Universal reference book for medicines
Name of the preparation: IMIPENEM AND CYLASTATIN JODAS (IMIPENEM & CILASTATIN JODAS)

Active substance: cilastatin, imipenem

Type: Carbapenem Group Antibiotic

Manufacturer: JODAS EXPOIM (India)
Composition, form of production and packaging
Powder for solution preparation for
intravenous administration 1 fl.

imipenem 500 mg

cilastatin sodium 500 mg

bottles (1) - packs of cardboard.

bottles (5) - packs cardboard.

bottles (10) - packs of cardboard.

INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2011.

PHARMACHOLOGIC EFFECT

Beta-lactam antibiotic of broad spectrum of action.
Suppresses the synthesis of the bacterial cell wall and has a bactericidal effect against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic.
Imipenem - a derivative of tienamycin, belongs to the group of carbapenems.

Cilastatin sodium inhibits dehydropeptidase, an enzyme that metabolizes imipenem in the kidneys, which significantly increases the concentration of unchanged imipenem in the urinary tract.
Cilastatin does not have its own antibacterial activity, does not inhibit? -lactamase bacteria.
The drug is active against Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus faecalis and Bacteroides fragilis.
Resistant to destruction by bacterial β-lactamase, which makes it effective against many microorganisms, such as Pseudomonas aeruginosa, Serratia spp. and Enterobacter spp., which are resistant to most beta-lactam antibiotics. The antibacterial spectrum includes virtually all clinically relevant pathogens.
It is active against gram-negative aerobic bacteria: Achromobacter spp., Acinetobacter spp.
(formerly Mima-Herellea), Aeromonas hydrophila, Alcaligenes spp., Bordetella bronchicanis, Bordetella bronchiseptica, Bordetella pertussis, Brucella melitensis, Campylobacter spp., Capnocytophaga spp., Citrobacter spp. (including Citrobacter diversus, Citrobacter freundii), Eikenella corrodens, Enterobacter spp. (including Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae), Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae (including strains forming beta-lactamase), Haemophilus parainfluenzae, Hafnia alvei, Klebsiella spp (inc. Klebsiella oxytoca, Klebsiella ozaenae, Klebsiella pneumoniae), Moraxella spp., Morganella morganii (formerly Proteus morganii), Neisseria gonorrhoeae (including strains forming penicillinase), Neisseria meningitidis, Yersinia spp. (formerly Pasteurella), incl. Yersinia multocida, Yersinia enterocolitica, Yersinia pseudotuberculosis; Plesiomonas shigelloides, Proteus spp. (including Proteus mirabilis, Proteus vulgaris), Providencia spp.(including Providencia alcalifaciens, Providencia rettgeri (formerly Proteus rettgeri), Providencia stuartii), Pseudomonas spp. (including Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas pseudomallei, Pseudomonas putida, Pseudomonas stutzeri), Salmonella spp. (including Salmonella typhi), Serratia spp.(including Serratia marcescens, Serratia proteamaculans), Shigella spp; (including penicillinase-producing strains), Staphylococcus epidermidis (including penicillinase-producing strains), Staphylococcus saprophyticus, Streptococcus (Staphylococcus epidermidis), Staphylococcus epidermidis (including strains forming penicillinase), Staphylococcus epidermidis (including strains forming penicillinase), Staphylococcus epidermidis, Staphylococcus epidermidis agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus group C, Streptococcus group G, greening streptococci including alpha and gamma-hemolytic strains); Gram-negative anaerobic bacteria: Bacteroides spp. (including Bacteroides distasonis, Bacteroides fragilis, Prevotella melaninogenica (formerly Bacteroides melaninogenicus), Bacteroides ovatus, Bacteroides thetaiotaomicronron, Bacteroides uniformis, Bacteroides vulgatus), Bilophila wadsworthia, Fusobacterium spp incl. (Fusobacterium necrophorum, Fusobacterium nucleatum), Porphyromonas asaccharolytica (formerly Bacteroides asaccharolyticus), Prevotella bivia (formerly Bacteroides bivius), Prevotella disiens (formerly Bacteroides disiens), Prevotella intermedia (formerly Bacteroides intermedius), Veillonella spp .; Gram-positive anaerobic bacteria: Actinomyces spp., Bifidobacterium spp., Clostridium spp. (including Clostridium perfringens), Eubacter spp., Lactobacillus spp., Microaerophilic streptococcus, Mobiluncus spp., Peptococcus spp., Peptostreptococcus spp., Propionibacterium spp. (including Propionibacterium acne); other microorganisms: Mycobacterium fortuitum, Mycobacterium smegmatis.
Some Staphylococcus spp.
(resistant to methicillin), Streptococcus spp. (Group D), Stenotrophomonas maltophilia, Enterococcus faecium and some strains of Pseudomonas cepacia are insensitive to imipenem. Effective against many infections caused by bacteria, resistant to cephalosporins, aminoglycosides, penicillins. In vitro acts synergistically with aminoglycosides against some strains of Pseudomonas aeruginosa.
PHARMACOKINETICS

