Amoxiclav - instructions for use, dose, side effects, contraindications

Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PSB) in the pathway for the biosynthesis of peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to loss of cell wall strength, which usually causes lysis and death of microorganism cells.

Amoxicillin is destroyed by the action of beta-lactamases produced by resistant bacteria,spectrum of activity of one amoxicillin does not include microorganisms that produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to penicillins. It inhibits some beta-lactamases, thereby preventing inactivation amoxicillin and extends its activity spectrum, including bacteria, usually resistant to amoxicillin, as well as to other penicillins and cephalosporins. By itself, clavulanic acid does not have a clinically significant antibacterial effect.

The drug Amoxiclav® has a bactericidal effect in vivo on the following microorganisms:

Gram-positive aerobes:

Staphylococcus aureus *

Streptococcus pneumoniae

Streptococcus pvosenes

Gram-negative aerobes:

Enterobacter spp. β

Escherichia coli *

Haemophilus influenzae *

Kinds kind Klebsiella *

Moraxella catarrhalis *

(Branhamella catarrhalis)

The drug Amoxiclav® has a bactericidal effect in vitro on the following microorganisms (however, the clinical dependence is still unknown):

Gram-positive aerobes:

Bacillis anthracis*

Kinds kind Corynebacterium

Enterococcus faecalis *

Enterococcus faecium*

Listeria monocytogenes

Nocardia asteroides

Coagulazo-negative staphylococci* (including Staphylococcus epidermidis)

Streptococcus agalactiae

Other kinds kind Streptococcus

Streptococcus viridans

Gram-positive anaerobes:

Kinds kind Clostridium

Types of genus Peptococcus

Types of genus Peptostreptococcus

Gram-negative aerobes:

Bordetella pertussis

Kinds kind Brucella

Gardnerella vaginalis

Helicobacter pylori

Kinds kind Legionella

Neisseria gonorrhoeae *

Neisseria meningitidis *

Pasteurella multocida

Proteus mirabilis *

Proteus vulgaris *

Kinds kind Salmonella *

Kinds kind Shigella *

Vibrio cholerae Yersinia enterocolitica *

Gram-negative anaerobes:

Kinds kind Bacteroides * (including Bacteroides fragilis)

Kinds kind Fusobacterium *

Other: Borrelia burgdorferi, Chlamydia spp., Leptospira icterohaemorrhagiae, Treponema pallidum

* - Some strains of these bacterial species produce beta-lactamases, which contribute to their insensitivity to monotherapy with amoxicillin

β - most strains of these bacteria are resistant to amoxicillin / clavulanic acid in vitro, However, the clinical efficacy of this combination has been demonstrated in the treatment of urinary tract infections caused by these strains.

Pharmacokinetics:

The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. The maximum concentration in blood plasma after a bolus injection of 1.2 g (1000 mg + 200 mg) of the drug is 105.4 mg / l for amoxicillin and 28.5 mg / l for clavulanic acid. Both components are characterized by a good volume distribution in the fluid and tissues of the body (lungs, middle ear, pleural and peritoneal fluids, uterus, ovaries, etc.). Amoxicillin also penetrates into the synovial fluid, liver, prostate, palatine tonsils, muscle tissue, gall bladder, the secret of the paranasal sinuses, saliva and bronchial secretions.

Amoxicillin and clavulanic acid do not penetrate the hematoencephalic barrier in non-inflamed meninges.

The maximum concentration in body fluids is observed 1 hour after administration. Amoxicillin and clavulanic acid penetrate the placental barrier and in trace concentrations are excreted by breast milk.

Amoxicillin and clavulanic acid are characterized by low binding to plasma proteins.

Amoxicillin is partially metabolized, clavulanic acid undergoes, apparently, intensive metabolism.

Amoxicillin is excreted by the kidneys practically unchanged through tubular secretion and glomerular filtration. Clavulanic acid is excreted by glomerular filtration, partly in the form of metabolites. Small amounts can be excreted through the intestines and lungs. The half-life of amoxicillin and clavulanic acid is 1-1,5 hours. In patients with severe renal failure, the period elimination half-life increases to 7.5 hours for amoxicillin and up to 4.5 hours for clavulanic acid.

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

Indications:

Infections caused by sensitive strains of microorganisms (including mixed infections caused by gram-negative and gram-positive aerobes and anaerobes):

- infections of the upper respiratory tract and ENT organs (acute and chronic sinusitis, acute and chronic otitis media, zaglugal abscess, tonsillitis, pharyngitis);

- infection of the lower respiratory tract (acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia);

- urinary tract infections;

- infection in gynecology;

- skin and soft tissue infections, including human and animal bites;

- infections of bone and connective tissues;

- infection of the abdominal cavity, incl. biliary tract (cholecystitis, cholangitis);

- odontogenic infections;

- Sexually transmitted infections (gonorrhea, soft chancre);

- prevention of infections after surgery.

