Ciprofloxacin, 200 mg/100 ml 100 ml

Pharmacotherapeutic group

Antimicrobial agent, fluoroquinolone

ATX code

J01MA02

Pharmacodynamics:

A broad-spectrum antimicrobial from the group of fluoroquinolones.

Acts bactericidal. The drug inhibits bacterial enzyme DNA-zytase, which disrupts DNA replication and synthesis of bacterial cell proteins. Ciprofloxacin acts both on multiplying microorganisms and on those which are in the quiescent phase.

Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: enterobacteriaceae (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 (Haemophilus 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 Mycobacterium avium-intracellulare.

The following Gram-positive aerobic bacteria are also sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus saprophyticus) Streptococcus spp. (Streptococcus pyogenes Streptococcus agalactiae). Bacillus anthracis is also sensitive to ciprofloxacin both in vitro and in vivo studies.

Most methicillin-resistant staphylococci are also resistant to ciprofloxacin.

The sensitivity of the bacteria Streptococcus pneumoniae Enterococcus faecalis is moderate.

Corynebacterium spp. Bacteroides fragilis Pseudomonas cepacia Pseudomonas maltophilia Ureaplasma urealyticum Clostridium difficile Nocardia asteroides. Pharmacokinetics:

After intravenous infusion of 200 mg or 400 mg, maximum concentration time (TCmax) is 60 min and maximum concentration (Cmax) is 21 mcg/ml and 46 mcg/ml, respectively. Distribution volume is 2-3 l/kg plasma protein binding is 20-40 %.

Good distribution in body tissues (excluding fatty tissue such as nerve tissue). Content in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are reached in saliva tonsils liver gallbladder bile intestine abdominal organs and small pelvis uterus seminal fluid prostatic tissue endometrium fallopian tubes and ovaries kidneys and urinary organs lung tissue bronchial secretion bone tissue muscles synovial fluid and articular cartilage peritoneal fluid skin.

In cerebrospinal fluid penetrates in small amounts where its concentration in uninflamed cerebrospinal fluid is 6-10% of that in blood serum and in inflamed – 14-37%. Ciprofloxacin also penetrates well into the ocular fluid pleura lymph through the placenta.

The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

It is metabolized in the liver (15-30%) with the formation of slightly active metabolites (diethylcyclofloxacin sulfociprofloxacin oxociprofloxacin formylciprofloxacin).

In intravenous administration the half-life (T1/2) is 5-6 hours with chronic renal failure up to 12 hours. It is eliminated mainly by the kidneys through tubular filtration and tubule secretion 50-70% unchanged and 10% as metabolites, the rest – through the gastrointestinal tract. A small amount is excreted with breast milk.

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

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

Patients with severe renal insufficiency (creatinine clearance below 20 ml/min/173 m2 should be administered half the daily dose of the drug.)

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to ciprofloxacin:

Ciprofloxacin is indicated for treatment of sepsis and peritonitis and for prevention and treatment of infections in immunocompromised patients (when treated with immunosuppressants).

Active ingredient

Composition

100 ml of the drug contains:

The active substance: ciprofloxacin (in the form of lactate) – 200 mg;

excipients: sodium chloride, disodium edetate, water for injection.

How to take, the dosage

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

In case of urinary tract infections it is taken 0.25-0.5 g 2 times daily; the course of treatment is 7-10 days.

In uncomplicated gonorrhea – 0.25-0.5 g once daily;

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

In meningococcal carriage in the nasopharynx – once, 0.5 or 0.75 g.

In case of chronic Salmonella carriage – orally, 0.25 g 4 times; treatment course – up to 4 weeks. If necessary the dosage may be increased up to 0.5 g 3 times a day.

In case of pneumonia, osteomyelitis – inside, 0.75 g 2 times a day. Duration of treatment of osteomyelitis can be up to 2 months.

Infections of gastrointestinal tract caused by Staphylococcus aureus – 0.75 g every 12 hours during 7-28 days. The treatment should be continued for at least 3 days after body temperature normalization or when clinical symptoms disappear.

In case of glomerular filtration rate (CK 31-60 ml/min/1.73 sq.m or serum creatinine concentration from 1.4 to 1.9 mg/100 ml) the maximum daily dose is 1 g. If glomerular filtration rate is below 30 ml/min/1.73 sq m or serum creatinine concentration is above 2 mg/100 ml, the maximum daily dose is 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 hemodialysis session.

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

The tablets should be swallowed whole with a small amount of liquid after a meal. When the tablet is taken on an empty stomach, the active ingredient is absorbed more quickly.

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

In case of necessity of intravenous treatment of particularly severe, life-threatening or recurrent infections caused by Pseudomonas, staphylococci or Streptococcus pneumoniae the dose can be increased up to 0.4 g with multiplicity of administration up to 3 times a day. Duration of treatment in osteomyelitis may be up to 2 months.

In case of chronic carrier of Salmonella – 0.2 g 2 times a day; the course of treatment – up to 4 weeks. If necessary the dosage may be increased up to 0.5 g 3 times per day.

In acute gonorrhea it is 0.1 g once.

For prophylaxis of infections during surgical interventions – 0.2-0.4 g 0.5-1 hour before operation; if the operation lasts more than 4 hours it is administered repeatedly in the same dose.

The average duration of treatment:

1 day – for acute uncomplicated gonorrhea and cystitis;

up to 7 days – for renal, urinary tract and abdominal infections, throughout the neutropenic phase – in patients with weakened body defenses, but not more than 2 months. – In osteomyelitis and
7-14 days – in all other infections.

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

The dose is reduced by 30% in elderly patients.

