Phthisopyram
Phthisopyram: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Phtizopyramum
ATX code: J04AC51
Active ingredient: pyrazinamide (pyrazinamide), isoniazid (isoniazid)
Manufacturer: Akrikhin, JSC (Russia)
Description and photo update: 28.11.2018
Phthisopyram is a combined anti-tuberculosis drug.
Release form and composition
The drug is available in the form of tablets: almost white or white, flat-cylindrical, with a dividing line and a chamfer (10 pcs. In blisters: in a cardboard box 5 or 10 packages and instructions for the use of Phthisopyram, for hospitals - in a cardboard box 100 packages; 50 or 100 pcs. in polypropylene or polyethylene cans, in a cardboard bundle 1 can; for hospitals: 500 or 1000 pcs. in polyethylene bags, in a polymer container 1 bag; 100 pcs. in cans, 25 cans in a cardboard box).
1 tablet contains:
- active ingredients: pyrazinamide - 500 mg, isoniazid - 150 mg;
- auxiliary components: stearic acid, sodium carboxymethyl starch, colloidal silicon dioxide, potato starch, talc.
Pharmacological properties
Pharmacodynamics
Phthisopyram is a combined preparation containing two active substances with anti-tuberculosis action. The mechanism of action of isoniazid is due to its ability to suppress the synthesis of mycolic acid, which is necessary for the formation of the cell wall of mycobacteria. It has a pronounced bactericidal effect against rapidly proliferating populations of Mycobacterium tuberculosis. Pyrazinamide is a nicotinamide derivative. Depending on its concentration and the sensitivity of microorganisms, it has a bactericidal or bacteriostatic effect.
Pharmacokinetics
After oral administration, absorption of isoniazid and pyrazinamide in the gastrointestinal tract occurs rapidly. Concomitant food intake reduces the absorption and bioavailability of isoniazid. With a single dose of 300 mg isoniazid, its maximum plasma concentration (C max) is reached after 1–2 hours. It takes the same time for pyrazinamide to reach C max in plasma, and 4–5 hours for pyrazinoic acid (an active metabolite of pyrazinamide).
Plasma protein binding: isoniazid - no more than 10%, pyrazinamide - 10–20%, pyrazinoic acid - 31%.
Pyrazinamide and isoniazid penetrate well into various body fluids and tissues. In cerebrospinal fluid, the content of pyrazinamide can be 87-100% of plasma concentrations. Both components are excreted in breast milk.
The main metabolic pathway of isoniazid is acetylation, which occurs in the liver. Its speed depends on the individual characteristics of the patient ("fast acetylators" and "slow acetylators"). Isoniazid metabolites have no antimicrobial activity.
Biotransformation of pyrazinamide occurs in the liver by hydrolysis. As a result of the action of microsomal enzymes, an active metabolite is formed - pyrazinoic acid, which is then converted into 5-hydroxypyrazinoic acid.
The half-life (T 1/2) of isoniazid in "fast acetylators" is 0.5-1.6 hours, in "slow acetylators" - from 2 to 5 hours.
T 1/2 of pyrazinamide is approximately 9.5 hours, pyrazinoic acid - 12 hours.
Isoniazid is excreted mainly through the kidneys (within 24 hours after administration): in the form of metabolites (N-acetylisoniazid) - from 75 to 95% of the administered dose, unchanged - up to 12% (in "fast acetylators") and up to 27% (for "slow acetylators").
Pyrazinamide is excreted mainly in the urine within 72 hours: unchanged - about 3%, in the form of pyrazinoic acid - 33%, in the form of other metabolites - 36%.
In case of impaired liver function, T 1/2 of the active components is lengthened. For pyrazinamide, it increases to 26 hours, and for pyrazinoic acid, up to 22 hours.
With severe renal failure in patients with a low rate of acetylation, cumulation of isoniazid is possible.
Indications for use
The use of Phthisopyram is indicated for the treatment of all forms and localizations of tuberculosis caused by mycobacteria sensitive to isoniazid and pyrazinamide.
Contraindications
- severe coronary insufficiency;
- uncontrolled arterial hypertension;
- epilepsy and other diseases, accompanied by a tendency to seizures;
- acute hepatitis;
- cirrhosis of the liver;
- peptic ulcer of the stomach and duodenum;
- myxedema;
- gout;
- bronchial asthma;
- hyperuricemia;
- psoriasis;
- period of pregnancy;
- breast-feeding;
- individual intolerance to the components of the drug.
Care should be taken when prescribing Phthisopyram tablets to patients with chronic renal failure, impaired liver function, malnutrition, and chronic alcohol dependence.
Phthisopyram, instructions for use: method and dosage
Prescribing a dose of Phthisopyram is carried out at the rate of 5-10 mg of isoniazid per 1 kg of patient weight.
The tablets are taken orally after meals, once a day, during the period of intensive care (within 90-120 days) - daily, then every other day. The duration of the general course of therapy depends on the nature of the disease, the tolerability of the treatment and the individual therapeutic effect.
