Amovicomb (Powder) Instructions for Use

Marketing Authorization Holder

Zhuhai United Laboratories, Co., Ltd (China)

ATC Code

J01CR02 (Amoxicillin and beta-lactamase inhibitor)

Active Substances

Clavulanic acid (Rec.INN registered by WHO)

Amoxicillin (Rec.INN registered by WHO)

Dosage Forms

	Amovicomb	Powder for preparation of solution for intravenous administration 500 mg+100 mg: vials 10 pcs.
		Powder for preparation of solution for intravenous administration 1000 mg+200 mg: vials 10 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of solution for intravenous administration white or almost white.

Vials (1) – cardboard packs.
Vials (1) – cardboard packs (10) – cardboard boxes.

Powder for preparation of solution for intravenous administration white or almost white.

Vials (1) – cardboard packs.
Vials (1) – cardboard packs (10) – cardboard boxes.

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Antibiotic, semi-synthetic penicillin + beta-lactamase inhibitor

Pharmacological Action

Amovicomb is a combination of amoxicillin and clavulanic acid.

Amoxicillin (a semi-synthetic aminopenicillin) suppresses the synthesis of peptidoglycan in the cell wall during the growth phase of the microorganism by competitive inhibition of transpeptidases.

Clavulanic acid has weak intrinsic antibacterial activity but irreversibly binds to beta-lactamases (forming a stable complex with them), providing resistance of amoxicillin to the effects of beta-lactamases produced by microorganisms.

Clavulanic acid inhibits beta-lactamases of types II-V according to the Richmond-Sykes classification and is not active against type I beta-lactamases produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.

The combination of amoxicillin and clavulanic acid has a broad spectrum of antibacterial action, showing activity against amoxicillin-susceptible strains, including beta-lactamase-producing strains.

• gram-positive aerobes Streptococcus Group A, B, C, G (Strep, pneumoniae, viridans, milled, faecalis, pyogenes, anthracis, agalactiae, bovis); Staphylococcus aureus, epidermidis (except methicillin-resistant strains); Enterococcus faecalis, faecium; Corynebacterium spp.; Listeria monocytogenes; Nocardia asteroides;
• gram-negative aerobes Aeromonas spp.; Bordetella pertussis; Branhamella cataxrhalis; Brucella spp.; Campylobacter jejuni; Citrobacter spp. (moderately susceptible); Escherichia coli; Eikenella corrodens; Gardnerella vaginalis; Haemophilus ducreyi, influenzae; Helicobacter pylori; Klebsiella spp., Klebsiella pneumoniae; Moraxella catarrhalis; Morganella spp. (moderately susceptible); Neisseria gonorrhoeae, meningitidis; Pasteurela multocida; Proteus mirabilis, vulgaris; Salmonella spp.; Shigella spp.; Vibrio cholerae; Yersinia enterocolitica (moderately susceptible).
• gram-positive anaerobes Actinomyces israeli; Clostridium spp. (except CI. difficile); Fusobacterium spp.; Peptococcus spp.; Peptostreptococcus spp.; Prevotella melaninogenica; Propionibacterium spp.;
• gram-negative anaerobes Bacteroides spp. (including B. fragilis).

Pharmacokinetics

The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar, and in combination they do not affect each other’s pharmacokinetics.

The peak plasma concentrations after intravenous administration in doses of 500/100 mg and 1000/200 mg are 32.2 and 105.4 µg/ml for amoxicillin, respectively, and 10.5 and 28.5 µg/ml for clavulanic acid, respectively.

The peak concentrations in body fluids are observed 1 hour after reaching peak plasma concentrations.

The bioavailability of amoxicillin is about 90%, the bioavailability of clavulanic acid is approximately 60%, the binding to plasma proteins of amoxicillin and clavulanic acid is 17-20% and 22-30%, respectively.

Both components are characterized by a good volume of distribution in body tissues and fluids – high concentrations of the drug are found in plasma, sputum, bronchial secretions, lung tissue, middle ear, prostate gland, peritoneal abscess, gallbladder, uterus, ovaries, adipose tissue, muscles, bones, skin, biological fluids (including synovial, peritoneal, pleural, bile, purulent discharge).

