ZIRPAN [Ciprofloxacin + Tinidazole] 500 + 600 mg Film-coated tablets

ZIRPAN

instructions for medical use of the medicinal product

Tradename

Zirpan, Zirpan

International non-proprietary name

Ciprofloxacin + Tinidazole, Ciprofloxacin + Tinidazole

Composition

Each film-coated tablet contains:

active substances: ciprofloxacin 500 mg, tinidazole 600 mg

excipients: starch, dextrin, microcrystalline cellulose, hypromellose, magnesium stearate, talc

Dosage form

Tablets.

Pharmacotherapeutic group

Combined antimicrobial agent, fluoroquinolone .

Pharmacological properties

Pharmacodynamics

Ciprofloxacin   - a broad-spectrum antibiotic from the group of fluoroquinolones. Inhibits the enzyme DNA gyrase of bacteria, as a result of which replication is disrupted   DNA   and synthesis of bacterial cellular proteins. Active against most aerobic Gram-positive and Gram-negative microorganisms such as E. coli , Klebsiella spp ., S. typhi and other strains of Salmonella , Proteus mirabilis , Proteus vulgaris , Yersinia enterocolitica , Pseudomonas aeruginosa , Shigella flexneri , Shigella sonnei , Haemophilus ducreyi , Haemophilus influenzae , Neisseria gonorrhoeae , Moraxella catarrhalis , Vibrio cholerae , Staphylococcus aureus (including methicillin-resistant strains), Staphylococcus epidermidis , Streptococcus pyogenes , Streptococcus pneumoniae , Chlamydia trachomatis , Chlamydia pneumonia , Mycoplasma pneumonia , Mycoplasma hominis , Legionella pneumophila and Mycobacterium tuberculosis .

Tinidazole has antiprotozoal and antimicrobial activity. The mechanism of action is associated with the inhibition of synthesis and disruption of the structure of DNA-sensitive microorganisms. Tinidazole is effective against protozoa ( Trichomonas vaginalis , Entamoeba histolytica , Lamblia spp .) and anaerobic ( Clostridium difficile , Clostridium perfringens , Bacteroides fragilis , Peptococcus , Fusobacterium spp ., Gardnerella vaginalis , Bacteroides melaninogenicus , Eubacterium spp . and Peptostreptococcus anaerobius ) microorganisms.

Pharmacokinetics

Ciprofloxacin and tinidazole are well absorbed in   GIT. Cmax of each component is achieved within 1-2 hours.

The bioavailability of ciprofloxacin is approximately 70%. When combined with food, the absorption of ciprofloxacin slows down. Approximately 20-40% of ciprofloxacin binds to plasma proteins. Ciprofloxacin penetrates well into body fluids and tissues: lungs, skin, adipose, muscle and cartilage tissues, as well as into bone tissue and organs of the genitourinary system, including the prostate gland. Ciprofloxacin is found in high concentrations in saliva, nasal mucus and bronchi, lymph, peritoneal fluid, bile and seminal fluid. Partially ciprofloxacin is metabolized by the liver. Approximately 50% of the dose taken is excreted unchanged by the kidneys, 15% is excreted by the kidneys in the form of active metabolites, such as oxocyprofloxacin. The rest of the dose is excreted in the bile, partially reabsorbed. Approximately 15-30% of ciprofloxacin is excreted through   GIT. T 1/2   is approximately 3.5–4.5 hours T 1/2   may be prolonged in severe renal insufficiency and in elderly patients.

Bioavailability of tinidazole   - 100%, binding to plasma proteins   - 12%. T 1/2   is approximately 12-14 hours. Tinidazole quickly penetrates into the tissues of the body, reaching high concentrations there, penetrates into the cerebrospinal fluid at a concentration equal to its plasma concentration, and undergoes reabsorption in the renal tubules. Tinidazole is excreted into the bile at concentrations slightly below 50% of its serum concentration. Approximately 25% of the dose taken is excreted unchanged by the kidneys. Metabolites account for 12% of the administered dose and are also excreted by the kidneys. Along with this, there is a slight excretion of tinidazole through the gastrointestinal tract.

Indications for use

Mixed bacterial infections caused by susceptible Gram-positive and Gram-negative microorganisms in association with anaerobic microorganisms and/or protozoa:

·   respiratory tract infections (acute bronchitis, chronic bronchitis in the acute stage, pneumonia, bronchiectasis);

·   infections of ENT organs (otitis media, sinusitis, frontal sinusitis, mastoiditis, tonsillitis, pharyngitis);

·   infections of the oral cavity (acute ulcerative gingivitis, periodontitis, periostitis);

·   kidney and urinary tract infections (cystitis, pyelonephritis);

·   infections of the pelvic organs and genital organs (prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvic peritonitis);

·   intra-abdominal infections (infections of the gastrointestinal tract, biliary tract, intraperitoneal abscesses);

·   infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon, ulcerative skin lesions in diabetic foot syndrome, bedsores);

·   bone and joint infections (osteomyelitis, septic arthritis);

·   postoperative infections.

