Tsifran OD - instructions for use, dose, side effects, contraindications

Excipients: sodium alginate (Keltone LVCR), hypromellose, sodium hydrogen carbonate, crospovidone (CLM), magnesium stearate, silicon dioxide colloid (200), talc.

Film sheath: Opaprai white 31В58910 *, talcum, hypromellose, purified water **, ink for writing black *** (Opacode -S-1-17823 black).

* Contamination of white 31B58910: hypromellose, lactose, titanium dioxide, macrogol 400;

** evaporates in the production process;

*** The composition includes: shellac 45% (20% esterified) in ethanol, isopropanol, n-butanol, propylene glycol, ammonia water 28%, iron oxide dye oxide black.

Description:

Tablets "Tsifran® OD 500 mg"

Tablets of oval form, from white to almost white color, covered with a film coating, printed on one side of the tablet with food ink "Cifran OD 500MG".

View. broken tablets: pressed mass from white to almost white.

Tablets "Tsifran® OD 1000 mg"

Tablets of oval form, from white to almost white color, covered with a film coating, printed on one side of the tablet with food ink "Cifran OD 1000MG".

Type of tablet on the break: pressed mass from white to almost white.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

The bactericidal action of fluoroquinolones is due to the inhibition of the bacterial enzyme - topoisomerase II (DNA gyrase). Topoisomerase II is necessary for the normal replication of bacterial DNA. This ATP-dependent process in the absence of topoisomerase II leads to uncontrolled replication of the damaged DNA, and, consequently, to a violation of the synthesis of normal proteins in the bacterial cell.

Antibacterial spectrum:

Ciprofloxacin has a pronounced in vitro activity against a wide range of gram-negative and gram-positive bacteria. Ciprofloxacin It acts both on multiplying microorganisms, and on being in a state of rest. As studies have shown in vitro and application in clinical trials, ciprofloxacin is active against most strains of the following microorganisms:

Aerobic Gram positive: Bacillus anthracis Enterococcus faecalis (most strains are relatively sensitive) Listeria monocytogenes Staphylococcus epidermidis Staphylococcus saprophyticus	Staphylococcus aureus (methicillin-sensitive and penicillinase-producing, partially methicillin-resistant strains) Streptococcus pneumoniae Streptococcus pyogenes
Aerobic Gram-negative: Campylobacter jejuni Citrobacter diversus Citrobacter freundii. Enterobacter cloacae Escherichia coli Haemophilus influenzae Haemophilus parainfluenzae Klebsiella pneumoniae Moraxella catarrhalis Morganella morganii Neisseria gonorrhoeae	Proteus mirabilis Proteus vulgaris Providencia rettgeri Pseudomonas aeruginosa Salmonella typhi Serratia marcescens Shigella boydii Shigella dysenteriae Shigella flexneri Shigella sonnei
In vitro studies ciprofloxacin in the minimum inhibitory concentration (MIC) <1 μg / ml is active against most (> 90%) strains of the following microorganisms, but the clinical significance of these data is still being specified.
Aerobic Gram-positive: Staphylococcus haemolyticus Staphylococcus hominis	Streptococcus pneumoniae
Aerobic Gram-negative: Acinetobacter lwoffii Aeromonas hydrophilia Edwardsiella tarda Klebsiella oxytoca Legionella pneumophila	Salmonella enteritidis Vibrio cholerae Vibrio parahaemolyticus Vibrio vulnificus Yersinia enterocolitica
Other microorganisms: Mycobacterium tuberculosis (relatively sensitive)
Most strains Burkholderia cepacia and some strains of Stenotrophomonas maltophilia are resistant to ciprofloxacin, like most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

Pharmacokinetics:

Suction

after oral administration ciprofloxacin quickly absorbed from the gastrointestinal tract. Tsifran® OD tablets provide a sustained, even release of ciprofloxacin, with the drug taken only once a day. One dose of Cyphran® OD 500 mg and Cyphran® OD 1000 mg.are able to maintain the necessary concentration of ciprofloxacin, which in other cases is provided by double application of conventional ciprofloxacin 250 mg or 500 mg respectively.