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

After intravenous administration it is possible to continue treatment orally.

Interaction

Concomitant administration of ciprofloxacin and theophylline may lead to increased plasma concentrations of theophylline due to competitive inhibition in cytochrome P450 binding sites, resulting in prolongation of the half-life of theophylline and an increased risk of theophylline-associated toxic effects.

Enhances the concentration and prolongs the T1/2 of oral hypoglycemic drugs indirect anticoagulants promotes reduction of the prothrombin index.

The simultaneous use of ciprofloxacin and anticoagulants prolongs bleeding time.

Concomitant use of ciprofloxacin and cyclosporine increases nephrotoxic effects of the latter.

When combined with other antimicrobial drugs (beta-lactam antibiotics aminoglycosides clindamycin metronidazole) synergism is usually observed; it can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp.with meslocillin azlocillin and other beta-lactam antibiotics in streptococcal infections; with isoxazolepenicillin and vancomycin in staphylococcal infections; with metronidazole and clindamycin in anaerobic infections.

Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures.

Methoclopramide accelerates absorption resulting in a shorter time to reach its Cmax.

The co-administration of uricosuric drugs leads to slower excretion (up to 50%) and increased plasma concentration of ciprofloxacin.

Preventing ciprofloxacin increases maximum concentration 7-fold (4 to 21-fold) and AUC 10-fold (6 to 24-fold) of tizanidine which increases the risk of significant reduction in blood pressure and drowsiness.

Concomitant use with warfarin increases the risk of bleeding.

Pharmaceutical interactions: Ciprofloxacin solution is incompatible with solutions or drugs with pH 3-4 that are physically or chemically unstable. Ciprofloxacin infusion solution is not compatible with solutions that have a pH greater than 7.

Special Instructions

Patients with a history of epilepsy, seizures, vascular disease and organic brain lesions due to the risk of adverse reactions of the central nervous system ciprofloxacin should be prescribed only with vital signs.

In case of severe and prolonged diarrhea during or after treatment with ciprofloxacin the diagnosis of pseudomembranous colitis must be excluded which requires immediate withdrawal of the drug and appropriate treatment.

In case of tendon pain or if the first signs of tendovaginitis appear, treatment should be discontinued because there have been isolated cases of inflammation and even tendon rupture during treatment with fluoroquinolones.

Any adequate fluid intake with normal diuresis should be maintained during treatment with ciprofloxacin.

People should avoid contact with direct sunlight during treatment with ciprofloxacin.

The use of ciprofloxacin in children is not recommended for the treatment of other diseases except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis and for the treatment and prevention of inhalational anthrax (after suspected or proven infection with Bacillus anthracis).

Patients taking ciprofloxacin should exercise caution when driving and engaging in other potentially hazardous activities that require increased attention and rapid psychomotor reactions (especially when alcohol is also used).

Contraindications

Hypersensitivity to fluoroquinolones children age (up to 18 years – completion of skeletal formation except therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis from 5 to 17 years; prevention and treatment of pulmonary anthrax) pregnancy lactation period simultaneous use with tizanidine.

Developed cerebral vascular atherosclerosis cerebral circulatory disorders mental illness seizure syndrome epilepsy pronounced renal and/or liver failure elderly age.

Pediatric use

Ciprofloxacin is not recommended for use in children under 18 years of age to treat other infectious diseases except for therapy of complications caused by Pseudomonas aeruginosa in children with pulmonary fibrosis and treatment and prevention of pulmonary anthrax (after suspected or proven infection with Bacillus anthracis) (in children aged 5 to 17 years).

Side effects

Gastrointestinal tract: nausea diarrhea vomiting abdominal pain flatulence anorexia cholestatic jaundice (especially in patients with past liver disease) hepatitis hepatonecrosis.

Nervous system disorders: dizziness headache increased fatigue anxiety tremor insomnia “nightmares” dreams peripheral paralgesia (abnormal perception of pain sense) sweating increased intracranial pressure confusion depression hallucinations, etc. Manifestations of psychotic reactions (occasionally progressing to states in which the patient can harm himself) migraine fainting cerebral artery thrombosis.

Sense organs: impaired taste and smell visual impairment (diplopia change in color perception) tinnitus tinnitus decreased hearing

Cardiovascular system disorders: tachycardia impaired heart rhythm decreased blood pressure “flushes” of blood to the skin of the face

Hematopoietic system: leukopenia granulocytopenia anemia thrombocytopenia leukocytosis thrombocytosis hemolytic anemia agranulocytosis.

Urinary system disorders: hematuria crystalluria (especially in alkaline urine and low diuresis) glomerulonephritis dysuria polyuria urinary retention albuminuria urethral bleeding decrease of renal nitrogen excretion function interstitial nephritis.

Muscular system disorders: arthralgia swelling in the joint area arthritis tendovaginitis tendon tears myalgia.

Allergic reactions: pruritus urticaria formation of blisters accompanied by bleeding and small nodules forming scabs drug fever pinpoint hemorrhages (petechiae) facial or laryngeal edema dyspnea eosinophilia vasculitis nodular erythema exudative multiform erythema Stevens-Johnson syndrome (malignant exudative erythema) toxic epidermal necrolysis (Lyell syndrome) anaphylactic shock.

Laboratory measures: hypoprothrombinemia increased “hepatic” transaminases and alkaline phosphatase activity hypercreatininemia hyperbilirubinemia hyperglycemia increased urea concentration.

Local reactions: pain and burning at the injection site phlebitis.

Others: superinfections (candidiasis pseudomembranous colitis) generalized weakness hypersensitivity to light.

Overdose

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