Amoxicillin and Clavulanic acid do not penetrate the blood-brain barrier when the meninges are not inflamed.

Amoxicillin and Clavulanic acid cross the placental barrier and are excreted in trace amounts in breast milk.

Amoxicillin is excreted mainly by the kidneys through tubular secretion and glomerular filtration, almost unchanged; Clavulanic acid is intensively metabolized in the liver and excreted by glomerular filtration, partially in the form of metabolites.

Small amounts may be excreted through the intestines and lungs. The T_1/2 of amoxicillin and clavulanic acid is 1-1.5 hours. In patients with severe renal failure, T_1/2 increases to 7.5 hours for amoxicillin and to 4.5 hours for clavulanic acid, which requires adjustment of the dosage regimen.

Both components are removed by hemodialysis and insignificant amounts by peritoneal dialysis.

Indications

Bacterial infections caused by susceptible pathogens

• Infections of the lower respiratory tract (bronchitis, pneumonia, pleural empyema, lung abscess);
• Infections of the ENT organs (sinusitis, tonsillitis, otitis media);
• Infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingo-oophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelvic peritonitis, chancroid, gonorrhea);
• Infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection);
• Osteomyelitis;
• Postoperative infections;
• Prevention of infections in surgery.

ICD codes

Dosage Regimen

Intravenously.

Doses are given in terms of both active substances (Amoxicillin+Clavulanic acid). The dosage regimen is set individually depending on the severity, location of the infection and the sensitivity of the pathogen.

Duration of treatment: 5-14 days. Treatment should not exceed 14 days without repeated medical examination!

Adults and adolescents over 12 years of age or weighing more than 40 kg – (1000+200) mg every 8 hours, for severe infections – every 4-6 hours.

For children weighing less than 40 kg, the dose is calculated based on body weight

• children aged 3 months to 12 years – (25+5) mg/kg every 8 hours, for severe infections – every 6 hours;
• children under 3 months of age weighing more than 4 kg – (25+5) mg/kg every 8 hours;
• children under 3 months of age weighing less than 4 kg – (25+5) mg/kg every 12 hours.

In children under 3 months of age, the drug should be administered only by slow infusion over 30-40 minutes.

For the prevention of postoperative infections during operations lasting less than 1 hour, it is administered intravenously at a dose of (1000+200) mg during induction anesthesia. For longer operations – (1000+200) mg every 6 hours for 24 hours. If there is a high risk of infection, administration may be continued for several days.

Preparation of solutions for intravenous injection

Dosage (500+100) mg: dissolve the contents of the vial in 10 ml of water for injections. Dosage (1000+200) mg: dissolve the contents of the vial in 20 ml of water for injections. Administer slowly, over 3-4 minutes.

Preparation of solution for intravenous infusion

Dosage (500+100) mg: dissolve the contents of the vial in 10 ml of water for injections and add the resulting solution to 50 ml of infusion fluid.

Dosage (1000+200) mg: dissolve the contents of the vial in 20 ml of water for injections and add the resulting solution to 100 ml of infusion fluid. Infusion is carried out over 30-40 minutes.

Stability and compatibility

Intravenous injections should be performed immediately after dissolution. Do not freeze the solution. Do not use the solution remaining after the performed intravenous injection.

Intravenous infusions can be carried out in various solutions

Dosage in functional liver impairment

In patients with signs of liver damage, its function should be checked regularly. If necessary, the dose should be reduced.

Adverse Reactions

From the digestive system nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of “hepatic” transaminases, in isolated cases – cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (may also develop after therapy), enterocolitis, increased bilirubin concentration.

From the hematopoietic organs reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

From the nervous system dizziness, headache, hyperactivity, anxiety, behavior change, convulsions.

Local reactions in some cases – phlebitis at the site of intravenous administration.

