Ciprofloxacin, vials 2mg/ml, 100ml

Pharmacological action

Pharmaceutical group:

antimicrobial agent-fluoroquinolone.

Pharmaceutical action:

 A broad-spectrum antimicrobial agent derived from fluoroquinolone suppresses bacterial DNA gyrase (topoisomerases II and IV, responsible for the supercoiling of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, bacterial growth and division; causes pronounced morphological changes (including cell walls and membranes) and rapid bacterial cell death.

It acts bactericidal on gram-negative organisms during dormancy and division (since it affects not only DNA gyrase, but also causes lysis of the cell wall), on gram-positive microorganisms-only during division. Low toxicity to macroorganism cells is explained by the absence of DNA gyrase in them. While taking ciprofloxacin, there is no parallel development of resistance to other drugs. actibiotics that do not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines, and many others. antibiotics.

Gram – negative aerobic bacteria are susceptible to ciprofloxacin: Enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp. ), other gram-negative bacteria (Naemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp. ), some intracellular pathogens-Legionella pneumophila, Brucella spp., Chlamydia trachomatis, 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).

Most methicillin-resistant staphylococci are also resistant to ciprofloxacin.

The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, and Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for their suppression). Resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, No-cardia asteroides.

It is effective against Treponema pallidum.

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

Pharmacokinetics:  

When taken orally, it is rapidly and fairly fully absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Food intake slows down absorption, but does not change Cmax or bioavailability. Bioavailability – 50-85%, volume of distribution-2-3.5 l / kg, plasma protein binding-20-40%. Cmax with oral use is 60-90 min, Cmax linearly depends on the dose taken and is 1.2,2.4,4.3 and 5.4 mcg/ml at doses of 250,500,750 and 1000 mg, respectively. 12 hours after oral use of 250,500 and 750 mg, the drug concentration in plasma decreases to 0.1,0.2 and 0.4 mcg / ml, respectively. After intravenous infusions of 200 mg or 400 mg, Cmax – 60 min, Cmax-2.1 mcg / ml and 4.6 mcg/ml, respectively. The volume of distribution is 2-3 l / kg.

It is well distributed in body tissues (excluding fat-rich tissue, such as nerve tissue). The concentration in tissues is 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 organs, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin.

It penetrates CSF in a small amount, where its concentration in the absence of inflammation of the meninges is 6-10% of that in the blood serum, and in inflamed cases – 14-37%.

Ciprofloxacin also penetrates well into the eye 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. The activity decreases slightly at pH values less than 6.

It is metabolized in the liver (15-30%) with the formation of low-level metabolites (diethylcyprofloxacin, sulfocyprofloxacin, oxocyprofloxacin, formylcyprofloxacin). T1 / 2 – about 4 hours with oral use and 5-6 hours-with IV, with CRF-up to 12 hours.

It is mainly excreted by the kidneys by tubular filtration and tubular secretion in unchanged form (with oral use-40-50%, with intravenous use-50-70%) and in the form of metabolites (with oral use-15%, with intravenous use-10%), the rest – through the gastrointestinal tract. A small amount is excreted in breast milk. After intravenous use, the concentration in the urine during the first 2 hours after use is almost 100 times higher than in the blood serum, which significantly exceeds the BMD for most pathogens of urinary tract infections. Renal clearance – 3-5 ml/min/kg; total clearance – 8-10 ml/min/kg.

With CRF (creatinine clearance 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 drug’s metabolism and excretion with feces. Patients with severe renal insufficiency (creatinine clearance below 20 ml/min/1.73 sq. m) should be prescribed 1/2 daily dose.

Indications

Bacterial infections caused by sensitive microorganisms: respiratory tract diseases – acute and chronic (in the acute stage) bronchitis, pneumonia, bronchiectasis, cystic fibrosis; ENT infections-otitis media, sinusitis, frontitis, sinusitis, mastoiditis, tonsillitis, pharyngitis; kidney and urinary tract infections-cystitis, pyelonephritis; pelvic and genital infections – prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvioperitonitis, gonorrhea, soft chancre, chlamydia; abdominal infections – bacterial infections of the gastrointestinal tract, biliary tract, peritonitis, intraperitoneal abscesses, salmonellosis, typhoid fever, campylobacteriosis, yersiniosis, shigellosis, cholera; skin and soft tissue infections – infected ulcers, wounds burns, abscesses, phlegmon; bones and joints – osteomyelitis, septic arthritis; sepsis; infections against the background of immunodeficiency (which occurs during treatment with immunosuppressive drugs or in patients with neutropenia); prevention of infections during surgical interventions.

