Ciprofloxacin Ecocifol, 500 mg 10 pcs

Pharmacotherapeutic group

Antimicrobial agent, fluoroquinolone

ATX Code

J01MA02

Pharmacodynamics:

The broad spectrum antimicrobial agent quinolone derivative inhibits bacterial DNA-gyrosis (topoisomerases II and IV responsible for the process of superspiralization of chromosomal DNA around nuclear RNA which is necessary for reading genetic information) disrupts DNA synthesis growth and division of bacteria; causes pronounced morphological changes (including cell wall, membrane and membrane).cell wall and membranes) and rapid death of the bacterial cell.

It acts bactericidally on Gram-negative organisms during resting and dividing (as it affects not only DNA-giase but also causes lysis of cell wall) on Gram-positive microorganisms – only during dividing.

Low toxicity for macroorganism cells is explained by the absence of DNA-hyrase in them. During ciprofloxacin administration there is no parallel development of resistance to other antibiotics which do not belong to DNA-Gyrase inhibitors group and this fact makes it highly effective against bacteria resistant to aminoglycosides, penicillins and cephalosporins and tetracyclines, for example.

Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: Enterobacteriaceae (Escherichia coli Salmonella spp. Shigella spp. Citrobacter spp. Klebsiella spp. Enterobacter spp. Proteus mirabilis Proteus vulgaris Serratia marcescens Hafnia alvei Edwardsiella tarda Providencia spp. Morganella morganii Vibrio spp. Yersinia spp.) other Gram-negative bacteria (Haemophilus spp. Pseudomonas aeruginosa Moraxella catarrhalis Aeromonas spp. Pasteurella multocida Plesiomonas shigelloides Campylobacter jejuni Neisseria spp.); some intracellular pathogens: Legionella pneumophila Brucella spp. Listeria monocytogenes Mycobacterium tuberculosis Mycobacterium kansasii.

The following Gram-positive aerobic bacteria are also sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus Staphylococcus haemolyticus Staphylococcus hominis Staphylococcus saprophyticus) Streptococcus spp. (Streptococcus pyogenes Streptococcus agalactiae).
Active against Bacillus anthracis.

Most methicillin-resistant staphylococci are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae Enterococcus faecalis Mycobacterium avium (located intracellularly) is moderate (high concentrations are required for their suppression).

Bacteroides fragilis Pseudomonas cepacia Pseudomonas maltophilia Ureaplasma urealyticum Clostridium difficile Nocardia asteroides are resistant to the drug. It is not effective against Treponema pallidum.

Resistance develops very slowly as there are practically no persistent microorganisms after ciprofloxacin action on the one hand and on the other hand bacterial cells have no enzymes which inactivate it. Pharmacokinetics:

In oral administration it is quickly and completely enough absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Food intake slows down absorption but does not change maximum concentration (Cmax) and bioavailability. Bioavailability – 50-85% volume of distribution – 2-35 l/kg binding to plasma proteins – 20-40%. Time to reach maximal concentration (TCmax) – 60-90 min, maximal concentration depends linearly on the dose taken and is 12 24 43 and 54 mcg/ml at doses of 250 500 750 and 1000 mg, respectively. Twelve hours after oral doses of 250,500 and 750 mg, the plasma concentration of the drug decreases to 01 02 and 04 mcg/ml, respectively.

The drug is well distributed in body tissues (excluding fat-rich tissue such as nerve tissue). Concentrations in tissues are 2-12 times higher than in plasma. Therapeutic concentrations are reached in saliva tonsils liver gallbladder bile intestine abdominal and pelvic organs (endometrium fallopian tubes and ovaries uterus) seminal fluid prostate tissue kidney and urinary organs lung tissue bronchial secretion bone tissue muscle synovial fluid and articular cartilage peritoneal fluid skin. Small amount of cerebrospinal fluid is infiltrated into the cerebrospinal fluid, where its concentration in the absence of inflammation of the meninges is 6-10% of that in blood serum, and 14-37% in inflamed ones. Ciprofloxacin also penetrates well into the ocular fluid pleura peritoneal lymph through the placenta. Concentration of ciprofloxacin in neutrophils is 2-7 times higher than in blood serum.

It is metabolized in the liver (15-30%) with the formation of slightly active metabolites (diethylcyclofloxacin sulfociprofloxacin oxociprofloxacin formylciprofloxacin).

The elimination half-life is about 4 hours in chronic renal failure up to 12 hours. It is eliminated mainly by kidneys by tubular filtration and tubule secretion unchanged (40-50 %) and as metabolites (15 %); the rest part is eliminated through gastrointestinal tract. A small amount is excreted with breast milk.

