Ciprolet^® (Tablets, Solution, Drops) 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

Broad-spectrum antibacterial drug from the fluoroquinolone group. It acts bactericidally. The drug inhibits the enzyme DNA gyrase of bacteria, resulting in disruption of DNA replication and synthesis of bacterial cellular proteins. Ciprofloxacin acts on both multiplying microorganisms and those in the resting phase.

The following gram-negative aerobic bacteria are sensitive to ciprofloxacin: Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafhia 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. (S.aureus, S.haemolyticus, S.hominis, S.saprophyticus), Streptococcus spp. (St. pyogenes, St.agalactiae). Most staphylococci resistant to methicillin are also resistant to ciprofloxacin.

The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis is moderate.

The following are resistant to the drug: Corynebacterium spp., Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. The effect of the drug on Treponema pallidum has not been sufficiently studied.

Pharmacokinetics

After IV infusion of 200 mg or 400 mg, T_max is 60 min, C_max is 2.1 µg/ml and 4.6 µg/ml, respectively. V_d is 2-3 L/kg, plasma protein binding is 20-40%.

It is well distributed in body tissues (excluding fat-rich tissue, such as nervous tissue). The 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 organs, lung tissue, bronchial secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. It penetrates into the CSF in small amounts, where its concentration with non-inflamed meninges is 6-10% of that in the blood serum, and with inflamed meninges it is 14-37%. Ciprofloxacin also penetrates well into the ocular fluid, bronchial secretions, pleura, peritoneum, lymph, and through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

Activity decreases slightly at acidic pH values.

It is metabolized in the liver (15-30%) to form low-active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

When administered IV, T_1/2 is 5-6 hours, in chronic renal failure – up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion unchanged (with IV administration – 50-70%) and in the form of metabolites (with IV administration – 10%), the rest is through the gastrointestinal tract. A small amount is excreted in breast milk. After IV administration, the concentration in urine during the first 2 hours after administration is almost 100 times greater than in serum, which significantly exceeds the MIC for most urinary tract infection pathogens.

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 through the kidneys decreases, but accumulation in the body does not occur due to a compensatory increase in drug metabolism and excretion in feces. Patients with severe renal failure (creatinine clearance below 20 ml/min/1.73 m²) should be prescribed half the daily dose.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to ciprofloxacin, including:

• Respiratory tract infections;
• ENT organ infections;
• Kidney and urinary tract infections;
• Genital infections (gonorrhea, prostatitis, adnexitis) and postpartum infections;
• Gastrointestinal tract infections (including mouth, teeth, jaws);
• Gallbladder and biliary tract infections;
• Skin, mucous membranes and soft tissue infections;
• Musculoskeletal system infections;
• Sepsis;
• Peritonitis.

Prevention and treatment of infections in patients with reduced immunity (during therapy with immunosuppressants).

ICD codes

Dosage Regimen

Tablets

The dose of Ciprolet^® depends on the severity of the disease, type of infection, body condition, age, body weight and kidney function.

For uncomplicated kidney and urinary tract diseases, 250 mg 2 times/day is prescribed, and in severe cases – 500 mg 2 times/day.

For moderately severe lower respiratory tract diseases – 250 mg 2 times/day, and in more severe cases – 500 mg 2 times/day.

For treatment of gonorrhea, a single dose of Ciprolet^® at a dose of 250-500 mg is recommended.

For gynecological diseases, enteritis and colitis with severe course and high fever, prostatitis, osteomyelitis, 500 mg 2 times/day is prescribed (for treatment of common diarrhea, it can be used at a dose of 250 mg 2 times/day).

The tablets should be taken on an empty stomach, with a sufficient amount of liquid.

The duration of treatment depends on the severity of the disease, but treatment should always continue for at least another 2 days after the symptoms of the disease have disappeared. Usually the duration of treatment is 7-10 days.

