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

Adults.
Bacterial infections caused by microorganisms sensitive to the drug:
– diseases of the lower respiratory tract (acute and chronic (in the acute stage) bronchitis, pneumonia, bronchiectasis, infectious complications of cystic fibrosis);
– infections of the ENT organs (acute sinusitis);
– kidney and urinary tract infections (cystitis, pyelonephritis);
– complicated intra-abdominal infections (in combination with metronidazole), including peritonitis;
– chronic bacterial prostatitis;
– uncomplicated gonorrhea;
– typhoid fever, campylobacteriosis, shigellosis, traveler’s diarrhea;
– infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
– bones and joints (osteomyelitis, septic arthritis);
– septicemia; infections due to immunodeficiency (occurring during treatment with immunosuppressive drugs or in patients with neutropenia).
Prevention of infections during surgical interventions.
Prevention and treatment of pulmonary anthrax.

Children.
Treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years. Prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis).

Pharmacological effect

A broad-spectrum antimicrobial agent, a fluoroquinolone derivative, suppresses bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling of chromosomal DNA around 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 membranes) and rapid death of the bacterial cell.

It has a bactericidal effect on gram-negative organisms during the period of rest and division (since it affects not only DNA gyrase, but also causes lysis of the cell wall); it acts on gram-positive microorganisms only during the period of division.

Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them. While taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of DNA gyrase inhibitors, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobacteria (Escherichiacoli, Salmonellaspp., Shigellaspp., Citrobacterspp., Klebsiellaspp., Enterobacterspp., Proteusmirabilis, Proteusvulgaris, Serratiamarcescens, Hafniaalvei, Edwardsiellatarda, Providencia spp., Morganellamorganii, Vibriospp., Yersiniaspp.), other gram-negative bacteria

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

– Legionellapneumophila, Brucellaspp., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae; gram-positive aerobic bacteria: Staphylococcus spp. (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 to suppress them).

The following are resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Not effective against Treponema pallidum.

Resistance develops extremely slowly, since, on the one hand, after the action of ciprofloxacin there are practically no persistent microorganisms left, and on the other hand, bacterial cells do not have enzymes that inactivate it.

Pharmacokinetics

After an intravenous infusion of 200 or 400 mg of ciprofloxacin, the maximum concentration (Cmax) is 2.1 and 4.6 μg/ml, respectively, the time to reach maximum concentration (TCmax) is 60 minutes. Communication with plasma proteins – 20-40%. Volume of distribution – 2-3.5 l/kg.

Well distributed in body tissues (excluding fat-rich tissue, such as nervous tissue). The concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestines, abdominal and pelvic organs, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary organs, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin.

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

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

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

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

With chronic renal failure (creatinine clearance (CC) above 20 ml/min), the percentage of the drug excreted through the kidneys decreases, but accumulation in the body does not occur due to a compensatory increase in the metabolism of the drug and its excretion by the intestines.

Special instructions

To avoid the development of crystalluria, it is unacceptable to exceed the recommended daily dose,
Adequate fluid intake and maintaining an acidic urine reaction are also necessary.

Active ingredient

Ciprofloxacin

Composition

Each 100 ml bottle contains:
active ingredient:
ciprofloxacin 200 mg;
excipients:
sodium chloride 900 mg,
disodium edetate 10 mg,
lactic acid 75 mg,
citric acid monohydrate 12 mg,
sodium hydroxide 8 mg,
hydrochloric acid 0.0231 ml,
water for injections up to 100 ml.

Contraindications

Hypersensitivity to ciprofloxacin and other drugs of the fluoroquinolone group, as well as to excipients,
pregnancy, lactation period (breastfeeding), childhood (up to 18 years – until the completion of the skeletal formation process,
except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis from 5 to 17 years of age;
prevention and treatment of pulmonary anthrax), simultaneous use with tizanidine (risk of a pronounced decrease in blood pressure, drowsiness).
With caution:
Severe cerebral atherosclerosis, cerebrovascular accident, mental illness,
epilepsy, severe renal and/or liver failure, old age,
increased risk of QT prolongation or torsade de pointes (eg, congenital long QT syndrome),
heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, with hypokalemia, hypomagnesemia), simultaneous use of drugs that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics), simultaneous use with inhibitors of CYP450 1A2 isoenzymes (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine);
patients with a history of tendon damage due to previous treatment with quinolones,
myasthenia gravis, glucose-6-phosphate dehydrogenase deficiency, convulsions, including a history.

Side Effects

Depending on the frequency of occurrence, the following groups of side effects are distinguished: often – more than 1%, infrequently – 0.1-1%, rarely – 0.01-0.1%, very rarely – less than 0.01%.

Interaction

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration of

and prolongs T1/2 of theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and helps reduce the prothrombin index.

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

Metoclopramide accelerates the absorption of ciprofloxacin, which leads to a decrease in the time to reach its Cmax.

Co-administration of uricosuric drugs leads to a slower elimination (up to 50%) and

increasing plasma concentrations of ciprofloxacin.

When combined with other antimicrobial drugs (beta-lactams, aminoglycosides, clindamycin, metronidazole), synergism is usually observed; can be successfully used in combination with azlocillin and ceftazidime for infections,

caused by Pseudomonas spp.; with mezlocillin, azlocillin and other beta-lactam antibiotics – for streptococcal infections; with isoxazolylpenicillins and vancomycin – for staphylococcal infections; with metronidazole and clindamycin

– for anaerobic infections.

Strengthens the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine,

Therefore, in such patients it is necessary to monitor this indicator 2 times a week.

When taken simultaneously, it enhances the effect of indirect anticoagulants.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs,

which are physicochemically unstable in an acidic environment (pH of the ciprofloxacin infusion solution is 3.5-4.6),

Do not mix the solution for intravenous administration with solutions having a pH greater than 7.

Overdose

Treatment:

a specific antidote is unknown.

It is necessary to carefully monitor the patient’s condition, perform gastric lavage, carry out the usual emergency measures, and ensure sufficient fluid intake.

Using hemo- or peritoneal dialysis, only a small (less than 10%) amount of the drug can be removed.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C.
Do not freeze.
Keep out of the reach of children!

Shelf life

3 years

Manufacturer

Amantha Healthcare Ltd, India