Левофлорипин®

General characteristics. Structure:

Active ingredients: 75 mg of an isoniazid, 200 mg of a levofloksatsin гемигидрат in terms of levofloxacin, 400 mg of Pyrazinamidum, 150 mg of rifampicin, 10 mg of a pyridoxine of a gidroyokhlorid.

Excipients: starch corn, cellulose mikrokristalliyochesky, silicon dioxide colloid, magnesium stearate, talc, carboxymethylstarch nayotriya, croscarmellose sodium, ready mix "Opadry Brown" (gipromelloza, ferrous oxide red, macrogoal-400, titanium dioxide, ferrous oxide yellow, ferrous oxide black).

Pharmacological properties:

Indications to use:

Tuberculosis (any forms, any localization).

It is applied in an intensive phase as a part of a combination therapy at for the first time the revealed patients, at a disease recurrence with high risk of a medicinal usyotoychivost of mycobacteria of tuberculosis.

Route of administration and doses:

Inside, irrespective of meal of 1 times a day, it is more preferable in the first poyolovina of day. Levofloripin is dosed on a levofloksatsina of 13,2 mg/kg of body weight, but no more than 5 tablets. Treatment duration - 3 months.

At body weight more than 80 kg the isoniazid in an evening vreyomya is in addition appointed (the general daily dose of an isoniazid to 10 mg/kg). According to indications ^{Levofloripin®} it sochetayotsya with Kanamycinum, amikacin, kapreomitsiny (intramusculary in a dose of 15 mg/kg of 1 times a day within 3 months).

Features of use:

Isoniazid. In certain cases during treatment fatal medicinal develops geyopatit which can arise even after several months of the end of use. The risk increases with age (the largest frequency in an age group of 35-64 years), osoyobenno at the daily use of ethanol. Therefore it is monthly necessary to kontroyolirovat function of a liver, to persons 35 years function of a liver in addition are more senior issleyodut before an initiation of treatment. Except the ethanol use accessory factors of risk are chronic diseases of a liver, parenteral use of HP and the poyoslerodovy period; under these circumstances control of function of a liver (laboratoryony and clinical) should be carried out more often. Patients have to be informed on need to report about any manifestations of damage of a liver (inexplicable anorexia, nausea, vomiting, urine darkening, jaundice, rash, paresthesias of brushes and feet, a slayobost, fatigue or fever lasting more than 3 days, abdominal pains, especially in right hypochondrium).

During treatment it is necessary to avoid the use of cheese (especially Swiss or Cheshire), fishes (especially a tuna, a sardinella, a skipdzhek) as at their odnoyovremenny use with izoniazndy emergence of the reactions (a dermahemia, an itch, feeling of heat or cold, heartbeat, the increased sweating, a fever, a headache, dizziness) connected with suppression of activity of monoamine oxidase (MAO) and diaminoxidase and leading to disturbance of metabolism of tyramine and the histamine which are contained in fish and cheese is possible.

It must be kept in mind that the isoniazid can cause a hyperglycemia with a vtorichyony glucosuria; tests with recovery of copper can be false positive; drug does not influence fermental glucose tests.

Levofloxacin. During treatment it is necessary to avoid solar and artificial UF-radiation in order to avoid damage of integuments (photosensitization).

At emergence of signs of a tendinitis, pseudomembranous colitis levofloxacin is immediately cancelled.

It must be kept in mind that at patients with damage of a brain in the anamnesis (a stroke, a severe injury) development of spasms is possible, at insufficiency glyukozo-6-fosfatdegidrogenazy - risk of development of hemolysis.

Pyrazinamidum. At prolonged treatment it is necessary to control activity of alaninaminotranspherase (ALT) and concentration of uric acid in blood once a month.

At patients with a diabetes mellitus the risk of emergence of a hypoglycemia increases.

Rifampicin. Against the background of treatment skin, a phlegm, sweat, kcal, the lacrimal liquid, urine gain orange-red color. Can paint soft contact lenses with firmness.

Women of reproductive age during treatment should apply nayodezhny methods of contraception (peroral hormonal contraceptives and dopolniyotelny non-hormonal methods of contraception). At prolonged use systematic control of a picture of peripheral blood and function of a liver is shown. During treatment it is impossible to apply microbiological methods of definition of concentration of folic acid and B12 vitamin in blood serum.

Pyridoxine. When determining urobilinigen by means of Ehrlich's reagent can distort results.

