Bacigen (Solution) Instructions for Use

Marketing Authorization Holder

Otsuka Pharmaceutical India, Private Limited (India)

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin

Dosage Form

Bacigen

Solution for infusion 2 mg/1 ml: bottle 100 ml 1 pc.

Dosage Form, Packaging, and Composition

100 ml – bottles (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

A broad-spectrum antimicrobial agent, a quinolone derivative, it 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 both the resting and division phases (as it affects not only DNA gyrase but also causes lysis of the cell wall), while it acts on gram-positive microorganisms only during the division phase.

Low toxicity to 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, and tetracyclines.

The following are sensitive to ciprofloxacin: gram-negative aerobic bacteria 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;

gram-positive aerobic bacteria: 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 ineffective 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 lack enzymes that inactivate it.

Pharmacokinetics

After IV infusion of 200 mg, the time to reach C_max is 60 min, C_max is 2.1 µg/ml, plasma protein binding is 20-40%. It is well distributed in body tissues. 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 secretions, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, and 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 plasma, and in the presence of inflammation, it is 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 plasma.

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

T_1/2 is 5-6 hours, in chronic renal failure – up to 12 hours. It is excreted mainly by the kidneys via tubular filtration and tubular secretion unchanged (50-70%) and as metabolites (10%), the remainder is excreted via 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 plasma, which significantly exceeds the minimum inhibitory concentration (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 (CrCl) 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.

Indications

Bacterial infections caused by microorganisms sensitive to ciprofloxacin

• Diseases of the lower respiratory tract (exacerbation of chronic bronchitis, pneumonia, bronchiectasis, infectious complications of cystic fibrosis);
• Infections of the ENT organs (acute sinusitis);
• Kidney and urinary tract infections (cystitis, pyelonephritis);
• Complicated intra-abdominal infections (in combination with metronidazole), including peritonitis;
• Chronic bacterial prostatitis;
• Uncomplicated gonorrhea;
• Typhoid fever;
• Infectious diarrhea (including campylobacteriosis, shigellosis, traveler’s diarrhea);
• Skin and soft tissue infections (infected ulcers, wounds, burns, abscesses, phlegmon);
• Bone and joint infections (osteomyelitis, septic arthritis);
• Septicemia;
• 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. Prevention of infections during surgical interventions.

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

The solution for infusion is administered intravenously by drip. The duration of IV infusion of 200 mg (100 ml of infusion solution) should be at least 30 minutes. Ready-to-use infusion solutions can be mixed with 0.9% sodium chloride solution, Ringer’s and Ringer-lactate solution, 5% and 10% dextrose solution, 10% fructose solution, as well as a solution containing 5% dextrose solution with 0.225-0.45% sodium chloride solution.

For lower respiratory tract infections – 200-400 mg 2 times a day.

For urinary tract infections: acute uncomplicated – 100 mg 2 times a day; cystitis in women (premenopausal) – 100 mg as a single dose; complicated – 200 mg 2 times a day.

For uncomplicated gonorrhea – 100 mg as a single dose, for extragenital – 100 mg 2 times a day.

Infectious diarrhea – 200 mg 2 times a day, course of treatment – 5-7 days.

Particularly severe infections (streptococcal pneumonia, infectious complications of cystic fibrosis, bone and joint infections, septicemia, peritonitis), especially those caused by Pseudomonas, Staphylococcus – 400 mg 3 times a day.

Pulmonary form of anthrax (treatment and prevention) – 400 mg 2 times a day.

For the prevention of infections during surgical interventions — 200-400 mg 0.5-1 hour before surgery; if the operation lasts more than 4 hours, it is administered again at the same dose.

For other infections (depending on severity) – 200-400 mg 2 times a day.

Elderly patients are prescribed lower doses depending on the severity of the infection and the CrCl value.

In pediatrics

For the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years – 10 mg/kg 3 times a day (maximum dose 1200 mg). Duration of treatment – 10-14 days.

For the pulmonary form of anthrax (prevention and treatment) – 10 mg/kg 2 times a day. Maximum single dose – 400 mg, daily – 800 mg. The total duration of ciprofloxacin administration is 60 days.

