2010/06/23

Factive

Composition, structure and packing

Tablets, coated in white or almost white, oblong shape.

1 tab. gemifloksatsin (in the form mesylate seskvigidrata) 160 mg.

Excipients: microcrystalline cellulose, polyvinylpyrrolidone (povidone), krospovidon (poliplasdon X EL-10), magnesium stearate.

Tablets, coated in white or almost white, oblong, with the risk from two sides.

1 tab. gemifloksatsin (in the form seskvigidrata mesylate) 320 mg.

Excipients: microcrystalline cellulose, polyvinylpyrrolidone (povidone), krospovidon (poliplasdon X EL-10), magnesium stearate.

Clinico-pharmacological group: antibacterial fluoroquinolone group.

Pharmacological action

Antibacterial fluoroquinolone group. Bactericidal action. Interferes with the replication, repair and transcription of bacterial DNA by inhibiting the enzymes DNA gyrase (topoisomerase II) and topoisomerase IV, essential for the growth of bacteria. Gemifloksatsin has high affinity with bacterial topoisomerase II and IV. The mechanism of action of fluoroquinolones, including gemifloksatsin differs from that of beta-lactam antibiotics, macrolides, aminoglycosides and tetracyclines. There was no cross-resistance between gemifloksatsinom and these groups of antibiotics. The main mechanism of resistance to fluoroquinolones are mutations in the genes of DNA gyrase and DNA topoisomerase IV, the frequency of occurrence of which is 10-7-10-10.

Strains of Streptococcus pneumonia, with mutations in the genes encoding these enzymes, resistant to most fluoroquinolones. However, in a therapeutically relevant concentrations gemifloksatsin able to inhibit the modified enzymes. Thus, some strains of Streptococcus pneumonia, resistant to fluoroquinolones may be susceptible to gemifloksatsinu.

The drug is active against a broad spectrum of microorganisms, both in conditions in vitro, and in vivo: Gram-positive aerobic bacteria: Streptococcus spp., Including Streptococcus pneumoniae (including strains resistant to penicillin and macrolides and the most resistant to ofloxacin / levofloxacin strains, including strains of group Streptococcus pneumoniae, including subspecies, previously known as PRSP (Streptococcus pneumoniae resistant to penicillin), and combining strains resistant to two or more of the following antibiotics: penicillin, cephalosporins II generation, macrolides, tetracyclines and trimethoprim / sulfamethoxazole), Streptococcus pyogenes (including macrolide-resistant), Streptococcus viridans, Streptococcus agalactiae, Streptococcus milleri, Streptococcus anginosius, Streptococcus constellatus, Streptococcus mitis; Staphylococcus spp. (Including Staphylococcus aureus / methicillin sensitive to /, Staphylococcus epidermidis, Staphylococcus saprophyticus, Staphylococcus haemolyticus), Enterococcus spp. (Including Enterococcus faecalis, Enterococcus faecium); Gram-negative aerobic bacteria: Haemophilus spp. (Including Haemophilus influenzae, including strains producing β-lactamases, Haemophilus parainluenzae), Moraxella spp. (Including Moraxella catarrhalis, and producing β-lactamase neprodutsiruyuschie), Klebsiella spp. (Including Klebsiella pneumoniae, Klebsiella oxytoca), Escherichia coli, Neisseria gonorrhoeae, Acinetobacter spp. (Including Acinetobacter lwoffii, Acinetobacter anitartus, Acinetobacter calcoaceticus, Acinetobacter haemolyticus), Citrobaster spp. (Including Citrobaster freundii, Citrobaster koseri), Salmonella spp., Shigella spp., Enterobacter spp. (Including Enterobacter aerogenes), Serratia spp. (Including Serratia marcescens), Proteus spp. (Including Proteus mirabilis, Proteus vulgaris), Providencia spp., Morganella spp. (Including Morganella morganii), Yersinia spp., Pseudomonas spp. (Including Pseudomonas aeruginosa), Bordetella spp. (Including Bordetella pertrussis); as well as atypical bacteria: Coxiella spp. (Including Coxiella burnetti), Mycoplasma spp. (Including Mycoplasma pneumoniae), Legionella spp. (Including Legionella pneumophila), Chlamydia spp. (Including Chlamydia pneumoniae); anaerobic bacteria: Peptostreptococcus spp., Clostridium spp. (Including Clostridium non-perfringes, Clostridium perfringes), Fusobacterium spp., Porphyromonas spp., Prevotella spp.