Distribution

after administration of a single dose, the maximum plasma concentrations (Cms) are reached within 6 hours and are 1.3 ± 0.4 Mkg / ml and 2.4 ± 0.7 Mkg / ml for Cyphran® OD 500 mg and Cyphran® OD 1000 mg, respectively. The corresponding area under the pharmacokinetic curve (AUC_0-t) 8.3 ± 2.1 and 18.9 ± 4.6 μg * ml / h. Protein binding of blood plasma from 20% to 40%.

Ciprofloxacin penetrates well into the tissues and body fluids: lungs, skin, adipose tissue, muscles, cartilage and bone tissue, the prostate gland, saliva, the secret of the mucous membrane of the nasal cavity and bronchi, sperm, lymph, peritoneal fluid and the secretion of the prostate.

Metabolamendment

ciprofloxacin is partially metabolized in the liver.

Excretion

About 50% of the ingested dose is excreted by the kidneys unchanged and about 15% in the form of active metabolites. Approximately 20-35% of the dose taken is secreted by the intestine. The elimination half-life (T1) Tsifran® OD is about 6.5-7.5 hours. T1 may be prolonged with severe renal failure and in elderly people.

Special patient groups

With impaired renal function: In patients with slightly impaired renal function, the half-life of ciprofloxacin may slightly increase. In this case, the dosage regimen must be corrected (See "Method of administration and dose").

With impaired liver function: In preliminary studies in patients with a stable course of cirrhosis, there were no significant changes in the pharmacokinetics of ciprofloxacin. However, studies on the kinetics of ciprofloxacin in patients with acute hepatic insufficiency have not been conducted.

Indications:

Tsifran® OD is indicated for the treatment of the following infectious-inflammatory diseases caused by susceptible microorganisms.

- acute sinusitis;

- Infectious-inflammatory diseases of the lower respiratory tract, including pneumonia, exacerbation of chronic bronchitis and infectious complications of cystic fibrosis;

- pyelonephritis, cystitis (including complicated);

- chronic bacterial prostatitis;

- gonorrhea;

- intra-abdominal infections (including peritonitis, intra-abdominal abscesses, cholangitis, cholecystitis, gallbladder empyema) is used in combination with metronidazole

- infectious diseases of the skin;

- infectious diseases of bones and joints (including acute and chronic osteomyelitis);

- Diarrhea of infectious genesis - incl. "Travelers' diarrhea";

- typhoid fever;

- anthrax.

Contraindications:

- pseudomembranous colitis;

- age to 18 years;

- pregnancy;

- lactation period;

- increased sensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones;

- simultaneous reception of tizanidine (risk of pronounced decrease in blood pressure, drowsiness);

- chronic renal failure (creatinine clearance less than 29 ml / min, including patients on hemodialysis).

Carefully:

pronounced atherosclerosis of cerebral vessels;
impaired cerebral circulation;
mental illness;
epilepsy;
renal failure (creatinine clearance 35-50 ml / min);
severe hepatic impairment,
elderly age;
the defeat of the tendons in the previous treatment with fluoroquinolones.

Pregnancy and lactation:

Tsifran® OD is not recommended during pregnancy.

Ciprofloxacin is excreted into breast milk, so during lactation, if it is necessary to use Cyphran® OD,then, based on the degree of importance of its use for the mother, it should be decided whether to stop taking the drug or breastfeeding.

Dosing and Administration:

Inside.

Do not break, chew, or otherwise destroy tablets. Tablets should be taken orally after meals, with plenty of water.

