Ciprofloxacin Ecociphol^® (Tablets) Instructions for Use

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

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

It acts bactericidally on gram-negative organisms during the resting and division phases (because it affects not only DNA gyrase but also causes lysis of the cell wall), and on gram-positive microorganisms – only during the division phase.

Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them. During the administration of ciprofloxacin, no parallel development of resistance to other antibiotics not belonging to the group of DNA gyrase inhibitors occurs, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines.

The following gram-negative aerobic bacteria are sensitive 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 (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.); some intracellular pathogens: Legionella pneumophila, Brucella spp., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.

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).

It is active against Bacillus anthracis.

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).

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

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

Lactulose, which is part of Ciprofloxacin-Ecociphol as a bifidogenic factor, is a synthetic disaccharide, the molecule of which consists of galactose and fructose residues. Lactulose is not absorbed and not hydrolyzed in the stomach and upper intestines. Lactulose released from Ciprofloxacin-Ecociphol tablets is fermented by the normal microflora of the large intestine as a substrate, stimulating the growth of bifidobacteria and lactobacilli. As a result of the hydrolysis of lactulose in the large intestine, organic acids are formed – lactic, acetic and formic acids, which suppress the growth of pathogenic microorganisms and thereby reduce the production of nitrogen-containing toxic substances.

Thus, lactulose as part of Ciprofloxacin-Ecociphol reduces the damaging effect of the antibiotic on the normal intestinal microflora and the risks of side effects associated with dysbiosis.

Pharmacokinetics

When taken orally, it is quickly and sufficiently completely absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Food intake slows down absorption but does not change the maximum concentration (Cmax) and bioavailability. Bioavailability is 50-85%, volume of distribution is 2-3.5 L/kg, plasma protein binding is 20-40%. Time to reach maximum concentration (Tmax) is 60-90 min, the maximum concentration depends linearly on the dose taken and is 1.2, 2.4, 4.3 and 5.4 mcg/ml for doses of 250, 500, 750 and 1000 mg, respectively. Twelve hours after oral administration of 250, 500 and 750 mg, the concentration of the drug in plasma decreases to 0.1, 0.2 and 0.4 mcg/ml, respectively.

It is 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, gallbladder, bile, intestines, abdominal and pelvic organs (endometrium, fallopian tubes and ovaries, uterus), seminal fluid, prostate tissue, kidneys and urinary organs, lung tissue, bronchial secretion, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. It penetrates into the cerebrospinal fluid in small amounts, where its concentration in the absence of meningeal inflammation 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, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in the blood serum.

It is metabolized in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

The elimination half-life is about 4 hours, in chronic renal failure – up to 12 hours. It is excreted mainly by the kidneys through tubular filtration and tubular secretion unchanged (40-50%) and in the form of metabolites (15%), the remainder – through the gastrointestinal tract. A small amount is excreted in breast milk.

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

In chronic renal failure (creatinine clearance above 20 ml/min), the percentage of ciprofloxacin excreted through the kidneys decreases, but accumulation in the body does not occur due to a compensatory increase in the metabolism of ciprofloxacin and excretion through the gastrointestinal tract.

Lactulose, which is part of Ciprofloxacin-Ecociphol, does not affect the main pharmacokinetic parameters characterizing the bioavailability of Ciprofloxacin.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms:

• 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);
• Infections of the kidneys and urinary tract (cystitis, pyelonephritis);
• Complicated intra-abdominal infections (in combination with metronidazole);
• 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);
• Infections against the background of immunodeficiency (occurring during treatment with immunosuppressive drugs or in patients with neutropenia);
• Prevention and treatment of the pulmonary form of anthrax.

Children

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

ICD codes

Dosage Regimen

Tablets

Orally. The tablets should be swallowed whole with a small amount of liquid after meals. When the tablet is taken on an empty stomach, the active substance is absorbed faster.

For mild to moderate lower respiratory tract infections – 0.5 g 2 times/day, for severe cases – 0.75 g 2 times/day. The course of treatment is 7-14 days.

For acute sinusitis – 0.5 g 2 times/day. The course of treatment is 10 days.

For mild to moderate skin and soft tissue infections – 0.5 g 2 times/day, for severe cases – 0.75 g 2 times/day. The course of treatment is 7-14 days.

For bone and joint infections – mild and moderate – 0.5 g 2 times/day, for severe cases – 0.75 g 2 times/day. The course of treatment is up to 4-6 weeks.

For urinary tract infections – 0.25-0.5 g 2 times/day; course of treatment – 7-14 days, for uncomplicated cystitis in women – 3 days.

For chronic bacterial prostatitis – 0.5 g 2 times/day, course of treatment – 28 days.

For uncomplicated gonorrhea – 0.25-0.5 g as a single dose.

Acute intestinal infections (salmonellosis, shigellosis, campylobacteriosis, etc.) – 0.5 g 2 times/day, course of treatment – 5-7 days.

For typhoid fever – 0.5 g 2 times/day; course of treatment – 10 days.

