination of amoxicillin with clavulanic acid.
The sensitivity of bacteria to the combination of amoxicillin with clavulanic acid varies depending on the region and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and analyzed for bacteriological sensitivity.
Amoxicillin is a broad-spectrum semi-synthetic 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 extend 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 has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is less effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid.
The presence of clavulanic acid in the preparation Augmentin® protects amoxicillin from destruction by enzymes-beta-lactamases, which allows you to expand the antibacterial spectrum of amoxicillin.
Delayed release of amoxicillin in Augmentin® CP allows you to maintain the sensitivity of those strains S. pneumoniae, in which resistance to amoxicillin is due to penicillin-binding proteins (penicillin-resistant S. pneumoniae, or PRSP).
Below is the activity of the combination of amoxicillin with clavulanic acid in vitro.
Bacteria usually sensitive to the combination of amoxicillin with clavulanic acid
Gram-positive airbags: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae1,2, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, group streptococci Viridans2, Streptococcus spp. (other beta-hemolytic streptococci)1,2, Staphylococcus aureus (sensitive to methicillin)1, Staphylococcus saprophyticus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin).
Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.
Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: Clostridium spp., Peptostreptococcus spp., incl. Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros.
Gram-negative anaerobes: Bacteroides spp., incl. Bacteroides fragilis, Capnocytophaga spp., Eikenella corrodens, Fusobacterium spp., incl. Fusobacterium nucleatum, Porphyromonas spp., Prevotella spp.
Bacteria that are likely to have acquired resistance to the combination of amoxicillin with clavulanic acid
Gram-negative aerobes: Escherichia coli1, Klebsiella spp., incl. Klebsiella oxytoca, Klebsiella pneumoniae1, Proteus spp., incl. Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp.
Gram-positive airbags: Corynebacterium spp., Enterococcus faecium.
Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid
Gram-negative aerobes: Acinetobacter spp., Citrobacter freundii, Enterobacter spp., Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia, Yersinia enterocolitica.
Other: Chlamydia spp., incl. Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, Mycoplasma spp.
1 For these types of microorganisms, 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-lactamases. The sensitivity of amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.
Resistance
Cross-resistance. Amoxicillin directly demonstrates cross-resistance with other beta-lactam antibiotics, as well as a combination of beta-lactam antibiotics with beta-lactamase inhibitors and cephalosporins.
Mechanisms of resistance. Clavulanic acid protects amoxicillin from the damaging effects of beta-lactamases. Delayed release of the active ingredients of the drug Augmentin® CP increases the effectiveness of amoxicillin against microorganisms whose resistance is due to modification of penicillin-binding proteins.
Suction
Both active ingredients of the drug Augmentin® CP, amoxicillin and clavulanic acid, are well soluble in aqueous solutions with a physiological pH value, are quickly and completely absorbed from the gastrointestinal tract after oral administration. The absorption of active substances is optimal in the case of taking the drug at the beginning of a meal.
The pharmacokinetic parameters of amoxicillin and clavulanic acid after taking 2 tablets of the drug Augmentin are shown below® CP by healthy volunteers at the beginning of a meal.
Table 1
Average values of pharmacokinetic parameters
| Medication | Dose, mg | T>IPC1, h (%)2 | Cmax, mg/l | Tmax, h | AUC, mcg * h/ml | T1/2, h |
| Amoxicillin | ||||||
| Augmentin SR 1000 mg 62.5 mg×2 | 2000 | 5,9 (49,4) | 17 | 1,5 | 71,6 | 1,27 |
Clavulanic acid | ||||||
| Augmentin SR 1000 mg 62.5 mg×2 | 125 | Not defined | 2,05 | 1,03 | 5,29 | 1,03 |
1 For bacteria with an MPC of 4 mg/l.
2 T>MPC, h (%) — the time (as a percentage of the time interval between doses) during which the concentration of the drug in the blood is higher than the BMD for a particular pathogen.
The drug Augmentin® CP has a unique pharmacological profile, the T>MPC index characteristic of this drug is not achieved when taking tablets with immediate release of active substances containing a combination of amoxicillin and clavulanic acid.
Distribution
As with the intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are created in various tissues and interstitial fluid (gallbladder, abdominal tissue, skin, adipose and muscle tissue, synovial and peritoneal fluid, bile, purulent discharge).
Amoxicillin and clavulanic acid have 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 the blood plasma binds to plasma proteins.
In animal studies, no accumulation of the components of the drug Augmentin was found® CP in any body.
