Cifloxinal^® (Tablets) Instructions for Use

Marketing Authorization Holder

PRO.MED.CS Praha, a.s. (Czech Republic)

ATC Code

J01MA02 (Ciprofloxacin)

Active Substance

Ciprofloxacin (Rec.INN registered by WHO)

Dosage Form

Cifloxinal®

Film-coated tablets, 250 mg: 10 or 20 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex.

Excipients: microcrystalline cellulose, corn starch, magnesium stearate, colloidal silicon dioxide, crospovidone, hypromellose, titanium dioxide, macrogol 4000.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antibacterial drug of the fluoroquinolone group

Pharmacotherapeutic Group

Antimicrobial agent – fluoroquinolone

Pharmacological Action

An antibacterial drug of 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. It is highly active against most gram-negative aerobic bacteria enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabillis, Proteus vulgaris, Serratia marcescens, Hafnia alvci, Edwardsiela tarda, Providencia multocida, Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarralis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.).

Ciprofloxacin is active against some intracellular pathogens: Legionella pneumonia, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium-intracellulare.

Also, the following are sensitive to ciprofloxacin: gram-positive aerobic bacteria: Staphylococcus spp. (S. areus, S. haemolyticus, S. hominis, S. saprophyticus), Streptococcus spp. (St. pyogenes, St. agalactiae). Most staphylococci resistant to methicillin are resistant to ciprofloxacin.

The sensitivity of Streptococcus pneumoniae, Enlerococcus faecalis is moderate. Resistance to ciprofloxacin rarely develops.

Pharmacokinetics

After oral administration, Ciprofloxacin is rapidly absorbed from the gastrointestinal tract, mainly from the duodenum and jejunum. It has a good ability to penetrate into body tissues and fluids.

C_max in blood plasma is reached in 60-90 minutes, being about 4 mg/l after taking 1000 mg of the drug and 2 mg/l – 500 mg of the drug. The bioavailability of the drug is 70-80%. V_d at steady state is 2-3 l/kg, which is associated with slight binding of ciprofloxacin to plasma proteins (20-30%) and high diffusion of the non-ionized form of the drug into the extravascular space. In this regard, the concentration of ciprofloxacin in some body fluids and tissues may significantly exceed the corresponding level in the serum. T_1/2 is 3-5 hours.

About 10-15% of the administered dose is metabolized in the liver to form metabolites that also have antibacterial activity, but less pronounced. Ciprofloxacin is mainly excreted through the kidneys (about 45% unchanged and about 11% as metabolites). Approximately 20% of ciprofloxacin is excreted through the gastrointestinal tract unchanged and about 5-6% as metabolites. Renal clearance is 2-3 ml/min. It penetrates the blood-brain barrier and placenta. It is excreted in breast milk.

Indications

Treatment of infectious and inflammatory diseases caused by pathogens sensitive to the drug

• Respiratory tract infections (especially those caused by Klebsiella spp., Enterobacter spp., Proteus spp., Pseudomonas spp., Legionella spp., Staphylococcus spp, Escherichia coli);
• CNS infections (including purulent bacterial meningitis, meningococcal carriage);
• Middle ear and paranasal sinus infections;
• Eye infections;
• Kidney and urinary tract infections;
• Pelvic organ infections (including adnexitis and prostatitis);
• Gonorrhea;
• Gastrointestinal tract infections;
• Gallbladder and biliary tract infections;
• Skin and soft tissue infections;
• Bone and joint infections.

ICD codes

Dosage Regimen

The dose of ciprofloxacin is set individually depending on the severity of the disease, type of infection, body condition, as well as the sensitivity of the microorganism.

Usually recommended doses

Respiratory tract infections 250-500 mg 2 times/day.

Kidney and urinary tract infections 250 – 500 mg 2 times/day.

For treatment of gonorrhea a single dose of ciprofloxacin at a dose of 250- 500 mg.

Adnexitis, enteritis and colitis with severe course and high fever, prostatitis: 500 mg 2 times/day.

Treatment of common diarrhea 250 mg 2 times/day.

Other infections 500-750 mg 2 times/day.

