TRADE NAME
Clavomed

INTERNATIONAL NON-PATENTED NAME
Amoxicillin аnd clavulanic acid

CHEMICAL NAME
Amoxicillin (as thrihydrate)
(2S,5R,6R)-6-[(R)-(-)-2-amino-2-(p-hydroxyphenyl) acetylamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]-heptane-2-carboxylic acid trihydrate
Clavulanic acid (as potassium salt)
Potassium (Z)-(2R,5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0.]-heptane-2-carboxylate

PHARMACEUTICAL FORM
Powder for preparation of suspension for oral use

COMPOSITION
Every 5 ml of suspension contain
For dosage                                                                 156.25 mg /5 ml     312.5 mg /5ml
Active ingredients:
Amoxicillin trihydrate
equivalent to amoxicillin                                             125 mg                250 mg,           
potassium clavulanate
equivalent to clavulanic acid                                       31.25 mg              62.5 mg.        
Inactive ingredients: xanthan gum, citric acid anhydrous, sodium citrate dihydrate, aspartame, sodium benzoate, flavour agent “Orange”, microcrystalline cellulose, silicon dioxide.

АТС CODE                J01CR02

PHARMACOTHERAPEUTIC GROUP
Antibiotic for system application. Group of semisynthetic penicillin containing inhibitor of β-lactamase of clavulanic acid.

PHARMACOLOGIC PROPERTIES

PHARMACODYNAMICS

Clavomed suspension presents a combination of amoxicillin (semisynthetic penicillin with a broad spectrum of antibacterial activity) and clavulanic acid (irreversible inhibitor of β- lactamases).

Clavulanic acid forms a stable inactivated complex with stated ferments and protects amoxicillin both against the loss of antibacterial activity due to the production of β- lactamases as the main pathogens and copathogens, and conditionally pathogen organisms. Clavulanic acid has an antibacterial activity.

Amoxicillin has a broad spectrum of antibacterial activity. It active in relation to such sensitive to amoxicillin strains and in relation to the strains producing β-lactamases:

Gram-positive microorganisms: Bacillis anthracis, Corynebacterium spp., Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes, Nocardia asteroides, Staphylococcus aureus, coagulase-negative staphylococcus (including Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans);

Gram-negative microorganisms: Bordetella pertussis, Brucella spp., Escherichia coli, Gardnerella vaginalis, Haemophilus influenzae, Helicobacter pylori, Klebsiella spp., Legionella spp., Moraxella catarrhalis (Branhamella catarrhalis), Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica;

Anaerobes: Bacreroides spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp., Actinomyces israelli.

pharmacokinetics
The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. After intake, both components have a good absorption; the food intake doesn’t influence on the absorption degree.

therapeutic indicationS
Clavomed suspension is prescribed for treatment of the following infections, caused by the sensitive to the combination of amoxicillin/ clavulanic acid strains:

- infection of the wind-pipes upper sections (acute and chronic sinusitis, acute and chronic otitis media, tonsillopharyngitis);
- infections of the bottom departments of respiratory ways (acute and chronic bronchitis and pneumonias, empyema);
- urinary tracts infections (including cystitis, urethritis and pyelonephritis);
- gynecological infections (including salpingitis, salpingoophoritis, endometritis, septic abortion, pelvioperitonitis);
- bone and connective tissues infections (including chronic osteomyelitis);
- skin and soft tissues infections (including phlegmon, traumatic fever);
- biliary tracts infections (cholecystitis, cholangitis);
- sexually transmitted diseases (gonorrhea, chancroid);
- odontogenic infections;
- infection prophylaxis after surgical operation.

CONTRAINDICATIONS
- hypersensitivity to penicillin antibiotics;
- cholestatic jaundice or hepatitis;
- liver impairment;
- infectious monoucleos, lymphatic leukemia.

SPECIAL INDICATIONS
Due to the possible development of cross sensitive, it is prescribed with cautious to the patients with allergic reactions on cephalosporins, penicillins and other allergens in patient’s anamnesis.

It is necessary to avoid the application of Clavomed at suspicion on infectious mononucleosis as in such cases amoxicillin can cause enanthesis, that complicates disease diagnostics.