The use of Cyphran® OA should continue for at least 2 more days after the symptoms disappear completely. Recommended dosages for adults:

Diseases	Gravity of the current	Dose	Frequency of application	Duration of therapy
Acute Sinusitis	Light / Medium	1000 mg	Every 24 hours	10 days
Infectious-inflammatory diseases of the lower respiratory tract	Light / Medium	1000 mg	Every 24 hours	7-14 days
	Heavy / Complicated	1500 mg	Every 24 hours	7-14 days
Urinary tract infections	Acute uncomplicated	500 mg	Every 24 hours	3 days
	Light / Medium	500 mg	Every 24 hours	7-14 days
	Heavy / Complicated	1000 mg	Every 24 Hours	7-14 days
Chronic bacterial prostatitis	Light / Medium	1000 mg	Every 24 hours	28 days
Gonorrhea	Acute uncomplicated	500 mg	Once	1 day
Gonorrhea	Complicated	500 mg	Every 24 hours	3-5 days
Intra-abdominal infections *	Complicated	1000 mg	Every 24 hours	7-14 days
Infectious diseases of skin	Light / Medium	1000 mg	Every 24 hours	7-14 days
Infectious diseases of skin	Heavy / Complicated	1500 mg	Every 24 hours	7-14 days
Infectious diseases of bones and joints	Light / Medium	1000 mg	Every 24 hours	4-6 weeks
Infectious diseases of bones and joints	Heavy / Complicated	1500 mg	Every 24 hours	> 4-6 weeks
Diarrhea of infectious genesis, incl. "Travelers diarrhea"	Light / Medium / Heavy	1000 mg	Every 24 hours	5-7 days
Typhoid fever	Light / Medium	1000 mg	Every 24 hours	10 days
anthrax	Prevention and treatment	1000 mg	Every 24 hours	60 days

* used in combination with metronidazole;

Correction of the dosing regimen for renal failure:

In case of impaired renal function, the following dosing regimen for adults is recommended:

Creatinine clearance (ml / min.)	Dose
>50	Usual Dose
30-50	500-1000 mg / day
5-29	The use of Cyphran® OD 500 mg and Cyphran® OD 1000 mg is not recommended
Patients on hemodialysis or peritoneal dialysis

If only the concentration of creatinine in the blood plasma is known, the following formula is recommended for determining the creatinine clearance:

Men: Creatinine clearance (ml / min.) = (Body weight (kg) x (140 - age)) / (72 x serum creatinine concentration (mg%))

Women: Creatinine clearance (ml / min.) = 0.85 x figure calculated for men.

Application in elderly patients

When using fluoroquinolones in elderly patients, it is necessary to pay attention to the possible age-dependent decrease in renal function, so it is necessary to correct the dosage regimen (see "Method of administration and dose").

Side effects:

From the digestive system: nausea, vomiting, diarrhea, abdominal pain, flatulence, anorexia, cholestatic jaundice (especially in patients with liver disease), hepatitis, hepatonecrosis.

From the nervous system: dizziness, photophobia, insomnia, paresthesia, irritability, headache, fatigue, anxiety, tremor, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), increased intracranial pressure, confusion, depression, hallucinations, and other manifestations psychotic reactions (occasionally progressing to conditions in which the patient can do harm to himself), migraine, fainting, thrombosis of the cerebral arteries.

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

From the side of the cardiovascular system: tachycardia, violations of the heart rhythm, lowering blood pressure, "tides" of blood to the skin of the face.

From the hematopoietic system: eosinophilia, leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia.

Laboratory indicators: hypoprothrombinemia, increased activity of "hepatic" transaminases, hypercreatininemia, hyperbilirubinemia, hyperglycemia, increased activity of alkaline phosphatase and lactate dehydrogenase.

From the urinary system: hematuria, crystalluria (primarily in the case of alkaline urine and low diuresis), acute interstitial nephritis (with possible development of acute renal failure), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen function.

Allergic reactions: skin itching, urticaria, the formation of blisters accompanied by bleeding, the appearance of small nodules that form scabs, drug fever,point bleeding on the skin (petechiae), swelling of the face or larynx, dyspnea, vasculitis, erythema nodosum, multiforme exudative erythema, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

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

Other: increased sweating, photosensitivity, general weakness, superinfections (candidiasis, pseudomembranous colitis).

Overdose:

Possible reversible toxic effects on the kidneys;

There is no specific antidote, therefore it is necessary to induce vomiting or to conduct gastric lavage and conduct symptomatic therapy:

- to take measures for adequate hydration of the body (infusion therapy);

- maintenance therapy.