The tablets should be swallowed whole, without chewing, with liquid. The duration of treatment depends on the severity of the disease. Treatment should be continued for at least 3 days after normalization of temperature and disappearance of disease symptoms. The usual course of treatment is from 7 to 14 days.

Patients with severe renal impairment the daily dose is reduced by half, elderly patients – by 1/3. Patients with chronic renal failure the dose of ciprofloxacin is set depending on creatinine clearance: 30-50 ml/min – 250-500 mg 2 times/day, 5-29 ml/min – 250-500 mg 1 time/day; patients on hemodialysis or peritoneal dialysis – 250-500 mg 1 time/day after dialysis.

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 CNS dizziness, headache, increased fatigue, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (abnormality of pain perception), sweating, increased intracranial pressure, confusion, depression, hallucinations (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, 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 the appearance of small nodules forming scabs, drug fever, pinpoint hemorrhages on the skin (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).

Contraindications

• Epilepsy;
• Viral keratitis;
• Pregnancy;
• Lactation period;
• Childhood and adolescence up to 18 years (until the completion of the skeletal formation process);
• Increased sensitivity to ciprofloxacin and other drugs of the quinolone series.

With caution in patients with a history of seizures, vascular diseases and organic brain lesions (due to the threat of developing side reactions from the CNS) Ciprofloxacin should be prescribed only if the intended benefit of therapy outweighs the potential risk of side effects.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Renal Impairment

Patients with severe renal impairment the daily dose is reduced by half. Patients with chronic renal failure the dose of ciprofloxacin is set depending on creatinine clearance: 30-50 ml/min – 250-500 mg 2 times/day, 5-29 ml/min – 250-500 mg 1 time/day; patients on hemodialysis or peritoneal dialysis – 250-500 mg 1 time/day after dialysis.

Pediatric Use

Contraindicated

• Childhood and adolescence up to 18 years (until the completion of the skeletal formation process).

Geriatric Use

Elderly patients the daily dose is reduced by 1/3.

Special Precautions

During the use of the drug, patients should receive a sufficient amount of fluid to prevent crystalluria.

If severe and prolonged diarrhea occurs during or after treatment, if pain in the tendons occurs, at the first signs of tenosynovitis, it is necessary to stop using the drug and consult a doctor.

During treatment with ciprofloxacin, it is necessary to ensure the intake of a sufficient amount of fluid; direct sunlight and UV radiation should be avoided.

Effect on 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.

Overdose

Symptoms: no specific symptoms.

Treatment: gastric lavage, use of emetic drugs, administration of a large amount of fluid, creation of an acidic urine reaction, additionally – hemodialysis and peritoneal dialysis; all measures are carried out against the background of maintaining vital functions.

Drug Interactions

Simultaneous administration with antacids containing aluminum hydroxide, magnesium hydroxide or calcium, as well as iron, bismuth and sucralfate preparations, cimetidine, ranitidine, vitamins with microelements, iron sulfate, zinc, didanosine, laxatives may cause a decrease in the absorption of ciprofloxacin, so the time interval between the administration of these drugs should be at least 4 hours.

The activity of ciprofloxacin increases when combined with beta-lactam antibiotics, aminoglycosides, vancomycin, clindamycin, metronidazole.

The combination of high doses of ciprofloxacin and theophylline may lead to an increase in the concentration of theophylline in the blood plasma due to competitive inhibition at the binding sites of cytochrome P450, which leads to an increase in T_1/2 of theophylline and an increased risk of developing toxic effects associated with theophylline.

With simultaneous use of ciprofloxacin and cyclosporine, the nephrotoxic effect of the latter is enhanced.

When interacting with very high doses of quinolones and some non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid), there is an increased risk of seizures.

Ciprofloxacin enhances the effect of warfarin and other anticoagulants (prolongs bleeding time).

Simultaneous use with drugs that block calcium secretion leads to an increase in the average T_1/2 of ciprofloxacin.

The likelihood of crystalluria increases with simultaneous use with drugs that alkalize urine (citrates, sodium bicarbonate, carbonic anhydrase inhibitors).

Storage Conditions

List B. Store at a temperature of 15-25°C (-13°F) in a dry, light-protected place, out of reach of children.

Shelf Life

Shelf life – 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.