Pharmacokinetics

Absorption

Once inside gemifloksatsin rapidly absorbed from the gastrointestinal tract. After a single dose of the drug at a dose of 320 mg Cmax plasma levels achieved during 0.5-2 hours after re-admission 320 mg Cmax in plasma was 1.61 ± 0.51 pg / ml (0.70-2.62 / ug / ml), and AUC - 9.93 ± 3.07 mg x h / ml (4.71-20.1 mg x h / ml). Eating virtually no effect on the pharmacokinetics gemifloksatsina, so the drug can be taken without regard to meals. Pharmacokinetics gemifloksatsina is linear in the dose range 40-640 mg. Drug is not cumulative (less than 30% at a dose of 640 mg for 7 days in advance).

Distribution

In exchange you receive 320 mg gemifloksatsina 1 time / Cmax is achieved on the third day. If readmission 55-73% of the drug bound to plasma proteins, the proportion of bound fraction does not depend on age.

Gemifloksatsin well into the lung tissue. The concentration gemifloksatsina in bronchoalveolar lavage above that of plasma.

Metabolism

In a small number gemifloksatsin metabolized in the liver. After 4 h after administration of unmodified gemifloksatsin prevails among the metabolites of the drug (65%) in blood plasma.

Gemifloksatsin not Biotransformation microsomal hepatic enzyme cytochrome P450.

Withdrawal

In healthy individuals 61.0 ± 9.5% dose gemifloksatsina eliminated through the intestines, and 36.0 ± 9.3% in the urine as unchanged drug and metabolic products. In hemodialysis the plasma displays 20-30% of the dose gemifloksatsina.

Pharmacokinetics in special clinical situations

The pharmacokinetics of the drug in children has not been studied.

In adult patients age does not affect the pharmacokinetics gemifloksatsina.

When liver failure possibly a slight increase in Cmax gemifloksatsina in blood plasma, which does not require dose adjustment.

In renal failure has been a slight increase in the time of elimination from the plasma gemifloksatsina unchanged Cmax.

Statement

Infectious-inflammatory diseases caused by microorganisms sensitive to the drug:
exacerbation of chronic bronchitis;
community-acquired pneumonia (including those caused by multiresistant strains);
Acute sinusitis.

Dosage regimen

Assign to 320 mg 1 time / day. With exacerbation of chronic bronchitis treatment is 5 days, with community-acquired pneumonia - 7 days for acute sinusitis - 5 days.

In mild and moderate renal dysfunction (QA more than 40 ml / min) dose correction is required. When expressed renal dysfunction (CC less than 40 ml / min), as well as patients who are on hemodialysis and continuous ambulatory peritoneal dialysis, long-term, the recommended dose is 160 mg 1 time / day.

Elderly patients, patients with impaired hepatic function changes dose regimen is not required.

The tablets should be taken by mouth, without chewing, drinking a small amount of water, regardless of the meal.

Side effect

Allergic reactions: sometimes - itching, rash, and in some cases - Stevens-Johnson syndrome (malignant exudative erythema multiforme), toxic epidermal necrolysis (Lyell's syndrome), increased photosensitivity, allergic pneumonitis.

On the part of the digestive system: nausea, diarrhea, and sometimes - vomiting, abdominal pain, flatulence, anorexia, rarely - acute liver failure, hepatitis, increase in liver transaminases, total bilirubin level.

From the side of the central nervous system and peripheral nervous system: Rarely - tremor, restlessness, anxiety, confusion, hallucinations, paranoid syndrome, depression, drowsiness (with symptoms of CNS lesions reception gemifloksatsina stop), in some cases - sensory or sensorimotor axonal polyneuropathy, manifested by paresthesias , hypoesthesia and other violations of sensitivity, weakness.

From the sensory organs: rarely - violations of taste and smell, visual disturbances (diplopia, changes in color vision), tinnitus, vertigo, hearing loss.