Renal clearance is 3-5 ml/min/kg; total clearance is 8-10 ml/min/kg.

In chronic renal failure (creatinine clearance greater than 20 ml/minute) the percentage of ciprofloxacin excreted through the kidneys decreases, but there is no cumulation in the body due to compensatory increase of ciprofloxacin metabolism excretion through the gastrointestinal tract.

Indications

Infectious and inflammatory diseases caused by susceptible microorganisms:

• lower respiratory tract diseases (acute and chronic (acute) bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis);
• infections of ENT organs (acute sinusitis);
• Kidney and urinary tract infections (cystitis, pyelonephritis);
• Complicated intra-abdominal infections (in combination with metronidazole);
• chronic bacterial prostatitis;
• uncomplicated gonorrhea;
• typhoid fever, campylobacteriosis, shigellosis, traveler’s diarrhea;
• Skin and soft tissue infections (infected ulcers, wounds, burns, abscesses, phlegmon);
• bones and joints (osteomyelitis, septic arthritis);
• infections against a background of immunodeficiency (arising from treatment with immunosuppressive drugs or in patients with neutropenia);
• prevention and treatment of pulmonary anthrax.

Children:

• the treatment of complications caused by Pseudomonas aeruginosa in children with pulmonary cystic fibrosis from 5 to 17 years;
• prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis).

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Active ingredient

Ciprofloxacin

Composition

One tablet contains:

Active ingredient:

ciprofloxacin hydrochloride monohydrate (in terms of ciprofloxacin) 500 mg;

Auxiliary substances:

Lactulose 600.0 mg,

povidone low molecular weight 28.0 mg,

croscarmellose sodium 65.0 mg,

microcrystalline cellulose 60.0 mg,

magnesium stearate 10.0 mg,

corn starch sufficient to produce an uncoated tablet of 1400.0 mg;

Shell excipients:

Hypromellose 19.04 mg, macrogol-4000 8.32 mg, talc 2.2 mg, titanium dioxide 10.44 mg.

How to take, the dosage

The tablets should be taken orally regardless of meals, without chewing and with a small amount of liquid. If the drug is taken on an empty stomach, the active ingredient is absorbed more quickly. In this case, do not wash down the tablets with milk products or beverages enriched with calcium (for example, milk yogurt and juices with high calcium content). Calcium in conventional foods has no effect on the absorption of ciprofloxacin.

The recommended dosing regimen:

• respiratory tract infections (depending on the severity of the infection and patient’s condition): 500 mg 2 times daily to 750 mg 2 times daily;
• urinary tract infections: acute uncomplicated: 250 mg 2 times daily to 500 mg 2 times daily; cystitis in women (before menopause): 500 mg once daily; complicated: from 500 mg 2 times daily to 750 mg 2 times daily;
• infections of the genitals (except gonorrhea): 500 mg 2 times a day to 750 mg 2 times a day;
• Gonorrhea: 500 mg 1 time a day once;
• diarrhea: 500 mg 2 times a day;
• other infections (see Other infections (see section “Indications for use”): 500 mg 2 times daily;
• severe life-threatening infections (especially with Pseudomonas spp. Staphylococcus spp. Streptococcus spp.) including Streptococcus pneumoniae bone and joint infections septicemia peritonitis: 750 mg twice daily.

Dosing regimen in elderly patients (after 65 years): elderly patients should be prescribed lower doses of ciprofloxacin depending on severity of illness and creatinine clearance rate.

Dosing regimen for patients with renal impairment: when creatinine clearance is 30 to 60 ml/min/173m2 or its plasma concentration is 14 to 19 mg/100 ml, the maximum daily dose of ciprofloxacin is 1000 mg; when creatinine clearance is below 30 ml/min/173m2 or its plasma concentration is 2 mg/100ml or more, the maximum daily dose of ciprofloxacin is 500 mg; patients with renal failure on hemodialysis: With a creatinine clearance of 30 to 60 mL/min/173m2 or a plasma concentration of 1.4 to 19 mg/100ml maximum daily dose of ciprofloxacin is 1000 mg; when creatinine clearance is 30 ml/min/173m2 or less or its plasma concentration of 2 mg/100ml or more maximum daily dose of ciprofloxacin is 500 mg. On days of hemodialysis, ciprofloxacin is taken after the procedure.

