For all dosage forms
Antacids, glucosamine, laxatives, aminoglycosides slow down the absorption, ascorbic acid increases the absorption.
Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion (probenecid) increase the concentration of amoxicillin (clavulanic acid is mainly excreted by glomerular filtration).
Simultaneous use of the drug Amoxiclav® and methotrexate increases the toxicity of methotrexate.
Administration together with allopurinol increases the frequency of exanthema. Concomitant use with disulfiram should be avoided.
Reduces the effectiveness of drugs, during the metabolism of which PABA is formed, ethinyl estradiol-the risk of breakthrough bleeding.
The literature describes rare cases of increased INR in patients with the combined use of acenocumarol or warfarin and amoxicillin. If concomitant use with anticoagulants is necessary, PV or INR should be carefully monitored when prescribing or discontinuing the drug.
The combination with rifampicin is antagonistic (mutual weakening of the antibacterial effect). The drug Amoxiclav® it should not be used simultaneously in combination with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides due to a possible decrease in the effectiveness of the drug Amoxiclav®.
The drug Amoxiclav® reduces the effectiveness of oral contraceptives.
For dispersible tablets and powder for preparation of suspension for oral administration in addition
Increases the effectiveness of indirect anticoagulants (suppressing intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). In some cases, taking the drug may prolong the PV, in this regard, caution should be exercised when using anticoagulants and the drug Amoxiclav at the same time®Quicktab.
Probenecid reduces the excretion of amoxicillin, increasing its serum concentration.
In patients receiving mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, there was a decrease in the concentration of the active metabolite — mycophenolic acid, before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect the overall changes in mycophenolic acid exposure.
For powder for preparation of solution for intravenous administration in addition
The drug Amoxiclav® and aminoglycoside antibiotics are chemically incompatible.
The drug Amoxiclav® do not mix in a syringe or infusion bottle with other drugs.
Avoid mixing with solutions of dextrose, dextran, sodium bicarbonate, as well as with solutions containing blood, proteins, lipids.
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 may 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.
Pharmacologically incompatible with solutions containing blood, proteins, lipids, glucose, dextran, bicarbonate, simultaneous administration with allopurinol increases the risk of exanthema, avoid simultaneous administration with disulfiram.
The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. Amoxicillin and clavulanic acid are well soluble in aqueous solutions with a physiological pH value and after taking the drug Amoxiclav® inside, they are quickly and completely absorbed from the gastrointestinal tract. The absorption of the active substances-amoxicillin and clavulanic acid-is optimal in the case of taking the drug at the beginning of a meal.
The bioavailability of amoxicillin and clavulanic acid after oral administration is about 70%.
Peak plasma concentrations are reached approximately 1 h after administration. Values of Cmax make up for amoxicillin (depending on the dose) 3-12 mcg/ml, for clavulanic acid-about 2 mcg/ml.
Cmax in the blood plasma after bolus injection at a dose of 1.2 g (1000 200 mg) of the drug is 105.4 mg/l - for amoxicillin and 28.5 mg / l — for clavulanic acid.
When using the drug Amoxiclav® The plasma concentrations of amoxicillin/clavulanic acid are similar to those of oral administration of the corresponding doses of amoxicillin or clavulanic acid separately at equivalent doses.
Both components are characterized by a sufficient Vd in various organs, tissues and fluid environments of the body (including in the lungs, abdominal organs, adipose, bone and muscle tissues, pleural, synovial and peritoneal fluids, in the skin, bile, urine, purulent discharge, sputum, interstitial fluid).
Plasma protein binding is moderate — 25% for clavulanic acid and 18% for amoxicillin.
Vd it is approximately 0.3–0.4 l / kg for amoxicillin and approximately 0.2 l / kg for clavulanic acid.
Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier in non-inflamed meninges.
Amoxicillin (like most penicillins) is excreted in breast milk. Trace amounts of clavulanic acid were also found in breast milk. Amoxicillin and clavulanic acid penetrate the placental barrier.
Amoxicillin is mainly excreted by the kidneys, whereas clavulanic acid is excreted by both the renal and extrarenal mechanisms. After a single oral administration of one tablet 250 125 mg or 500 125 mg, approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged in the urine for the first 6 hours. About 10-25% of the initial dose of amoxicillin is excreted in the urine as inactive penicillic acid. Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4 - (2-hydroxyethyl) - 5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butane-2-one and is excreted in the urine and feces
Average T1/2 amoxicillin/clavulanic acid is approximately 1 h, the average total clearance is approximately 25 l / h in healthy patients. In the course of various studies, it was found that the excretion of amoxicillin in the urine for 24 hours is approximately 50-85%, clavulanic acid-27-60%. The greatest amount of clavulanic acid is excreted within the first 2 hours after ingestion.
The pharmacokinetic parameters of amoxicillin and clavulanic acid are summarized in Table 1.
Table 1
| Mean (±SD) pharmacokinetic parameters | |||||
| Active ingredients Amoxicillin/clavulanic acid | Dose, mg | Cmax, mcg / ml | Tmax, h | AUC(0-24), mcg * h / ml | T1/2, h |
| Amoxicillin | |||||
| 875 mg/125 mg | 875 | 11,64±2,78 | 1,5 (1–2,5) | 53,52±12,31 | 1,19±0,21 |
| 500 mg/125 mg | 500 | 7,19±2,26 | 1,5 (1–2,5) | 53,52±8,37 | 1,15±0,2 |
| Clavulanic acid | |||||
| 875 mg/125 mg | 125 | 2,18±0,99 | 1,25 (1–2) | 10,16±3,04 | 0,96±0,12 |
| 500 mg/125 mg | 125 | 2,4±0,83 | 1,5 (1–2) | 15,52±3,86 | 0,98±0,12 |
Patients with impaired liver function
In patients with severe renal insufficiency T1/2 increases to 7.5 hours for amoxicillin and 4.5 hours for clavulanic acid.
For patients with impaired liver function, the dose of the drug should be selected with caution: constant monitoring of the liver condition is necessary.
Both components are removed by hemodialysis and minor amounts are removed by peritoneal dialysis.
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>MPC1, h (%) 2 | Cmax, mg/l | Tmax, h | AUC, mcg * h/ml | T1/2, h |
| Amoxicillin | ||||||
| Amoclan 1000 mg 62.5 mg×2 | 2000 | 5,9 (49,4) | 17 | 1,5 | 71,6 | 1,27 |
| Clavulanic acid | ||||||
| Amoclan 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").
The pharmacokinetics of amoxicillin and clavulanic acid are similar. After intravenous administration in doses of 1200 mg and 600 mg Smax amoxicillin — 105.4 mcg / ml and 32.2 mcg/ml, respectively, clavulanic acid-28.5 mcg/ml and 10.5 mcg/ml, respectively. Plasma protein binding: amoxicillin-17-20%, clavulanic acid-23-30%. Both components are metabolized in the liver: amoxicillin - 10% of the administered dose, clavulanic acid-50%. T1/2 after intravenous administration at a dose of 1.2 g and 600 mg-0.9 and 1.07 hours for amoxicillin, 0.9 and 1.12 hours-for clavulanic acid, respectively. It is mainly excreted by the kidneys (glomerular filtration and tubular secretion): 50-78% and 25-40% of the dose of amoxicillin and clavulanic acid, respectively, is excreted unchanged during the first 6 hours after administration.