On the part of the hematopoietic system: sometimes - leukopenia; rarely - thrombocytopenia, in some cases - pancytopenia, thrombocytopenic purpura, agranulocytosis, anemia (including hemolytic and aplastic).

On the part of the urinary tract: rare - crystalluria, in some cases - interstitial nephritis, acute renal failure.

On the part of the musculoskeletal system: rarely - arthralgia, arthritis, abscess, myalgia, tendon rupture shoulder, hand, Achilles tendon or other tendons.

From the laboratory tests: rarely - to improve the content of sodium, potassium reduction, reduction of calcium levels, changes in hematocrit, increased activity of CK.

Other: rarely - vasculitis, superinfection (candidiasis, a pseudomembranous colitis).

Contraindications
Pregnancy
Lactation (breastfeeding);
childhood and adolescence to 18 years;
lengthening of the QT interval on ECG (including congenital);
tendon injury, previously deferred due to the use of fluoroquinolones;
individual intolerance gemifloksatsina and other fluoroquinolones.

Precautions should be prescribed the drug at an increased risk of arrhythmias (including clinically significant bradycardia, and acute myocardial ischemia), and deficiency of glucose-6-phosphate dehydrogenase (the risk of hemolytic reactions), patients, especially elderly receiving SCS (because of their increased risk of injury to tendons) , epilepsy and a tendency to seizures, while receiving chemotherapy, prolong the interval QT (antiarrhythmics class I A (quinidine, procainamide) and class III (amiodarone, sotalol), for violations of water-electrolyte imbalance (hypokalemia, gipomagniemiya).

Pregnancy and lactation

Drug is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Application for violations of liver function

Patients with impaired liver function changes in dosage regimen is not required.

Application for violations of renal function

In mild and moderate renal dysfunction (QA more than 40 ml / min) doses of correction is required.

When expressed renal dysfunction (CC less than 40 ml / min), as well as patients who are on continuous hemodialysis and long-term ambulatory peritoneal dialysis, the recommended dose is 160 mg 1 time / day.

Cautions

During treatment gemifloksatsinom need to supply a sufficient amount of fluid subject to normal diuresis.

When receiving the drug (as the use of other fluoroquinolones), photosensitivity reactions may occur, it is recommended to avoid contact with direct sunlight. Treatment should be discontinued if symptoms of photosensitivity (eg, change skin like sunburn).

The risk of tendon injury may increase in patients receiving SCS, especially in elderly patients. At the first sign of tendonitis (pain and swelling in the tendons) to use the drug should be stopped, deleted exercise and consult your doctor.

In patients with diarrhea developed after the start of treatment Factiva, we can assume the development of pseudomembranous colitis. The most frequent causative agent of colitis is Clostridium difficile. In most cases, stopping treatment is sufficient for the disappearance of symptoms of colitis (in rare cases may require the appointment of antibacterial drugs active against Slostridium difficile).

Effects on ability to drive vehicles and management mechanisms

Be careful when driving or busy with other potentially hazardous activities that require high concentration and speed of psychomotor reactions, especially with simultaneous use of ethanol.

Overdose

Treatment: gastric lavage, artificial vomiting, excessive drinking, if necessary, carry symptomatically. The specific antidote is known. In hemodialysis of blood plasma displays 20-30% of the dose gemifloksatsina.

Drug Interactions

At the same time appointing Factiva c antacids containing aluminum and magnesium sulfate or iron bioavailability gemifloksatsina reduced. Antacids should be taken not less than 3 hours before or not earlier than 2 h after administration gemifloksatsina.

Sukralfat while applying reduced bioavailability gemifloksatsina. Sukralfat should be taken no earlier than 2 h after administration gemifloksatsina.

Estrogen-gestagen oral contraceptives significantly reduces the bioavailability gemifloksatsina.

Course reception gemifloksatsina not affect the pharmacokinetics of oral contraceptive preparations containing ethinylestradiol / levonorgestrel.

Terms and Conditions of storage

The drug should be stored in a dry, protected from light and away from children at or above 25 ° C.

Shelf life - 3 years.