Ambulatory patients with renal failure on continuous peritoneal dialysis: maximum daily dose of ciprofloxacin is 500 mg.

Patients with hepatic insufficiency: no dose adjustment is required.

The duration of treatment depends on the severity of the disease clinical and bacteriological control. It is important to continue treatment systematically for at least 3 days after disappearance of fever or other clinical symptoms. Average duration of treatment: 1 day in acute uncomplicated gonorrhea and cystitis; up to 7 days in kidney infections of the urinary tract and intra-abdominal infections; the entire period of neutropenia in immunocompromised patients; not more than 2 months in osteomyelitis; 7 to 14 days in other infections. In case of infections caused by Streptococcus spp. due to risk of late complications the treatment should be continued for at least 10 days; in case of infections caused by Chlamydia spp. the treatment should also be continued for at least 10 days.

Interaction

Due to the reduction of microsomal oxidation processes in hepatocytes, increases the concentration and prolongs the elimination half-life of theophylline (and other xanthines such as caffeine) oral hypoglycemic drugs indirect anticoagulants promotes reduction of the prothrombin index. In concomitant administration with theophylline it is recommended to carry out continuous monitoring of plasma concentration of theophylline and if necessary to reduce the dose of theophylline.

In combination with other antimicrobial drugs (beta-lactam antibiotics aminoglycosides clindamycin metronidazole) synergism is usually observed; can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp.with meslocillin azlocillin and other beta-lactam antibiotics in streptococcal infections; with isoxazolylpenicillin and vancomycin in staphylococcal infections; with metronidazole and clindamycin in anaerobic infections.

The nephrotoxic effect of cyclosporine is increased serum creatinine in these patients requires monitoring of this index 2 times a week.

In concomitant administration with indirect anticoagulants, the international normalized ratio should be monitored frequently enough and also within a short time after completion of combined therapy. Oral administration together with iron-containing drugs sucralfate and antacids containing magnesium calcium and aluminum salts leads to decreased absorption of ciprofloxacin, therefore it should be administered 1-2 hours before or 4 hours after taking the above mentioned drugs.

Combined administration of ciprofloxacin with dairy products or beverages enriched with minerals (e.g., yogurt, calcium-enriched orange juice) should be avoided because absorption of ciprofloxacin may be decreased. However, calcium in other foods has no significant effect on absorption of ciprofloxacin.

Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures. Fluoroquinolones form chelated compounds with magnesium and aluminum ions of the buffer system of didanosine which dramatically reduces absorption of the antibiotic; therefore, ciprofloxacin is taken two hours before didanosine or two hours after taking the indicated drug.

Methoclopramide accelerates absorption, which leads to a decrease in time to reach its maximum concentration.

Ciprofloxacin due to reduction of microsomal oxidation processes in hepatocytes increases plasma concentration and prolongs T1/2 of glibenclamide which may cause hypoglycemia in rare cases. Concomitant use of ciprofloxacin with glibenclamide may enhance the effect of the latter.

Concomitant use of ciprofloxacin and phenytoin has been observed to alter (increase or decrease) the plasma levels of phenytoin. To avoid weakening of anticonvulsant effect of phenytoin due to decreasing of its concentration and to prevent side effects associated with phenytoin overdose it is recommended to monitor phenytoin therapy in patients receiving both drugs when ciprofloxacin is discontinued. including determination of phenytoin plasma content during the whole period of concomitant use of both drugs and for a short time after completion of combined therapy. Caution should be exercised when concomitant use of ciprofloxacin as well as other fluoroquinolones in patients receiving drugs which cause prolongation of QT interval (for example antiarrhythmic drugs of class 1A or class III. tricyclic antidepressants, macrolides, neuroleptics) (see section “Special indications”).

The co-administration of uricosuric drugs leads to slower excretion (up to 50%) and increased plasma concentration of ciprofloxacin. Increases the maximum concentration 7-fold (4 to 21-fold) and the area under the concentration-time curve 10-fold (6 to 24-fold) of tizanidine, which exceeds the risk of marked decrease in blood pressure and drowsiness.

When used concomitantly with omeprazole, there may be a slight decrease in the maximum plasma concentration of the drug and a decrease in the AUC.

Probenecid inhibits renal excretion of ciprofloxacin leading to increased ciprofloxacin concentrations.

In a study in healthy volunteers it was found that concomitant use of preparations containing lidocaine and ciprofloxacin moderate inhibitor of CYP1A2 isoenzyme resulted in 22% lower clearance of lidocaine when administered intravenously. Despite good tolerability of lidocaine, an increase in side effects due to interaction is possible when used concomitantly with ciprofloxacin.