C max imipenem with iv administration at a dose of 250, 500 or 1000 mg for 20 minutes - 14-24, 21-58 and 41-83 μg / ml, respectively.
C max cilastatin with iv administration at a dose of 250, 500 or 1000 mg for 20 minutes - 15-25, 31-49 and 56-80 mcg / ml. Binding to plasma proteins imipenem - 20%, cilastatin - 40%.Quickly and well distributed in most tissues and body fluids. The highest concentrations are achieved in pleural effusion, peritoneal and interstitial fluids and reproductive organs. In low concentrations it is found in the cerebrospinal fluid. V d in adults is 0.23-0.31 l / kg, in children 2-12 years - 0.7 l / kg, in newborns - 0.4-0.5 l / kg.
Blocking tubular secretion of imipenem with cilastatin results in inhibition of its renal metabolism and accumulation in the urine in unchanged form.
Cilastatin is metabolized to the N-acetyl compound. With iv introduction of T 1/2 imipenem and cilastatin in adults - 1 h, in children 2-12 years - 1-1.2 h, in newborns T 1/2imipenem - 1.7-2.4 h, cilastatin - 3.8-8.4 h; when renal function T 1/2 imipenem is broken down - 2.9-4 hours, cilastatin - 13.3-17.1 hours. It is mainly excreted by the kidneys (70-76% within 10 hours) by glomerular filtration (2/3) and active tubular secretion (1 / 3); 1-2% is excreted through the gastrointestinal tract and 20-25% by the extrarenal route (the mechanism is unknown).
Quickly and effectively (73-90%) is excreted by hemodialysis (as a result of a 3-hour session of intermittent hemofiltration, 75% of the dose is removed).

INDICATIONS

Infectious-inflammatory diseases caused by sensitive microorganisms (polymicrobial or mixed aerobic-anaerobic infections):

- infections of the lower respiratory tract;

- urinary tract infections;

- intra-abdominal infections;

- skin and soft tissue infections;

- infections of bones and joints;

- peritonitis;

- sepsis;

- endocarditis;

- inflammatory diseases of the pelvic organs.

Prevention of postoperative complications.

DOSING MODE

In / in the drip.
The following doses are calculated for a body weight of 70 kg and more and a KC of 70 ml / min / 1.73 m2 and more . For patients with SC less than 70 ml / min / 1.73 m2 and / or less body weight , the dose should be proportionally reduced.
The average therapeutic dose for adults (calculation for imipenem) with iv introduction - 1-2 g / day, divided into 3-4 injections;
the maximum daily dose is 4 g or 50 mg / kg, depending on which dose is lower.
Patients with mild infection severity - 250 mg 4 times / day, medium degree - 500 mg 3 times / day or 1 g 2 times / day, severe - 500 mg 4 times / day, with aninfection endangering the patient's life - 1 g 3-4 times / day.

The dose of imipenem less than or equal to 500 mg should be administered iv in 20-30 minutes.
A dose of more than 500 mg should be administered iv in 40-60 minutes. Patients who had nausea during infusion should slow the rate of injection.
For the prevention of postoperative infections - 1 g during introductory anesthesia and 1 g - after 3 hours. In the case of surgical intervention with a high risk of infection (operation on the colon and rectum), 500 mg are additionally administered at 8 and 16 hours after general anesthesia .

Maximum daily doses for intravenous administration in patients with renal insufficiency , depending on the severity of the infection and the values ​​of CK (ml / min / 1.73 m 2) and a body weight of? 70 kg:

- for a mild course of infection and CC 41-70 ml / min - 250 mg after 8 hours, CC 21-40 ml / min - 250 mg after 12 hours, CC 6-20 ml / min - 250 mg after 12 hours ;

- for infection of medium severity and CK 41-70 ml / min - 250 mg after 6 hours, KK 21-40 ml / min - 250 mg after 8 hours, KK 6-20 ml / min - 250 after 12 hours;

- in severe cases (moderately sensitive strains, including Pseudomonas aeruginosa) and CC 41-70 ml / min - 500 mg every 6 hours, CC 21-40 ml / min - 500 mg after 8 hours, QC 6-20 ml / min - 500 mg every 12 hours;

- for severe life-threatening life-threatening events and CC 41-70 ml / min - 750 mg every 8 hours, CC 21-40 ml / min - 500 mg after 6 hours, KK 6-20 ml / min - 500 mg after 12 hours.

