Ciprobid (Tablets, Solution) 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 antimicrobial agent, a fluoroquinolone derivative, inhibits bacterial DNA gyrase, 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. Ciprofloxacin acts on both multiplying microorganisms and those in the resting phase.

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., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae; gram-positive aerobic bacteria Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Both in vitro and according to in vivo study data, Bacillus anthracis is also sensitive to ciprofloxacin.

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. It is not effective against Treponema pallidum.

Pharmacokinetics

When taken orally, Ciprofloxacin is rapidly absorbed from the gastrointestinal tract. The bioavailability of the drug is 50-85%. C_max of the drug in the blood serum of healthy volunteers after oral administration (before meals) of 250, 500, 750 and 1000 mg of the drug is achieved after 1-1.5 hours and is 1.2, 2.4, 4.3 and 5.4 µg/ml, respectively.

Orally administered Ciprofloxacin is distributed in body tissues and fluids. High concentrations of the drug are achieved in bile, lungs, kidneys, liver, gallbladder, uterus, seminal fluid, prostate tissue, tonsils, endometrium, fallopian tubes and ovaries. The concentration of the drug in these tissues is higher than in serum. Ciprofloxacin also penetrates well into bones, ocular fluid, bronchial secretions, saliva, skin, muscles, pleura, peritoneum, and lymph.

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

V_d in the body is 2-3.5 l/kg. The drug penetrates into the cerebrospinal fluid in small amounts, where its concentration is 6-10% of that in serum.

The degree of binding of ciprofloxacin to plasma proteins is 30%.

In patients with unchanged renal function, T_1/2 is usually 3-5 hours. In case of impaired renal function, T_1/2 increases.

The main route of elimination of ciprofloxacin from the body is the kidneys. 50-70% is excreted by the kidneys. From 15 to 30% is excreted 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.

Patients with severe renal failure (creatinine clearance below 20 ml/min/1.73 m²) should be prescribed half the daily dose of the drug.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms

• Respiratory tract diseases (bronchitis, pneumonia, bronchiectasis, cystic fibrosis);
• Infections of the ENT organs (otitis media, sinusitis);
• Infections of the kidneys and urinary tract (cystitis, pyelonephritis);
• Infections of the pelvic organs and genital organs (prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubal abscess, gonorrhea, chancroid);
• Infections of the digestive system (including the mouth, teeth, jaws); gallbladder and biliary tract;
• Infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
• Infections of bones and joints;
• Prevention and treatment of infections in patients with reduced immunity (during therapy with immunosuppressants), as well as prevention and treatment of the pulmonary form of anthrax (infection with Bacillus anthracis).

Use in pediatrics

• Therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs aged 5 to 17 years;
• Prevention and treatment of the pulmonary form of anthrax.

ICD codes

Dosage Regimen

Tablets

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

• uncomplicated diseases 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 treatment of gonorrhea, a single dose of ciprofloxacin 250-500 mg is recommended;
• gynecological diseases, enteritis and colitis with severe course and high fever, prostatitis – 500 mg 2 times a day (for the treatment of common diarrhea, it can be used at a dose of 250 mg 2 times a day);
• infections of bones and joints – 750 mg 2 times a day.

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

For treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs aged 5 to 17 years, the recommended dose of ciprofloxacin is 20 mg/kg body weight 2 times a day (maximum dose 1500 mg). The duration of treatment is 10-14 days.

Prevention and treatment of the pulmonary form of anthraxadults – 500 mg 2 times a day; children (5-17 years) – 15 mg/kg body weight 2 times a day, the maximum single dose should not exceed 500 mg and the daily dose should not exceed 1000 mg. Taking the drug should be started immediately after suspected and confirmed infection. The total duration of ciprofloxacin administration for the pulmonary form of anthrax is 60 days.

Patients with impaired renal function should have their dosage regimen adjusted.

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

Solution

For adults with uncomplicated infections, 125-500 mg is prescribed orally 2 times/day; for complicated infections – 250-500 mg 2 times/day. In more severe cases, it is possible to increase the dose to 750 mg 2 times/day.