Contraindications

Hypersensitivity, children’s age (up to 18 years – before the completion of the skeletal formation process), pregnancy, lactation.

With caution. Severe atherosclerosis of the cerebral vessels, impaired cerebral circulation, mental illnesses, epilepsy, epileptic syndrome, severe renal and / or liver failure, elderly age.

Side effects

From the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hematonecrosis.

From the nervous system: dizziness, headache, increased fatigue, anxiety, tremor, insomnia, “nightmare” dreams, peripheral paralgesia (abnormal perception of pain), increased sweating, increased intracranial pressure, confusion, depression, hallucinations, etc. manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can harm himself), migraines, fainting states, cerebral artery thrombosis.

From the sensory organs: taste and smell disorders, visual disturbances (diplopia, color perception changes), tinnitus, hearing loss.

From the cardiovascular system: tachycardia, cardiac arrhythmias, decreased blood pressure.

From the hematopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia. From the laboratory parameters: hypoprothrombinemia, increased activity of “hepatic” transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

From the urinary system: hematuria, crystalluria (especially with alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, hematuria, decreased nitrogen-releasing function of the kidneys, interstitial nephritis.

Allergic reactions: pruritus, urticaria, blistering accompanied by bleeding and the appearance of small nodules forming scabs, drug fever, spot hemorrhages on the skin (petechiae), swelling of the face or larynx, shortness of breath, eosinophilia, increased photosensitivity, vasculitis, erythema nodosum, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal Necrolysis (Lyell’s syndrome).

Others: arthralgia, arthritis, tendovaginitis, tendon tears, asthenia, myalgia, superinfections (candidiasis, pseudomembranous colitis), “hot flashes” of blood to the face.

Interaction

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and prolongs T1/2 of theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and helps to reduce the prothrombin index.

When combined with others.antimicrobial drugs (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) are usually synergistic; it can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp. ; with mezlocillin, azlocillin, etc. beta-lactam antibiotics – for streptococcal infections; with isoxazolpenicillins and vancomycin-for staphylococcal infections; with metronidazole and clindamycin – for anaerobic infections.

Increases the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine, in such patients it is necessary to monitor this indicator 2 times a week.

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

Oral use together with Fe-containing drugs, sucralfate and antacid drugs containing Mg2+, Ca2+ and Al3+ leads to a decrease in the absorption of ciprofloxacin, so it should be prescribed 1-2 hours before or 4 hours after taking the above drugs.

NSAIDs (excluding ASA) increase the risk of seizures.

Didanosine reduces the absorption of ciprofloxacin due to the formation of complexes with Al3+ and Mg2+contained in didanosine.

Metoclopramide accelerates absorption, which leads to a shorter time to reach its Cmax.

Co-use of uricosuric drugs leads to a slowdown in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physically and chemically unstable in an acidic environment (the pH of the ciprofloxacin infusion solution is 3.9-4.5).

Do not mix the solution for intravenous use with solutions having a pH of more than 7.

How to take, course of use and dosage

Inside,0.25 g 2-3 times a day, with severe infections – 0.5-0.75 g 2-3 times a day.

For urinary tract infections – 0.25-0.5 g 2 times a day; the course of treatment is 7-10 days.

For uncomplicated gonorrhea-0.25-0.5 g once;

for a combination of gonococcal infection with chlamydia and mycoplasma-0.75 g every 12 hours for 7-10 days. With chancroid – 0.5 g 2 times a day for several days.

With meningococcal carrier in the nasopharynx-once,0.5 or 0.75 g.

In case of chronic carriage of salmonella-inside,0.25 g 4 times; the course of treatment is up to 4 weeks. If necessary, the dosage can be increased to 0.5 g 3 times a day.

For pneumonia, osteomyelitis-inside,0.75 g 2 times a day. The duration of treatment for osteomyelitis can be up to 2 months.

For gastrointestinal infections caused by Staphylococcus aureus-0.75 g every 12 hours for 7-28 days. Treatment should be continued for at least 3 days after body temperature has returned to normal or clinical symptoms have disappeared.

When the glomerular filtration rate (KK 31-60 ml/min/1.73 square meters or serum creatinine concentration from 1.4 to 1.9 mg/100 ml) a maximum daily dose of 1 g. When the glomerular filtration rate is below 30 ml/min/1.73 square meters or serum creatinine above 2 mg/100 ml maximum daily dose of 0.5 g.