During treatment by the drug Levofloripin® it is necessary to observe an ostoyorozhnost at control of vehicles and occupation other potentially dangerous types of activity demanding the increased concentration of attention and a byyostrota of psychomotor reactions.

Side effects:

From a nervous system: headache, dizziness, paresthesias, oneyomeniye of extremities, peripheral neuropathy; seldom - excessive fatigue or weakness, irritability, euphoria, sleep disorders, a tremor, concern, fear, galyolyutsination, confusion of consciousness, a polyneuritis, toxic psychosis, an emotional layobilnost, a depression, spasms, toxic neuropathy, memory disturbance, dvigatelyyony frustration.

From cardiovascular system (CCC): heartbeat, stenocardia, increase or lowering of arterial pressure (ABP), vascular collapse, tachycardia, lengthening of an interval of Q-T.

From the alimentary system: nausea, vomiting, gastralgia. diarrhea (including with blood), digestion disturbance, a loss of appetite, erosive gastritis, pain in a zhivoyota, псевдомембранозньш colitis, increase in activity of "hepatic" transaminases, a gi-perbilmrubinemiya, a hepatomegalia, jaundice, a yellow hepatatrophia; round ulcer aggravation, dysbacteriosis; seldom - toxic hepatitis, including with a lethal outcome.

From bodies of a hemopoiesis and system of a hemostasis: eosinophilia, thrombocytopenia, hemolitic and sideroblastny anemias, leukopenia, neutropenia, pancytopenia, vacuolation of erythrocytes, agranulocytosis, porphyria, hypercoagulation, спленомегалня, hemorrhages.

From sense bodys: vision disorder, optic neuritis, sniyozheniye of hearing, sense of smell, flavoring and tactile sensitivity.

From a musculoskeletal system: arthralgia, muscular weakness, mialgiya, rupture of sinews, tendinitis, рабдомиолиз.

From an urinary system: dysuria, giperkreatininemiya, intersticial nephrite, acute renal failure.

Allergic reactions: photosensitization, itch and dermahemia, skin rash (korevidny, makulopapulezny, exfoliative, purpura), small tortoiseshell, cutaneous dropsy and mucous membranes, malignant exudative erythema (Stephens-Johnson's syndrome), toxic epidermal necrolysis (Lyell's disease), bronchospasm. to an uduyoshya, acute anaphylaxis, Quincke's disease, allergic pneumonitis, likhoyoradka, arthralgia, lymphadenopathy, vasculitis.

From a metabolism: B6 hypovitaminosis, pellagra, hyperglycemia, metayobolichesky acidosis, gynecomastia.

Others: very seldom - a dysmenorrhea; induction of a porphyria, persistent fever, razyovity superinfections, acne, increase in concentration of serumal iron.

Interaction with other medicines:

Reception of a levofloksatsin together with an isoniazid, rifampicin and, especially, piraziiamidy, considerably increases antimicrobic activity concerning chuvstyovitelny and steady MBT.

Isoniazid. At a combination with paracetamol also nephrotoxicity increases gepatoto-; the isoniazid induces system of P450 cytochrome. therefore metabolism of paracetamol increases up to toxic products.

Ethanol raises a hepatotoxic of an isoniazid and accelerates his metabolism.

Reduces theophylline metabolism that can lead to increase in its kontsenyotration in blood.

Reduces metabolic transformations and increases concentration in alfentanil blood.

Cycloserinum and Disulfiramum strengthen adverse central effects of an isoniazid.

Raises a rifampicin hepatotoxic.

The combination to a pyridoxine reduces danger of development peripheral, neuritis.

With care it is necessary to combine with potentially neuro, gepato-and nefrotoksichny medicines because of danger of strengthening collateral a deystyoviya.

Strengthens action of derivatives of coumarin and an indandion, benzodiazepines, carbamazepine, a teofillnn as reduces their metabolism due to activation of isoenzymes of R-450 cytochrome.

Glucocorticosteroids accelerate metabolism in a liver and reduce active konyotsentration in blood.

Suppresses metabolism of Phenytoinum that leads to increase in its concentration in blood and to strengthening of toxic effect (correction of the mode of a doziyorovaniye of Phenytoinum, especially at patients with slow acetylation of an isoniazid can be required); sleyodut to consider at appointment as an anticonvulsant at a peredoziyorovka as an isoniazid.

Antiacid medicines (especially aluminum-bearing) zamedyolyat absorption and reduce concentration of an isoniazid in blood (antacids should be priyonimat not earlier than in 1 h after reception of an isoniazid).

At simultaneous use with enflurany the isoniazid can increase an obyorazovaniye of the inorganic fluoric metabolite possessing a nefrotoksichny deyyostviye.

