Amclav^® Sar (Tablets) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

ATC Code

J01CR02 (Amoxicillin and beta-lactamase inhibitor)

Active Substances

Amoxicillin (Rec.INN registered by WHO)

Clavulanic acid (Rec.INN registered by WHO)

Dosage Forms

	Amclav® Sar®	Dispersible tablets 125 mg+31.25 mg
		Dispersible tablets 250 mg+62.5 mg
		Dispersible tablets 500 mg+125 mg
		Dispersible tablets 875 mg+125 mg

Dosage Form, Packaging, and Composition

Dispersible tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs (2 pcs.) – cardboard packs (20 pcs.) – Prescription only
14 pcs. – jars – cardboard packs (14 pcs.) – Prescription only
16 pcs. – jars – cardboard packs (16 pcs.) – Prescription only
20 pcs. – jars – cardboard packs (20 pcs.) – Prescription only
24 pcs. – jars – cardboard packs (24 pcs.) – Prescription only
4 pcs. – blister packs – cardboard packs (4 pcs.) – Prescription only
4 pcs. – blister packs (4 pcs.) – cardboard packs (16 pcs.) – Prescription only
4 pcs. – blister packs (6 pcs.) – cardboard packs (24 pcs.) – Prescription only
5 pcs. – blister packs (3 pcs.) – cardboard packs (15 pcs.) – Prescription only
7 pcs. – blister packs – cardboard packs (7 pcs.) – Prescription only
7 pcs. – blister packs (2 pcs.) – cardboard packs (14 pcs.) – Prescription only

Dispersible tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs (2 pcs.) – cardboard packs (20 pcs.) – Prescription only
14 pcs. – jars – cardboard packs (14 pcs.) – Prescription only
16 pcs. – jars – cardboard packs (16 pcs.) – Prescription only
20 pcs. – jars – cardboard packs (20 pcs.) – Prescription only
24 pcs. – jars – cardboard packs (24 pcs.) – Prescription only
4 pcs. – blister packs – cardboard packs (4 pcs.) – Prescription only
4 pcs. – blister packs (4 pcs.) – cardboard packs (16 pcs.) – Prescription only
4 pcs. – blister packs (6 pcs.) – cardboard packs (24 pcs.) – Prescription only
5 pcs. – blister packs (3 pcs.) – cardboard packs (15 pcs.) – Prescription only
7 pcs. – blister packs – cardboard packs (7 pcs.) – Prescription only
7 pcs. – blister packs (2 pcs.) – cardboard packs (14 pcs.) – Prescription only

Dispersible tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs (2 pcs.) – cardboard packs (20 pcs.) – Prescription only
14 pcs. – jars – cardboard packs (14 pcs.) – Prescription only
16 pcs. – jars – cardboard packs (16 pcs.) – Prescription only
20 pcs. – jars – cardboard packs (20 pcs.) – Prescription only
24 pcs. – jars – cardboard packs (24 pcs.) – Prescription only
4 pcs. – blister packs – cardboard packs (4 pcs.) – Prescription only
4 pcs. – blister packs (4 pcs.) – cardboard packs (16 pcs.) – Prescription only
4 pcs. – blister packs (6 pcs.) – cardboard packs (24 pcs.) – Prescription only
5 pcs. – blister packs (3 pcs.) – cardboard packs (15 pcs.) – Prescription only
7 pcs. – blister packs – cardboard packs (7 pcs.) – Prescription only
7 pcs. – blister packs (2 pcs.) – cardboard packs (14 pcs.) – Prescription only

Dispersible tablets

10 pcs. – jars – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs – cardboard packs (10 pcs.) – Prescription only
10 pcs. – blister packs (2 pcs.) – cardboard packs (20 pcs.) – Prescription only
14 pcs. – jars – cardboard packs (14 pcs.) – Prescription only
16 pcs. – jars – cardboard packs (16 pcs.) – Prescription only
20 pcs. – jars – cardboard packs (20 pcs.) – Prescription only
5 pcs. – blister packs – cardboard packs (5 pcs.) – Prescription only
5 pcs. – blister packs (2 pcs.) – cardboard packs (10 pcs.) – Prescription only
7 pcs. – jars – cardboard packs (7 pcs.) – Prescription only
7 pcs. – blister packs – cardboard packs (7 pcs.) – Prescription only
7 pcs. – blister packs (2 pcs.) – cardboard packs (14 pcs.) – Prescription only
8 pcs. – blister packs – cardboard packs (8 pcs.) – Prescription only
8 pcs. – blister packs (2 pcs.) – cardboard packs (16 pcs.) – Prescription only

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Systemic antibacterial agents; beta-lactam antibacterial agents, penicillins; combinations of penicillins, including combinations with beta-lactamase inhibitors

Pharmacological Action

A combined preparation of amoxicillin and clavulanic acid, a beta-lactamase inhibitor. It acts bactericidally by inhibiting the synthesis of the bacterial cell wall.

Active against aerobic gram-positive bacteria (including beta-lactamase-producing strains): Staphylococcus aureus; aerobic gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis. The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; and also aerobic gram-negative bacteria (including beta-lactamase-producing strains): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic gram-negative bacteria (including beta-lactamase-producing strains): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV, and V beta-lactamases; it is not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, thereby forming a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin by beta-lactamases.

