Ciprofloxacin Ecocifol® tablets 500 mg

Instructions for use of Ciprofloxacin Ecocifol® tablets 500 mg

Brand name: Ciprofloxacin ECOcifol

International Nonproprietary Name

Ciprofloxacin

Dosage Form

Film-coated tablets 250 mg and 500 mg.

Composition

One tablet contains

Active substance: ciprofloxacin hydrochloride monohydrate (equivalent to ciprofloxacin) 250 mg or 500 mg

Excipients: low molecular weight povidone, croscarmellose sodium, microcrystalline cellulose, magnesium stearate, corn starch,

Coating composition: hypromellose, macrogol-4000, talc, titanium dioxide (E171).

Description

Capsule-shaped tablets with a biconvex surface, coated with a white or almost white film coating. The cross-section is white.

Pharmacotherapeutic Group

Antimicrobials for systemic use - quinolone derivatives. Fluoroquinolones.

ATC Code J01MA02

Pharmacological Properties

Pharmacokinetics

After oral administration, it is rapidly and sufficiently completely absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Food intake slows absorption but does not change the maximum concentration (Cmax) or 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 minutes; the maximum concentration depends linearly on the administered dose and is 1.2, 2.4, 4.3, and 5.4 µg/ml for doses of 250, 500, 750, and 1000 mg, respectively. Twelve hours after oral administration of 250, 500, and 750 mg, the plasma concentration decreases to 0.1, 0.2, and 0.4 µg/ml, respectively.

It is well distributed in body tissues (excluding fat-rich tissue such as nervous tissue). Tissue concentrations are 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 tract, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, and skin. It penetrates the cerebrospinal fluid in small amounts, where its concentration in the absence of meningeal inflammation is 6-10% of that in serum, and 14-37% with inflamed meninges. Ciprofloxacin also penetrates well into ocular fluid, 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%) to form low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

The half-life is about 4 hours; in chronic renal failure, up to 12 hours. It is excreted mainly by the kidneys via tubular filtration and tubular secretion unchanged (40-50%) and as metabolites (15%); the remainder is excreted via 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 the drug excreted by the kidneys decreases, but no accumulation occurs in the body due to a compensatory increase in drug metabolism and excretion via the gastrointestinal tract.

Pharmacodynamics

A broad-spectrum antimicrobial agent, a quinolone derivative. It inhibits 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, growth, and division of bacteria; causes significant morphological changes (including in the cell wall and membranes) and rapid death of the bacterial cell.

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

Low toxicity to macroorganism cells is explained by the absence of DNA gyrase in them. During ciprofloxacin administration, parallel development of resistance to antibacterial drugs not belonging to the gyrase inhibitor group does not occur, making it effective against bacteria resistant, for example, to aminoglycosides, penicillins, cephalosporins, and tetracyclines.

Microorganisms sensitive to ciprofloxacin include:

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., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.

Gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Active against Bacillus anthracis.

Most staphylococci resistant to methicillin are also resistant to ciprofloxacin. Sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for suppression).

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 because, on the one hand, there are practically no persisting microorganisms left after ciprofloxacin action, and on the other hand, bacterial cells lack enzymes that inactivate it.

Indications for Use

Infectious-inflammatory diseases caused by susceptible microorganisms: Lower respiratory tract infections (acute bronchitis and chronic bronchitis exacerbation, pneumonia, bronchiectasis, infectious complications of cystic fibrosis); ENT infections (acute sinusitis); Kidney and urinary tract infections (cystitis, pyelonephritis); Complicated intra-abdominal infections (in combination with metronidazole); Chronic bacterial prostatitis; Uncomplicated gonorrhea; Typhoid fever, campylobacteriosis, shigellosis, traveler's diarrhea; Skin and soft tissue infections (infected ulcers, wounds, burns, abscesses, phlegmon); Bone and joint infections (osteomyelitis, septic arthritis); Infections in immunocompromised states (occurring during treatment with immunosuppressive drugs or in patients with neutropenia); Prevention and treatment of pulmonary anthrax;

Children: Prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis) from 6 years of age.

Dosage and Administration

Orally. Tablets should be swallowed whole with a small amount of liquid after meals. Taking the tablet on an empty stomach accelerates the absorption of the active substance.

• Lower respiratory tract infections (mild to moderate): 0.5 g twice daily. Severe: 0.75 g twice daily. Course: 7-14 days.
• Acute sinusitis: 0.5 g twice daily. Course: 10 days.
• Skin and soft tissue infections (mild to moderate): 0.5 g twice daily. Severe: 0.75 g twice daily. Course: 7-14 days.
• Bone and joint infections (mild to moderate): 0.5 g twice daily. Severe: 0.75 g twice daily. Course: up to 4-6 weeks.
• Uncomplicated urinary tract infections: 0.25-0.5 g twice daily. Course: 7-14 days. Complicated urinary tract infections: 0.5 g every 12 hours for 7-14 days.
• Chronic prostatitis: 0.5 g twice daily. Course: 28 days.
• Uncomplicated gonorrhea: 0.25 g as a single dose.
• Acute severe intestinal infections (salmonellosis, shigellosis, campylobacteriosis, etc.): 0.5 g twice daily. Course: 5-7 days.
• Typhoid fever: 0.5 g twice daily. Course: 10 days.
• Complicated intra-abdominal infections: 0.5 g every 12 hours for 7-14 days.
• Prevention and treatment of pulmonary anthrax: 0.5 g twice daily for 60 days.
• Immunocompromised patients: Treatment is prescribed depending on the severity of the infection and the type of pathogen. Therapy is conducted throughout the period of neutropenia.
• Chronic renal failure: Creatinine clearance (CrCl) > 50 ml/min: no dose adjustment; CrCl 30-50 ml/min: 0.25-0.5 g every 12 hours; CrCl 5-29 ml/min: 0.25-0.5 g every 18 hours. Patients on hemodialysis or peritoneal dialysis: 0.25-0.5 g per day; the drug should be taken after the dialysis session.
• Pediatrics: Pulmonary anthrax (prevention and treatment): 15 mg/kg twice daily. Maximum single dose: 0.5 g, daily dose: 1 g. Total duration of ciprofloxacin administration: 60 days.