Patients with liver dysfunction are necessary to use Clavomed cautiously.

Crystalluria occurs very seldom among the patients with lowered diuresis, mainly at parenteral therapy. It is recommended to accept enough of a liquid and to support adequate diuresis when taking amoxicillin in high doses for reduction of crystals amoxicillin formation probability.

It is recommended to supervise periodically kidneys, liver functions, and hematosis during the long therapy by Clavomed 

Influence on ability for driving and for operating with other mechanisms

Clavomed doesn’t influence on the ability to drive and to operate with the mechanisms demanding the high psychomotor action rate.

 
SIDE EFFECTS

Side effects are weak and quickly passing in most cases.

From the digestive system: appetite loss, nausea, vomiting, diarrhoeia.

Such undesirable effects can be avoided by taking Clavomed suspension while eating.

Allergic reactions: itch, appearance of skin rash; in single cases: Stevens-Johns syndrome.

Others: single reports about the appearance of cholestatic jaundice, hepatitis, liver dysfunction, superinfection development (including candidosis), reversible augmentation of prothrombine time.

DOSAGE AND ADMINISTRATION
For oral administration. Shake the suspension before every use!

Directions for reconstitution:

Dissolve the powder in 100 ml of boiled and cooled water in two portions (to the mark on the bottle) and shake well after each addition.

Clavomed should be used while eating for possible side digestive reactions prevention.

For infants and children under 3 months: standard dose makes 30 mg (amoxicillin)/kg of body weight/day, divided in 2 doses.

Children from 3 months and older (body weight is less than 40 kg):

The recommended doses of suspensions (156.25 mg/ml and 312.5 mg/ml) are determined against the body weight of children and infection severity. Usage: 3 times/day.

Maximum daily dose of amoxicillin makes for adults 6 g and 45 mg/kg of body weight for children.

Maximum daily dose of clavulanic acid (as potassium salt) makes for adults 600 mg and 10 mg/kg of body weight for children.

For the patients with severe renal insufficiency (creatinine clearance 10-30 ml/min) must be sufficiently lowered the dose or increased the interval between intakes.

The treatment with Clavomed suspension can continue during 14 days. Then, the patient should visit his/her doctor.

OVERDOSE
Sympthoms: gastrointestinal disorders and water-electrolytic balance disturbances can occur. Amoxicillin crystalluria is described, in some cases leading to the development of renal insufficiency.

Treatment: symptomatic therapy, correction of water-electrolytic balance. Clavomed is removed from blood by hemodialysis.

interaction WITN OTHER MEDICAMENTS
Co-application of Clavomed suspension and methotrexate raises the toxicity of the last. The prescription with allopurinol raises the frequency of appearance skin rash (exanthema).

In some cases Clavomed suspension can prolong the prothrombin time; in connection with it one should be cautious at concomitant prescription of anticoagulants and Clavomed.

One should avoid the co-application with disulphiram.

Clavomed suspension should not be applied in combination with bacteriostatic antibiotics (macrolides, tetracyclines), with sulphanilamides due to the possible lowering of effectiveness of the preparation.

It is antagonistic in combination with rimfampicine.

It is shown that antibiotics lower the effectiveness of peroral contraceptives.

Probenecid lowers the elimination of amoxicillin, increasing its serum concentration.

APPLICATION DURING PREGNANCY AND BREAST-FEEDING
Clavomed can be taken during the pregnancy, if expected benefit for mother exceeds its potential risk for foetus.

Only small amounts of amoxicillin and clavulanic acid are excreted in breast milk, therefore during the treatment with Clavomed one should cease the breast feeding.

PACKAGING
Powder for preparation of suspension for oral use 156.25 mg/5ml or 312.5 mg/5 ml.

Polyethylene vial 100 ml, closed by stopper with protection ring.

1 vial with measuring spoon in carton box together with enclosed insert.

STORAGE CONDITIONS
Store in a dry place at the temperature not exceeding 25ºС.

Store the reconstituted suspension at the temperature from 2°С to 8°С. It must be used within 7 days.

Keep out of reach of children.

SHELF LIFE
2 years from the manufacture date.

Do not use if the labeled working life is expired.

SALES TERMS
Sold under prescription.