Phthisopyram B6 - instructions for use, dose, side effects, contraindications

Active substanceIsoniazid + Pyrazinamide + PyridoxineIsoniazid + Pyrazinamide + Pyridoxine

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Phthisopyram® B6

pills inwards

Dosage form: & nbsppills

Composition:

1 tablet contains

active substances: pyrazinamide - 500 mg, isoniazid-150 mg, pyridoxine hydrochloride - 15 mg

Excipients: silicon dioxide colloid, potato starch, sodium carboxymethyl starch, talc, stearic acid.

Description:tablets from white to white with a cream or yellowish hue of color, flat-cylindrical, with a facet and a risk. Presence of marble is admissible.

Pharmacotherapeutic group:Anti-tuberculosis drug combined

ATX: & nbsp

J.04.A.C.51 Isoniazid in combination with other drugs

Pharmacodynamics:

Isoniazid has a bactericidal effect on the actively dividing cells of Mycobacterium tuberculosis. The mechanism of its action is the inhibition of the synthesis of mycolic acids, which are a component of the cell wall of mycobacteria. For mycobacteria tuberculosis, the minimum inhibitory concentration (MIC) is 0.025-0.05 mg / l. Isoniazid has a moderate effect on slowly - and rapidly growing atypical mycobacteria.

Pyrazinamide: the pyrazinamide target is the mycobacterial fatty acid synthase gene, which is involved in the biosynthesis of mycolic acid. Pyrazinamide has bactericidal action at acidic pH values.Well penetrates into the tuberculosis foci. Its activity is high in caseous-necrotic processes, caseous lymphadenitis, tuberculomas. To manifest the bactericidal activity of pyrazinamide, the preparation is subjected to enzymatic conversion into the active form - pyrazinic acid. At acidic pH values, the MPC of pyrazinamide in vitro is 20 mg / L. On non-tuberculosis pathogens does not work.

Pyridoxine hydrochloride

Vitamin product. Participates in the metabolism. It is necessary for the normal functioning of the central and peripheral nervous system. Anti-TB drugs cause peripheral polyneuropathy, the occurrence of which can reduce pyridoxine. In this regard, the daily dose of vitamin increases to 60 mg. With the simultaneous administration of pyridoxine inwards with isoniazid and ethambutol, there is no interaction of these drugs at the pharmacokinetic and microbiological levels.

Pharmacokinetics:

Isoniazid quickly absorbed after ingestion, but with the simultaneous intake of the drug with food, its absorption and bioavailability are reduced.After a single oral intake of 300 mg of isoniazid, the maximum plasma concentrations are noted after 1-2 hours. The half-life period (T1 / 2) is 0.5-1.6 hours ("fast ascitators") or 2-5 hours ("slow"). If the liver function is impaired, the time (T1 / 2) of isoniazid is prolonged.

Connection with plasma proteins - up to 10%. Isoniazid well penetrates into various tissues and body fluids, including bones and spinal fluid. Isoniazid acetylated and hydrolyzed in the liver. Acetylation is the main pathway of isoniazid metabolism. The rate of acetylation depends on the individual characteristics of the patient. Metabolites of isoniazid do not have antimicrobial activity.

Within 24 hours with urine, 75-95% of the administered dose in the form of metabolites (N-acetylisoiniazide, etc.) is excreted. Part of isoniazid is excreted unchanged in urine: up to 12% in fast acetylators and up to 27% in slow acetylators. With severe renal failure in slow acetylenes, cumulation of the drug is possible.

Pyrazinamide quickly and almost completely absorbed into the digestive tract, it penetrates well into various tissues and body fluids. Its concentration in the cerebrospinal fluid is 87-100% of plasma concentrations.After a single oral intake, the maximum plasma concentrations of pyrazinamide are noted after 1-2 hours, pyrazinic acid after 4-5 hours.

The bond of pyrazinamide to plasma proteins is 10-20%, pyrazinic acid is 31%.

