Cifran^® CT (Tablets) Instructions for Use

ATC Code

J01R (Antimicrobial drugs in combination)

Active Substances

Tinidazole (Rec.INN registered by WHO)

Ciprofloxacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Combined drug with antiprotozoal and antibacterial action

Pharmacotherapeutic Group

Combined antimicrobial agent

Pharmacological Action

Combined antimicrobial agent.

Ciprofloxacin is a broad-spectrum antibiotic active against most aerobic gram-positive and gram-negative microorganisms such as Escherichia coli, Klebsiella spp., Salmonella typhi and other Salmonella strains, Proteus mirabilis, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Shigella flexneri, Shigella sonnei, Haemophilus ducreyi, Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella catarrhalis, Vibrio cholerae, Bacteroides fragilis, Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Mycoplasma, Legionella and Mycobacterium tuberculosis.

Tinidazole is an antiprotozoal and antimicrobial agent, an imidazole derivative, effective against anaerobic microorganisms such as Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, Peptococcus and Peptostreptococcus anaerobius.

Pharmacokinetics

Both ciprofloxacin and Tinidazole are well absorbed in the gastrointestinal tract after oral administration. The time to reach C_max for each component is 1-2 hours. The drug quickly penetrates into body tissues, reaching high concentrations there. It is found in high concentrations in saliva, nasal and bronchial secretions, semen, lymph, peritoneal fluid, bile, and prostatic secretion.

The bioavailability of tinidazole is 100%, protein binding is 12%. T_1/2 is 12-14 hours. Tinidazole penetrates the cerebrospinal fluid at a concentration equal to that in plasma and undergoes reabsorption in the renal tubules. Tinidazole is excreted in bile at concentrations slightly below 50% of its plasma concentration. About 25% is excreted unchanged in the urine, 12% as metabolites. Minor amounts are excreted in the feces.

The bioavailability of ciprofloxacin is about 70%. Concurrent food intake slows absorption. Protein binding is 20-40%. Ciprofloxacin penetrates well into body fluids and tissues: lungs, skin, adipose, muscle and cartilage tissues, as well as bone tissue and organs of the urinary system, including the prostate gland. Ciprofloxacin is partially metabolized in the liver. T_1/2 is about 3.5-4.5 hours, may be prolonged in severe renal failure and in elderly patients. About 50% is excreted unchanged in the urine, 15% as active metabolites (including oxociprofloxacin). The remainder is excreted in the bile, partially reabsorbed. About 15-30% of ciprofloxacin is excreted in the feces.

Indications

Chronic sinusitis; lung abscess; empyema; intra-abdominal infections; inflammatory gynecological diseases; postoperative infections with possible presence of aerobic and anaerobic bacteria; chronic osteomyelitis; skin and soft tissue infections; skin ulcers in diabetic foot; bedsores; oral infections (including periodontitis and periostitis); diarrhea or dysentery of amoebic or mixed (amoebic and bacterial) etiology.

ICD codes

Dosage Regimen

Take the tablets orally, with a full glass of water.

Administer the 250/300 mg strength tablet twice daily.

Administer the 500/600 mg strength tablet twice daily.

Complete the full prescribed course of treatment, even if symptoms improve.

Take the dose at least 2 hours before or 4 hours after consuming antacids, sucralfate, or products containing iron, zinc, magnesium, or aluminum.

For most indications, the typical treatment duration is 5 to 14 days, depending on the severity and type of infection.

Adjust the dosage interval in patients with severe renal impairment (e.g., creatinine clearance less than 30 mL/min); consult specific dosing guidelines.

Do not crush or chew the tablets.

Maintain adequate hydration to prevent crystalluria.

Strictly adhere to the dosage and frequency prescribed by your physician.

Adverse Reactions

From the digestive system: decreased appetite, dry oral mucosa, metallic taste in the mouth, nausea, vomiting, diarrhea, abdominal pain, flatulence, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis, hepatonecrosis.

