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

Amoxicillin is a semisynthetic aminopenicillin belonging to a group of beta-lactam antibiotics that have a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative microorganisms. Amoxicillin is destroyed by the action of microbial enzymes (beta-lactamases) and does not affect the microorganisms that produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to penicillins, which has the ability to inactivate beta-lactamases. The presence of clavulanic acid protects amoxicillin from the damaging effect of beta-lactamases and effectively expands the spectrum of amoxicillin activity, which includes many bacteria, usually resistant to amoxicillin, as well as to other penicillins and cephalosporins.Thus, Medoclav® combines a broad spectrum of antimicrobial activity and the ability to inhibit beta-lactamase.

Medoklav® has a bactericidal effect in vivo on the following microorganisms:

Gram-positive aerobes:

Staphylococcus aureus *, Streptococcus pneumoniae, Streptococcus pyogenes.

Gram-negative aerobes:

Klebsiella spp., Enterobacter spp. (most strains of these bacteria are resistant to Medoklavu® in vitro, however, the clinical efficacy of the drug was demonstrated in the treatment of urinary tract infections caused by these strains), Escherichia coli*, Haemophilus influenzae, Moraxella catarrhalis* (Branhamella catarrhalis).

Medoklav® has a bactericidal effect in vitro on the following microorganisms, however, the clinical significance of this action is still unknown:

Gram-positive aerobes:

Bacillis anthracis* Corynebacterium spp., Enterococcus faecalis*, Enterococcus faecium*, Listeria monocytogenes, Nocardia asteroides, coagulase-negative staphylococci * (including Staphylococcus epidermidis*), Streptococcus agalactiae, Streptococcus spp., Streptococcus spp. groups viridans.

Dramp-positive anaerobes:

Clostridium spp., Peptococcus spp., Peptostreptococcus spp.

Gram-negative aerobes:

Bordetella pertussis, Brucella spp., Gardnerella vaginalis., Helicobacter pylori, Legionella spp., Neisseria gonorrhoeae *, Neisseria meningitides *, Pasteurella multocida, Proteus mirabilis *, Proteus vulgaris *, Salmonella spp. *, Shigella spp. *, Vibrio cholerae, Yersinia enter ocolitica *.

Gram-negative anaerobes:

Bacteroides spp. * (including Bacetroides fragilis), Fusobacterium spp. *

Other:

Borrelia burgdorferi, Chlamydiae spp., Leptospira icterohaemorrhagiae, Treponema pallidum.

* some strains of these bacterial species produce beta-lactamases, which makes them insensitive to monotherapy with amoxicillin.

Pharmacokinetics:

The pharmacokinetic parameters of amoxicillin and clavulanic acid are similar and do not affect the pharmacokinetics of each other. With an intravenous (IV) dose of 1000 mg / 200 mg (1.2 g), the maximum concentration (C_M_Oh) of amoxicillin is 105.4 μg / ml, and clavulanic acid - 28.5 μg / ml; the half-life (T1 / 2) is 0.9 hours for amoxicillin and 0.9 hours for clavulanic acid.

Distribution

After intravenous administration, therapeutic concentrations of amoxicillin and clavulanic acid are created in the abdominal cavity, fat and muscle tissues and interstitial fluid, in the skin, lungs and pleural fluid, in the gallbladder, as well as in synovial and peritoneal fluids, bile and pus.

Both active components do not have a high ability to bind to plasma proteins, only 13-20 % of each component of the drug in the plasma is associated with proteins. Amoxicillin and clavulanic acid penetrate the placenta. Amoxicillin, like most penicillins, penetrates into breast milk. Breast milk also found trace amounts of clavulanic acid. Both components do not cumulate.

Excretion

Amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid is through both renal and extrarenal mechanisms.Approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted by the kidneys unchanged in the first 6 hours after one bolus injection of 1000 mg / 200 mg.

