Trade name of the drug : Ultraflox

Active ingredient (INN): Ciprofloxacin (in the form of ciprofloxacin hydrochloride).

Dosage form: Film-coated tablets.

Ingredients :

tablets 250 mg:

active substance: ciprofloxacin hydrochloride in terms of ciprofloxacin 250 mg;

excipients: crospovidone, corn starch, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, sodium lauryl sulfate, purified talc, aerosil (silicon dioxide colloidal anhydride ), magnesium stearate, Wincoat green shell coating, WT-3124 shell coating -3128 “green.

tablets 500 mg:

active substance: ciprofloxacin hydrochloride in terms of ciprofloxacin 500 mg;

excipients: crospovidone, corn starch, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, sodium lauryl sulfate, purified talc, aerosil (silicon dioxide colloidal anhydride ), magnesium stearate, Wincoat green shell coating, WT-3124 shell coating -3128 “green.

Description:

tablets 250 mg: round, biconvex film-coated tablets from light green to dark green in color and smooth on both sides.

tablets 500 mg: capsule-shaped film-coated tablets from light green to dark green in color, with a tear line on one side and smooth on the other side.

Pharmacotherapeutic group: Antibacterial synthetic agent (fluoroquinolone group).

ATX code: J01MA02

 

Pharmacological properties

A broad-spectrum antimicrobial agent, a fluoroquinolone derivative, inhibits bacterial DNA gyrase, disrupts DNA synthesis, growth and division of bacteria; causes pronounced morphological changes and rapid death of the bacterial cell.

Acts bactericidal on gram-negative organisms during dormancy and division, on gram-positive microorganisms – only during division.

Low toxicity for cells of a 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 gyrase inhibitors, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Sensitive to ciprofloxacin are gram-negative aerobic bacteria – enterobacteria (Echerichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus alwards. , Morganella morganii, Vibrio spp., Yersinia spp.), Other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejunella spp.) pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae).

Грамположительные аэробные бактерии — 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 bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required to suppress them).

Resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroids. 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, and on the other hand, bacterial cells do not have enzymes that inactivate it.

 

Pharmacokinetics

When taken orally, it is rapidly and completely absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Food intake slows down absorption, but does not change the maximum concentration and bioavailability. Bioavailability – 50-85%, volume of distribution – 2-3.5 l / kg, connection with plasma proteins – 20-40%. The time of maximum concentration for oral administration is 60-90 minutes, C _m ax linearly depends on the value of the dose taken and is at doses of 250, 500, 750 and 1000 mg – 1.2, 2.4, 4.3 and 5.4 μg / ml, respectively. 12 hours after ingestion of 250, 500 or 750 mg, the concentration of the drug in the plasma decreases to 0.1, 0.2 and 0.4 μg / ml, respectively. V _d in the body is 2-3, 4 l / kg.

Well distributed in body tissues (excluding tissue rich in fats, such as nerve tissue). Content 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 tract, 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 its concentration with non-inflamed meninges is 6-10% of that in the blood serum, and with inflamed meninges – 14-37%. Ciprofloxacin also penetrates well into the eye fluid, pleura, peritoneum, lymph, through the placenta.

Metabolizes in the liver (15-30%) with the formation of low-activity metabolites (diethylcyprofloxacin, sulfocyprofloxacin, oxocyprofloxacin, formylcyprofloxacin).

The half-life is about 4 hours for the oral route of administration. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (40-50%) and in the form of metabolites (15%), the rest through the gastrointestinal tract. A small amount is excreted in breast milk.

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

In chronic renal failure (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 metabolism of the drug and excretion through the gastrointestinal tract in masses. Patients with severe renal failure (CC below 20 ml / min / 1.73 m2) should be prescribed half the daily dose.

 

Indications for use

– infections of the kidneys and urinary tract (acute or chronic pyelonephritis, cystitis, complicated or recurrent urinary tract infections, prostatitis, epididymitis);

– respiratory tract infections (pneumonia, bronchopneumonia, pleurisy, lung abscess, infected bronchiectasis, exacerbation of chronic bronchitis);

– infections of the skin and soft tissues (infected ulcers, wound infections, abscesses, cellulitis, infected burns);

– infections of the gastrointestinal tract (cholangitis, cholecystitis, empyema of the gallbladder, typhoid fever, bacterial diarrhea, etc.);

– infections of the abdominal cavity (peritonitis, intra-abdominal abscess);

– infections of the ENT organs (inflammation of the paranasal sinuses);

– eye infections;

– infections of the musculoskeletal system;

– genital infections;

– infections of the pelvic organs;

– prevention and treatment of infections in patients with decreased immunity (during therapy with immunosuppressants).