Amoxicillin, like most penicillins, can be detected in breast milk. Trace amounts of clavulanic acid were also found in breast milk. With the exception of the possibility of diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of infants fed with breast milk are known.
Studies of reproductive function in animals when taking the drug Augmentin® CP showed that amoxicillin and clavulanic acid penetrate 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 undergoes intensive metabolism to 2,5-dihydro-4 - (2-hydroxyethyl) - 5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butane-2-one and is excreted by the kidneys, through the gastrointestinal tract, and with exhaled air in the form of carbon dioxide.
Output
Like other penicillins, amoxicillin is mainly excreted by the kidneys, while clavulanic acid is excreted through both the renal and extrarenal mechanisms.
Studies have shown that, on average, about 60-70% of amoxicillin and about 40-65% of clavulanic acid is excreted unchanged by the kidneys.
Simultaneous administration of probenecid slows the elimination of amoxicillin, but does not slow the elimination of clavulanic acid (see "Interaction").
At a temperature not exceeding 25 °C.
Keep out of reach of children.
Shelf life of the drug Augmentin® WED2 года.Do not use after the expiration date indicated on the package.
| Modified-release film-coated tablets | 1 table. |
| An immediate release layer | |
| active ingredients: | |
| amoxicillin trihydrate | 654.1 mg |
| (equivalent to 562.5 mg of amoxicillin) | |
| potassium clavulanate | 76.2 mg |
| (equivalent to 62.5 mg of clavulanic acid) | |
| excipients: MCC — 136.4 mg, sodium carboxymethyl starch-18 mg, colloidal anhydrous silicon dioxide-6.3 mg, magnesium stearate-9 mg | |
| A layer that provides gradual release | |
| active substance: | |
| amoxicillin sodium | 480.8 mg |
| (equivalent to 437.5 mg of amoxicillin) | |
| excipients: MCC — 111.7 mg, xanthan gum-14 mg, citric acid-78 mg, colloidal anhydrous silicon dioxide-1.5 mg, magnesium stearate-14 mg | |
| Water film shell: hypromellose 6 cps-11.6 mg, hypromellose 15 cps-3.9 mg, titanium dioxide-15.1 mg, macrogol 3350-2.3 mg, macrogol 8000 — 2.3 mg |
Modified release film-coated tablets, 1000 mg 62.5 mg. In a blister made of PVC or PE / aluminum foil, 2 pcs. 2 blisters in a combined package with a dividing line between them. 4, 7 or 10 combined packages in a pack of cardboard.
In studies of reproductive function in animals, oral and parenteral administration of the drug Augmentin® CP did not cause teratogenic effects.
In a single study in women with premature rupture of the fetal membranes, it was found that preventive therapy with the drug may be associated with an increased risk of necrotizing enterocolitis in newborns. Like all medications, Augmentin® CP is not recommended for use during pregnancy, except in cases where the expected benefit to the mother exceeds the potential risk to the fetus.
The drug Augmentin® CP can be used during breastfeeding. With the exception of the possibility of diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active substances of this drug into breast milk, no other adverse effects were observed in infants who were breastfed. In the event of adverse effects in infants who are breastfed, it is necessary to stop breastfeeding.
Inside.
To optimize absorption, the drug should be taken at the beginning of a meal.
Treatment should not last more than 14 days without reviewing the clinical situation.
Tablets of the drug Augmentin® The SRS have a dividing groove that allows them to be broken in half for ease of ingestion, but not to reduce the dose: both halves must be taken simultaneously. The recommended dose of the drug is 2 tablets. 2 times a day.
Adults (16 years and older). Respiratory tract infections: 2 table. 2 times a day for 7-10 days, including the following diseases:
- community-acquired pneumonia — 2 tables. 2 times a day for 7-10 days,
- exacerbation of chronic bronchitis — 2 tables. 2 times a day for 7 days,
- acute sinusitis of bacterial etiology — 2 tables. 2 times a day for 10 days.
Prevention of local infections after surgical dental interventions: 2 tables. 2 times a day for 5 days starting 3 hours after the intervention.
Special patient groups
Children under 16. Not applicable.
Elderly patients. No dosage adjustment is required.
Patients with impaired renal function. No dosage adjustment is required for creatinine Cl ≥30 ml/min. It is not recommended to prescribe the drug to patients with creatinine Cl <30 ml/min.
Patients on hemodialysis. Not recommended.
Impaired liver function. Treatment is carried out with caution, liver function is regularly monitored. There is insufficient data to recommend a dosage regimen for this group of patients.
J01CR02 Amoxicillin in combination with a beta-lactamase inhibitor