Contraindications:

Hypersensitivity to any of the components of the drug; heightened sensitivity in the anamnesis to penicillins,cephalosporins and other beta-lactam antibiotics; the presence in the anamnesis of indications of cholestatic jaundice and / or other violations of the liver function caused by the use of amoxicillin / clavulanic acid; infectious mononucleosis and lymphocytic leukemia.

Carefully:

With pseudomembranous colitis in history, diseases of the gastrointestinal tract, liver failure, severe impairment of kidney function, pregnancy, lactation, with simultaneous use with anticoagulants.

Pregnancy and lactation:

In pregnancy and during lactation, Amoxiclav® is used only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.

Amoxicillin and clavulanic acid penetrate into breast milk in small amounts.

Dosing and Administration:

Intravenously.

Children:

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

Less than 3 months with a body weight of less than 4 kg - 30 mg / kg (in terms of the total Amoxiclav® preparation) every 12 hours.

Less than 3 months with a body weight of more than 4 kg - 30 mg / kg (in terms of the total Amoxiclav® preparation) every 8 hours.

In children younger than 3 months, the drug Amoxiclav® should be administered only slowly infusion for 30-40 minutes.

Children aged 3 months to 12 years: 30 mg / kg body weight (in terms of the entire preparation Amoxiclav®) at an interval of 8 hours, in the case of severe infection - at intervals of 6 hours.

Children with impaired renal function

Dose adjustment is based on the maximum recommended dose of amoxicillin.

Patients with creatinine clearance (CK) above 30 ml / min are not required to adjust the dose.

Children weighing <40 kg

KK 10-30 ml / min	For 25 mg / 5 mg per kg every 12 hours
CK <10 ml / min	At 25 mg / 5 mg per kg every 24 hours
Hemodialysis	At 25 mg / 5 mg per kg every 24 hours, plus a dose of 12.5 mg / 2.5 mg per kg at the end of the dialysis session (due to a decrease in concentrations of amoxicillin and clavulanic acid serum).

Every 30 mg of Amoxiclav® contain 25 mg of amoxicillin and 5 mg of clavulan acid.

Adults and children over 12 years of age or weighing more than 40 kg:

1.2 g of the drug (1000 mg + 200 mg) at an interval of 8 hours, in the case of severe infection - at intervals of 6 hours.

Prophylactic doses during surgical interventions:

1.2 g with an initial anesthesia (if the duration of the operation is less than 2 hours).

With longer operations, 1.2 grams up to 4 times a day.

For patients with renal insufficiency, the dose and / or interval between injections of the drug should be adjusted according to the degree of insufficiency:

Creatinine clearance
> 0.5 ml / s (30 ml / min)	correction of the dose is not required.
0.166-0.5 ml / s (10-30 ml / min)	the first dose is 1.2 g (1000 mg + 200 mg) and then 600 mg (500 mg + 100 mg) intravenously every 12 hours.
less than 0.166 ml / s (less than 10 ml / min)	the first dose is 1.2 g (1000 mi+200 mg), and then 600 mg (500 mg + 100 mg) intravenously every 24 hours.
anuria	the dosing interval should be increased to 48 hours or more

Since 85% of the drug is removed by hemodialysis, at the end of each hemodialysis procedure, it is necessary to administer the usual dose of Amoxiclav®.

With peritoneal dialysis, dose adjustments are not required.

The course of treatment is 5-14 days. The duration of the course of treatment is determined by the attending physician. With a reduction in the severity of the symptoms for the continuation of therapy, it is recommended to switch to oral forms of Amoxiclav®.

Preparation of solutions for intravenous injection.

Dissolve the contents of the vial in water for injection 600 mg (500 mg + 100 mg) in 10 ml of water for injection or 1.2 g (1000 mg + 200 mg) in 20 ml (not more) water for injection. Intravenous injection slowly (within 3-4 minutes).

The drug Amoxiclav® should be administered within 20 minutes. after preparation of solutions for intravenous administration.

Preparation of solutions for intravenous infusion.

For infusion administration of Amoxiclav®, further dilution is necessary: prepared solutions containing 600 mg (500 mg + 100 mg) or 1.2 g (1000 mg + 200 mg) of the drug should be diluted in 50 ml or 100 ml of infusion solution, respectively. Duration of infusion 30-40 minutes.

When using the fluids listed below, in the recommended volumes, the necessary concentrations of the antibiotic remain in the infusion solutions.

	period of stability
	at 25 ° C	at 5 ° C
Water for injections	4 hours	8 ocloc'k
Sodium chloride solution 0.9% for intravenous infusion	4 hours	8 ocloc'k
Ringer's lactate solution for intravenous infusion.	3 hours
Calcium, chloride and sodium chloride solution for intravenous infusions	3 hours

Solution Amoxiclav® should not be mixed with solutions of dextrose, dextran or sodium bicarbonate.

Only clear solutions should be used. Prepared solutions should not be frozen.

