Ertapenem

When ATH:
J01DH03

Pharmacological action

Beta-lactam antibiotic, Bactericidal activity is due to inhibition of cell wall synthesis, and it is mediated by binding to penicillin proteins (PSB). In Escherichia coli it exhibits a strong affinity to the DPM 1 alpha, 1 beta, 2, 3, 4 and 5, and preferably by the PSB 2 and 3. Ertapenem possesses considerable stability to beta-lactamases hydrolyze most classes, including penicillinase, cephalosporinase and beta-lactamase spread spectrum, but not metallo-beta-lactamase. It is active against most strains of the following microorganisms: aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus aureus (including strains, penicillinase; metitsillinoustoychivye resistant staphylococci), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes; aerobic and facultative anaerobic gram-negative microorganisms: Escherichia coli, Haemophilus influenzae (including strains, producing beta-lactamase), Klebsiella pneumoniae, Moraxella catarrhalis, Proteus is wonderful; anaerobic microorganisms: Bacteroides fragilis, etc.. Bacteroides species group, Clostridium spp. (other than Clostridium difficile), Eubacter spp., Peptostreptococcus spp., Porphyromonas asaccharolytica, Prevotella spp. The clinical relevance of these data on the value of the IPC, obtained in vitro, unknown: IPC at least 2 ug / ml active against most (more 90%) strains of microorganisms of the genus Streptococcus, including Streptococcus pneumoniae, at a concentration of less than 4 ug / ml - for most (more 90%) штаммов Haemophilus spp. and at a concentration of less than 4 ug / ml - against most (more 90%) aerobic and facultative anaerobic gram-positive microorganisms: Staphylococcus spp., methicillin-sensitive coagulase (metitsillinoustoychivye resistant staphylococci), Streptococcus pneumoniae (penitsillinoustoychivye), Streptococci viridans. Many strains of microorganisms, having multiresistant to other. Antibiotic, such as penicillins, cephalosporins (incl. Generation III) and aminoglycosides, sensitive to the drug: aerobic and facultative anaerobic gram-negative microorganisms [Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, producing ESBLs (beta-lactamase extended spectrum) Escherichia coli, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, producing ESBLs, Morganella morganii, Proteus vulgaris, Serratia wilting]; anaerobic bacteria - Fusobacterium spp. Many strains are resistant Enterococcus faecalis and most strains of Enterococcus faecium, Methicillin-resistant staphylococci.

Pharmacokinetics

Well absorbed after the / m. Bioavailability - 92%. After the / m 1 g / day TCmax - 2 no. Actively bound to plasma proteins; Feedback decreases with increasing plasma concentration: approximately 95% at a concentration of less than 100 ug / ml to 85% at concentrations 300 ug / ml. The dose range 0,5 to 2 Mr. AUC increases almost directly proportional to the dose. After repeated on / in a dose range from 0,5 to 2 g per day or / m administration of 1 g daily accumulation is not observed. The concentration of ertapenem in breast milk of lactating women after the last / in the 1 r is the last day of treatment (5-14 days after birth) less 0,38 ug / ml, to 5 day after stopping treatment is not defined or defined in trace amounts (less 0,13 ug / ml). About 6% metabolized by hydrolyzing the beta-lactam ring into inactive metabolite (with open ring). About 80% the drug is excreted in urine (38% - Unchanged, about 37% - In Vide metabolite), 10% - With feces. T1/2 — 4 no. The concentration of ertapenem in elderly patients after in / in the dose 1 and 2 g slightly higher (approximately 39 and 22% respectively), than in younger. The pharmacokinetics of ertapenem in children and in patients with hepatic impairment has not been studied. Due to the low intensity of its metabolism in the liver can be expected, abnormal liver function that should not affect the pharmacokinetics of. After a single in / introduction 1 g ertapenem AUC in patients with mild chronic renal failure (CC 60-90 ml / min) not changed; with moderate CKD (CC 31-59 ml / min) increases approximately 1,5 times; with severe chronic renal failure (QC 5-30 ml / min) increases approximately 2,6 times; with end-stage renal disease (CC less than 10 ml / min) AUC increased approximately 2,9 times. After a single on / in a single dose 1 g ertapenem immediately before hemodialysis about 30% the administered dose is determined in dialysate.