Contraindications

·   blood diseases (history);

·   oppression of bone marrow hematopoiesis;

·   organic diseases of the central nervous system;

·   pregnancy and breastfeeding period ;

·   simultaneous reception with tizanidine (risk of a pronounced decrease in blood pressure, drowsiness);

·   acute porphyria;

·   children and adolescents up to 18 years of age;

·   hypersensitivity to the components of the drug;

·   Hypersensitivity to fluoroquinolone or imidazole derivatives.

Dosage and administration

Taken orally, 1 hour before meals or 2 hours after meals . Tablets are swallowed whole, without chewing, drinking plenty of water.

The recommended dose is 1 tab. 2 times / day for 5-10 days.

Special instructions and precautions

Consideration should be given to the possibility of cross-allergic reactions. Patients with hypersensitivity to other imidazole derivatives may develop cross-sensitivity to tinidazole; the development of a cross-allergic reaction to ciprofloxacin is also possible in patients with hypersensitivity to other fluoroquinolone derivatives.

During treatment, it is recommended to avoid contact with direct sunlight. If photosensitivity reactions occur, the drug should be discontinued immediately.

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

In order to avoid the development of crystalluria, the recommended daily dose should not be exceeded, sufficient fluid intake and maintenance of an acid urine reaction are also necessary.

The drug causes dark staining of urine, which has no clinical significance.

Patients with epilepsy, a history of seizures, vascular diseases and organic brain damage, due to the threat of adverse reactions from the central nervous system, with severe renal and / or hepatic insufficiency, in elderly patients, the drug should be prescribed only for health reasons.

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.

Treatment should be discontinued if there is pain in the tendons or when the first signs of tendovaginitis appear.

At treatment more than 6 days it is necessary to control a picture of peripheral blood.

Influence on the ability to drive vehicles and mechanisms

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

Use during pregnancy and during breastfeeding

The use of the drug during pregnancy and during breastfeeding is contraindicated. If it is necessary to use the drug during breastfeeding, breastfeeding should be discontinued for the period of treatment.

Interaction with other drugs

Effects due to ciprofloxacin

Due to a decrease in the activity of microsomal oxidation processes in hepatocytes, it increases the concentration and lengthens T 1/2   theophylline and other xanthines, incl. caffeine, oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index.

Co-administration with iron-containing drugs, sucralfate and antacid drugs containing Mg 2+, Ca 2+, A l 3+, with didanosine leads to a decrease in the absorption of ciprofloxacin. Therefore, the drug should be prescribed 1-2 hours before or 4 hours after taking these drugs.

With simultaneous use with NSAIDs (excluding acetylsalicylic acid), the risk of convulsions increases.

Metoclopramide accelerates the absorption of ciprofloxacin, which leads to a decrease in Tmax .

Co-administration of uricosuric drugs leads to a slowdown in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

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

Compatible with sulfonamides and antibiotics (beta-lactam antibiotics, aminoglycosides, erythromycin, rifampicin, cephalosporins), in combination with which synergism is usually observed.

Effects due to tinidazole

Enhances the effect of indirect anticoagulants. To reduce the risk of bleeding, the dose of the drug is reduced by 50%.

Enhances the effect of ethanol (disulfiram-like reactions).

Phenobarbital accelerates the metabolism of tinidazole.

It is not recommended to prescribe the drug simultaneously with ethionamide.

Side effect

From the digestive system:   loss of appetite, dryness of the 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 side of the central nervous system and peripheral nervous system:   headache, dizziness, fatigue, impaired coordination of movements (including locomotor ataxia), dysarthria, peripheral neuropathy; rarely - convulsions, weakness, anxiety, tremor, insomnia, nightmares, peripheral paralgesia (anomaly in the perception of pain), increased intracranial pressure, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions, migraine, syncope, cerebral artery thrombosis , increased sweating.

From the sense organs:   violations of taste and smell, visual impairment (diplopia, change in color perception), tinnitus, hearing loss.

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

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

From the urinary system:   hematuria, crystalluria (with an alkaline reaction of urine and a decrease in diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, decreased nitrogen excretion of the kidneys, interstitial nephritis.

Allergic reactions:   pruritus, urticaria, skin rash, drug fever, petechiae, angioedema, shortness of breath, eosinophilia, vasculitis, erythema nodosum, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

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

From the side of laboratory indicators:   hypoprothrombinemia, increased activity of hepatic transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Others:   asthenia, superinfections (candidiasis, pseudomembranous colitis), flushing of the face, photosensitivity.

If any of the side effects listed in the instructions get worse, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

Symptoms:   in cases of acute overdose, symptoms of reversible damage to the urinary system will prevail, convulsions are possible.

Treatment:   induction of vomiting, gastric lavage. Symptomatic, supportive therapy (including adequate hydration of the body). There is no specific antidote. With the help of hemo- or peritoneal dialysis, tinidazole can be completely removed from the body, and ciprofloxacin - slightly (less than 10%).

Storage conditions

Store in a cool dry place, at a temperature not exceeding 25°C.

Keep out of the reach of children.

Best before date

3 years. Do not use after the expiry date stated on the package.

Holiday conditions

Released by prescription.

Release form

10 tablets in an aluminum foil blister. 1 blister with instructions for use in a cardboard box.