The course of treatment averages 5-15 days. Treatment should be continued until the signs of the disease disappear and for the next 2-3 days.

For intravenous administration, a single dose 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 averages 1-2 weeks, longer if necessary. The drug can be administered intravenously as a bolus, but drip infusion over 30 minutes (for a dose of 200 mg) and 60 minutes (for a dose of 400 mg) is recommended.

For acute gonorrhea, 100 mg is administered intravenously.

For prevention of postoperative infectious complications, 200-400 mg is administered intravenously 30-60 minutes before surgery.

Elderly patients are prescribed the drug in lower doses (depending on the severity of the disease).

Patients with impaired renal function are initially prescribed the drug in average therapeutic doses, then they are reduced taking into account creatinine clearance values.

Adverse Reactions

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

From the nervous system dizziness, headache, increased fatigue, anxiety, tremor, insomnia, “nightmare” dreams, peripheral ataralgesia (abnormality in pain perception), 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 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, increased activity of “liver” 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.

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

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 and larynx, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative multiforme erythema, Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell’s syndrome).

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

Contraindications

• Concomitant use of tizanidine (risk of pronounced decrease in blood pressure, drowsiness);
• Pregnancy;
• Lactation period;
• Childhood and adolescence up to 18 years (until the completion of the skeletal formation process), except for cases of therapy for complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs aged 5 to 17 years; prevention and treatment of the pulmonary form of anthrax;
• Pseudomembranous colitis;
• Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolone group.

With caution severe cerebral atherosclerosis, cerebrovascular accident, mental illness, epileptic syndrome, epilepsy, severe renal and/or hepatic insufficiency, elderly age.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation period.

Use in Hepatic Impairment

Use with caution in severe hepatic insufficiency.

Use in Renal Impairment

For patients with chronic renal failure and impaired renal function, dose adjustment is necessary (see dosage regimen).

Pediatric Use

Contraindicated in childhood and adolescence up to 18 years (until the completion of the skeletal formation process), except for cases of therapy for complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs aged 5 to 17 years.

Use for the prevention and treatment of the pulmonary form of anthrax is permitted.

Geriatric Use

Use with caution in elderly age.

Special Precautions

For 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 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 due to the fact that isolated cases of inflammation and even tendon rupture have been described during treatment with fluoroquinolones.

During treatment with ciprofloxacin, it is necessary to ensure sufficient fluid intake while maintaining normal diuresis.

During treatment with ciprofloxacin, UV radiation should be avoided.

Effect on the ability to drive vehicles and mechanisms

Patients taking Ciprofloxacin should exercise caution when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Overdose

Reversible toxic effects on the kidneys have been noted. A 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

When ciprofloxacin is used concomitantly with didanosine, the absorption of ciprofloxacin is reduced due to the formation of complexes between ciprofloxacin and the aluminum and magnesium salts contained in didanosine.

Concomitant administration of ciprofloxacin with theophylline or oral hypoglycemic agents may lead to an increase in their plasma concentration due to competitive inhibition at cytochrome P450 binding sites, which leads to an increase in the half-life of these drugs and an increased risk of toxic effects.

When combined with other antimicrobial agents (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.

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

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

Concomitant administration 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 plasma concentration of tizanidine by 7 times (from 4 to 21 times), which increases the risk of pronounced hypotension and drowsiness.

Concomitant intake of antacids, as well as drugs containing aluminum, zinc, iron or magnesium ions, may cause a decrease in the absorption of ciprofloxacin, so the interval between the administration of these drugs should be at least 4 hours.

When ciprofloxacin and anticoagulants are used concomitantly, bleeding time is prolonged.

When ciprofloxacin and cyclosporine are used concomitantly, the nephrotoxic effect of the latter is enhanced.

Storage Conditions

List B. At a temperature not exceeding 30°C (86°F). Keep out of reach of children.

Shelf Life

Shelf life – 3 years.

Dispensing Status

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.