Trade name

Novoksiklav

 

Active factor (INN – International Non-proprietary Name)

Amoxicillin sodium and clavulanic acid

 

Code ATC:

 

Pharmacotherapeutic group

Antibiotics (a group of Penicillins)

 

Pharmaceutical form

0.6 and 1.2 g powder vials for injection

 

Pharmacological properties

Combined broad-spectrum antibiotic resistants to β-lactamases, it  includes amoxicillin and clavulanic acid.
Amoxicillin is a semisynthetic beta-lactamase-susceptible penicillin, which has bactericidal activity against a broad spectrum of non beta-lactamase-producing Gram-positive and Gram-negative organisms. The spectrum of activity does not include those organisms that produce lactamase.
Clavulanic acid – It is β-lactam compound, which possesses the ability to inactivate a wide range of beta-lactamase. The presence of clavulanic acid in various dosage formulations protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin.
The drug has a bactericidal effect.
Activity against gram-positive microorganisms: Streptococcus pneumoniae, S.pyogenes, S.viridans, S.bovis, Staphylococcus aureus (exception is methicillin-resistant strains), S.epidermidis (exception is methicillin-resistant strains), Listeria spp., Enterococcus spp.
Gram-negative microorganisms: Bordetella pertussis, Brucella spp., Campylobacter jejuni, E.coli, Gardnerella vaginalis, H.influenzae, H.ducreyi, Klebsiella spp., Moraxella catarrhalis, N.gonorrhoeae, N.meningitidis, Pasteurella multocida, Proteus spp., Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica.
Anaerobic microorganism: Pertococcus spp., Pertostreptococcus spp., Clostridum spp., Bacteroides spp., Actinomyces israelil.

 

Pharmacokinetics

Main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. Amoxicillin and clavulanic acid in combination do not affect each other. The maximum concentration (Cmax) given as bolus intravenous injection (1.2g)  is 105.4 mg/L for amoxicillin and 28.5 mg/L for clavulanic acid. Therapeutic concentrations of both medicines have been found in the interstitial fluid and tissues (lung, pleural, peritoneal, synovial fluid, tonsils, bronchial secretions, prostate, peritoneal abscess, muscle, adipose tissue, secretions of the sinuses, middle ear).
Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanate can also be detected in breast milk. With the exception of the risk of sensitisation associated with this excretion, there are no known detrimental effects for the breastfed infant.
The major route of elimination for amoxicillin is via the kidney, by tubular secretion and glomerular filtration. The elimination for clavulanic acid is glomerular filtration, partly in the form of metabolites.  Small quantities can be displayed through the intestines and lungs.
The elimination half-life (Т ½)   of amoxicillin and clavulanic acid are approximately 1- 1.5 hour.
Both components are removed by hemodialysis, in a few amounts by peritoneal dialysis.

 

Indications

Novoksiklav is indicated for the treatment of infections caused by resistant organisms’:
- Upper respiratory tract infections ( infection of ear, through and nose) such as tonsillitis, sinusitis and recurrent otitis media, caused by Streptococcus pneumoniae, Hаеmophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes;
- Lower respiratory track infection (such as bronchitis and bronchopneumonia, caused by Streptococcus pneumoniae, Hаеmophilus influenzae and Moraxella catarrhalis);
- Genito-urinary tract infections (cystitis, urethritis, pyelonephritis, female genital infections, caused by Enterobacteriaceae (Escherichia coli), Staphylococcus saprophyticus and Enterococcus spp., also gonorrhea, caused by Neisseria gonorrhoeae);
- Skin and soft tissue infections, caused by Streptococcus aureus, Streptococcus pyogenes and Bacteroides spp.;
- Bone and joint infection, (osteomyelitis, caused by Streptococcus aureus);
- other infections (septic abortion, puerperal sepsis, intra-abdominal sepsis, septicaemia, peritonitis, postsurgical infections, also it is indicated for prophylaxis against infection which may be associated with major surgical procedures such as gastro-intestinal, pelvic, head and neck, cardiac, renal, joint replacement and biliary tract surgery).

 

Dosage and administration

The drug is administered intravenously (IV). The dose depends on the age, body weight, kidney function and severity of infection. Adults and children over 12 years — usually 1.2 g (1000 mg + 200 mg) 8 hourly (in more serious infection — 6 hourly intervals); children 3 months – 12 years — 30 mg/kg 8 hourly (in more serious infection — 6 hourly intervals); children 0- 3 months — 30 mg/kg every 12 hours in infant, from 0 to 3 мес — every 8 hours.
Dosage for surgical prophylaxis is 1.2 g of the drug intravenous given at induction of anaesthesia. Longer operations require subsequent doses of 1.2g  up to 4 doses in 24 hours.
The dose or interval between administrations should be based on the creatinine clearance of the   patients with renal impairment.

