Phthisopyram® (Phtizopyramum®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceIsoniazid + PyrazinamideIsoniazid + Pyrazinamide
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  • Protubipira®
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    FARMASINTEZ, JSC (Irkutsk)     Russia
  • Phthisopyram®
    pills inwards 
    AKRIKHIN HFK, JSC     Russia
    • Dosage form: & nbsppills
    Composition:

    Active substances: andzoniazide - 0.15 g, nirazinamide 0.5 g;

    Excipients: potato starch, sodium glycolate, stearic acid, talc, silicon dioxide colloid (aerosil).

    Description:Tablets are white or almost white in color, flat-cylindrical, with a facet and a risk.
    Pharmacotherapeutic group:Anti-tuberculosis combination drug
    ATX: & nbsp

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

    Pharmacodynamics:

    Isoniazid is a specific anti-tuberculosis drug that has a pronounced bactericidal effect, mainly in relation to rapidly proliferating populations of mycobacterium tuberculosis. Isoniazid suppresses the synthesis of mycolic acid, which is necessary for the formation of the cell wall of mycobacteria.

    Pyrazinamide, a derivative of nicotinamide, has a high anti-tuberculosis activity. Its action can be both bactericidal and bacteriostatic, depending on the concentration of the drug and the sensitivity of microorganisms.

    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 (T1/2) is 0.5-1.6 hours ("fast acetylators") or 2-5 hours ("slow"). When a violation of the liver (T1/2) isoniazid is lengthened.

    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-acetyl isosine, etc.). 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 acetylators" the 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 connection of pyrazinamide with plasma proteins is 10-20%, pyrazinic acid is 31%.

    Undergoes biotransformation 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-hydroxypyrazinic acid. (T1/2) pyrazinamide - about 9.5 hours, pyrazinic acid - about 12 hours. With renal failure (T1/2) increases to 26 hours and 22 hours, respectively. The drug is excreted mainly with urine for 72 hours: about 3% - in the form of unchanged drug, 33% - in the form of pyrazinic acid and 36% - in the form of other metabolites.
    Indications:

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

    Contraindications:

    Phthisopyram® is contraindicated in patients with hypersensitivity to isoniazid and pyrazinamide, epilepsy and other diseases accompanied by a tendency to convulsions, uncontrolled hypertension, severe coronary insufficiency, liver cirrhosis, acute hepatitis, stomach ulcer and duodenal ulcer, myxedema, bronchial asthma, psoriasis, hyperuricemia, gout, pregnancy and lactation.

    Carefully:

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

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

    Pregnancy and lactation:

    During pregnancy, phthisopyram® is prescribed only for "vital" indications.

    Isoniazid and pyrazinamide excreted in breast milk. Women who take Ftyzopyram® should not breast-feed.

    Dosing and Administration:

    The preparation of Phthisopyram® is administered orally after meals, once a day.

    Dosing Ftyzoprama® 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® for each patient is individual and depends on the nature of the disease, the effectiveness of the treatment and the tolerability.

    Side effects:

    Isoniazid

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

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

    From the nervous system: headache, dizziness, rarely - irritability, euphoria, insomnia, psychosis. Sometimes the development of peripheral neuropathy is possible, 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. For the prevention of peripheral neuropathy it is recommended to take pyridoxine. 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

    From the hepatobiliary system: the liver reactions vary from asymptomatic liver function abnormalities, which are detected only with the help of laboratory methods, to severe violations of the 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.

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

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

    On the part of the organs of hematopoiesis and the system of hemostasis: thrombocytopenia, sideroblastic anemia, erythrocyte vacuolization, porphyria, increased blood coagulation, splenomegaly.

    From the musculoskeletal system: arthralgia, myalgia.

    From the urinary system: dysuria, interstitial nephritis.

    Allergic reactions: skin rash, hives, photosensitivity.

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

    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, reduces the concentration of ketoconazole and cyclosporine in the blood.

    Antacids reduce the absorption of isoniazid.

    Reduces the effectiveness of oral contraceptives, glipizide, tolbutamide, theophylline, tolazomide, vitamin AT1; enhances the side effects of phenytoin; Suppresses the excretion of triazolam, enhances the excretion of the vitamin AT1; 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, blood concentrations and the effectiveness of cyclosporine may decrease.

    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 (a vitamin AT6).

    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 the activity of ALT and ACT in the plasma and monthly 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, since an asymptomatic transient increase in the level of hepatic enzymes that does not require discontinuation of the drug is often observed. When developing acute or chronic hepatitis isoniazid it is necessary to cancel, in the latter case, it is impossible to resume isoniazid therapy.

    Effect on the ability to drive transp. cf. and fur:

    When taken in 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:

    Tabletki, 150 mg + 500 mg.

    Packaging:

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

    10 tablets per contour cell pack.

    Each jar or 5 or 10 contour squares, together with the instruction for use, is placed in a pack of cardboard.

    For 500 or 1000 tablets per package of polyethylene film; The plastic bag together with the instruction for use is placed in a container of polypropylene or polyethylene (for in-patient department).

    For 25 cans of 100 tablets or 100 contiguous cell packs, together with an equal number of instructions for use are placed in a box of cardboard (for inpatient).

    Storage conditions:

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

    Keep out of the reach of children.

    Shelf life:

    2 years and 6 months.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:P N003731 / 01
    Date of registration:16.10.2009 / 27.07.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia
    Manufacturer: & nbsp
    Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia
    Information update date: & nbsp09.01.2017
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