Pyrazinamide is biotransformed in the liver, where, under the influence of microsomal enzymes, it is first hydrolyzed to pyrazinic acid (which is an active metabolite), and then converted to 5-hydroxypyrazinoic acid. The half-life (T1 / 2) of pyrazinamide is about 9.5 hours, pyrazinic acid is about 12 hours. With renal failure (T1 / 2) increases to 26 hours and 22 hours, respectively. The drug is excreted mainly in the urine for 72 hours: about 3% unchanged drug, 33% - in the form of pyrazinic acid and 36% - in the form of other metabolites.

Pyridoxine hydrochloride

Absorbed rapidly throughout the small intestine, a larger amount is absorbed in the jejunum. Metabolised in the liver with the formation of pharmacologically active metabolites (pyridoxal phosphate and pyridoxamine phosphate). Pyridoxal phosphate with plasma proteins binds to 90%.Well penetrate into all tissues; accumulates mainly in the liver, less - in the muscles and central nervous system (CNS).

Penetrates through the placenta, is secreted with breast milk. T1 / 2- 15-20 days. It is excreted by the kidneys.

Indications:Treatment of tuberculosis caused by sensitive mycobacteria to isoniazid and pyrazinamide (all forms and localizations).

Contraindications:Phthisopyram® B6 is contraindicated in patients with hypersensitivity to isoniazid and pyrazinamide, epilepsy and other diseases accompanied by a tendency to convulsions, uncontrolled arterial hypertension, severe coronary insufficiency, liver cirrhosis, acute hepatitis, gastric ulcer and 12-colon, myxedema, bronchial asthma , psoriasis, hyperuricemia, gout, pregnancy and lactation. Children under 3 years (for this dosage form).

Carefully:With caution, prescribe the drug to people with chronic kidney failure.

Phthisopyram® B6 can have a hepatotoxic effect, so it should be used with caution in patients with impaired liver function in people with chronic alcoholism, as well as in patients with hypotrophy.

Pregnancy and lactation:

During pregnancy, phthisopyram® B6 is prescribed only for "vital" indications. Isoniazid and pyrazinamide excreted in breast milk. Women receiving phthisopyrine B6 should not breast-feed their baby.

Dosing and Administration:The drug Ftyzopyram® B6 is administered orally after meals once a day. Dosage of phthizopyram ® B6 for adults and children is carried out by isoniazid: 5-10 mg / kg of patient weight. The drug is used daily in the intensive care period (3-4 months), in the subsequent time - every other day. The total course dose of Ftyzoprama ® B6 for each patient is individual and depends on the nature of the disease, the effectiveness of treatment and tolerability.

Side effects:

Isoniazid

From the hepato-biliary system: there may be a violation of liver function, especially in patients with hypotrophy or previous liver diseases, as well as in the elderly.

From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain.

From the nervous system: headache, dizziness, rarely - irritability, euphoria, insomnia, psychosis. Sometimes it is possible to develop peripheral neuropathy, especially in elderly patients,pregnant women, patients with hypotrophy, patients with diabetes mellitus, as well as in patients with chronic liver diseases, including alcoholic etiology. Seizures can occur in patients with epilepsy.

From the cardiovascular system: palpitation, angina, increased blood pressure.

Allergic reactions: skin rash, itching.

Other: very rarely - gynecomastia, menorrhagia.

Pyrazinamide

On the part of the hepato-biliary system: the reactions from the liver vary from asymptomatic abnormalities of hepatic cell function, detected only by laboratory methods, to severe impairment of liver function manifested by jaundice. These side effects usually do not occur when taking pyrazinamide in doses not exceeding 25 mg / kg of body weight per day; the addition of pyrazinamide to rifampicin and isoniazid does not increase the overall incidence of toxic liver damage.

On the part of the digestive system: there may be a decrease in appetite, nausea, vomiting, diarrhea, a "metallic" taste in the mouth, exacerbation of the peptic ulcer.

From the side of the central nervous system: headache, dizziness, sleep disturbances, increased excitability, depression; in some cases - hallucinations, convulsions, confusion.

From the hematopoiesis and hemostasis system: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, increased blood coagulation, splenomegaly.

From the musculoskeletal system: arthralgia, myalgia.

From the side of the urinary system: dysuria, interstitial nephritis.

Allergic reactions: skin rash, hives, photosensitivity.

Other: hyperthermia, acne, hyperuricemia, increased serum iron concentration. Can develop gouty arthritis.