Pharmacokinetics

After oral administration, both components are rapidly absorbed from the gastrointestinal tract. Simultaneous food intake does not affect absorption. T_Cmax – 45 min. After oral administration in a dose of 250/125 mg every 8 h, C_max of amoxicillin is 2.18-4.5 mcg/ml, of clavulanic acid is 0.8-2.2 mcg/ml; in a dose of 500/125 mg every 12 h, C_max of amoxicillin is 5.09-7.91 mcg/ml, of clavulanic acid is 1.19-2.41 mcg/ml; in a dose of 500/125 mg every 8 h, C_max of amoxicillin is 4.94-9.46 mcg/ml, of clavulanic acid is 1.57-3.23 mcg/ml; in a dose of 875/125 mg, C_max of amoxicillin is 8.82-14.38 mcg/ml, of clavulanic acid is 1.21-3.19 mcg/ml.

The time to reach a maximum inhibitory concentration of 1 mcg/ml for amoxicillin is similar when administered every 12 h and 8 h in both adults and children.

Plasma protein binding: Amoxicillin – 17-20%, Clavulanic acid – 22-30%.

Both components are metabolized in the liver: Amoxicillin – 10% of the administered dose, Clavulanic acid – 50%.

T_1/2 after administration of 375 and 625 mg doses is 1 and 1.3 h for amoxicillin, and 1.2 and 0.8 h for clavulanic acid, respectively. It is excreted mainly by the kidneys (glomerular filtration and tubular secretion): 50-78% and 25-40% of the administered dose of amoxicillin and clavulanic acid, respectively, is excreted unchanged within the first 6 h after administration.

Indications

Treatment of infectious and inflammatory diseases caused by susceptible pathogens: lower respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess); ENT infections (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); skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection); osteomyelitis; postoperative infections.

ICD codes

Dosage Regimen

Doses are given in terms of Amoxicillin. The dosage regimen is set individually depending on the patient’s age, severity and location of the infection, and the sensitivity of the pathogen.

Children under 12 years: 20-40 mg/kg/day in 2-3 divided doses.

Adults and children over 12 years or weighing 40 kg and more: 250-500 mg 2-3 times/day or 875 mg 2 times/day.

Maximum daily dose of amoxicillin for adults and children over 12 years is 6 g, for children under 12 years – 45 mg/kg of body weight.

Adverse Reactions

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

From the hematopoietic system 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.

From the urinary system interstitial nephritis, crystalluria, hematuria.

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

Other candidiasis, development of superinfection.

Contraindications

Hypersensitivity to amoxicillin and other penicillins, clavulanic acid, to other beta-lactam antibiotics (cephalosporins, carbapenems, monobactams); cholestatic jaundice and/or other liver function disorders caused by the use of amoxicillin/clavulanic acid in history; severe renal impairment (CrCl <30 ml/min) (for the dosage form intended for use in children from 3 months to 12 years); children under 3 months of age.

With caution

Impaired liver function, impaired renal function.

Use in Pregnancy and Lactation

Should be used with caution during pregnancy and during lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in episodes of jaundice or liver function impairment as a result of previous use of amoxicillin/clavulanic acid.

With caution: severe hepatic insufficiency

Use in Renal Impairment

In chronic renal failure, dose and frequency adjustment is performed depending on CrCl.

Pediatric Use

Used in children over 3 months of age according to indications and in dosage forms appropriate for the age.

Special Precautions

Use of this combination is not recommended if infectious mononucleosis is suspected.

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

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

The development of superinfection due to the growth of non-susceptible microflora is possible, which requires an appropriate change in antibacterial therapy.

It may cause false-positive results when determining glucose in the urine. In this case, it is recommended to use the glucose-oxidase method for determining the concentration of glucose in the urine.

In patients with hypersensitivity to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.

Drug Interactions

Antacids, glucosamine, laxative medications, aminoglycosides slow down and reduce absorption; ascorbic acid increases absorption.

Bacteriostatic antibiotics (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect.

When combined with rifampicin, a mutual weakening of the antibacterial effect is observed.

It enhances the effectiveness of indirect anticoagulants (by suppressing the intestinal microflora, it reduces the synthesis of vitamin K and the prothrombin index). When taking anticoagulants concurrently, blood coagulation parameters should be monitored.

It reduces the effectiveness of oral contraceptives, medicinal products metabolized to form PABA, ethinylestradiol – increasing the risk of breakthrough bleeding.

Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion increase the concentration of amoxicillin (Clavulanic acid is primarily eliminated by glomerular filtration).

Concomitant use with methotrexate increases the toxicity of methotrexate.

Allopurinol increases the risk of skin rash.

Concomitant use with probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin. Concomitant use may lead to an increase and prolongation of the blood concentration of amoxicillin, but not of clavulanic acid.

Concomitant use with disulfiram should be avoided.

Concomitant use of amoxicillin and digoxin may lead to an increased concentration of digoxin in the blood plasma.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.