Only minor amounts of ciprofloxacin (<10%) can be removed with hemo- and peritoneal dialysis.

Interaction:

Due to the inhibition of microsomal enzymes in the liver, it increases the concentration and. prolongs T1 / 2 theophylline and other xanthines (eg, caffeine), oral hypoglycemic drugs (eg, glibenclamide), indirect anticoagulants (eg, warfarin and its derivatives).If it is necessary to use together with the preparations of these groups, it is necessary to control the concentration of the drug in the blood and, accordingly, to correct the dosage regimen.

In the presence of antacid preparations containing magnesium hydroxide or aluminum hydroxide, the absorption of ciprofloxacin decreases. Thus, simultaneous reception of these drugs should be excluded. In such cases ciprofloxacin should be taken either 1-2 hours before or 4 hours after taking these drugs. Didanosine reduces the absorption of ciprofloxacin. This is due to the formation of complexes with magnesium salts contained in didanosine preparations.

When combined with probenecid and other drugs that block tubular secretion, renal excretion of ciprofloxacin is reduced.

Metoclopramide accelerates the absorption of the drug, which leads to a decrease in the time to reach its Cmax.

Joint appointment of uricosuric drugs leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

When combined with other antimicrobial agents (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) synergy is usually observed; can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp .; with mezlocillin, azlocillin and other beta-lactam antibiotics - with streptococcal infections; with isoxazolylpenicillins and vancomycin - with staphylococcal infections; with metronidazole and clindamycin - with anaerobic infections. Ciprofloxacin increases the nephrotoxic effect of cyclosporine. An increase in serum creatinine is noted. Such patients need control of this indicator 2 times a week.

The simultaneous use of tizanidine with ciprofloxacin, which is an inhibitor of the CYP1A2 isoenzyme, leads to a 10-fold increase in the aUC of tizanidine. The result of a combined application may be a clinically significant and prolonged decrease in blood pressure, leading to drowsiness, dizziness, inhibited psychomotor reactions.

In patients receiving therapy with ciprofloxacin and phenytoin, the variability (decrease or increase) of the concentration of phenytoin in the blood plasma was noted.

Joint use with non-steroidal anti-inflammatory drugs (NSAIDs), increases the likelihood of side effects of ciprofloxacin from the side of the central nervous system (risk of seizures).

Absorption of ciprofloxacin for oral administration decreases after cytotoxic therapy with antitumor and immunosuppressive drugs.

Special instructions:

In some patients who received fluoroquinolones, photosensitivity reactions were observed. Avoid unnecessary exposure to direct sunlight and UV irradiation. If a photosensitivity reaction occurs, it is recommended to stop using the drug. Since Cyfran® OD is a drug with a possible reversible toxic effect on the kidneys, it is not recommended for patients with impaired renal function, with a creatinine clearance of <29 Ml / min or patients on hemodialysis or peritoneal dialysis.

With the use of virtually all antimicrobial agents, including Cyphran® OD, pseudomembranous colitis may develop, varying in severity from mild to life-threatening.If a severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be deleted, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, sufficient fluid intake and maintenance of acid urine reaction are also necessary.

Patients with epilepsy, seizures in history, vascular diseases and organic brain lesions, in connection with the threat of developing adverse reactions from the central nervous system, Tsifran® OD should be prescribed only for "vital" indications.

When pain occurs in the tendons or when the first signs of tendovaginitis appear, treatment should be discontinued (individual cases of inflammation and even rupture are described tendons during treatment with fluoroquinolones).

Effect on the ability to drive transp. cf. and fur:During treatment, one should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated 500 mg, 1000 mg.

Packaging:

5 tablets in a blister consisting of aluminum foil on one side and aluminum foil covered with a polyamide film and a PVC film on the other side; 1 or 2 blisters in a cardboard box with instructions for use.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N014995 / 01-2003

Date of registration:15.12.2008

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp23.10.2015

Illustrated instructions

Instructions

Tsifran® OD (Cifran OD)