Pyridoxine hydrochloride

Allergic reactions, hypersecretion of hydrochloric acid, numbness, the appearance of a feeling of compression in the limbs - a symptom of "stocking" and "gloves", rarely - a skin rash, itching of the skin.

Overdose:

Symptoms of overdose: nausea, vomiting, abdominal pain, jaundice, increased liver enzymes, acute pulmonary edema, impaired consciousness, coma, convulsions, respiratory failure, hyperglycemia, metabolic ketoacidosis.

Treatment: gastric lavage with the introduction of activated carbon, forced diuresis, general measures to maintain vital functions, hemodialysis.

Interaction:

Isoniazid.

Isoniazid slows the metabolism of certain medicines, including phenytoin, carbamazepine, valproat. At a simultaneous appointment with isoniazid dose of these drugs is recommended to reduce.

It is necessary to avoid the simultaneous use of isoniazid and disulfiram, since this can lead to mental disorders. The mechanism of this interaction is not established.

Isoniazid increases the serum concentrations of carbamazepine and phenytoin and reduces the concentrations of ketoconazole and cyclosporine.

Antacids reduce the absorption of isoniazid.

Reduces the effectiveness of oral contraceptives, glipizide, tolbutamide, theophylline, tolazomide, vitamin B1; enhances the side effects of phenytoin; suppresses the excretion of triazolam, enhances the excretion of vitamin B1; reduces the content of zinc ions in the blood, increases their excretion.

Drinking alcohol with isoniazid therapy can increase the risk of hepatitis.

Pyrazinamide.

Pyrazinamide can increase serum uric acid concentrations and reduce the effectiveness of anti-gout drugs, such as allopurinol, colchicine, probenicide, sulfinpyrazone.In such cases, an increase in the dose of antidotal agents may be required.

When used simultaneously with pyrazinamide, the concentration of cyclosporin in the blood and the effectiveness may be reduced.

Special instructions:

During treatment with the drug, patients should refrain from drinking alcohol.

With prolonged therapy, as well as in patients with impaired liver function, it is recommended to regularly monitor the general blood test and liver function tests.

For the prevention and treatment of peripheral neuropathy, which can develop with isoniazid therapy, additional administration of pyridoxine (vitamin Bb) is recommended.

In some cases, especially in patients with a history of gout, it is recommended to periodically monitor the level of uric acid in the serum.

When prescribing pyrazinamide, patients with hypoplastic anemia should consider the effect of the drug on the time of blood coagulation.

It is recommended to monitor ALT and ACT levels in plasma and monthly to assess liver function. Isoniazid should be abolished only in cases where the levels of transaminases are more than 3 times higher than the upper limit of the norm,as often there is an asymptomatic transient increase in the level of hepatic enzymes, which does not require discontinuation of the drug. When developing acute or chronic hepatitis isoniazid it is necessary to cancel, in the latter case, it is impossible to resume isoniazid therapy.

When taking isoniazid and high doses, it is possible to develop adverse reactions from the nervous system (peripheral neuropathy), which affects the ability to drive and work with complex equipment.

Pyridoxine hydrochloride weakens the action levodopa with their joint application. Pyridoxine hydrochloride reduces the risk of toxic effects of antituberculosis drugs on the central and peripheral nervous system.

Effect on the ability to drive transp. cf. and fur:When taking isoniazid and high doses, it is possible to develop adverse reactions from the nervous system (peripheral neuropathy), which affects the ability to drive and work with complex equipment.

Form release / dosage:

Pills.

Packaging:

For 50 or 100 tablets in a can of polyethylene or in a can of polypropylene.

Each bank along with the instruction for use is placed in a pack of cardboard.

25 cans of 100 tablets together with an equal number of instructions for use are placed in a box of cardboard (for inpatient).

For 500 or 1000 tablets per package of polyethylene film; a polyethylene bag together with instructions for use in a container made of polyethylene or polypropylene (for inpatient).

Storage conditions:List B. In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of reach of children.

Shelf life:2 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002336

Date of registration:09.12.2011

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp09.12.2011

Illustrated instructions

Instructions

Phthisopyram® B6 (Phtizopyramum B6)