Betaclav, 875 mg+125 mg 14 pcs

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to amoxicillin and clavulanic acid combination:

– upper respiratory tract infections (including ENT organ 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 exacerbation of chronic bronchitis, lobular 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 genitalia, usually caused by species of the family Enterobacteriaceae¹ (mostly Escherichia coli^#), Staphylococcus saprophyticus and species of the genus Enterococcus, as well as gonorrhea caused by Neisseria gonorrhoeae^#;

– Skin and soft tissue infections, usually caused by Staphylococcus aureus^#, Streptococcus pyogenes and species of the genus Bacteroides^#;

-bone and joint infections, such as osteomyelitis, usually caused by Staphylococcus aureus^#, with possible long-term therapy if necessary;

– odontogenic infections such as periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis;

– other mixed infections (eg, septic abortion, postpartum sepsis, intra-abdominal sepsis) within step therapy.

^#Some of these microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin (see also section “Pharmacological properties”).

Infections caused by amoxicillin-sensitive microorganisms can be treated with Betaclav^® because amoxicillin is one of its active ingredients. Betaclav^® is also indicated for the treatment of mixed infections caused by amoxicillin-sensitive microorganisms and beta-lactamase-producing microorganisms sensitive to the combination of amoxicillin and clavulanic acid.

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. If necessary, microbiologic specimens should be collected and bacteriologic sensitivity testing should be performed.

Active ingredient

Composition

for 1 film-coated tablet, 500 mg + 125 mg / 875 mg + 125 mg:

Core

Active substances:

Amoxicillin trihydrate 573.892 mg / 1,004.310 mg, equivalent to amoxicillin 500,000 mg / 875,000 mg

Potassium clavulanate + Microcrystalline cellulose (1:1) 303.834 mg / 303.834 mg, equivalent to potassium clavulanate 151.915 mg / 151.915 mg, equivalent to clavulanic acid 125.000 mg / 125.000 mg

Supplementary substances: microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, sodium carboxymethyl starch

Wrapping film: Opadray white Y-1-7000 ?

? Opadray white Y-1-7000: Hypromellose 5 cP (E464), titanium dioxide (E171), macrogol-400

White Opadray Y-1-7000: Hypromellose 5 cP (E464), titanium dioxide (E171), macrogol 400

How to take, the dosage

For oral administration.

The dosing regimen is individually adjusted according to the patient’s age, body weight, renal function, and the severity of the infection.

To reduce potential gastrointestinal disorders and to optimize absorption, the drug should be taken at the beginning of meals.

The minimum course of antibiotic therapy is 5 days.

Treatment should not last more than 14 days without revision of the clinical situation. If necessary, a step-by-step therapy (at first, intravenous administration of the drug containing amoxicillin and clavulanic acid in a dosage form for preparation of solution for intravenous injection, followed by switching to the drug containing amoxicillin and clavulanic acid in dosage forms for oral administration) is possible.

Adults and children 12 years and older or with a body weight of 40 kg or more

1 tablet 500 mg + 125 mg 3 times daily.

1 tablet 875 mg + 125 mg 2 times a day.

Special patient groups

Children under 12 years of age or with a body weight of less than 40 kg

Other dosage forms of the drug containing amoxicillin and clavulanic acid are recommended.

Elderly patients

No dosing regimen adjustment is 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

The dosing regimen adjustment is based on the maximum recommended dose of amoxicillin and creatinine clearance (CK) value.

Creatinine clearance

Dosing regimen of Betaclav®

> 30 ml/min

No dosing regimen correction required

10-30 ml/min

1 tablet 500 mg + 125 mg (in moderate to severe infection) 2 times a day

< 10 ml/min

1 tablet 500 mg + 125 mg (in moderate to severe course of infection) once a day

Patients on hemodialysis

The dosing adjustment is based on the maximum recommended dose of amoxicillin.

1 tablet 500 mg + 125 mg every 24 hours.

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

Tablets 875 mg + 125 mg should be used only in patients with CK> 30 ml/min and no dosing regimen adjustment is required.

In most cases, parenteral therapy should be preferred if possible.

Patients with liver dysfunction

Treatment is performed with caution and liver function is monitored regularly.

There is insufficient data to change the dosing recommendation in these patients.