Side Effects

Anorexia, nausea, vomiting, abdominal pain, flatulence, diarrhea, cholestatic jaundice (especially in patients with previous liver disease), hepatitis, hepatonecrosis; dizziness, headache, increased fatigue, anxiety, tremor, insomnia, "nightmare" dreams, peripheral paralgesia (abnormal pain perception), sweating, increased intracranial pressure, confusion, depression, hallucinations, and other manifestations of psychotic reactions (occasionally progressing to states where the patient may self-harm).

Rarely: migraine, syncope, cerebral artery thrombosis; taste and smell disturbances, visual disturbances (diplopia, color vision changes), tinnitus, hearing loss; tachycardia, cardiac arrhythmias, QT interval prolongation, decreased blood pressure; leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia; hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia; hematuria, crystalluria (primarily with alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen excretion, interstitial nephritis; skin itching, urticaria, blistering accompanied by bleeding and appearance of small nodules forming scabs, drug fever, skin petechiae, facial or laryngeal edema, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative multiforme erythema, Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome); arthralgia, arthritis, tenosynovitis, tendon ruptures, myalgia; general weakness, increased photosensitivity, superinfections (candidiasis, pseudomembranous colitis), facial flushing.

Contraindications

Hypersensitivity to ciprofloxacin, other fluoroquinolones, or excipients of the drug; concurrent use with tizanidine (risk of pronounced hypotension, drowsiness); children and adolescents under 18 years (until the skeleton formation process is complete), prevention and treatment of pulmonary anthrax – children under 6 years; pregnancy and lactation; tendon disorders associated with previous treatment with fluoroquinolones; tendon disorders, including tenosynovitis, tendon rupture, muscle disorders (rhabdomyolysis); pseudomembranous colitis.

Drug Interactions

Due to reduced activity of microsomal oxidation in hepatocytes, it increases the concentration and prolongs the half-life of theophylline (and other xanthines, e.g., caffeine), oral hypoglycemic agents, indirect anticoagulants.

Combination with other antimicrobial agents (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) usually shows synergism. Can be successfully combined 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.

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

During concurrent administration, it enhances the effect of indirect anticoagulants and contributes to a decrease in the prothrombin index.

Oral administration with iron-containing drugs, sucralfate, and antacid drugs containing magnesium, calcium, and aluminum salts leads to reduced absorption of ciprofloxacin; therefore, it should be administered 1-2 hours before or 4 hours after taking the aforementioned drugs.

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

Fluoroquinolones form chelate complexes with magnesium and aluminum ions contained in the dosage form of didanosine, which sharply reduces the absorption of the fluoroquinolone; therefore, ciprofloxacin should be taken 2 hours before or 2 hours after taking didanosine.

Metoclopramide accelerates absorption, leading to a reduced time to reach its maximum plasma concentration.

Concurrent administration of uricosuric drugs leads to slowed excretion (up to 50%) and increased plasma concentration of ciprofloxacin.

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 hypotension and drowsiness.

Special Instructions

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

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

In patients with epilepsy, a history of seizures, vascular diseases, and organic brain lesions, due to the threat of central nervous system side effects, 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 discontinuation of the drug and appropriate treatment.

If tendon pain occurs or at the first signs of tenosynovitis, 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 exposure (including contact with direct sunlight).

Effect on ability to drive and operate machinery.

During treatment, refrain from potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Overdose

Symptoms: Reversible toxic effects on the kidneys have been noted.

Treatment: No specific antidote is known. Carefully monitor the patient's condition, perform gastric lavage, implement standard emergency measures, ensure adequate fluid intake. Only a small amount (less than 10%) of the drug can be removed by hemodialysis or peritoneal dialysis.

Dosage Form and Packaging

10 tablets of 250 mg or 5 tablets of 500 mg are placed in a blister pack made of polyvinyl chloride film and printed lacquered aluminum foil (PVC/Al) or soft aluminum foil and hard aluminum foil (Al/Al).

1 or 2 blister packs of 250 mg or 2 blister packs of 500 mg, together with the instructions for medical use in the state and Russian languages, are placed in a cardboard carton.

Storage Conditions

Store in a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf Life

2 years. Do not use after the expiration date printed on the packaging.

Pharmacy Supply Terms

By prescription.

Manufacturer

JSC "AVVA RUS", Russia

610044, Kirov, Luganskaya St., 53 A

Tel. (8332) 53-60-11,

(495) 956-75-54

www.avva-rus.ru

Name and Country of the Marketing Authorization Holder

JSC "AVVA RUS", Russia