Concomitant use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days showed an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively. The patient’s condition should be monitored and, if necessary, the dosing regimen of clozapine should be adjusted during its concomitant use with ciprofloxacin and for a short time after completion of combined therapy.

Concomitant use of ciprofloxacin and methotrexate results in delayed renal-channel transport of methotrexate potentially leading to increased plasma concentrations of methotrexate which may increase the risk of methotrexate-related toxic reactions. Therefore it is necessary to monitor the condition of patients during treatment with methotrexate and concomitant administration of ciprofloxacin.

In clinical studies it has been shown that concomitant use of duloxetine and potent CYP1A2 isoenzyme inhibitors (such as fluvoxamine) may lead to increased AUC and Cmax of duloxetine. Despite the lack of clinical data on possible interaction with ciprofloxacin, it is possible to foresee the possibility of such interaction when ciprofloxacin and duloxetine are used simultaneously.

Concomitant use of ropinirole with ciprofloxacin may result in increased concentrations of ropinirole which may be accompanied by an increased risk of adverse reactions. In case of concomitant use it is necessary to monitor the adverse effects of ropinirole during its concomitant use with ciprofloxacin and for a short time after completion of combined therapy.

Concomitant use of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg resulted in a 2-fold increase in Cmax and AUC of sildenafil. The use of this combination is possible only after an assessment of the benefit/risk ratio.

Special Instructions

Patients with a history of epilepsy, seizures, vascular disease and organic brain lesions due to the risk of CNS adverse reactions, ciprofloxacin should be prescribed only for vital signs.

In case of severe and prolonged diarrhea during or after treatment with ciprofloxacin the diagnosis of pseudomembranous colitis should be excluded which requires immediate withdrawal of the drug and appropriate treatment. The use of drugs suppressing intestinal peristalsis is contraindicated.

In case of tendon pain or the first signs of tendovaginitis, treatment should be discontinued because there have been some cases of inflammation and even tendon rupture during treatment with fluoroquinolones.

Any adequate fluid intake with normal diuresis should be maintained during treatment with ciprofloxacin.

People should avoid contact with direct sunlight during treatment with ciprofloxacin.

As women have a longer average QT interval compared to men, they are more sensitive to drugs that cause QT interval prolongation. Ciprofloxacin should be used with caution in combination with QT prolonging agents (e.g. antiarrhythmic agents of classes IA and III tricyclic antidepressants macrolides neuroleptics) in patients with increased risk of patients at increased risk of QT prolongation or pirouette arrhythmias (e.g., congenital long QT syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalances (e.g., hypokalemia, hypomagnesemia).

When using ciprofloxacin, there have been cases of liver necrosis and life-threatening liver failure. In the presence of symptoms of liver disease such as anorexia jaundice darkened urine itching abdominal pain the use of ciprofloxacin should be discontinued. In patients with severe myasthenia gravis ciprofloxacin should be used with caution as exacerbation of symptoms is possible.

When using ciprofloxacin there may be cases of tendonitis and tendon rupture (mainly Achilles tendon) sometimes bilaterally during the first 48 hours after the start of therapy inflammation and tendon rupture may occur even several months after ciprofloxacin treatment is stopped. In elderly patients and in patients with tendon diseases receiving concomitant treatment with glucocorticosteroids there is an increased risk of tendinopathy.

When using ciprofloxacin it was reported about cases of epileptic status ciprofloxacin like other fluoroquinolones can provoke seizures and lower the seizure threshold. If seizures occur, the drug should be discontinued psychiatric reactions may occur even after the first use of fluoroquinolones including ciprofloxacin.

In patients using fluoroquinolones including ciprofloxacin, cases of sensory and sensorimotor axonal polyneuropathy affecting small and/or large axons and resulting in paresthesia, hyposthesia, dysesthesia and weakness have been reported. Symptoms may manifest soon after initiation of use and may be irreversible. If a patient develops symptoms of neuropathy including pain, tingling sensation, numbness and/or weakness or other sensory disturbances including tactile pain temperature vibration sensitivity and sense of position, the use of ciprofloxacin should be discontinued immediately.

In rare cases, depression or psychotic reactions may progress to suicidal ideation and self-harming behavior such as suicide attempts including those that have occurred. If a patient develops one of these reactions, the drug should be stopped and the physician should be informed; caution should be exercised when concomitant use of ciprofloxacin and drugs metabolized by CYP4501A2 isoenzymes such as ropinirole olanzapine theophylline methylxanthine caffeine duloxetine clozapine.