Side effects
- on the part of the hepatobiliary system: liver dysfunction (including jaundice), more often with hypotrophy, previous liver diseases, in the elderly patient;
- from the digestive system: metal taste in the mouth, abdominal pain, nausea, vomiting, loss of appetite, diarrhea, exacerbation of peptic ulcers;
- from the nervous system: irritability, headache, sleep disturbances, dizziness, depression; rarely - insomnia, irritability, psychosis, euphoria; sometimes - peripheral neuropathy (more often in old age, during pregnancy, malnutrition, diabetes mellitus, chronic liver diseases, alcoholism); in some cases - convulsions, hallucinations, confusion; in patients with epilepsy - increased frequency of seizures;
- on the part of the cardiovascular system: increased blood pressure (BP), palpitations, angina pectoris;
- from the hemostasis system and hematopoietic organs: increased blood coagulation, thrombocytopenia, porphyria, sideroblastic anemia, splenomegaly, erythrocyte vacuolization;
- from the urinary system: interstitial nephritis, dysuria;
- on the part of the musculoskeletal system: myalgia, arthralgia;
- allergic reactions: itchy skin, rash, urticaria, photosensitivity;
- others: hyperthermia, hyperuricemia, acne, increased serum iron levels, gouty arthritis; very rarely - gynecomastia, menorrhagia.
Overdose
Symptoms: abdominal pain, nausea, vomiting, respiratory failure, increased levels of liver enzymes, jaundice, convulsions, impaired consciousness, acute pulmonary edema, hyperglycemia, metabolic ketoacidosis, coma.
Treatment: immediate gastric lavage, taking activated charcoal, prescribing forced diuresis, hemodialysis, taking general measures to maintain vital body functions.
special instructions
The use of alcohol and ethanol-containing drugs is contraindicated throughout the entire course of drug treatment.
It is recommended to carry out regular monitoring of indicators of liver function and complete blood count in patients with impaired liver function or, if necessary, long-term therapy. Periodic monitoring of serum uric acid levels is required, especially if there is a history of gout attacks.
There is a risk of developing peripheral neuropathy during isoniazid therapy, therefore, simultaneous administration of pyridoxine (vitamin B 6) is recommended for its prevention and treatment.
Consideration should be given to the effect of pyrazinamide on blood coagulation time when prescribing Phthisopyram to patients with hypoplastic anemia.
It is recommended to assess monthly liver function and monitor the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma.
With an asymptomatic transient increase in the level of liver enzymes, you should not stop taking Phthisopyram. If the level of ALT or AST exceeds the upper limit of the norm by more than 3 times, isoniazid withdrawal is required. Also, the drug should be canceled with the development of an acute or chronic form of hepatitis, in the latter case, it is impossible to resume isoniazid therapy.
It should be borne in mind that isoniazid can increase the excretion of zinc ions, reducing their concentration in the blood.
Influence on the ability to drive vehicles and complex mechanisms
While taking high doses of Phthisopyram, it is possible to develop peripheral neuropathy and other undesirable phenomena from the nervous system, which have a negative effect on the patient's ability to drive vehicles or work with complex mechanisms.
Application during pregnancy and lactation
The use of Phthisopyram tablets during gestation and breastfeeding is contraindicated.
Prescribing the drug to pregnant women is allowed only in special cases for health reasons.
If necessary, taking isoniazid and pyrazinamide during lactation, breastfeeding should be discontinued.
With impaired renal function
It is recommended to use Phthisopyram with caution for the treatment of patients with chronic renal failure.
For violations of liver function
The use of Phthisopyram is contraindicated in acute hepatitis and liver cirrhosis.
The drug can have a hepatotoxic effect, therefore, it should be prescribed with caution in case of impaired liver function, chronic alcoholism.
Drug interactions
Possible drug interactions while using Phthisopyram:
- phenytoin, carbamazepine, valproate: these drugs, under the influence of isoniazid, slow down their metabolism, therefore, when combined with the drug, it is recommended to reduce their doses; isoniazid increases serum concentrations of carbamazepine and phenytoin, increases the side effects of the latter;
- disulfiram: simultaneous administration with isoniazid contributes to the development of mental disorders, therefore, this combination should be avoided;
- ketoconazole, cyclosporine: may decrease their concentration in the blood and reduce their effectiveness;
- antacids: help to reduce the absorption of isoniazid;
- glipizide, tolbutamide, oral contraceptives, theophylline, tolazamide: in combination with isoniazid, they decrease their therapeutic efficacy;
- phenytoin: when taken with isoniazid, the side effects of phenytoin increase;
- triazolam: isoniazid inhibits the excretion of triazolam;
- ethanol: when taken together with isoniazid, the risk of developing hepatitis increases;
- allopurinol, colchicine, sulfinpyrazone, probenecid: when taken simultaneously with pyrazinamide, they reduce their effectiveness, since it increases the concentration of uric acid in the blood serum (in this situation, you should consider increasing the dose of anti-gout drugs);
- vitamin B 1: Isoniazid increases the excretion of vitamin B 1, reducing its effectiveness.
Analogs
Phthisopyram analogues are: Phthisopyram B 6, Protubpira, Protubetam, Phtizoetam, Mak-Paz plus, Iso-Eremfat, Izosid Comp., Isoniazid, etc.
Terms and conditions of storage
Keep out of the reach of children.
Store at temperatures up to 25 ° C, protected from moisture and light.
The shelf life is 2.5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Phthisopyram
There are currently no reviews of patients on Phthisopyram on social networks.
Price for Phthisopyram in pharmacies
The price for Phthisopyram for a package containing 50 tablets in a polymer can can be from 152 rubles, 100 tablets - from 218 rubles.
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