Amoxicillin in an amount equivalent to 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of inactive penicillic acid. Clavulanic acid in the human body undergoes intensive metabolism to 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2- is excreted by the kidneys.

Indications:

Bacterial infections caused by susceptible amoxicillin + clavulanic acid pathogens:

- Infections of the lower respiratory tract (exacerbation of chronic bronchitis, pneumonia, empyema of the pleura, lung abscess).

- infection of the ENT organs (sinusitis, otitis media, tonsillitis).

- infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingoophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelvic peritonitis, gonorrhea).

- skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection).

osteomyelitis.

Prevention of infections in surgery.

Contraindications:

Hypersensitivity to beta-lactam antibiotics (for example, to penicillins and cephalosporins) and to clavulanic acid; with history of jaundice or liver function associated with amoxicillin / clavulanic acid; infectious mononucleosis (including when there is a measles-like rash).

Carefully:

- Weighed allergic anamnesis;

- Children born to mothers with hypersensitivity to penicillin;

- impaired liver function;

- impaired renal function (creatinine clearance <30 ml / min);

- Diseases of the gastrointestinal tract (GIT) (including in the presence of a history of colitis associated with the reception of penicillins).

Pregnancy and lactation:

During pregnancy, use the drug only in those cases where the intended use for the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, the question of abolishing breastfeeding should be resolved, in lactating women, traces of amoxicillin and clavulanic acid in breast milk were found.

Dosing and Administration:

In / in the introduction of a slow injection (3-4 minutes) directly into the vein or in the form of infusion for 30-40 minutes.

The drug is not intended for intramuscular injection!

Prepared injectable solution injected or drip. Doses are expressed in terms of amoxicillin and depend on age, body weight, kidney function and severity of the infectious process.

The minimum course of antibiotic therapy is 5 days. The maximum duration of therapy can be 14 days, after which it should be evaluated its effectiveness and tolerability

Adults and children over 12 years of age and weighing more than 40 kg: 1 g every 8 hours a day, with severe infections - every 4-6 hours.

Prophylaxis in surgery:

In an operation lasting up to 1 hour - in / in, once for 1 g during induction anesthesia. At operations with a high risk of infection and lasting for more than 1 hour, 1 g is injected during the anesthesia induction in combination with the administration of up to 4 doses of 1 g for a 24 hour period. These doses are usually given at 0, 8, 16 and 24 hours. If the procedure is accompanied by an increased risk of infection, this therapeutic regimen can be maintained for several days.

Dosage regimen for renal failure

Creatinine clearance> 30 ml / min	Creatinine clearance 10-30 ml / min	Creatinine clearance <10 ml / min
Correction of the dose is not required.	Initial dose 1 g IV, then 500 mg IV every 12 hours	The initial dose of 1 g IV, then 500 mg IV every 24 hours.

Patients on hemodialysis

Dose adjustment is based on the maximum recommended dose of amoxicillin. Initially, a dose of 1 g is administered, followed by 500 mg every 24 hours and an additional 500 mg at the end of the hemodialysis session (to compensate for a decrease in the concentration of amoxicillin and clavulanic acid in the plasma).

Dosage regimen for hepatic impairment

Treat with caution; regularly monitor liver function. Currently, there is not enough data to provide reliable recommendations for the dosing regimen.

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 - 25 mg / kg every 12 hours.

Less than 3 months with a body weight of more than 4 kg - 25 mg / kg every 8 hours.

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

From 3 months to 12 years - 25 mg / kg every 6-8 hours, depending on the severity of the infection.

Children with impaired renal function

Correction of the dose is based on the maximum recommended dose of amoxicillin:

Creatinine clearance> 30 ml / min	Creatinine clearance 10-30 ml / min	Creatinine clearance <10 ml / min
Correction of the dose is not required.	25 mg / kg 2 times a day	25 mg / kg every 24 hours.