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

Table of recommended doses of the drug for patients with chronic renal failure

Solution

The drug should be administered intravenously by drip over 30 minutes (200 mg) and 60 minutes (400 mg). The infusion solution is compatible with 0.9% sodium chloride solution, Ringer’s solution, 5% and 10% dextrose solution, 10% fructose solution, as well as a solution containing 5% dextrose solution with 0.225% or 0.45% sodium chloride solution.

The dose of Ciprolet^® depends on the severity of the disease, type of infection, body condition, age, body weight and kidney function of the patient.

A single dose, on average, is 200 mg (for severe infections – 400 mg), frequency of administration is 2 times/day. The duration of treatment depends on the severity of the disease and is 1-2 weeks; if necessary, longer administration of the drug is possible.

For acute gonorrhea, the drug is prescribed intravenously as a single dose of 100 mg.

For prevention of postoperative infections, it is administered intravenously 30-60 minutes before surgery at a dose of 200-400 mg.

Drops

Apply topically.

For mild and moderately severe infection, instill 1-2 drops into the conjunctival sac of the affected eye every 4 hours, for severe infection – 2 drops every hour. After the condition improves, the dose and frequency of instillations are reduced.

For bacterial corneal ulcer, 1 drop every 15 minutes for 6 hours is prescribed, then 1 drop every 30 minutes during waking hours; on the 2nd day – 1 drop every hour during waking hours; from the 3rd to the 14th day – 1 drop every 4 hours during waking hours. If after 14 days of therapy epithelialization has not occurred, treatment can be continued.

Adverse Reactions

From the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, anorexia, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis, increased activity of hepatic transaminases and alkaline phosphatase.

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

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

From the cardiovascular system: tachycardia, heart rhythm disturbances, decreased blood pressure, flushing of the skin of the face.

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

From laboratory parameters: hypoprothrombinemia, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

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

Allergic reactions: skin itching, urticaria, formation of blisters accompanied by bleeding and small nodules forming scabs, drug fever, pinpoint hemorrhages (petechiae), swelling of the face or larynx, shortness of breath, eosinophilia, increased photosensitivity, 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, superinfections (candidiasis, pseudomembranous colitis).

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

Contraindications

• Pseudomembranous colitis;
• Glucose-6-phosphate dehydrogenase deficiency;
• Pregnancy;
• Lactation period (breastfeeding);
• Childhood and adolescence up to 18 years (until the completion of the skeletal formation process);
• Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolone group.

The drug should be prescribed with caution in cases of severe cerebral atherosclerosis, cerebrovascular accident, mental illness, convulsive syndrome, epilepsy, severe renal and/or hepatic insufficiency, as well as to elderly patients.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation.

Special Precautions

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

If pain in the tendons occurs or at the first signs of tenosynovitis, treatment should be discontinued.

During treatment with Ciprolet^®, it is necessary to ensure a sufficient amount of fluid while maintaining normal diuresis.

During treatment with Ciprolet^®, contact with direct sunlight should be avoided.

Effect on ability to drive vehicles and mechanisms

Patients taking Ciprolet^® should exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions (especially when consuming alcohol simultaneously).

Overdose

Treatment: specific antidote is unknown. 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 T_1/2 of theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and contributes to a decrease in the prothrombin index.

NSAIDs (excluding acetylsalicylic acid) increase the risk of seizures.

Metoclopramide accelerates the absorption of ciprofloxacin, leading to a reduction in the time to reach its C_max.

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

When combined with other antimicrobial drugs ( beta-lactams, 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, therefore, in such patients, it is necessary to monitor this indicator 2 times a week.

With simultaneous administration, it enhances the effect of indirect anticoagulants.

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 3.5-4.6). The solution for intravenous administration must not be mixed with solutions having a pH greater than 7.

Storage Conditions

List B. The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature up to 25°C (77°F); do not freeze.

Shelf Life

The shelf life is 3 years.

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.