Amoxiclav Quicktab dispersible tablets 500 mg/125 mg blister 20 pcs.

Composition

amoxicillin, clavulanic acid;

1 tablet contains 500 mg of amoxicillin in the form of amoxicillin trihydrate and 125 mg of clavulanic acid in the form of potassium salt;

Excipients: aspartame (E 951), colloidal silicon dioxide, yellow iron oxide (E 172), tropical blend flavor, sweet orange flavor, talc, hydrogenated castor oil, silicified microcrystalline cellulose.

Release form

The tablets are dispersed.

Pharmacodynamics.

Mechanism of action

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic metabolism of bacterial peptidoglycan, an integral structural component of the cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, resulting in cell lysis and death.

Amoxicillin is susceptible to cleavage by beta-lactamases produced by resistant bacteria, therefore the spectrum of activity of amoxicillin as monotherapy does not include organisms that produce these enzymes.

Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid as monotherapy has no clinically useful antibacterial effect.

Resistance mechanisms

There are two mechanisms of resistance to amoxicillin/clavulanic acid:

• inactivation by bacterial beta-lactamases that are not inhibited by clavulanic acid themselves, including class B, C and D;
• conversion of PSB, which reduces the affinity of the antibacterial drug for the target.

Bacterial permeability or the reflux pump mechanism can cause or contribute to bacterial resistance, particularly in Gram-negative bacteria.

Pharmacokinetics.

Absorption. Amoxicillin and clavulanic acid completely dissociate in aqueous solution at physiological pH. Both components are rapidly and well absorbed after oral administration. The bioavailability of amoxicillin and clavulanic acid is approximately 70% after oral administration. The plasma profiles of both components are identical, and the time to maximum plasma concentration (Tmax) for each component is approximately one hour.

The serum concentrations of amoxicillin and clavulanic acid achieved with amoxicillin/clavulanic acid are identical to those achieved with oral administration of equivalent doses of amoxicillin and clavulanic acid alone.

Distribution: Approximately 25% of the total plasma clavulanic acid and 18% of the total drug in plasma are protein bound. The volume of distribution is approximately 0.3-0.4 l/kg for amoxicillin and approximately 0.2 l/kg for clavulanic acid.

Following administration, amoxicillin and clavulanic acid have been detected in the gallbladder, abdominal tissue, skin, adipose tissue, muscle tissue, synovial and peritoneal fluids, bile and pus. Amoxicillin does not partition sufficiently into cerebrospinal fluid.

Metabolism: Amoxicillin is partially excreted in the urine as inactive penicilloic acid in amounts equivalent to 10-25% of the initial dose. Clavulanic acid is extensively metabolized in humans and is excreted in the urine and feces and as carbon dioxide in exhaled air.

Excretion: The primary route of elimination for amoxicillin is the kidneys, whereas clavulanic acid is eliminated by both renal and extrarenal mechanisms.

In healthy volunteers, the mean elimination half-life of the drug/clavulanic acid is approximately one hour and the mean total clearance is approximately 25 l/h. Various studies have shown that urinary excretion is 50-85% for amoxicillin and 27-60% for clavulanic acid over a 24-hour period. In the case of clavulanic acid, a large amount of the substance is excreted within the first 2 hours after administration.

Treatment of bacterial infections caused by microorganisms sensitive to Amoxiclav Quicktab:

• acute bacterial sinusitis (confirmed);
• acute otitis media;
• confirmed exacerbation of chronic bronchitis;
• community-acquired pneumonia;
• cystitis;
• pyelonephritis;
• skin and soft tissue infections, including cellulitis, animal bites, severe dentoalveolar abscesses with widespread cellulitis;
• bone and joint infections, including osteomyelitis.

Hypersensitivity to amoxicillin, clavulanic acid or other components of the drug, history of allergic reactions to any penicillin antibiotic, infectious mononucleosis and lymphocytic leukemia.

History of severe hypersensitivity reactions (including anaphylaxis) associated with the use of other β-lactam agents (including cephalosporins, carbapenems or monobactams).

History of jaundice or liver dysfunction associated with the use of amoxicillin/clavulanate.

Oral anticoagulants. Oral anticoagulants and penicillin antibiotics are widely used in clinical practice without any reported interactions. However, cases of increased international normalization ratio have been reported in patients receiving acenocoumarol or warfarin and who were prescribed amoxicillin. If concomitant use is necessary, the prothrombin time or international normalization ratio should be closely monitored when amoxicillin is added or withdrawn. In addition, dose adjustment of oral anticoagulants may be required (see sections 4.4 and 4.8).

