Ificipro^® (Solution) Instructions for Use

Marketing Authorization Holder

Unique Pharmaceutical Laboratories (India)

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Dosage Form

Ificipro®

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

Dosage Form, Packaging, and Composition

Solution for infusion transparent, from colorless to light yellow.

Excipients: disodium edetate – 0.05 mg, sodium hydroxide – 0.2 mg, sodium chloride – 8.641 mg, lactic acid (88% purity) – 0.727 mg (equivalent to lactic acid 100% purity – 0.64 mg), water for injections – q.s. to 1 ml.

100 ml – low-density polyethylene bottles (1) – cellophane wrappers (1) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

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

Sensitive to ciprofloxacin are 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.), 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.

Also sensitive to ciprofloxacin are gram-positive aerobic bacteria: 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 bacteria Streptococcus pneumoniae, Enterococcus faecalis is moderate.

Resistant to the drug are: 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, C_max is reached within 60 min and is 2.1 µg/ml and 4.6 µg/ml, respectively. V_d – 2-3 l/kg, plasma protein binding – 20-40%.

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, 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 the cerebrospinal fluid in small amounts, where its concentration with non-inflamed meninges is 6-10% of that in the blood serum, and with inflamed meninges – 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 somewhat at acidic pH values. It is metabolized in the liver (15-30%) to form low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

With IV administration T _1/2 – 5-6 h, in chronic renal failure – up to 12 h. It is excreted mainly by the kidneys through tubular filtration and tubular secretion unchanged (with IV administration – 50-70%) and in the form of metabolites (with IV administration – 10%), the rest – 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 – 3-5 ml/min/kg; total clearance – 8-10 ml/min/kg. In chronic renal failure (creatinine clearance more than 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) should be prescribed half the daily dose.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to ciprofloxacin

• Respiratory tract;
• Ear, throat and nose: otitis media, sinusitis, frontal sinusitis, sinusitis, mastoiditis, tonsillitis, pharyngitis;
• Kidneys and urinary tract: cystitis, pyelonephritis;
• Genital organs: prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubo-ovarian abscess, pelvic peritonitis, gonorrhea, chancroid, chlamydia;
• Digestive system (including mouth, teeth, jaws); gallbladder and biliary tract: peritonitis, intra-abdominal abscesses, salmonellosis, typhoid fever, campylobacteriosis, yersiniosis, shigellosis, cholera;
• Skin, mucous membranes and soft tissues: infected ulcers, wounds, burns, abscesses, phlegmon;
• Musculoskeletal system: osteomyelitis, septic arthritis;

Prevention of infections during surgical interventions.

Ciprofloxacin is indicated for the treatment of sepsis and peritonitis, as well as for the prevention and treatment of infections in patients with reduced immunity (during therapy with immunosuppressants).

ICD codes

Dosage Regimen

Administered intravenously.

The drug should be administered by IV drip over 30 minutes (200 mg) and 60 minutes (400 mg). The infusion solution can be combined 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 ciprofloxacin depends on the severity of the disease, type of infection, body condition, age, weight, and renal function of the patient. Recommended usual doses

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

For acute gonorrhea – a single IV dose of 100 mg.

For prevention of postoperative infections – 30-60 minutes before surgery IV 200-400 mg.

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 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, cardiac arrhythmias, 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 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, 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).

Other: arthralgia, arthritis, tenosynovitis, tendon ruptures, general weakness, myalgia, superinfections (candidiasis, pseudomembranous colitis), pain and burning at the injection site, phlebitis.

Contraindications

• Pseudomembranous colitis;
• Childhood (up to 18 years – until the completion of the skeletal formation process);
• Pregnancy;
• Lactation period;
• Hypersensitivity.

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

Use in Pregnancy and Lactation

Contraindicated.

Use in Hepatic Impairment

With caution – severe hepatic insufficiency.

Use in Renal Impairment

With caution – severe renal insufficiency.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

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 tendon pain occurs or at the first signs of tenosynovitis, treatment should be discontinued.

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

During treatment with ciprofloxacin, contact with direct sunlight should be avoided.

Effect on the ability to drive vehicles and mechanisms

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

Overdose

There is no specific antidote. It is necessary to carefully monitor the patient’s condition, perform gastric lavage, carry out conventional emergency measures, and ensure adequate 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 T_1/2 of theophylline (and other xanthines, e.g., caffeine), oral hypoglycemic drugs, and indirect anticoagulants, and contributes to a decrease in the prothrombin index. NSAIDs (excluding acetylsalicylic acid) increase the risk of seizures.

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

Concomitant administration of uricosuric drugs leads to a slowdown 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), synergy 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 twice a week.

When taken simultaneously, 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).

Do not mix the solution for intravenous administration with solutions having a pH greater than 7.

Storage Conditions

List B. Store at a temperature not exceeding 30°C (86°F) in a place protected from light and out of the reach of children. Do not freeze.

Shelf Life

The shelf life is 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.