Patients with SC less than 5 ml / min are prescribed only if, not later than 48 hours after the infusion of the drug, hemodialysis is performed.
The introduction of the drug to such patients is recommended only in those. cases where the benefit of its use exceeds the potential risk of seizures. When treating patients with SC less than 5 ml / min on hemodialysis , doses should be used for patients with CC of 6-20 ml / min and body weight less than 70 kg (see below). The drug is administered after a hemodialysis session and then at 12-hour intervals from the end of the procedure, with careful monitoring of patients (especially if they have central nervous system diseases).
At present, there is insufficient data on the dosage regimen for preoperative prophylaxis of patients with SC less than 70 ml / min / 1.73 sq.m.

Below is the dosing regimen for patients with renal dysfunction and / or body weight less than 70 kg.

a) The maximum daily dose of 1 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 250 mg every 8 hours 125 mg every 6 hours 250 mg every 12 hours 125 mg every 12 hours

50-59 125 mg every 6 hours 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours

40-49 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours 125 mg every 12 hours

30-39 By 125 mg every 8 hours By 125 mg every 8 hours By 125 every 12 hours By 125 every 12 hours




b) The maximum daily dose of 1.5 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 250 mg every 6 hours 250 mg every 8 hours 250 mg every 8 hours 250 mg every 12 hours

50-59 By 250 mg every 6 hours By 250 mg every 8 hours By 250 mg every 12 hours By 250 mg every 12 hours

40-49 250 mg every 8 hours 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours

30-39 By 125 mg every 6 hours By 125 mg every 8 hours By 125 every 8 hours By 125 every 12 hours

c) The maximum daily dose of 2 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 500 mg every 8 hours 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours

50-59 250 mg every 6 hours 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours

40-49 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours 250 mg every 12 hours

30-39 By 250 mg every 8 hours By 125 mg every 6 hours By 125 every 8 hours By 125 every 12 hours


d) The maximum daily dose of 3 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 750 mg every 8 hours 500 mg every 8 hours 500 mg every 8 hours 500 mg every 12 hours

50-59 500 mg every 6 hours 500 mg every 8 hours 250 mg every 6 hours 250 mg every 12 hours

40-49 500 mg every 8 hours 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours

30-39 250 mg every 6 hours 250 mg every 8 hours 250 every 8 hours 250 every 12 hours


e) The maximum daily dose of 4 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 1000 mg every 8 hours 750 mg every 8 hours 500 mg every 8 hours 500 mg every 12 hours

50-59 750 mg every 8 hours 500 mg every 6 hours 500 mg every 8 hours 500 mg every 12 hours

40-49 500 mg every 6 hours 500 mg every 8 hours 250 mg every 6 hours 250 mg every 12 hours

30-39 By 500 mg every 8 hours By 250 mg every 6 hours By 250 every 8 hours By 250 every 12 hours

At present, there is insufficient data to recommend the use of the drug for patients on peritoneal dialysis.

Children with a body weight of 40 kg or more are prescribed the same doses as adults.
Children older than 3 months and with a body weight of less than 40 kg - 15 mg / kg 4 times / day; the maximum daily dose is 2 g.
Preparation of a solution for intravenous infusions

Imipenem + cilastatin for IV infusions should not be mixed or added to other antibiotics.

The following solvents are used to prepare the infusion solution: 0.9% sodium chloride solution, 5% aqueous dextrose solution, 10% aqueous dextrose solution, 5% dextrose solution and 0.9% sodium chloride.
In a ratio of 100 ml of solvent and 500 mg of imipenem. The concentration of imipenem in the resulting solution is 5 mg / ml.
Vials with a capacity of 20 ml and 30 ml

When using the drug in vials of 20 ml or 30 ml capacity, the contents of the vial are previously dissolved in 10 ml of a suitable solvent.

The resulting solution can not be used for administration!

The solution is shaken well, then transferred to a vial or container with the rest of the solvent (90 ml).
The total volume of the solvent is 100 ml. For complete transfer of the drug: 20 ml of the previously obtained solution are added to the vial, shaken well and transferred back to the vial or container with the solution already obtained. Only after this, the solution is ready for use.
SIDE EFFECT

From the nervous system: myoclonia, mental disorders, hallucinations, confusion, epileptic seizures, paresthesia.
From the urinary system: oliguria, anuria, polyuria, acute renal failure (rarely).
On the part of the digestive system: nausea, vomiting, diarrhea, pseudomembranous enterocolitis, hepatitis (rarely).