Methotrexate: Penicillins may reduce the excretion of methotrexate, leading to a potential increase in toxicity.

Probenecid. Concomitant use of probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Concomitant use of probenecid may lead to increased levels and duration of amoxicillin (but not clavulanic acid) in the blood.

Mycophenolate mofetil. In patients treated with mycophenolate mofetil, the overdosage concentration of the active metabolite mycophenolic acid may be reduced by approximately 50% after initiation of oral amoxicillin/clavulanic acid. This change in overdosage level may not fully reflect the change in overall mycophenolic acid exposure. Therefore, a change in mycophenolate mofetil dosage is not usually necessary unless there is clinical evidence of graft dysfunction. However, close monitoring is necessary during coadministration and for some time after antibiotic therapy.

Before initiating therapy with amoxicillin/clavulanic acid, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam drugs.

Serious and occasionally fatal hypersensitivity reactions (including anaphylactic reactions and cutaneous adverse reactions) have been reported in patients treated with penicillin. Such reactions are more likely to occur in patients with a history of penicillin hypersensitivity and in patients with atopic diseases. If an allergic reaction occurs, amoxicillin/clavulanic acid should be discontinued and appropriate alternative therapy should be initiated.

If the infection is proven to be caused by an organism(s) susceptible to amoxicillin, a switch from amoxicillin/clavulanic acid to amoxicillin should be considered according to standard practice.

This formulation of Amoxiclav Quicktab is not suitable for use when there is a high risk that the potential pathogens have reduced susceptibility or resistance to beta-lactam drugs not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This formulation should not be used for the treatment of penicillin-resistant S. pneumoniae.

In patients with impaired renal function and in patients taking high doses of the drug, seizures may occur.

The use of amoxicillin/clavulanic acid should be avoided in suspected infectious mononucleosis, as in this case, the use of amoxicillin was associated with the development of a croup-like rash.

Concomitant use of allopurinol during treatment with amoxicillin increases the likelihood of allergic skin reactions.

Prolonged use may lead to excessive proliferation of microorganisms insensitive to the drug.

Hepatic complications have been reported predominantly in men and elderly patients and may be associated with long-term treatment. Such complications have been reported extremely rarely in children. In all patient groups, symptoms usually occur during or shortly after treatment, but in some cases may not appear until a few weeks after the end of treatment. Such events are usually reversible. Hepatic complications can be severe and, in rare cases, fatal. Such events have almost always been observed in patients with severe underlying disease or in those taking concomitant medications with a known potential to cause hepatic complications (see section 4.8).

Use during pregnancy or breastfeeding

Pregnancy. Animal reproduction studies with oral and parenteral forms of Amoxiclav have not revealed any teratogenic effects. In one study involving women with premature rupture of membranes, it was reported that prophylactic use of Amoxiclav may be associated with an increased risk of necrotizing enterocolitis in newborns. As with other drugs, the use of the drug should be avoided during pregnancy, especially during the first trimester, unless considered essential by the physician.

Breastfeeding. Both active components of the drug are excreted in breast milk (there is no information on the effect of clavulanic acid on a breastfed infant). Accordingly, diarrhea and fungal infection of the mucous membranes may occur in a breastfed infant, so breastfeeding should be discontinued. The possibility of allergic reactions should be considered. Amoxiclav can be used during breastfeeding only if, in the opinion of the doctor, the benefit of use outweighs the risk.

Ability to influence reaction speed when driving vehicles or other mechanisms

No studies have been conducted to study the ability of the drug to affect the reaction speed when driving or using other mechanisms. However, adverse reactions (e.g. allergic reactions, dizziness, convulsions) may occur that may affect the ability to drive or use other mechanisms.

The product should be used in accordance with official antibiotic treatment guidelines and local antibiotic susceptibility data. Susceptibility to amoxicillin/clavulanate varies between regions and may change over time. Local susceptibility data should be consulted and microbiological determination and susceptibility testing should be performed as appropriate.

The range of suggested doses depends on the expected pathogens and their sensitivity to antibacterial drugs, the severity of the disease and the location of the infection, the age, body weight and renal function of the patient.

Adults and children weighing ≥ 40 kg: 1 tablet 3 times a day (daily dose is 1500 mg amoxicillin/375 mg clavulanic acid).

Children aged 6 years and over with a body weight of 25 to 40 kg.

Dose from 20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day, divided into 3 doses. The maximum daily dose is 2400 mg amoxicillin/600 mg clavulanic acid (4 tablets).

Since the tablet cannot be divided in children weighing less than 25 kg, this dosage form should not be prescribed.