Children on hemodialysis

Correction of the dose is based on the maximum recommended content of amoxicillin. 25 mg / kg every 24 hours and an additional 12.5 mg / kg at the end of the hemodialysis session (to compensate for the decrease in concentration of amoxicillin and clavulanic acid in plasma) and further 25 mg / kg per day.

Children with impaired liver function

Treat with caution; regularly monitor liver function. Currently, there is insufficient data to introduce changes in the dosing regimen in such patients

Preparation of solution for intravenous injection

The contents of the vial (1.2 g) are dissolved in 20 ml of water for injection. During the dilution, a temporary pink staining of the solution may appear. The finished solution has a light yellow color. The resulting solution must be introduced within 20 minutes after dilution.

Preparation of a solution for intravenous infusion

The contents of the vial (1.2 g) are dissolved in 20 ml of water for injection and add the resulting solution to 100 ml of infusion fluid.

Various infusion solutions can be used as infusion solutions.

The concentration of antibiotics persists for the period indicated below:

Infusion solution	Stability at 25 ° С
Water for injections	2 hours
Sodium chloride 0,9% Sodium chloride 0.9% for IV infusion	2 hours
Sodium lactate for intravenous infusion (1.85%)	2 hours
Ringer's solution	2 hours
Ringer lactate (Hartman solution)	2 hours
A solution of potassium chloride (0.3%) and sodium chloride (0.9%)	2 hours

The drug is less stable in infusion solutions containing glucose, dextran or sodium bicarbonate.

The solution is not subject to freezing!

The bottle with the drug can not be used many times.

Side effects:

According to the classification, side effects are divided into the following categories: very often (> 1/10), often (> 1/100, <1/10), not often (> 1/1 000, <1/100), rarely (> 1/10 000, <1/1 000), very rarely (<1/10 000)

From the gastrointestinal tract: Often: diarrhea. Infrequently: nausea, vomiting, dyspepsia, moderate increase in the activity of "liver" transaminases: ACT (aspartate aminotransferase) and / or ALT (alanine aminotransferase). Rarely: pseudomembranous and hemorrhagic colitis (with parenteral administration less likely), hepatitis, cholestatic jaundice, enterocolitis, candidiasis, black hairy tongue, darkening of tooth enamel, gastritis, stomatitis, glossitis, increased activity of alkaline phosphatase and / or bilirubin concentration.

Adverse reactions from the liver are observed mainly in men and in elderly patients and may be associated with the duration of therapy. Symptoms and symptoms are usually observed during or shortly after the end of therapy, but in some cases they may appear only a few weeks after discontinuation of therapy. These phenomena, as a rule, are reversible.

On the part of the organs of hematopoiesis: Rarely: leukopenia (including neutropenia), thrombocytopenia. Rarely: agranulocytosis, hemolytic anemia, increased prothrombin time and time of bleeding, thrombocytosis, eosinophilia.

Allergic reactions: Infrequently: skin rash, itching, hives. Rarely: angioedema, anaphylactic shock, exudative erythema multiforme. Rarely: syndrome similar to serum sickness, exfoliative dermatitis, Stevens-Johnson syndrome, allergic vasculitis, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. If any allergic reactions occur, discontinue therapy.

From the genitourinary system: Rarely: interstitial nephritis, crystalluria, hematuria.

From the nervous system: Infrequently: dizziness, headache Rarely: hyperreactivity, anxiety, insomnia, agitation, change behavior, convulsions (can be observed in patients with impaired renal function or received high doses of the drug).

Local Reactions (rarely): thrombophlebitis at the site of administration.

Other: Candidamycosis, development of superinfection.

Overdose:

Symptoms: disturbance of the function of the gastrointestinal tract and water-electrolyte balance. There is no specific antidote.

Treatment: symptomatic. In acute overdose, hemodialysis is effective. While taking high doses of amoxicillin to avoid the possibility of developing amoxicillin crystals, it is recommended to maintain adequate fluid intake and urine output.