Side effects:

From the digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, liver dysfunction, hepatic insufficiency (more often in the elderly, men, with prolonged therapy), hemorrhagic colitis (also may develop after therapy), enterocolitis, increased activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and / or bilirubin level in blood plasma, cholestatic jaundice, hepatitis, pseudomembranous colitis.

Allergic reactions: itching, urticaria, erythematous rashes; rarely-multiform exudative erythema, angioedema, anaphylactic shock, allergic vasculitis; in isolated cases - exfoliative dermatitis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, a syndrome similar to serum sickness, toxic epidermal necrolysis.

From the hemopoietic system and lymphatic system: reversible leukopenia (including neutropenia), thrombocytopenia, hemolytic anemia, reversible increase in prothrombin time (with co-administration with anticoagulants), reversible, increased bleeding time, eosinophilia, pancytopenia, thrombocytosis, agranulocytosis.

From the nervous system: dizziness, headache, convulsions (may occur in patients from impaired renal function when taking high doses of the drug), hyperactivity, anxiety, insomnia, behavioral change, agitation.

From the urinary system: very rarely - interstitial nephritis, crystalluria, hematuria.

Other: candidiasis and other types of superinfection.

Overdose:

There are no reports of death or the occurrence of life-threatening side effects due to an overdose of the drug.

In most cases, symptoms of overdose include disorders of the gastrointestinal tract (abdominal pain, diarrhea, vomiting), are also possible agitation, insomnia, dizziness, and in rare cases - seizures.

In case of an overdose, the patient should be under the supervision of a physician, treatment - symptomatic. The drug Amoxiclav® is removed by hemodialysis.

Interaction:

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

The simultaneous use of Amoxiclav® and methotrexate raises the toxicity of methotrexate.

Bacteriological drugs (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect. Reduces the effectiveness of drugs, in the process of metabolism which produces para-aminobenzoic acid, ethinyl estradiol - the risk of bleeding "breakthrough". In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with joint use of acenocoumarol or warfarin and amoxicillin are described. If necessary, simultaneous use with anticoagulants prothrombin time or INR should be carefully monitored when the drug is prescribed or withdrawn.

The appointment together with allopurinol increases the frequency of development of exanthema.

In some cases, taking the drug may prolong the prothrombin time, so caution should be exercised with simultaneous administration of anticoagulants and Amoxiclav®.

Do not use concomitantly with disulfiram.

The drug Amoxiclav® and aminoglycoside antibiotics are physically and chemically incompatible.

The drug Amoxiclav® is not mixed in a syringe or infusion bottle with other medicines.

Avoid mixing with solutions of dextrose, dextran, sodium bicarbonate, as well as with solutions containing blood, proteins, lipids.

Amoxiclav® reduces the effectiveness of oral contraceptives.

Special instructions:

In course treatment it is necessary to monitor the status of the function of the organs of hematopoiesis, liver, kidneys.

Patients with severe renal dysfunction require adequate dose adjustment or an increase in the intervals between dosing.

Perhaps the development of superinfection due to the growth of insensitive microflora, which requires a corresponding change in antibacterial therapy.

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

In women with premature rupture of membranes, it was found that prophylactic therapy with amoxicillin + clavulanic acid may be associated with an increased risk of necrotizing colitis in infants.

Amoxicillin and clavulanic acid may provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which may be the cause of a false positive Coombs test.

In patients with reduced diuresis, crystalluria is very rare. During the administration of large doses of amoxicillin, it is recommended to take a sufficient amount and maintain adequate diuresis to reduce the likelihood of crystals of amoxicillin.

The drug contains potassium.

Information for patients, observing a diet with a lower sodium content: in each vial 600 mg (500 mg + 100 mg) contains 29.7 mg of sodium. In each vial, 1.2 g (1000 mg + 200 mg) contains 59.3 mg of sodium. The amount of sodium in the maximum daily dose exceeds 200 mg.

Lab tests: high concentrations of amoxicillin give a false positive reaction to urine glucose when using a Benedict reagent or Felling solution. It is recommended to use enzymatic reactions with glucose oxidase.

Special precautions for destruction, unused medicinal product.

There is no need for special precautions when destroying an unused Amoxiclav® preparation.

Effect on the ability to drive transp. cf. and fur:

Because of the possibility of developing side effects from the central nervous system, such as: dizziness, headache, convulsions, during treatment, care should be taken when driving and engaging in other activities that require concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of a solution for intravenous administration of 500 mg + 100 mg. 1000 mg + 200 mg.

Packaging:For 500 mg of amoxicillin and 100 mg of clavulanic acid or 1000 mg of amoxicillin and 200 mg of clavulanic acid in a vial of clear glass covered with a rubber stopper and crimped with an aluminum cap with a plastic lid. 5 bottles along with the instruction for medical use are placed in a cardboard box.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children!

Shelf life:

2 years.

Do not use the product after the expiry date printed on the package!

Terms of leave from pharmacies:On prescription

Registration number:П N012124 / 02

Date of registration:29.06.2011

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp29.06.2011

Illustrated instructions

Instructions

Amoxiclav® (Amoksiklav®)