If the patient is undergoing hemodialysis or peritoneal dialysis-0.25-0.5 g/day, but the drug should be taken after a hemodialysis session.

For severe infections (such as recurrent cystic fibrosis, abdominal, bone and joint infections) caused by Pseudomonas or staphylococci, acute pneumonia caused by Streptococcus pneumoniae, and chlamydial infections of the genitourinary tract, the dose should be increased to 0.75 g every 12 hours.

Tablets should be swallowed whole with a small amount of liquid after a meal. When taking the tablet on an empty stomach, the Active ingredient is absorbed faster.

IV drip: the duration of the infusion is 30 minutes at a dose of 0.2 g and 60 minutes at a dose of 0.4 g. Ready-to-use infusion solutions can be combined with 0.9% NaCl solution, Ringer’s solution and Ringer’s lactate,5% and 10% dextrose solution,10% fructose solution, as well as a solution containing 5% dextrose solution with 0.225% or 0.45% NaCl solution. For uncomplicated urinary tract infections, lower respiratory tract infections, a single dose is 0.2 g; for complicated upper urinary tract infections, with severe infections (including pneumonia, osteomyelitis), a single dose is 0.4 g.

If intravenous treatment of particularly severe, life-threatening or recurrent infections caused by Pseudomonas, staphylococci or Streptococcus pneumoniae is necessary, the dose can be increased to 0.4 g with a multiplicity of use up to 3 times a day. The duration of treatment for osteomyelitis can reach up to 2 months.

For chronic carriers of salmonella – 0.2 g 2 times a day; the course of treatment is up to 4 weeks. If necessary, the dosage can be increased to 0.5 g 3 times a day.

In acute gonorrhea – 0.1 g once.

For the prevention of infections during surgical interventions – 0.2-0.4 g 0.5-1 h before surgery; if the duration of the operation is more than 4 hours, it is re-administered in the same dose.

Average duration of treatment:

1 day – for acute uncomplicated gonorrhea and cystitis;

up to 7 days – for infections of the kidneys, urinary tract and abdominal cavity, during the entire period of the neutropenic phase-in patients with weakened body defenses, but not more than 2 months – for osteomyelitis and 7-14 days-for all other infections.

For streptococcal infections due to the risk of late complications, as well as for chlamydial infections, treatment should last at least 10 days. In patients with immunodeficiency, treatment is carried out during the entire period of neutropenia. Treatment should be carried out at least 3 days after normalization of body temperature or disappearance of clinical symptoms. When the glomerular filtration rate (KK 31-60 ml/min/1.73 square meters or serum creatinine concentration from 1.4 to 1.9 mg/100 ml), the maximum daily dose is 0.8 When the glomerular filtration rate (KK below 30 ml/min/1.73 square meters or serum creatinine above 2 mg/100 ml), the maximum daily dose – 0.4 g.

In elderly patients, the dose is reduced by 30%.

For peritonitis, intraperitoneal use of infusion solutions at a dose of 50 mg 4 times a day per 1 liter of dialysate is acceptable.

After intravenous use, oral treatment can be continued.

Special instructions

With simultaneous intravenous use of ciprofloxacin and drugs for general anesthesia from the group of barbituric acid derivatives, constant monitoring of heart rate, blood pressure, and ECG is necessary.

To avoid the development of crystalluria, it is unacceptable to exceed the recommended daily dose, as well as sufficient fluid intake and maintaining an acidic urine reaction.

During treatment, you should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Patients with epilepsy, seizures in the anamnesis, vascular diseases and organic brain damage, due to the threat of adverse reactions from the central nervous system, ciprofloxacin should be prescribed only for “vital” indications. If severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and appropriate treatment.

If there is pain in the tendons or if the first signs of tendovaginitis appear, treatment should be discontinued (individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones have been described). During the treatment period, avoid contact with direct sunlight.

Storage conditions

Store in a dark place at a temperature of 5 ° C to 20°C out of the reach of children.

Active ingredient

Ciprofloxacin

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as prescribed by a doctor, for children as prescribed by a doctor

Indications

Skin Infections, Osteomyelitis, Respiratory Tract Infections, Sinusitis, Prostatitis, Urinary Tract Infections, Infectious Diseases, Pneumonia, Intestinal Infections, Biliary Tract Infections, Otitis