On the part of the hematopoiesis and hemostasis system: eosinophilia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, thrombocytosis, monocytosis, lymphocytosis, basophilia, hemoglobin decrease, prothrombin time lengthening.

Laboratory indicators: increased activity of hepatic transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased concentration of urea nitrogen;
direct positive Coombs test.
Allergic reactions: skin rash, itching, urticaria, multiforme exudative erythema (including Stevens-Johnson syndrome), angioedema, toxic epidermal necrolysis (rare), exfoliative dermatitis (rarely), fever, anaphylactic reactions.

Local reactions: thrombophlebitis.

Other: candidiasis, a taste disorder.

CONTRAINDICATIONS

- Pregnancy;

- lactation period;

- early childhood (up to 3 months);

- in children with impaired renal function (serum creatinine concentration more than 2 mg / dL);

- Hypersensitivity to the components of the drug, to carbapenems and other beta-lactam antibiotics.

With caution

Diseases of the central nervous system, gastrointestinal tract (including in the anamnesis), elderly age.

PREGNANCY AND LACTATION

The drug is contraindicated for use in pregnancy and lactation.

APPLICATION FOR FUNCTIONS OF THE LIVER

In / in the drip.
The following doses are calculated for a body weight of 70 kg and more and a KC of 70 ml / min / 1.73 m2 and more . For patients with SC less than 70 ml / min / 1.73 m2 and / or less body weight , the dose should be proportionally reduced.
The average therapeutic dose for adults (calculation for imipenem) with iv introduction - 1-2 g / day, divided into 3-4 injections;
the maximum daily dose is 4 g or 50 mg / kg, depending on which dose is lower.
Patients with mild infection severity - 250 mg 4 times / day, medium degree - 500 mg 3 times / day or 1 g 2 times / day, severe - 500 mg 4 times / day, with aninfection endangering the patient's life - 1 g 3-4 times / day.

The dose of imipenem less than or equal to 500 mg should be administered iv in 20-30 minutes.
A dose of more than 500 mg should be administered iv in 40-60 minutes. Patients who had nausea during infusion should slow the rate of injection.
For the prevention of postoperative infections - 1 g during introductory anesthesia and 1 g - after 3 hours. In the case of surgical intervention with a high risk of infection (operation on the colon and rectum), 500 mg are additionally administered at 8 and 16 hours after general anesthesia .

Maximum daily doses for intravenous administration in patients with renal insufficiency , depending on the severity of the infection and the values ​​of CK (ml / min / 1.73 m 2) and a body weight of? 70 kg:

- for a mild course of infection and CC 41-70 ml / min - 250 mg after 8 hours, CC 21-40 ml / min - 250 mg after 12 hours, CC 6-20 ml / min - 250 mg after 12 hours ;

- for infection of medium severity and CK 41-70 ml / min - 250 mg after 6 hours, KK 21-40 ml / min - 250 mg after 8 hours, KK 6-20 ml / min - 250 after 12 hours;

- in severe cases (moderately sensitive strains, including Pseudomonas aeruginosa) and CC 41-70 ml / min - 500 mg every 6 hours, CC 21-40 ml / min - 500 mg after 8 hours, QC 6-20 ml / min - 500 mg every 12 hours;

- for severe life-threatening life-threatening events and CC 41-70 ml / min - 750 mg every 8 hours, CC 21-40 ml / min - 500 mg after 6 hours, KK 6-20 ml / min - 500 mg after 12 hours.

Patients with SC less than 5 ml / min are prescribed only if, not later than 48 hours after the infusion of the drug, hemodialysis is performed.
The introduction of the drug to such patients is recommended only in those. cases where the benefit of its use exceeds the potential risk of seizures. When treating patients with SC less than 5 ml / min on hemodialysis , doses should be used for patients with CC of 6-20 ml / min and body weight less than 70 kg (see below). The drug is administered after a hemodialysis session and then at 12-hour intervals from the end of the procedure, with careful monitoring of patients (especially if they have central nervous system diseases).
At present, there is insufficient data on the dosage regimen for preoperative prophylaxis of patients with SC less than 70 ml / min / 1.73 sq.m.

