Tsifran SR.

General characteristics. Structure:

Цифран® ST of 250/300 mg
Each tablet, coated, contains:
Ciprofloxacin USP hydrochloride,
equivalent to Ciprofloxacin - 250 mg
Tinidazolum of BP - 300 mg
Excipients: microcrystallic cellulose, colloid anhydrous silicon, magnesium stearate, sodium of starch glikolit, sodium lauryl sulfate. Ingredients of an enveloping layer of granules: sodium of starch glikolit, the talc purified sodium lauryl sulfate, microcrystallic cellulose, colloid anhydrous silicon, magnesium stearate. Cover: опадрай yellow, the water purified.

Цифран® ST of 500/600 mg
Each tablet, coated, contains:
Ciprofloxacin USP hydrochloride,
equivalent to Ciprofloxacin - 500 mg
Tinidazolum of BP - 600 mg
Excipients: microcrystallic cellulose, colloid anhydrous silicon, magnesium stearate, sodium of starch glikolit, sodium lauryl sulfate. Ingredients of an enveloping layer of granules: sodium of starch glikolit, the talc purified sodium lauryl sulfate, microcrystallic cellulose, colloid anhydrous silicon, magnesium stearate. Cover: опадрай yellow, the water purified.

Description:

For tablets - 250mg/300 mg: Tablets of an oval form, yellow color, film coated.

For tablets forte - 500mg/600 mg: Tablets of an oval form, yellow color, with dividing line on one party, film coated

Pharmacological properties:

Pharmacokinetics. Both ciprofloxacin, and Tinidazolum are well absorbed in a GIT. Cmax of each component are reached during 1–2 h. Full bioavailability of Tinidazolum — 100%, and binding by proteins of a blood plasma — 12%. T1/2 is about 12-14 h. Drug quickly gets into body tissues, reaching high concentration there.
Tinidazolum creates in cerebrospinal liquid of concentration, equal to its concentration in plasma, and is exposed to a reabsorption in renal tubules. Tinidazolum is excreted in bile in concentration slightly lower than 50% of its concentration in plasma. About 25% of the accepted dose are removed in not changed view with urine. Metabolites make 12% of the entered dose and are removed also with urine. Along with it, insignificant removal of Tinidazolum with a stake is observed.
Ciprofloxacin is well absorbed after intake. Bioavailability of ciprofloxacin about 70%. At combined use with food, absorption of ciprofloxacin is slowed down. 20–40% of drug communicate proteins of plasma. Ciprofloxacin well gets on liquid Wednesdays and body tissues: lungs, skin, fatty, muscular and cartilaginous fabrics, and also in a bone tissue and bodies of an urinary system, a prostate. Drug is found in high concentration in saliva, slime of a nasal cavity and a bronchial secret, sperm, a lymph, peritoneal liquid, bile and a secret of a prostate. Partially ciprofloxacin is metabolized by a liver. About 50% of the accepted dose are removed in not changed view with urine, 15% — in the form of active metabolites, such as oxyciprofloxacin. Other part of a dose is removed with bile, being partially soaked up repeatedly. About 15-30% of ciprofloxacin are removed with a stake. T1/2 — about 3,5-4,5 p. T1/2 can be extended at the expressed renal failure and at elderly patients.

Pharmacodynamics. The combined drug intended for therapy of the mikst-infections caused by anaerobic and aerobic microorganisms, and also GIT infections, for example diarrhea or dysentery, amoebic or mixed (amoebic and bacterial) the nature.
Tinidazolum is effective concerning anaerobic microorganisms, such as Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, Peptococcus and Peptostreptococcus anaerobius. Anaerobic microorganisms cause, generally diseases of abdominal organs, a small pelvis, lungs or bodies of an oral cavity. At a mephitic gangrene, most often, there is a mix of anaerobic and aerobic bacteria. Therefore at the mixed mephitic gangrene the antibiotic, active concerning aerobic bacteria is added to therapy.
Ciprofloxacin — an antibiotic of a broad spectrum of activity, active concerning the majority of aerobic gram-positive and gram-negative microorganisms, such as E.coli, Klebsiella spp., S.typhi and other strains of Salmonella, P.mirabilis, P.vulgaris, Yersinia enterocoilitica, Ps.aeruginosa, Shigella flexneri, Shigella sonnei, H.ducreyi, H.influenzae, N.gonorrhoeae, M.catarrhalis, V.cholerae, B.fragilis, St.aureus (including Methicillinum - resistant strains), St.epidermidis, S.pyogenes, S.pneumoniae, Chlamidia, Mycoplasma, Legionella and Mycobacterium tuberculosis.