Interaction

Simultaneous use of Betaclav® and probenecid is not recommended. Probenecid decreases the tubular secretion of amoxicillin, and therefore concomitant use of Betaclaw® and probenecid may lead to increased concentration and persistence of amoxicillin in blood, but not clavulanic acid.

Concurrent use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there are no data in the literature about the simultaneous use of amoxicillin with clavulanic acid and allopurinol.

Penicillins can slow down excretion of methotrexate by inhibiting its tubular secretion, therefore concomitant use of Betaclav® and methotrexate may increase methotrexate toxicity.

Like other antibacterials, Betaclave® may affect the gut microflora, resulting in decreased absorption of estrogen from the GI tract and decreased efficacy of oral combination contraceptives.

The literature describes rare cases of increased international normalized ratio (INR) in patients with concomitant use of acenocoumarol or warfarin and amoxicillin. If concomitant administration of Betaclav® with anticoagulants is necessary, prothrombin time or INR should be carefully monitored when prescribing or withdrawing Betaclav®, oral anticoagulants dose adjustment may be required.

In patients receiving mycophenolate mofetil, a decrease of approximately 50% in the concentration of the active metabolite, mycophenolic acid, was observed after initiation of a combination of amoxicillin and clavulanic acid before the next dose of the drug. Changes in this concentration cannot accurately reflect overall changes in mycophenolic acid exposure.

Special Instructions

Betaclav® should be used with caution in patients with impaired liver function.

Children younger than 12 years or with body weight less than 40 kg

Other dosage forms of the drug containing amoxicillin and clavulanic acid are recommended.

Children 12 years and older or with a body weight of 40 kg or more

1 tablet 500 mg + 125 mg 3 times daily.

1 tablet 875 mg + 125 mg 2 times a day.

Elderly Patients

No dosing regimen adjustment is 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

The dosing regimen adjustment is based on the maximum recommended dose of amoxicillin and creatinine clearance (CK) value.

Creatinine clearance

Dosing regimen of Betaclav®

> 30 ml/min

No dosing regimen correction required

10-30 ml/min

1 tablet 500 mg + 125 mg (in moderate to severe infection) 2 times a day

< 10 ml/min

1 tablet 500 mg + 125 mg (in moderate to severe infection) once daily

Patients with impaired liver function

Treatment is performed with caution and liver function is monitored regularly.

There is insufficient data to change the dosing recommendations for these patients.

Before starting treatment with Betaclav®, a detailed history of prior hypersensitivity reactions to penicillins, cephalosporins or other substances that cause allergic reactions in the patient should be taken.

Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. In case of allergic reactions it is necessary to stop the treatment with Betaclove® and start an appropriate alternative therapy. In case of severe anaphylactic reactions, epinephrine should be administered to the patient immediately. Oxygen therapy, intravenous glucocorticosteroids, and airway management including intubation may also be necessary.

In case of skin allergic reactions, treatment with Betaclav® should be stopped.

Betaclav® should not be used if infectious mononucleosis is suspected because in patients with this disease amoxicillin may cause a skin rash, which complicates the diagnosis.

Prolonged treatment with Betaclav® may result in overgrowth of insensitive microorganisms.

Cases of pseudomembranous colitis have been described when taking antibiotics, the severity of which can range from mild to life-threatening. Therefore, it is important to consider the possibility of pseudomembranous colitis in patients with diarrhea during or after the use of antibiotics. If diarrhea is prolonged or severe, or if the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be evaluated.

In general, Betaclav® is well tolerated and has low toxicity common to all penicillins. During long-term therapy with Betaclav® it is recommended to periodically assess kidney, liver and hematopoiesis function.

In patients who received combination of amoxicillin with clavulanic acid concomitantly with indirect (for oral administration) anticoagulants in rare cases an increase in prothrombin time (INR) was reported. When concomitant use of indirect (oral) anticoagulants with the combination of amoxicillin with clavulanic acid it is necessary to monitor the corresponding indicators. Dose adjustments may be required to maintain the desired effect of oral anticoagulants.

In patients with impaired renal function, the dose of Betaclav® should be reduced according to the degree of impairment (see section “Dosage and administration”, subsection “Patients with impaired renal function”).