Below is the dosing regimen for patients with renal dysfunction and / or body weight less than 70 kg.

a) The maximum daily dose of 1 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 250 mg every 8 hours 125 mg every 6 hours 250 mg every 12 hours 125 mg every 12 hours

50-59 125 mg every 6 hours 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours

40-49 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours 125 mg every 12 hours

30-39 By 125 mg every 8 hours By 125 mg every 8 hours By 125 every 12 hours By 125 every 12 hours




b) The maximum daily dose of 1.5 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 250 mg every 6 hours 250 mg every 8 hours 250 mg every 8 hours 250 mg every 12 hours

50-59 By 250 mg every 6 hours By 250 mg every 8 hours By 250 mg every 12 hours By 250 mg every 12 hours

40-49 250 mg every 8 hours 125 mg every 6 hours 125 mg every 8 hours 125 mg every 12 hours

30-39 By 125 mg every 6 hours By 125 mg every 8 hours By 125 every 8 hours By 125 every 12 hours

c) The maximum daily dose of 2 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 500 mg every 8 hours 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours

50-59 250 mg every 6 hours 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours

40-49 250 mg every 6 hours 250 mg every 8 hours 250 mg every 12 hours 250 mg every 12 hours

30-39 By 250 mg every 8 hours By 125 mg every 6 hours By 125 every 8 hours By 125 every 12 hours


d) The maximum daily dose of 3 g

Body weight (kg) Creatinine clearance (ml / min / 1.73 m 2)

? 71 41-70 21-40 6-20

60-69 750 mg every 8 hours, 500 mg every 8 hours, 500 mg every 8 hours 500 mg every 12 hours
50-59 500 mg every 6 hours, 500 mg every 8 hours 250 mg every 6 hr 250 mg every 12 hours
40-49 500 mg every 8 hours 250 mg every 6 hours, 250 mg every 8 hours 250 mg every 12 hours
30-39 250 mg every 6 hours, 250 mg every 8 hours, every 8 250 By 250 hours every 12 hours

d) The maximum daily dose of 4 g
body weight (kg) creatinine clearance (ml / min / 1.73 m)
? 71 41-70 21-40 6-20
60-69 By 1000 mg every 8 hours 750 mg every 8 hours on 500 mg every 8 hours on 500 mg every 12 hours
50-59 750 mg every 8 hours on 500 mg every 6 hours on 500 mg every 8 hours on 500 mg every 12 hours
40-49 500 mg every 6 hours, 500 mg every 8 hours, 250 mg every 6 hours on 250 mg every 12 hours
30-39 500 mg every 8 hours, 250 mg every 6 hours 250 every 8 hours every 250 12h
currently insufficient data to recommend the use of the drug to patients who are on peritoneal dialysis.
Babies with 40 kg body weight and more designate the same dose as adults. Children aged 3 months and weighing less than 40 kg - 15 mg / kg 4 times / day; the maximum daily dose - 2 grams
APPLICATION FOR CHILDREN

Babies with 40 kg body weight and more designate the same dose as adults. Children aged 3 months and weighing less than 40 kg - 15 mg / kg 4 times / day; the maximum daily dose - 2 grams
Contraindicated:

- Early childhood (up to 3 months);
- in children with impaired renal function (serum creatinine concentration of greater than 2 mg / dl).
APPLICATION IN ELDERLY PATIENTS

It should be borne in mind that in elderly patients likely to have age-related renal dysfunction, which may require dose reduction.
SPECIAL INSTRUCTIONS

It is not recommended for treatment of meningitis.
Urine stains in a reddish color.
A dosage form for in / administration should not be used for w / o or vice versa.
Before therapy for a thorough medical history of previous allergic reactions to beta-lactam antibiotics should be collected.
In persons with a history of diseases of the gastrointestinal tract (especially colitis), there is an increased risk of pseudomembranous enterocolitis.
Therapy antiepileptic drugs in patients with brain injuries or a history of seizures must continue throughout the period of drug treatment (to avoid side effects from the CNS).
It should be borne in mind that in elderly patients likely to have age-related renal dysfunction, which may require dose reduction.
OVERDOSE

Symptoms may increase side effects.
Treatment is symptomatic. Imipenem and cilastatin undergo hemodialysis. However, the effectiveness of this procedure with an overdose of the drug is unknown.
DRUG INTERACTION

Pharmaceutically compatible with lactic acid salt, other antibacterial agents.
While the use of penicillins and cephalosporins can be cross-allergy; antagonises in relation to other beta-lactam antibiotics (penicillins, cephalosporins and monobactams).
Ganciclovir increases the risk of generalized seizures.
Drugs that block tubular secretion, and slightly increase the concentration in plasma and T 1/2 imipenem (if required high concentration of imipenem, to use these drugs at the same time is not recommended).
TERMS AND CONDITIONS OF STORAGE

3 years.

Do not use after expiry date.
Storage conditions
Stored in a dry place, protected from light at a temperature not higher than 25 ° C. Keep out of reach of children. Conditions of supply of pharmacies by prescription.
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