Testimony

Heavy to moderate infections, caused by susceptible strains of microorganisms (incl. for initial empiric antibiotic therapy until the results of susceptibility testing of bacterial pathogens): abdominal infections, infections of the skin and subcutaneous tissue (incl. infections of the lower limbs in diabetes), community-acquired pneumonia, urinary tract infection (incl. pyelonephritis), acute pelvic infection (incl. postpartum endometritis, septic abortion and post-operative infection), bakterialynaya septicemia.

Contraindications

Hypersensitivity (incl. to others. beta-lactam antibiotics), Children up to age 3 Months. When using lidocaine hydrochloride as a solvent in the / m introduction: hypersensitivity to amide local anesthetic drugs, severe hypotension, violation of intracardiac conduction.

Carefully. Pregnancy, lactation.

Dosage regimen

B / infusion (during 30 m), / m. The dose for adults and children over 13 years - 1 g, multiplicity of introduction - 1 once a day. Children 3 Months before 12 years - 15 mg / kg, razdelennaya of 2 introduction (but not more 1 g / day).

V / m administration can be used as an alternative to / infusion.

The course of treatment - 3-14 days, depending on the severity of the disease and the type of pathogen. If there is clinical improvement suppose the transition to subsequent adequate oral antimicrobial therapy.

Patients with chronic renal failure: with CC more 30 ml / min correct dosing regimen is not required. When CC less than or equal 30 ml / min, incl. Patients, on hemodialysis, - 500 mg / day.

Patients, hemodialysis when administered daily dose 500 mg in the coming 6 hours before hemodialysis must also enter 150 mg after. If the drug is administered in more than 6 hours before hemodialysis, introduction of an additional dose is not required. At the present time there is insufficient data on the optimal dosing regimen in patients, on peritoneal dialysis or hemofiltration.

Patients with hepatic impairment dose adjustment is required.

Preparation of the solution for i / v infusion: the contents of the vial is diluted 10 ml 0,9% NaCl solution or water for injection, shaken. The resulting solution was added to the vial of 50 ml 0,9% NaCl solution. The introduction of the drug should be made for 6 hours after dilution.

Preparation of the solution for i / m injection: the contents of the vial is dissolved in 3,2 ml 1-2% lidocaine, shaken until complete dissolution, after which the solution was immediately drawn into a syringe and injected deep into / m. Solution for i / m administration must be used within 1 no.

Side effect

Frequent (1–10%): headache, postinfuzionny phlebitis / thrombophlebitis, diarrhea, nausea, vomiting.

Few (0,1–1%): dizziness, weakness / fatigue, drowsiness, insomnia, convulsions, confusion; decrease in blood pressure; dyspnoea; candidiasis of the oral mucosa, psevdomembranoznыy colitis, вызванный Clostridium difficile (often manifested by diarrhea), dry mouth, dyspepsia (incl. constipation, regurgitation content), anorexia, abdominal pain, dysgeusia; skin rash (incl. эritematoznaya, hives), itchy skin; vaginal candidiasis (vaginal itching), swelling, fever, chest pain.

Allergic and anaphylactic reactions (more frequently in persons, with a history of allergy polyvalent, incl. penicillin, etc.. beta-lactam antibiotics), superimposed infection.

Laboratory findings: often - increased ALT, ACT, AP and thrombocytosis, less often - increasing direct, indirect and total bilirubin, partial thromboplastin time, eozinofilija, monocytic, hypercreatininemia and hyperglycemia; reducing the number of segmented neutrophils and leukopenia, decrease in hematocrit and Hb, thrombocytopenia; bacteriuria, increase of urea nitrogen in serum, epithelial cells in urine, eritrotsiturii.

Overdose

Symptoms: accidental introduction to 3 g / day did not lead to clinically significant adverse events.

Treatment: removal of the drug, supports. Hemodialysis is effective, However, the experience of its use in overdose has not.

Drug Interactions

Not used as solvent solutions, dextrose.

When coadministered with drugs, block tubular secretion, correction dosing regime is not required.

No effect on the metabolism of xenobiotics, mediated six major cytochrome P450 isoenzymes: CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 и CYP3A4.

Interactions with drugs, due to inhibition of tubular secretion, violation of binding to P-glycoprotein or by changing the intensity of microsomal oxidation, unlikely.

Cautions.

Perhaps the development of pseudomembranous colitis, the severity of which can range from mild to life-threatening, therefore it is necessary to bear in mind the possibility of its development in patients with diarrhea.

When i / m administration is necessary to avoid inadvertent injection into a blood vessel.