Rapiclav

Rapiclav is an antibacterial drug for systemic use.

Indications Rapiclava

It is used to eliminate bacterial infectious pathologies caused by microbes sensitive to the drug:

• acute form of bacterial sinusitis;
• acute form of inflammation of the middle ear;
• confirmed exacerbation of chronic bronchitis;
• community-acquired pneumonia;
• pyelonephritis or cystitis;
• infectious processes within soft tissues and skin (this includes animal bites, cellulitis and severe forms of dental abscesses, accompanied by widespread cellulitis);
• infections in the joints or bones (including osteomyelitis).

Release form

The product is released in tablets; 1 blister contains 3 tablets. 7 blister strips are placed in a separate pack.

Pharmacodynamics

Rapiclav is a combination drug containing clavulinic acid (irreversible β-lactamase inhibitor), amoxicillin and penicillin with a wide range of antibacterial activity. The drug forms stable complex bonds of a negative nature with enzymes and protects the substance amoxicillin from their effects.

Amoxicillin has bactericidal properties – it inhibits the process of cell wall binding during bacterial growth (by competitively inhibiting transpeptidase activity). Clavulinic acid has a minor antibacterial effect, but it is capable of irreversibly synthesizing β-lactamases, preventing the destruction of amoxicillin.

The drug has a wide range of action, actively influencing microbes sensitive to amoxicillin, and in addition to this, resistant microorganisms that form β-lactamases, including:

• Gram-positive aerobic bacteria (Anthrax bacillus, Corynebacterium, Enterococcus faecalis, Listeria monocytogenes, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus bovis, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans);
• gram-positive anaerobic microorganisms: clostridia, peptococci and peptostreptococci;
• Gram-negative aerobic microbes: whooping cough bacillus, brucella, Escherichia coli, influenza bacillus, Moraxella catarrhalis, Proteus, Klebsiella, gonococcus, meningococcus, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Salmonella, Shigella and Vibrio cholerae;
• Gram-negative anaerobic microorganisms: bacteroides (including Bacteroides fragilis).

Some representatives of these types of microbes produce β-lactamase, as a result of which they become resistant to monotherapy using amoxicillin.

Pharmacokinetics

Clavulinic acid and amoxicillin are similar in their pharmacokinetics. They are rapidly absorbed when taken orally; food does not affect the extent of absorption. They reach peak serum levels 1-1.25 hours after ingestion.

The half-life of amoxicillin is 78 minutes, and that of clavulanate is about 60-70 minutes. Both elements are capable of penetrating into most tissues and fluids (into the middle ear, lungs, tonsils and prostate, gall bladder and liver, as well as the ovaries and uterus; in addition to this, into the secretions of the sinuses of the nose and maxillary sinuses, peritoneal with pleural fluid, and also into the secretions of the bronchi, sputum and synovium), and along with this through the placenta and the BBB (in the latter case - with meningitis).

About 17-20% of amoxicillin, as well as 22-30% of clavulinic acid, are synthesized with plasma protein.

Both components are excreted via the kidneys: most of the amoxicillin is excreted unchanged, but clavulanate is excreted as decay products. Some of the substances can be excreted via the lungs with the intestines, and also get into breast milk.

The active ingredient can be removed from the body using a hemodialysis procedure.

Dosing and administration

The drug should be used taking into account existing official recommendations for antibiotic therapy, as well as information on local susceptibility to the antibiotic. Tolerability of clavulanate and amoxicillin varies from place to place and may change over time. If it exists, information on local susceptibility should be studied and, if necessary, microbiological testing and a tolerance test should be performed.

The range of recommended dosages depends on the pathogenic bacteria present in the body, as well as their sensitivity to antibacterial drugs. Along with this, on the severity of the disease and the location of the infection, as well as the weight, age and renal function of the person.

Children weighing ≥40 kg and adults are required to take 1750 mg amoxicillin/250 mg clavulanate per day (the dose is 2 tablets). The daily dose should be divided into 2 doses.

Children weighing <40 kg may take no more than 1000-2800 mg amoxicillin/143-400 mg clavulanate per day (if prescribed as below).

The duration of the course is determined taking into account the patient's clinical response. In certain infections (such as osteomyelitis), long-term therapy is necessary.

For children weighing <40 kg: daily dose within 253.6-456.4 mg/kg. Divide the dose into 2 portions.

Dose sizes in case of functional liver disorder.

The drug should be taken with caution, regularly monitoring changes in liver function. There is insufficient information on dosages in this case.

Dose sizes in functional renal disorder.

Rapiclav in the amount of 875/125 mg can be prescribed only to persons whose CC indicator is at least 30 ml/minute. In case of renal failure, in which CC is less than 30 ml/minute, this form of the drug cannot be used.

The tablet is taken whole, without chewing. If necessary, it can be divided in half, then swallowed both halves.

The duration of the course is selected individually. The therapy cannot be continued for more than 2 weeks without assessing the patient's condition.

The treatment process may begin with the introduction of the drug parenterally. Later, the drug is transferred to oral administration.

