Ciprolet, 2 mg/ml 100 ml

A broad spectrum antimicrobial agent, fluoroquinolone derivative, inhibits bacterial DNA-giase (topoisomerases II and IV, responsible for the process of superspiralization of chromosomal DNA around the nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth and division of bacteria; causes pronounced morphological changes (including cell wall and membrane) and rapid death of the bacterial cell.

It acts bactericidally on Gram-negative organisms during quiescence and division (as it affects not only DNA-giase but also causes lysis of cell wall), on Gram-positive microorganisms it acts only during division.

Low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of ciprofloxacin use there is no parallel development of resistance to other antibiotics which do not belong to DNA-gyrase inhibitors group and this fact makes it highly effective with respect to bacteria which are resistant to, for example, aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is susceptible to Gram-negative aerobic bacteria: Enterobacteriaceae (Escherichiacoli, Salmonellaspp., Shigellaspp., Citrobacterspp., Klebsiellaspp., Enterobacterspp, Proteusmirabilis, Proteusvulgaris, Serratiamarcescens, Hafniaalvei, Edwardsiellatarda, Providencia spp., Morganellamorganii, Vibriospp., Yersiniaspp.), other Gram-negative bacteria

(Haemophilusspp, Pseudomonasaeruginosa, Moraxellacatarrhalis, Aeromonasspp., Pasteurellamultocida, Plesiomonasshigelloides, Campylobacterjejuni, Neisseriaspp.), some intracellular pathogens

– Legionellapneumophila, Brucellaspp, Listeriamonocytogenes, Mycobacteriumtuberculosis, Mycobacteriumkansasii, Corynebacteriumdiphtheriae; Gram-positive aerobic bacteria: Staphylococcusspp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).
Active against Bacillus anthracis in vitro.

Most staphylococci resistant to methicillin are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for their suppression).

Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides are resistant to the drug. It is not effective against Treponema pallidum.

Resistance develops very slowly because after the action of ciprofloxacin there are practically no persistent microorganisms and on the other hand bacterial cells have no enzymes which inactivate it.

Pharmacokinetics

After intravenous infusion of 200 or 400 mg of ciprofloxacin, the maximum concentration (Cmax) is 2.1 and 4.6 µg/ml, respectively; time to reach maximum concentration (TCmax) is 60 min. Binding to plasma proteins is 20-40%. Distribution volume is 2-3.5 l/kg.

It is well distributed in body tissues (excluding fat-rich tissue, such as nerve tissue). Concentrations in tissues are 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gallbladder, bile, intestines, abdominal and pelvic organs, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary tract, lung tissue, bronchial secretion, bone tissue, muscles, synovial fluid and joint cartilage, peritoneal fluid, skin.

In cerebrospinal fluid penetrates in small amounts, where the concentration, in the absence of inflammation of the meninges, is 6-10% of that in blood serum, and in the presence of inflammation – 14-37%. Ciprofloxacin also penetrates well into the ocular fluid, bronchial secretion, pleura, peritoneum, lymph, and through the placenta. Concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

Metabolized in the liver (15-30%) with the formation of slightly active metabolites (oxo-, diethyl-, sulfo-, formylciprofloxacin).
Half-life (T1/2) is about 5-6 hours, in chronic renal failure (ChRI) – up to 12 hours. It is eliminated mainly by kidneys by tubular filtration and tubular secretion unchanged (50-70%) and as metabolites (10%), the rest – through the intestine. A small amount is excreted with breast milk.

After intravenous administration the concentration in urine during the first 2 hours after administration is almost 100 times higher than in blood serum, which significantly exceeds the minimum suppressive concentration (MSC) for most pathogens of urinary tract infections.

Renal clearance is 3-5 ml/min/kg; total clearance is 8-10 ml/min/kg.

In CKD (creatinine clearance (CK) above 20 ml/minute) the percentage of the drug excreted through the kidneys decreases, but there is no cumulation in the body due to compensatory increase of the drug metabolism and its excretion by the intestine.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

By reducing the activity of microsomal oxidation processes in hepatocytes, increases the concentration

and prolongs T1/2. Theophylline (and other xanthines, such as caffeine), oral hypoglycemic drugs, indirect anticoagulants, helps reduce the prothrombin index.

NSAIDs (excluding acetylsalicylic acid) increase the risk of seizures.

Methoclopramide accelerates absorption of ciprofloxacin, which leads to decreased time to reach its Cmax.

The co-administration of uricosuric drugs leads to slower excretion (up to 50%) and

increased plasma concentration of ciprofloxacin.

In combination with other antimicrobial agents (beta-lactams, aminoglycosides, clindamycin, metronidazole) synergism is usually observed; it can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp.

In combination with meslocillin, azlocillin and other beta-lactam antibiotics in streptococcal infections; with isoxazolylpenicillin and vancomycin in staphylococcal infections; with metronidazole and clindamycin

In anaerobic infections.

It enhances the nephrotoxic effect of cyclosporine, an increase in serum creatinine is noted,

so in these patients it is necessary to control this index 2 times a week.

In concomitant administration increases the effect of indirect anticoagulants.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable in an acidic environment (the pH of ciprofloxacin infusion solution is 3.5-4.6),

Intravenous solutions should not be mixed with solutions that have a pH greater than 7.

Special Instructions

Contraindications

Side effects

Overdose

Treatment:

A specific antidote is unknown.

The patient’s condition should be monitored carefully, gastric lavage should be performed, the usual first aid measures should be carried out, and adequate fluid intake should be ensured.

Only a small amount (less than 10%) of the drug can be eliminated by hemo- or peritoneal dialysis.

Similarities