 

Creatinine clearance

Dosage

30 mL/min

No dosage adjustment

10-30 mL/min

First dose – 1,2 g, and then 600 mg (500 mg + 100 mg) IV, 12 hourly

10 mL/min

First dose – 1,2 g, and then 600 mg IV,  every 24 hours

Anuria

The interval between administrations should be increased for 48 hours

 

85% of the drug is removed by hemodialysis, the drug should be administered at the end of hemodialysis. If peritoneal dialysis it does not require correction of dosing regimen. The course of treatment is 5-14 days.
There are rules for preparation and administration intravenous injection. 1.2g is dissolved to 20 ml of water for injection. The solution is administered slowly during 3-4 min.
There are rules for preparation and administration intravenous infusion. 1.2g is dissolved to 100mL infusion fluid.  Infuse over 30-40 minutes.

 

Side effects

Skin and subcutaneous tissue disorders: angioedema, anaphylaxis, hypersensitivity vasculitis; rare - skin rash, pruritus, urticaria; very rare - Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis.  
Gastrointestinal disorders: Diarrhoea, Nausea, vomiting, indigestion; Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis)
A moderate rise in AST and/or ALT, but the significance of these findings is unknown; rare - hepatitis and cholestatic jaundice.
Blood system disorders: Reversible leucopenia (including neutropenia and agranulocytosis ), thrombocytopenia and haemolytic anaemia.
Blood clotting disorders: Prolongation of bleeding time and prothrombin time.
Nervous system disorders: Dizziness, headache, reversible hyperactivity and convulsions.
Renal and urinary disorders: nterstitial nephritis, crystalluria.
Vascular disorders: Thrombophlebitis at the site of injection. 

 

Contraindications

- The drug is contraindicated in patients with a previous history of amoxicillin/clavulanic -associated jaundice/hepatic dysfunction;
- Hypersensitivity to penicillins;
- Hypersensitivity to amoxicillin, clavulanic acid or other components of the drug.

 

Interactions

Probenecid and similar drug (diuretics, phenylbutazone, NSAID) decreases the renal tubular secretion. Concurrent use with Novoksiklav may result in increased and prolonged blood levels of Amoxicillin but not of clavulanic acid.
Patients receiving the drug rarely are observed prolongation of prothrombin time and, therefore, while the use of anticoagulants is necessary to conduct appropriate monitoring.
The concurrent administration of allopurinol and ampicillin substantially increases the incidence of allergic rashes. There is no data on Augmentin and allopurinol administered concurrently. Novoksiklav may reduce the efficacy of oral contraceptives and patients should be warned accordingly. Also it can enhance the toxicity of methotrexate.
Avoid the simultaneous use with disulfiram. The drug should not be mixed in an infusion syringe or vial with other medicaments. Avoid mixing drug solutions with dextrose (glucose), dextran, sodium bicarbonate, and solutions containing blood, proteins and lipids.

 

Precautions

During the course of the drug treatment is necessary to monitor the function of blood, liver and kidneys.

In patients with renal impairment, dosage or interval between administrations should be adjusted.
The drug should be avoided if infectious mononucleosis or lymphocytic leukemia is suspected since the occurrence of a morbilliform rash has been associated with this condition following
the use of amoxicillin. The drug contains potassium. Patients follow a diet with restriction of sodium, should be noted that in each 1.2g vial contains 59.3 mg sodium. The amount of sodium in a maximum daily dose exceeding 200 mg.
During the drug treatment in high dose can be a false positive readings when testing for the presence of glucose in the urine are common with Benedict's reagent or solution Falling (enzymatic glucose oxidase methods should be used).
Careful enquiry should be made concerning previous hypersensitivity reactions to cephalosporins, with pseudomembranous colitis, evidence of hepatic dysfunction, renal impairment.
The drug treatment during pregnancy can be used only with the presence of a doctor's testimony. Amoxicillin and clavulanic acid in small amounts are excreted in breast milk.
Adverse effects on the ability to drive or operate machinery have not been observed
The drug should be keep out of reach of children and does not use after the expiration date.

 

Overdosage

There are no reports of deaths or life-threatening occurrence of side effects due to drug overdose.
Symptoms: nausea, vomiting and diarrhoea; it is also possible anxious arousal, insomnia, dizziness, and in some cases - seizures.
Treatment: symptomatic therapy, medical supervision is necessary. The drug can be removed by hemodialysis.

 

Storage conditions

In a dry protected from light place, at temperature not exceeding 25°C.

 

Shelf life

2years.

 

Dispensing

Dispensed with a prescription.

 

Novoksiklav

Hepatoprotectors
Antibiotics
Local anaesthetic drugs
Nootropic drugs
Antihypertensive drugs
Drugs for a parenteral food
Medicines applied at poisonings and intoxications
Medicines for metabolic processes correction
Medicines for peripheric blood circulation
Mineral drugs, microcells
Salt solutions
Analgesic and antispasmodic drugs
Nonsteroidal anti-inflammatory drugs
Haemostatics