 

Method of administration and dosage

Inside, 250 mg 2-3 times a day, with severe infections – 500-750 mg 2 times a day (every 12 hours). The drug should be taken on an empty stomach with plenty of fluids. The dose of ciprofloxacin depends on the severity of the disease, type of infection, body condition, age, weight and kidney function in the patient. Usually recommended doses:

– uncomplicated infections of the kidneys and urinary tract – 250 mg, and in complicated cases, 500 mg 2 times a day;

– uncomplicated infections of the lower respiratory tract – 250 mg, and in more severe cases, 500-750 mg, 2 times a day;

– for the treatment of gonorrhea, cystitis in women (before menopause), a single dose of ciprofloxacin at a dose of 250-500 mg is recommended;

– gynecological diseases, enteritis and colitis with a severe course and high fever, prostatitis – 500 mg 2 times a day (for the treatment of banal diarrhea, you can use a dose of 250 mg 2 times a day);

– infections of bones and joints, skin and soft tissues – 500 mg 2 times a day, in severe cases, 750 mg 2 times a day.

Patients with severe renal impairment should be given half the dose of the drug.

The duration of treatment depends on the severity of the disease, but treatment should always continue for at least two more days after the symptoms of the disease have disappeared. Usually, the duration of treatment is 7-10 days.

 

Clearance of creatinine	Dose
>50	Usual dosing regimen
30-50	250-500 mg once every 12 hours
5-29	250-500 mg once every 18 hours
Patients on hemo- or peritoneal dialysis	after dialysis 250-500 mg once every 24 hours

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

 

Side effects I

From the gastrointestinal tract: nausea, diarrhea, vomiting, abdominal pain, flatulence, loss of appetite, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis.

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

From the senses: disturbances in taste and smell, visual impairment (diplopia, change in color perception), tinnitus, hearing loss.

From the side of the cardiovascular system : tachycardia, cardiac arrhythmias, decreased blood pressure, “hot flushes” of blood to the skin of the face.

From the hematopoietic system : leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia.

Laboratory indicators : hypoprothrombinemia, increased activity of hepatic transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

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

From the musculoskeletal system : arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia.

Allergic reactions : pruritus, urticaria, blistering accompanied by bleeding and the appearance of small nodules that form scabs, drug fever, punctate hemorrhages on the skin (petechiae), edema of the face or larynx, shortness of breath, eosinophilia, vasculitis, erythema nodosum multiforme, exudate , Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell’s syndrome).

Others: increased photosensitivity, asthenia, superinfection (candidiasis, pseudomembranous colitis).

 

Contraindications

Hypersensitivity, concomitant use with tizanidine (risk of severe lowering of blood pressure, drowsiness), pseudomembranous colitis, 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 of the lungs from 5 to 17 years old; prevention and treatment of pulmonary anthrax), pregnancy, lactation, glucose-6-phosphate dehydrogenase deficiency.

Precautions

Severe atherosclerosis of the vessels of the brain, cerebrovascular accident, mental illness, epileptic syndrome, epilepsy, severe renal and / or hepatic failure, old age.

 

Drug Interactions I

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and lengthens T _{1/2 of} theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index. Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures.

When combined with other antimicrobial drugs (beta-lactam antibiotics, 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 isoxazolpenicillins and vancomycin – for staphylococcal infections; with metronidazole and clindamycin – for anaerobic infections.

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

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

Oral administration in conjunction with iron-containing drugs, sucralfate and antacids containing magnesium, calcium and aluminum ions leads to a decrease in the absorption of ciprofloxacin, therefore it should be prescribed 1-2 hours before or 4 hours after taking the above drugs.

Didanosine reduces the absorption of ciprofloxacin due to the formation of complexes with it with aluminum and magnesium salts contained in didanosine.

Metoclopramide accelerates absorption, which leads to a decrease in the time to reach it C _m ax .

The joint appointment of uricosuric drugs leads to a slowdown in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Increases _{Cm ax by} 7 times (from 4 to 21 times) and AUC by 10 times (from 6 to 24 times) tizanidine, which increases the risk of a pronounced decrease in blood pressure and drowsiness.

 

special instructions

Patients with epilepsy, a history of seizures, vascular diseases and organic brain lesions due to the threat of adverse reactions from the central nervous system Ciprofloxacin should be prescribed only for health reasons.

If severe and prolonged diarrhea occurs during or after treatment with Ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

If pain occurs in the tendons or when the first signs of tendovaginitis appear, treatment should be discontinued due to the fact that isolated cases of inflammation and even rupture of tendons during treatment with fluoroquinolones have been described.

During the period of treatment with Ciprofloxacin, it is necessary to provide a sufficient amount of fluid while maintaining normal urine output.

During the period of treatment with Ciprofloxacin, contact with direct sunlight should be avoided.

Influence on the ability to drive vehicles and control mechanisms:

Patients taking Ciprofloxacin should be careful when driving a car and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions (especially with the simultaneous use of alcohol).

 

Overdose

Symptoms: No specific symptoms. In several cases, a reversible toxic effect on the renal parenchyma has been noted. It is recommended to monitor kidney function.

Treatment: the specific antidote is unknown. It is necessary to carefully monitor the patient’s condition, carry out gastric lavage and other emergency measures, and ensure sufficient fluid intake. With the help of hemo – or peritoneal dialysis, only a small (less than 10%) amount of the drug can be removed.

 

Release form

10 tablets in blisters.

1, 3 or 10 blisters in a cardboard box with instructions for use.

 

Storage conditions

In a dry, dark place at a temperature not exceeding 25 ° C.

 

Shelf life

3 years.

 

Conditions of dispensing from pharmacies

On prescription.