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Use Rapiclava during pregnancy

Reproductive tests of parenteral and oral forms of the drug on animals (doses used were 10 times higher than human doses) did not reveal a teratogenic effect. During one of the tests involving pregnant women with premature rupture of the membranes, it was found that the use of Rapiclava for prevention may increase the risk of developing NEC in the newborn. As with other drugs, it is necessary to avoid taking the drug during pregnancy (especially in the first trimester). The only exceptions are cases when the potential benefit is higher than the risk of developing disorders.

The active ingredients of the drug can penetrate into breast milk (there is no information on the effect of clavulinic acid on infants), so infants may develop fungus in the mucous membranes and diarrhea. As a result, it is necessary to stop breastfeeding for the period of taking the drug.

In general, during lactation, it is recommended to take Rapiclav only in cases where the doctor assesses the benefits of using the drug as higher than the likelihood of the risk of negative consequences.

Contraindications

Among the contraindications:

• high sensitivity to the components of the drug, as well as any antibacterial drugs from the penicillin category;
• history of severe manifestations of intolerance (including anaphylaxis) associated with the use of other β-lactam substances (this includes monobactams and carbapenems, as well as cephalosporins);
• history of liver dysfunction or jaundice caused by clavulanate or amoxicillin;
• It is prohibited to use it in the treatment of children under 12 years of age.

Side effects Rapiclava

Taking Rapiclava may provoke the development of the following side effects:

• infectious and invasive processes: candidiasis often occurs in the mucous membranes or skin. An excessive increase in the number of resistant microbes is observed occasionally;
• hematopoietic system: rarely, curable leukopenia (including neutropenia) or thrombocytopenia may occur. Occasionally, curable agranulocytosis appears, as well as a hemolytic form of anemia. The time of PTI and bleeding may also be prolonged;
• manifestations of allergy: anaphylaxis, Quincke's edema, allergic vasculitis, and serum sickness develop occasionally;
• NS reactions: headaches or dizziness rarely occur. Seizures, reversible hyperactivity and aseptic meningitis may occur sporadically. Seizures usually occur in people with kidney disorders, as well as in people taking drugs in large doses;
• Gastrointestinal organs: adults usually experience diarrhea; less commonly, vomiting or nausea. Children often experience both vomiting and nausea, as well as diarrhea (nausea usually develops due to taking a large dose; the above-mentioned gastrointestinal reactions can be reduced by taking the drug before meals). Digestive disorders occur rarely. Antibiotic-associated colitis (including hemorrhagic and pseudomembranous forms of the disease) and black hairy tongue are observed sporadically;
• hepatobiliary system reactions: occasionally, moderate increases in ALT or AST levels occur in individuals taking β-lactam antibiotics. Intrahepatic cholestasis or hepatitis develop occasionally. Similar reactions occur when using other penicillins and cephalosporins. Hepatitis mostly develops in men and the elderly, and its occurrence may be associated with prolonged therapy. Similar reactions have been observed in children only occasionally. Symptoms of the disease develop during treatment or immediately after its completion, but in some cases they have developed several weeks after completion of therapy. Such signs are often reversible. Fatal cases have been observed only occasionally, but they have always occurred in people with a severe form of the underlying pathology or in those who were simultaneously taking medications that have a negative effect on the liver;
• subcutaneous layers and skin: urticaria, itching and skin rashes were rare. Occasionally, erythema multiforme developed. Lyell's syndrome or Stevens-Johnson syndrome, Ritter's disease and acute exanthematous pustulosis (generalized type) were isolated. If an allergic form of dermatitis occurs, treatment must be stopped;
• urinary system and kidneys: crystalluria or tubulointerstitial nephritis appeared sporadically.

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Overdose

Overdose may cause gastrointestinal reactions and water and electrolyte imbalance. These symptoms should be treated symptomatically, while restoring the electrolyte balance with water. There is also information about the development of crystalluria, which later sometimes transformed into renal failure.

Rapiclav can be removed from the body using hemodialysis.

Interactions with other drugs

It is forbidden to combine with probenecid, as it reduces the excretion of amoxicillin through the renal tubules. When combined with Rapiclav, a prolonged increase in amoxicillin levels in the blood is possible, but probenecid does not affect clavulanate levels.

The combination of amoxicillin and allopurinol may increase the risk of developing an allergy. There is no information on the combined use of Rapiclav and allopurinol.

Like other antibiotics, Rapiclav can affect the intestinal microflora, which reduces estrogen reabsorption and weakens the effectiveness of combined oral contraception.

There is some information about the increase of INR values in people using warfarin or acenocoumarol in combination with amoxicillin. If such a combination is necessary, it is necessary to carefully monitor the level of PT or INR (this should also be done for some time after discontinuation of Rapiclav).

In humans treated with mycophenolate mofetil, pre-dose levels of the active metabolite mycophenolate may decrease (by approximately 50%) after initiation of oral amoxicillin and clavulanate. This change may not be exactly correlated with changes in mycophenolate acid AUC.

Penicillins can reduce the excretion of methotrexate, which may increase the toxic properties of the latter.

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Storage conditions

The medicine should be kept at a temperature not exceeding 25°C.

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Shelf life

Rapiclav can be used for a period of 2 years from the date of release of the drug.