Interaction:

Combined use of Medoklav® and probenecid is not recommended. Probenecid reduces tubular secretion of amoxicillin, i.e. can lead to an increase and maintain the level of amoxicillin in the blood, but not clavulanic acid.

Do not mix in one syringe with aminoglycoside antibiotics in connection with the loss of their activity.

Less stable in solutions containing glucose, dextran and sodium bicarbonate.

Pharmaceutically incompatible with blood preparations, other liquids containing protein (including protein hydrolysates) and fat emulsions for IV administration.

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 have been described. With this in mind, prothrombin time and INR should be carefully monitored when Medodocla® is prescribed or withdrawn.

Simultaneous application with allopurinol increases the risk of skin rash, exanthema (the mechanism of this phenomenon is still not clear).

Simultaneous application with methotrexate increases the toxicity of the latter.

Like other broad-spectrum antibiotics, Medoclav® can reduce efficiency oral hormonal contraceptives, and patients should be informed about this.

Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) have a synergistic effect, bacteriostatic (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) antagonistic.

Disulfiram: simultaneous use should be avoided.

Special instructions:

Before starting treatment with the drug, you need to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious and sometimes lethal hypersensitivity reactions (anaphylactic reactions) to penicillins are described. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to penicillins. In case of an allergic reaction, it is necessary to stop treatment with the drug and begin therapy with an antibiotic of another group. In case of serious hypersensitivity reactions, appropriate measures should be taken immediately. Epinephrine, oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

It is necessary to refrain from using the drug in case of suspected infectious mononucleosis, since in patients with this disease amoxicillin can cause a skinlike skin rash that makes diagnosis difficult.

Prolonged treatment with the drug sometimes leads to excessive reproduction of insensitive microorganisms.

During prolonged therapy with the drug it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis. The drug should be used with caution in patients with impaired liver function. Monitoring of liver function should be performed on a regular basis. In patients with impaired renal function, the dose of the drug should be reduced, respectively, the degree of impairment (see Section "method of administration and dose").

If parenteral administration of the drug is necessary for patients on a diet low in salt, the presence of sodium ion in the preparation should be taken into account. 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 reaction in the Coombs sample.

In patients with reduced diuresis, crystalluria is very rare, mainly with parenteral drug therapy.

During the administration of large doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihood of amoxicillin crystals.

During drug therapy it is necessary to remember the possible development of superinfection (usually caused by bacteria of the genus Pseudomonas spp. or fungi of the genus Candida). In that case, discontinue drug therapy and / or prescribe appropriate treatment.

In women with premature rupture of membranes, it was found that preventive therapy with amoxicillin / clavulanic acid may increase the risk of necrotizing enterocolitis in newborns.

The administration of the drug leads to a high content of amoxicillin in the urine, which can lead to false positive results in the determination of glucose in the urine (for example, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidase method to determine the concentration of glucose in the urine.

If it is necessary to simultaneously use the drug with anticoagulants prothrombin time or INR should be carefully monitored when the drug is prescribed or withdrawn.

Each Medoclav®® 1.2 g bottle contains approximately 1.0 mmol of potassium and 2.7 mmol of sodium.

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

Care should be taken when driving vehicles and engaging in other activities that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

By 1.2 g powder in glass bottles type II (EP) with a capacity of 20 ml, corked with rubber stoppers, crimped with aluminum caps.

By 1,5, 10 or 100 bottles together with instructions for use in a cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002083

Date of registration:31.05.2013

The owner of the registration certificate:Medocemi Co., Ltd.Medocemi Co., Ltd. Cyprus

Manufacturer: & nbsp

MEDOCHEMIE, Ltd. Cyprus

Representation: & nbspMEDOKEMI LTD. MEDOKEMI LTD. Cyprus

Information update date: & nbsp17.04.2014

Illustrated instructions

Instructions

Medoklav (Medoclav)