From the nervous system: headache, dizziness, increased fatigue, impaired coordination of movements (including locomotor ataxia), dysarthria, peripheral neuropathy, rarely – seizures, weakness, tremor, insomnia, increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions, migraine, cerebral artery thrombosis.

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

From the cardiovascular system: tachycardia, arrhythmia, decreased blood pressure, fainting.

From the hematopoietic organs: leukopenia, granulocytopenia, anemia (including hemolytic), thrombocytopenia, leukocytosis, thrombocytosis.

From the urinary system: hematuria, crystalluria (with alkaline urine reaction and decreased diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, decreased renal nitrogen excretion, interstitial nephritis.

Allergic reactions: skin itching, urticaria, skin rash, drug fever, petechiae, facial or laryngeal edema, shortness of breath, eosinophilia, photosensitivity, vasculitis, erythema nodosum, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

From laboratory parameters: hypoprothrombinemia, increased activity of “hepatic” transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

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

Other: superinfections (candidiasis, pseudomembranous colitis), facial flushing, increased sweating.

Contraindications

Hypersensitivity (including to fluoroquinolone or imidazole derivatives); blood diseases (in history); bone marrow hematopoiesis depression; acute porphyria; organic diseases of the central nervous system; age under 18 years; pregnancy; lactation period.

With caution: severe cerebral atherosclerosis, cerebrovascular accident, mental illness, epilepsy, history of seizures, severe renal and/or hepatic insufficiency, elderly age.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

With caution: severe hepatic insufficiency.

Use in Renal Impairment

With caution: severe renal insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

With caution: elderly age.

Special Precautions

It is recommended to avoid excessive exposure to sunlight during treatment. If photosensitivity reactions occur, the drug should be discontinued immediately.

When using tinidazole (an imidazole derivative), the development (rarely) of generalized urticaria, facial and laryngeal edema, decreased blood pressure, bronchospasm and dyspnea is possible. Therefore, in patients with hypersensitivity to other imidazole derivatives, cross-sensitivity to Tinidazole may develop; the development of a cross-allergic reaction to ciprofloxacin is also possible in patients with hypersensitivity to other fluoroquinolone derivatives. The possibility of cross-allergic reactions should be considered.

During treatment, it is not recommended to take ethanol (risk of disulfiram-like reactions due to tinidazole, which is part of the drug).

To avoid the development of crystalluria, the recommended daily dose should not be exceeded, and sufficient fluid intake and maintenance of an acidic urine reaction are also necessary. Causes dark discoloration of urine, which has no clinical significance.

In patients with epilepsy, a history of seizures, vascular diseases and organic brain lesions, due to the threat of developing side effects from the central nervous system, the drug 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 appropriate treatment.

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

During treatment, the peripheral blood picture should be monitored.

During treatment, one should refrain from engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Tinidazole.

Enhances the effect of indirect anticoagulants (to reduce the risk of bleeding, the dose is reduced by 50%) and the effect of ethanol (disulfiram-like reactions).

Compatible with sulfonamides and antibiotics (aminoglycosides, erythromycin, rifampicin, cephalosporins).

Not recommended to be prescribed with ethionamide.

Phenobarbital accelerates metabolism.

Ciprofloxacin.

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, including caffeine), oral hypoglycemic drugs, indirect anticoagulants, and contributes to a decrease in the prothrombin index.

When combined with other antimicrobial drugs ( beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole), synergy is usually observed.

Enhances the nephrotoxic effect of cyclosporine, an increase in serum creatinine is noted; in such patients, this indicator should be monitored 2 times a week.

Oral administration together with iron-containing drugs, sucralfate and antacid drugs containing magnesium, calcium, aluminum salts leads to a decrease in the absorption of ciprofloxacin, so it should be prescribed 1-2 hours before or 4 hours after taking the above drugs.

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

Didanosine reduces the absorption of ciprofloxacin due to the formation of complexes with magnesium and aluminum ions contained in didanosine.

Metoclopramide accelerates absorption, which leads to a reduction in the time to reach C_max.

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

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.