Crystalluria is very rare in patients with decreased diuresis, mostly during parenteral therapy. 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 (see section “Overdose”).

Administration of Betaclav® orally causes high amoxicillin content in urine, which may lead to false positive results in urine glucose determination (e.g., Benedict test, Felling test). In this case it is recommended to use glucose oxidase method to determine the concentration of glucose in urine.

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

Misuse and drug dependence

There have been no drug dependence, addiction, or euphoric reactions associated with the use of Betaclove®.

Because use of Betaclave® may cause dizziness, patients should be warned about caution when driving or operating moving machinery.

Synopsis

Tablets 500 mg + 125 mg:

Capsule-shaped film-coated tablets, white or nearly white, with “I 06” engraved on one side, phenols are possible.

Tablets 875 mg + 125 mg:

Capsule-shaped film-coated tablets, white or nearly white, with “I 07” engraved on one side, specks are possible.

Contraindications

– Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (eg, penicillins, cephalosporins) in the history.

– Previous episodes of jaundice or liver function disorder with a history of amoxicillin/clavulanic acid combination.

– Child age

Side effects

The adverse reactions presented below are listed according to organ and organ system involvement and frequency of occurrence. The frequency is defined as follows: very common (≥1/10), common (≥1/100 and < 1/10), infrequent (≥1/1000 and < 1/100), rare (≥1/10000 and < 1/1000), very rare (< 1/10000, including individual cases). Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Frequency of adverse reactions

Infectious and parasitic diseases:

often: candidiasis of skin and mucous membranes.

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 rarely: angioedema, anaphylactic reactions, serum-like syndrome, allergic vasculitis.

Nervous system disorders:

very rarely: reversible hyperactivity, seizures (seizures may be seen in patients with impaired renal function as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior changes.

Gastrointestinal tract disorders:

Adults

very often: diarrhea;

often: nausea, vomiting.

Children

often: diarrhea, nausea, vomiting.

All population

Nausea was most commonly associated with the use of high doses of the drug. If unwanted gastrointestinal reactions are observed after starting the drug, they can be eliminated if Betaclove® is taken at the beginning of a meal.

infrequent: digestive disorders;

very rarely: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see section “Special Indications”), black “hairy” tongue, gastritis, stomatitis.

Liver and biliary tract disorders:

infrequent: moderate increase in aspartataminotransferase and/or alanine aminotransferase (ACT and/or ALT) activity. This reaction has been 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 other penicillin-type antibiotics and cephalosporins), increased bilirubin concentration and alkaline phosphatase.

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

The signs and symptoms listed usually occur during or immediately after therapy, but in some cases may not occur for several weeks after completion of therapy. The adverse reactions are generally reversible. Adverse reactions on the liver side can be severe, in exceptionally 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 simultaneously.

Skin and subcutaneous tissue disorders:

infrequent: skin rash, pruritus, urticaria;

rare: erythema multiforme;

very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis;

frequency unknown: drug rash with eosinophilia and systemic manifestations (DRESS syndrome).

Kidney and urinary tract disorders:

very rarely: interstitial nephritis, crystalluria (see section “Overdose”), hematuria.

Overdose

Symptoms

Gastrointestinal symptoms and electrolyte-water balance disorders may occur. Amoxicillin crystalluria has been described, in some cases leading to renal failure (see section “Cautions”).

Seizures may be observed in patients with impaired renal function as well as in those receiving high doses of the drug.

Treatment

Gastrointestinal symptoms – symptomatic therapy, focusing on normalization of water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

The results of a prospective study that involved 51 children in a toxicology center showed that administration of amoxicillin at a dose less than 250 mg/kg did not result in significant clinical symptoms and did not require gastric lavage.

Pregnancy use

Pregnancy

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

In a single study in women with premature fetal rupture, it was found that prophylactic therapy may be associated with an increased risk of necrotizing enterocolitis in newborns. As with all medications, Betaclav® is not recommended for use during pregnancy unless the expected benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

Betaclav® can be used during breastfeeding. Except for possible sensitization, diarrhea or candidiasis of oral mucous membranes related to penetration of trace amounts of the drug active ingredients into breast milk, no other adverse effects in breastfed children have been observed. In case of adverse effects in breastfed infants, breastfeeding should be discontinued.

Similarities