In some cases hypersensitivity to the drug, including allergic reactions, may develop after the first dose of ciprofloxacin and the physician should be informed immediately. In extremely rare cases anaphylactic reactions up to and including anaphylactic shock may occur after the first use. In these cases the use of ciprofloxacin should be stopped immediately and appropriate treatment should be carried out.

Because ciprofloxacin has some activity against Mycobacterium tuberculosis, false negative culture results may be obtained when samples are taken during ciprofloxacin treatment.

Influence on driving and motor skills:

With treatment, refrain from driving and engaging in potentially hazardous activities that require increased concentration and quick psychomotor reactions.

Contraindications

Hypersensitivity, concomitant use with tizanidine (risk of marked decrease in blood pressure, somnolence), age under 18 years (before the completion of skeletal formation, except for the therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis from 5 to 17 years; prevention and treatment of pulmonary anthrax), pregnancy, lactation period.

With caution

Developed atherosclerosis of cerebral vessels, cerebral circulatory disorders, mental illness, epilepsy, expressed renal and/or hepatic insufficiency, advanced age.

Side effects

Digestive system: nausea diarrhea vomiting abdominal pain flatulence decreased appetite and the amount of food taken anorexia cholestatic jaundice (especially in patients with past liver disease) hepatitis pancreatitis hepatonecrosis.

Nervous system disorders: Dizziness headache increased fatigue tremor insomnia “nightmare” dreams paresthesias and dysesthesias hypoesthesia hyperesthesia seizures vertigo movement coordination disorders sweating anxiety psychomotor hyperactivity/anxiety disorientation confusion hallucinations psychotic reactions (which may lead to self-harming behaviors such as suicidal acts/thoughts and suicide attempts or successful suicides) depression (which can lead to self-harming behaviors such as suicidal acts/thoughts and suicide attempts or successful suicides) epilepsy attacks benign intracranial hypertension peripheral neuropathy and polyneuropathy

Sense organs: disorders of taste and smell visual disturbances (diplopia change in color perception) tinnitus tinnitus hearing loss hearing loss.

Cardiovascular system disorders: tachycardia prolongation of QT interval ventricular arrhythmias (including tina “pirouette” decreased blood pressure flushes to the skin vasodilation.

Hematopoietic system: neutropenia leukopenia agranulocytosis granulocytopenia anemia thrombocytopenia leukocytosis thrombocytosis hemolytic anemia pancytopenia (life threatening).

Laboratory parameters: increase of “liver” transaminases and alkaline phosphatase activity hypercreatininemia hyperbilirubinemia hyperglycemia hypoglycemia increase of international normalized ratio (in patients receiving vitamin K antagonists) change of prothrombin increase of amylase activity.

Relative system disorders: hematuria crystalluria (especially in alkaline urine and low diuresis) renal failure renal interstitial nephritis.

Allergic reactions: Itchy skin rash urticaria formation of blisters accompanied by bleeding and small nodules forming scabs drug fever pinpoint hemorrhages (petechiae) facial or laryngeal edema eosinophilia increased photosensitivity vasculitis nodular erythema exudative multiform erythema acute generalized pustular exanthema Stevens-Johnson’s syndrome (malignant erythema exudative) toxic epidermal necrolysis (Lyell’s syndrome) angioedema anaphylactic reactions anaphylactic shock (life-threatening) serum sickness.

Others: respiratory disorders (including bronchospasm) arthralgia arthritis tendovaginitis tendon ruptures general weakness myalgia increased muscle tone muscle cramps muscle weakness exacerbation of myasthenia gravis symptoms gait disorders superinfections (candidiasis pseudomembranous colitis).

Overdose

Symptoms: nausea vomiting confusion dizziness tremor headache fatigue seizures hallucinations mental agitation QTc interval prolongation GI disturbances hepatic and renal disorders crystalluria hematuria.

The specific antidote is unknown. Careful monitoring of the patient’s condition is necessary to perform gastric lavage and the usual first aid measures to ensure adequate fluid intake. Only small amounts (less than 10%) of the drug may be eliminated by hemo- or peritoneal dialysis.

In order to prevent the development of crystalluria, it is recommended that renal function be monitored, including urine pH and acidity.

Similarities

Ciprofloxacin, Ciprolet, Cifran, Ciprofloxacin, Cipromed, Cifran OD, Ciprofloxacin, Cipromed, Ciprofloxacin Teva, Ciprofloxacin Renewal