Allergic reactions urticaria, erythematous rashes, rarely – multiform exudative erythema, anaphylactic shock, angioneurotic edema, extremely rarely – exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), allergic vasculitis, serum sickness-like syndrome, acute generalized exanthematous pustulosis.

Others: candidiasis, development of superinfection, interstitial nephritis, crystalluria, hematuria.

Contraindications

• Infectious mononucleosis (including when a measles-like rash appears),
• Episodes of jaundice or impaired liver function as a result of previous use of amoxicillin/clavulanic acid.
• Hypersensitivity to amoxicillin, clavulanic acid, to penicillins, cephalosporins and other beta-lactam antibiotics,

With caution in pregnancy and during lactation; as well as in the treatment of patients with allergic diathesis, bronchial asthma, urticaria or hay fever; in severe hepatic insufficiency, gastrointestinal diseases (including a history of colitis associated with the use of penicillins), chronic renal failure (creatinine clearance less than 30 ml/min); in premature newborns and children under 1 year of age.

Use in Pregnancy and Lactation

The use of Amovicomb during pregnancy and lactation is possible provided that the expected benefit to the mother outweighs the potential risk to the fetus and child. When prescribing the drug, it should be taken into account that Amoxicillin and Clavulanic acid penetrate into breast milk in small amounts.

Use in Hepatic Impairment

In patients with signs of liver damage, its function should be checked regularly. If necessary, the dose should be reduced.

Use in Renal Impairment

For patients with impaired renal function, the dose and/or interval between administrations of the drug should be adjusted depending on the degree of renal failure

Pediatric Use

Prescribed to children in recommended doses

Special Precautions

During course treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver, and kidneys.

To reduce the risk of developing side effects from the gastrointestinal tract, the drug should be taken with meals.

Development of superinfection due to the growth of microflora insensitive to it is possible, which requires an appropriate change in antibacterial therapy.

In patients with hypersensitivity to cephalosporin antibiotics, there is a risk of developing cross-allergic reactions. In this case, treatment should be discontinued.

The drug should not be used if infectious mononucleosis is suspected, as this increases the likelihood of erythematous skin rashes (measles-like rash) in such patients.

In patients with gonorrhea and suspected primary syphilis, serological tests should be performed for at least four months before starting treatment.

High concentrations of amoxicillin can give a false-positive reaction for urine glucose when using Benedict’s reagent or Fehling’s solution (non-enzymatic methods for determining glucose in urine). The use of enzymatic reactions with glucose oxidase is recommended.

May affect the determination of urobilinogen and leads to positive results of the direct Coombs test. Should not be administered intramuscularly.

Effect on the ability to drive vehicles and mechanisms

During treatment, caution should be exercised when driving a car and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Overdose

Since the combination of amoxicillin and clavulanic acid is non-toxic, its overdose is unlikely. If symptoms of overdose appear – nausea, diarrhea, vomiting – treatment is symptomatic. Hemodialysis is effective in acute overdose.

Drug Interactions

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs that block tubular secretion increase the concentration of amoxicillin (Clavulanic acid is excreted mainly by glomerular filtration).

Antacids, glucosamine, laxatives, aminoglycosides slow down and reduce absorption; ascorbic acid increases absorption.
Bacteriostatic drugs (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect. Methotrexate – concurrent use increases the toxicity of methotrexate. Allopurinol increases the risk of skin rash.

Amovicomb enhances the effectiveness of indirect anticoagulants (by suppressing intestinal microflora, it reduces the synthesis of vitamin K and the prothrombin index). When taken concomitantly with anticoagulants, blood clotting parameters should be monitored. Reduces the effectiveness of oral contraceptives, drugs in the metabolism of which para-aminobenzoic acid (PABA) is formed, ethinylestradiol – there is a risk of breakthrough bleeding. Concurrent use with disulfiram should be avoided.

Should not be mixed in the same syringe or infusion vial with other drugs.

Alcohol consumption should be avoided during treatment and for several days thereafter. In some patients, a disulfiram-like effect, characterized by “flushing,” sweating, headache, and tachycardia, has been described when taken together with alcohol.

Storage Conditions

In a dry place, protected from light, at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.