Indications to use:

Treatment of the mikst-infections caused by sensitive anaerobic and aerobic microorganisms: 
- chronic sinusitis; 
- lung abscess; 
- empyema; 
- intra belly infections; 
- inflammatory gynecologic diseases; 
- postoperative infections (at possible presence of aerobic and anaerobic bacteria); 
- chronic osteomyelitis; 
- infections of skin and soft tissues; 
- ulcers on diabetic foot; 
- decubituses; 
- infections of an oral cavity (including periodontitis and a periostitis).
Treatment of diarrhea or dysentery amoebic or mixed (amoebic and bacterial) etiologies.

Route of administration and doses:

Inside, after food, washing down with enough water.
It is not necessary to break, chew or to otherwise destroy a tablet.
The recommended dose for adults
Цифран® ST of 250/300 mg — 2 tab. 2 times a day.
Цифран® ST of 500/600 mg — 1 tab. 2 times a day.

Features of use:

It is recommended to avoid excessive insolation during a therapy course the drug Tsifran® ST as at some patients receiving ftorkhinolona phototoxicity reactions were noted. At emergence of reactions of phototoxicity it is necessary to stop drug use immediately.
At use of Tinidazolum perhaps (but it is rare) development of a generalized small tortoiseshell, face edema and throat, a lowering of arterial pressure, a bronchospasm and диспноэ. If the patient has an allergy on any derivative an imidazole, then cross sensitivity and on Tinidazolum can develop; development of cross allergic reaction to ciprofloxacin is possible as well at patients with an allergy to other derivatives of ftorkhinolon. Therefore if the patient had any allergic reactions to similar drugs, it is necessary to consider possibility of cross allergic reactions to Tsifran® of ST.
At combined use of Tinidazolum with alcohol there can be cricks in a stomach, nausea and vomiting. Therefore combined use of Tsifran® of ST and alcohol contraindicated.
In order to avoid development of a crystalluria exceeding of the recommended daily dose is inadmissible, also sufficient consumption of liquid and maintenance of acid reaction of urine is necessary. Causes dark coloring of urine.
During treatment it is necessary to refrain from occupations potentially dangerous types of activity requiring special attention and speed of mental and motor reactions.
The patient with epilepsy, attacks of spasms in the anamnesis, vascular diseases and organic lesions of a brain, in connection with threat of development of side reactions from TsNS, it is necessary to appoint drug only according to vital indications.
At emergence in time or after treatment of heavy and long diarrhea it is necessary to exclude the diagnosis of pseudomembranous colitis which demands immediate drug withdrawal and purpose of the corresponding treatment.
At emergence of pains in sinews or at manifestation of the first symptoms of a tendovaginitis treatment should be stopped.
In the course of treatment it is necessary to control a pattern of peripheral blood.
Safety and efficiency of use for treatment and prevention of mephitic gangrenes at children are younger than 12 years is not established.

Side effects:

From the alimentary system: a loss of appetite, dryness of a mucous membrane of an oral cavity, "metal" smack in a mouth, nausea, vomiting, diarrhea, an abdominal pain, a meteorism, cholestatic jaundice (especially at patients with the postponed liver diseases), hepatitis, гепатонекроз.
From TsNS: a headache, dizziness, increased fatigue, lacks of coordination of movements (including a locomotory ataxy), a dysarthtia, a peripheral neuropathy, seldom spasms, weakness, a tremor, sleeplessness, the increased sweating, increase in intracranial pressure, confusion of consciousness, a depression, hallucinations, and also other manifestations of psychotic reactions, migraine, unconscious states, thrombosis of cerebral arteries.
From sense bodys: disturbances of taste and sense of smell, vision disorder (diplopia, change of color perception), sonitus, decrease in hearing.
From cardiovascular system: tachycardia, disturbances of a cordial rhythm, lowering of arterial pressure.
From the hemopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolitic anemia.
From laboratory indicators: prothrombinopenia, increase in activity of hepatic transaminases and ShchF, hypercreatinemia, hyperbilirubinemia, hyperglycemia.
From an urinary system: a hamaturia, a crystalluria (at alkalinuria and a hypouresis), a glomerulonephritis, a dysuria, a polyuria, an ischuria, decrease in azotovydelitelny function of kidneys, intersticial nephrite.
Allergic reactions: a skin itch, a small tortoiseshell, blistering, followed by bleedings, and emergence of the small small knots forming crusts, medicinal fever, dot hemorrhages on skin (petechia), a face edema or throats, an otdyshka, an eosinophilia, the raised photosensitivity, a vasculitis, a nodal erythema, a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).
Others: an arthralgia, arthritis, a tendovaginitis, ruptures of sinews, an adynamy, a mialgiya, superinfections (candidiasis, pseudomembranous colitis), rushes of blood to the person.

Interaction with other medicines:

Tinidazolum
Strengthens effect of indirect anticoagulants (for reduction of risk of development of bleedings the dose is reduced by 50%) and effect of ethanol (disulfiramopodobny reactions).
Let's combine with streptocides and antibiotics (aminoglycosides, erythromycin, rifampicin, cephalosporins).
It is not recommended to appoint with Etioniamidum.
Phenobarbital accelerates metabolism.
Ciprofloxacin
Owing to decrease of the activity of processes of a microsomal oxidation in hepatocytes increases concentration and extends theophylline T1/2 (and other xanthines, for example caffeine), peroral hypoglycemic HP, indirect anticoagulants, promotes decrease in a prothrombin ratio.
At a combination to other antimicrobic HP (beta лактамные antibiotics, aminoglycosides, clindamycin, metronidazole) a synergism is usually observed.
Strengthens nephrotoxic effect of cyclosporine, increase in serumal creatinine is noted; at such patients control of this indicator 2 times a week is necessary.
At a concomitant use strengthens effect of indirect anticoagulants.
Oral administration jointly in ferriferous HP, sukralfaty and the antiacid HP containing Mg2+, Ca2+ A13+ leads to decrease in absorption of ciprofloxacin therefore it is necessary to appoint it for 1–2 h to or in 4 h after reception above the specified HP.
NPVS (excepting acetylsalicylic acid) increase risk of development of spasms.
Didanozin reduces absorption of ciprofloxacin owing to formation of complexes with Mg2+ which are contained in the didanozena, A13+.
Metoclopramidum accelerates absorption that leads to reduction of time of achievement of its maximum concentration.
Joint purpose of uricosuric HP leads to removal delay (up to 50%) and increase in plasma concentration of ciprofloxacin.

Contraindications:

● hypersensitivity to any derivatives of a ftorkhinolon or an imidazole;
● hematologic diseases;
● organic neurologic lesions;
● oppression of a marrowy hemopoiesis;
● porphyria;
● children's age (up to 18 years).
With care: the expressed atherosclerosis of vessels of a brain; disturbance of cerebral circulation; mental diseases, epilepsy, epileptic syndrome; the expressed renal and/or liver failure.
At use of drug at elderly any significant problems are noted. However at elderly patients depression of function of kidneys, perhaps dependent on age, therefore it is necessary to be careful at use of drug for such patients.

Overdose:

Treatment: therapy at overdose of the drug Tsifran® ST has to be symptomatic and include the following events:
- induction of vomiting or gastric lavage,
- carrying out measures for adequate hydration of an organism (infusional therapy);
- maintenance therapy.
The specific antidote does not exist.

Storage conditions:

List B. In the dry place, at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, coated. On 10 tablets in a blister strip packaging (blister). On 1 or on 10 packagings in a cardboard box with the application instruction.