For complicated intra-abdominal infections – 0.5 g every 12 hours for 7-14 days.

For the prevention and treatment of the pulmonary form of anthrax – 0.5 g 2 times/day for 60 days.

In patients with immunodeficiency, treatment is prescribed depending on the severity of the infection and the type of pathogen. Antibiotic therapy is carried out throughout the period of neutropenia.

In pediatrics

For the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years – 20 mg/kg 2 times/day (maximum dose 1.5 g). Duration of treatment is 10-14 days.

For the pulmonary form of anthrax (prevention and treatment) – 15 mg/kg 2 times/day. Maximum single dose – 0.5 g, daily – 1 g. The total duration of ciprofloxacin administration is 60 days.

Chronic renal failure: with creatinine clearance (CC) greater than 50 ml/min, no dose adjustment is required; with CC 30-50 ml/min – 0.25-0.5 every 12 hours; with CC 5-29 ml/min – 0.25-0.5 g every 18 hours. If the patient is undergoing hemodialysis or peritoneal dialysis – 0.25-0.5 g/day, the drug should be taken after the hemodialysis session.

Adverse Reactions

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

From the central nervous system: dizziness, headache, increased fatigue, feeling of anxiety, tremor, insomnia, “nightmare” dreams, peripheral paralgesia (abnormality in the perception of pain sensation), sweating, increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions (occasionally progressing to states in which the patient can harm themselves), migraine, fainting, cerebral artery thrombosis.

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

From the cardiovascular system: tachycardia, heart rhythm disturbances, decreased blood pressure.

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

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

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

Allergic reactions: skin itching, urticaria, formation of blisters accompanied by bleeding, and the appearance of small nodules forming scabs, drug fever, pinpoint hemorrhages on the skin (petechiae), swelling of the face or larynx, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative multiforme erythema, Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell’s syndrome).

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

Other: general weakness, increased photosensitivity, superinfections (candidiasis, pseudomembranous colitis), facial flushing.

Contraindications

• Hypersensitivity;
• Concomitant use with tizanidine (risk of pronounced decrease in blood pressure, drowsiness);
• Age under 18 years (until the completion of the skeletal formation process, except for therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years; prevention and treatment of the pulmonary form of anthrax);
• Pregnancy;
• Lactation period.

Use with caution

Severe cerebral atherosclerosis, cerebrovascular accident, mental illness, epilepsy, severe renal and/or hepatic impairment, elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use with caution in severe hepatic impairment.

Use in Renal Impairment

Use with caution in severe renal impairment.

Pediatric Use

Contraindicated in children, except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis from 5 to 17 years of age.

Geriatric Use

Use with caution in the elderly.

Special Precautions

Ciprofloxacin is not the drug of choice for suspected or confirmed pneumonia caused by Streptococcus pneumoniae.

To avoid the development of crystalluria, exceeding the recommended daily dose is unacceptable; adequate fluid intake and maintenance of acidic urine reaction are also necessary.

During treatment, one should refrain from engaging in potentially hazardous activities requiring increased attention and speed of mental and motor reactions.

In patients with epilepsy, a history of seizures, vascular diseases, and organic brain lesions, due to the threat of developing 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 with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate drug withdrawal and appropriate treatment.

If tendon pain occurs or at the first signs of tendovaginitis, treatment should be discontinued due to isolated cases of inflammation and even tendon rupture reported during treatment with fluoroquinolones.

During treatment with ciprofloxacin, avoid UV irradiation (including contact with direct sunlight).

Overdose

No specific antidote is known. It is necessary to carefully monitor the patient’s condition, perform gastric lavage, carry out usual emergency measures, and ensure sufficient fluid intake. Only a small amount (less than 10%) of the drug can be removed by hemodialysis or peritoneal dialysis.

Drug Interactions

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and prolongs the half-life of theophylline (and other xanthines, e.g., caffeine), oral hypoglycemic drugs, indirect anticoagulants, and contributes to a decrease in the prothrombin index.

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 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.

It enhances the nephrotoxic effect of cyclosporine, an increase in serum creatinine is noted; in such patients, monitoring of this indicator twice a week is necessary.

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

Oral administration together with iron-containing drugs, sucralfate, and antacid drugs containing magnesium, calcium, and aluminum salts leads to a decrease in the absorption of ciprofloxacin, so it should be administered 1-2 hours before or 4 hours after taking the above drugs.

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

Fluoroquinolones form chelate compounds with magnesium and aluminum ions of the didanosine drug form buffer system, which sharply reduces the absorption of antibiotics, so Ciprofloxacin is taken 2 hours before taking didanosine or 2 hours after taking the specified drug.

Metoclopramide accelerates absorption, leading to a reduction in the time to reach its maximum concentration.

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

It increases the maximum concentration of tizanidine by 7 times (from 4 to 21 times) and the area under the concentration-time curve by 10 times (from 6 to 24 times), which increases the risk of pronounced arterial hypotension and drowsiness.

Storage Conditions

In a dry place protected from light at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

The shelf life is 2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.