Elderly patients. No dose adjustment is required. If necessary, adjust the dose depending on renal function.

Children aged 6 years and over with a body weight of 25 to 40 kg. Since the tablet cannot be divided, this dosage form should not be administered to children over 6 years of age with a body weight of 25 to 40 kg, a creatinine clearance of less than 30 ml/min, or children on hemodialysis.

Hepatic impairment: Use with caution; liver function should be monitored at regular intervals.

For optimal absorption and to reduce possible side effects from the digestive tract, the drug should be taken at the beginning of a meal. Dissolve the tablet in 1/2 glass of water (at least 100 ml), mix thoroughly before taking or chew before swallowing.

The duration of treatment is determined individually and should not exceed 14 days without assessment of the patient’s condition. The duration of treatment will be determined by the patient’s clinical response to treatment. Some infections (e.g. osteomyelitis) require prolonged treatment.

If high doses of amoxicillin are required for treatment, formulations with a different amoxicillin/clavulanic acid ratio should be used to avoid unnecessarily high doses of clavulanic acid.

Treatment can be initiated with parenteral administration and then continued with oral administration.

Children: This dosage form should be used in children aged 6 years and over with a body weight of at least 25 kg.

Symptoms

Gastrointestinal symptoms and fluid and electrolyte imbalance may occur. Amoxicillin-associated crystalluria has been reported, leading in isolated cases to renal failure.

In patients with impaired renal function and in patients taking high doses of the drug, seizures may occur.

Amoxicillin precipitation in bladder catheters has been reported, mainly after administration of high doses. Catheter patency should be checked regularly.

Treatment

Gastrointestinal symptoms can be treated symptomatically, with attention to fluid/electrolyte balance.

Amoxicillin/clavulanic acid can be removed from the bloodstream by hemodialysis.

Side effects of Amoxiclav Quicktab are usually mild and resolve quickly. The most common side effects are gastrointestinal (diarrhea, nausea). These reactions can be prevented by taking the drug with food.

The generally accepted classification of adverse reactions by frequency is: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), rare (<1/10000), unknown (frequency cannot be estimated due to lack of data).

• Infections and infestations: common – candidiasis of the genitals (vaginal discharge and itching), skin and mucous membranes; frequency unknown – development of superinfection, excessive growth of insensitive microflora.
• On the part of the blood: isolated – reversible leukopenia (including neutropenia) and thrombocytopenia; rare – reversible agranulocytosis and hemolytic anemia, eosinophilia, pancytopenia, myelosuppression, increased bleeding time and prothrombin index.
• From the nervous system: often – dizziness, headache, convulsions (mainly in patients with impaired renal function or when using high doses of the drug); rare – reversible hyperactivity; frequency unknown – aseptic meningitis.
• Mental disorders: rarely – hyperactivity, anxiety, insomnia, confusion, agitation, aggressive behavior.
• From the digestive tract: very often – diarrhea; often – nausea (more often associated with high doses of the drug), vomiting, abdominal pain, anal itching; infrequently – dyspepsia, indigestion, flatulence, glossitis, stomatitis associated with taking antibiotics, antibiotic (including hemorrhagic and pseudomembranous colitis). There are individual reports of discoloration of the surface of the teeth, but these reports relate to the use of the drug in the form of a suspension. Oral hygiene should be observed to prevent these phenomena. Rarely – staining of the tongue in black, “black hairy tongue”.
• From the urinary system: rarely – interstitial nephritis, hematuria, crystalluria.
• Skin: often – rash, itching, urticaria; infrequently – erythema multiforme; rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), Lyme syndrome. With the appearance of any allergic dermatitis, further use of the drug should be discontinued.
• On the part of the immune system: often – angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis, drug fever; rare – severe anaphylactoid reactions requiring emergency therapy with adrenaline and other agents.
• Hepatobiliary system: infrequently – moderate increase in AST and ALT is noted in patients treated with beta-lactam antibiotics; rare – hepatitis and cholestatic jaundice. These phenomena occur when using other penicillins and cephalosporins. On the part of the liver, they are noted mainly in men and elderly patients and are associated with prolonged use of the drug (more than 14 days). Such phenomena occurred very rarely in children.

These events may be severe but are usually reversible. They develop during or immediately after treatment, although sometimes they do not appear until several weeks after discontinuation of the drug. Very rarely, fatalities have been reported in patients with severe underlying disease or in patients receiving concomitant medications that have a negative effect on the liver.

Store at a temperature not exceeding 25 °C in a dry place. Keep out of reach of children. Shelf life – 3 years.