Use in patients with chronic renal failure

With glomerular filtration rate (CrCl 31-60 ml/min/1.73 sq.m or plasma creatinine concentration from 1.4 to 1.9 mg/100 ml) the maximum daily dose is 800 mg. With glomerular filtration rate (CrCl below 30 ml/min/1.73 sq.m or plasma creatinine concentration above 2 mg/100 ml) and during hemodialysis, the maximum daily dose is 400 mg; during hemodialysis, Ciprofloxacin is administered after the hemodialysis session. During peritoneal dialysis, the infusion solution is added to the dialysate (intraperitoneally) at a dose of 50 mg per 1 liter of dialysate 4 times a day (every 6 hours).

Average course of treatment: 1 day – for acute uncomplicated gonorrhea and cystitis; up to 7 days – for kidney, urinary tract, and abdominal infections; throughout the neutropenic phase in patients with weakened defenses, but not more than 2 months – for osteomyelitis and 7-14 days – for all other infections. For streptococcal infections, due to the risk of late complications, treatment should last at least 10 days.

Treatment should be continued for at least 3 days after normalization of body temperature or disappearance of clinical symptoms.

After IV use, treatment can be continued orally.

Adverse Reactions

From the digestive system nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite, cholestatic jaundice (especially in patients with a history of liver disease), hepatitis, hepatonecrosis.

From the nervous system dizziness, headache, increased fatigue, anxiety, tremor, insomnia, “nightmare” dreams, peripheral paralgesia (abnormality in pain perception), increased intracranial pressure, 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, cardiac arrhythmias, decreased blood pressure.

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

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

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

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

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

Local reactions: phlebitis, pain at the injection site.

Other asthenia, superinfections (candidiasis, pseudomembranous colitis), increased sweating, facial “flushing”, increased photosensitivity.

Contraindications

Hypersensitivity to ciprofloxacin, any other component of the drug, or other drugs from the fluoroquinolone group, simultaneous administration with tizanidine (risk of pronounced decrease in blood pressure, drowsiness), children and adolescents under 18 years of age (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). With caution: severe cerebral atherosclerosis, cerebrovascular accident, mental illness, epilepsy, severe renal and/or hepatic insufficiency, elderly age, tendon damage during previous treatment with quinolones.

Use in Pregnancy and Lactation

Contraindicated: pregnancy, lactation period.

Use in Hepatic Impairment

Use with caution: severe hepatic insufficiency.

Use in Renal Impairment

Use with caution: severe renal insufficiency.

Pediatric Use

Contraindicated: children and adolescents under 18 years of age (except for the therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis from 5 to 17 years of age).

Geriatric Use

Use with caution: elderly age. Elderly patients are prescribed lower doses depending on the severity of the infection and the creatinine clearance value.

Special Precautions

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

With simultaneous intravenous administration of ciprofloxacin and drugs for general anesthesia from the group of barbituric acid derivatives, constant monitoring of heart rate, blood pressure, and electrocardiogram is necessary. To avoid the development of crystalluria, exceeding the recommended daily dose is unacceptable; sufficient fluid intake and maintenance of acidic urine reaction are also necessary.

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, 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 or the first signs of tendovaginitis appear, treatment should be discontinued (isolated cases of inflammation and even rupture of tendons during treatment with fluoroquinolones have been described).

During the treatment period, contact with direct sunlight and artificial UV radiation should be avoided.

Effect on the ability to drive vehicles and mechanisms. Patients taking Ciprofloxacin should refrain from driving cars and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Overdose

Treatment: specific antidote is unknown. It is necessary to carefully monitor the patient’s condition, take other emergency measures, and ensure sufficient fluid intake. Hemodialysis or peritoneal dialysis can remove only a small amount (less than 10%) of the drug.

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 (enhancing their effect), 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 concentration is noted; in such patients, it is necessary to monitor this indicator twice a week.

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

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

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physically and chemically unstable in an acidic environment (pH of the ciprofloxacin infusion solution is 3.5-4.6). The solution for intravenous administration should not be mixed with solutions having a pH greater than 7.

Storage Conditions

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

Shelf Life

Shelf life. 3 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.