At joint reception with rifampicin reduces concentration of a ketokonazol in blood.

Increases concentration of valproic acid in blood (control of concentration of valproic acid is necessary; correction of the mode a dozirovayoniya can be required).

Levofloxacin. Increases an elimination half-life (T,/2) cyclosporine.

The effect is reduced by the medicines oppressing motility of intestines, сукральфат, aluminum - and magnesium - the containing antiacid medicines and salts of iron (the break between reception not less than 2 h is necessary).

Non-steroidal anti-inflammatory drugs (NPVP), theophylline, proizyovodny a hnolona increase risk of development of spasms, glucocorticosteroids increase risk of a rupture of sinews.

At simultaneous use with indirect anticoagulants - proizvodnyyom of coumarin control of the International normalized relation (MHO) is necessary.

Cimetidinum and medicines blocking canalicular secretion zayomedlyat removal.

Pyrazinamidum. Pyrazinamidum is combined with other antitubercular drugs.

The probability of development of gepatoksichesky effect of drug increases at combined use with rifampicin.

Development of a hypoglycemia in patients with a diabetes mellitus is possible. At odnoyovremenny use with probenetsidy decrease in excretion and, owing to это­го, strengthening of toxic reactions is possible.

Rifampicin. Reduces activity of indirect anticoagulants, peroral hypoglycemic medicines (M), hormonal contraceptives, cardiac glycosides, antiarrhytmic medicines (Disopyramidum, пирменол, quinidine, мексилетин, токсалоид), GKS, dapsone, Phenytoinum, hexobarbital, a nortriptilin, benzodiazepines, theophylline, chloramphenicol, a ketokonazol, an itrakonazol, cyclosporine, Azathioprinum, beta adrenoblockers, blockers of "slow" calcium channels (BMKK), enalapril, Cimetidinum (rifampicin causes induction of isoenzymes of R-450 cytochrome, accelerating their metabolism). Antacids, narcotic analgetics, anticholinergic medicines and кетоконазол reduce (in case of a concomitant use inside) bioavailability of rifampicin. The isoniazid and/or Pyrazinamidum increase the frequency and weight of abnormal liver functions more than at purpose of one rifampicin, at patients with the previous liver disease.

Pyridoxine. Strengthens effect of diuretics; weakens activity of a levodopa.

The isoniazid, Penicillaminum, Cycloserinum and estrogensoderzhashchy peroral konyotratseptiva weaken effect of a pyridoxine.

Contraindications:

. hypersensitivity to an isoniazid, a levofloksatsin, Pyrazinamidum, rifampicin, a pyridoxine;

 

· pregnancy, lactation period;

· children's age up to 18 years (the period of formation and growth of a skeleton);

· a peptic ulcer of a stomach and a 12-perstny gut in an aggravation stage;

· ulcer colitis in an aggravation stage;

· the medicinal hepatitis which is recently postponed (less than 1 year) infektsionyony hepatitis, jaundice, a liver failure,

· liver diseases in obostyoreniye stages, cirrhosis;

· diseases of the central nervous system (epilepsy and other diseases with tendency to convulsive attacks);

· heavy pulmonary heart;

· chronic renal failure (CRF);

· gout;

· thrombophlebitis:

· damage of sinews at earlier carried out treatment of a hinolonama.

With care. Alcoholism, a liver failure, peripheral neuropathy, HIV infection, dekompensirovanny diseases of cardiovascular system (the chronic heart failure (CHF), the coronary heart disease (CHD), arterial hypertension), a hypothyroidism, advanced age (risk of existence of the accompanying decrease in a funkyotion of kidneys), a hyperuricemia, deficit glyukozo-6-fosfatdegidrogenazy.

Overdose:

Overdose cases are not registered ^{by the drug Levofloripin®} so far.

Storage conditions:

In the dry, protected from light place, at a temperature not over 25 to °s.khranit in the place, unavailable to children. Not to apply but expiry date. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

 

Tablets, film coated, 75 mg + 200 mg + 400 mg + 150 mg + 10 mg. On 50 or 100 tablets in bank from polypropylene or in bank from polyethylene of high pressure or polyethylene of low pressure. Each can together with the application instruction is placed in a pack from a cardboard. On 500 or 1000 tablets in a package from a film of polyethylene not stabilized. The plastic bag together with the application instruction is placed in a konyoteyner from polypropylene or in a container from polyethylene of high pressure or a poliyoetilen of low pressure (for a hospital).