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 pieces each in blister packs: in a cardboard box there are 5 or 10 packs and instructions for use of Ftisopyram, for hospitals - in a cardboard box 100 packs ; 50 or 100 pcs in polypropylene or polyethylene cans, 1 can in a cardboard pack; for hospitals: 500 or 1000 pcs in plastic bags, 1 bag in a polymer container; 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.
Analogues of the drug according to ATC codes:
ISOZIDE COMP. ISONIAZIDE + PYRAZINAMIDE + PYRIDOXINE ISONIAZIDE + ETHAMBUTOL ISONIAZIDE + ETHAMBUTOL + PYRIDOXINE MAC-PAS PLUS PROTUBPYRA PROTUBETAM HIXOSIDE All
Before using the drug FTIZOPYRAM you should consult your doctor. These instructions for use are for informational purposes only. For more complete information, please refer to the manufacturer's instructions.
Pharmacological properties
Pharmacodynamics
Ftisopyram is a combination drug containing two active substances with anti-tuberculosis activity. The mechanism of action of isoniazid is due to its ability to suppress the synthesis of mycolic acid, 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 sensitivity of microorganisms, it has a bactericidal or bacteriostatic effect.
Pharmacokinetics
After oral administration, absorption of isoniazid and pyrazinamide in the gastrointestinal tract occurs quickly. Concomitant food intake reduces the absorption and bioavailability of isoniazid. With a single dose of isoniazid 300 mg, its maximum concentration (Cmax) in plasma is reached after 1–2 hours. To achieve Cmax in plasma, pyrazinamide requires the same time, pyrazinoic acid (the active metabolite of pyrazinamide) - 4–5 hours.
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 the cerebrospinal fluid, the content of pyrazinamide can be 87–100% of plasma concentrations. Both components are excreted in breast milk.
The main pathway of isoniazid metabolism is acetylation, which occurs in the liver. Its speed depends on the individual characteristics of the patient (“fast acetylators” and “slow acetylators”). Metabolites of isoniazid do not have 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 (T1/2) of isoniazid for “fast acetylators” is 0.5–1.6 hours, for “slow acetylators” – from 2 to 5 hours.
T1/2 of pyrazinamide is approximately 9.5 hours, pyrazinoic acid - 12 hours.
Isoniazid is excreted primarily 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% (for “fast acetylators”) and up to 27% (for “slow acetylators”).
Pyrazinamide is excreted primarily in the urine within 72 hours: unchanged - about 3%, in the form of pyrazinoic acid - 33%, in the form of other metabolites - 36%.
If liver function is impaired, T1/2 of the active components is prolonged. For pyrazinamide it increases to 26 hours, and for pyrazinoic acid – up to 22 hours.
In cases of severe renal failure in patients with low acetylation rates, accumulation of isoniazid is possible.
Phthizopiram®
Isoniazid:
Taking isoniazid at the same time with certain medications may increase or decrease the effect.
Isoniazid inhibits the isoenzymes CYP2C19, CYP1A2, CYP2A6, CYP2E1 and CYP3A of the liver cytochrome P450 system, which may lead to a slower elimination of drugs metabolized by these enzymes.
The administration of other drugs may affect the metabolism of isoniazid.
In “slow acetylators” and in patients concomitantly using aminosalicylic acid, tissue concentrations of isoniazid may be increased and the incidence of side effects may be increased.
Possible interactions are presented below:
Alpha-1 blockers
Alfuzosin
The type of interaction is an increase in the concentration of alfuzosin in the blood.
The clinical implication is hemodynamic monitoring at the start of therapy.
Alcohol dehydrogenase inhibitors
Disulfiram
The type of interaction is an increase in dopamine activity due to inhibition of dopamine metabolism by isoniazid and disulfiram.
Clinical consequence: Monitoring for neurological changes (such as dizziness, ataxia, mood swings or behavioral changes) is necessary, in which case therapy should be discontinued or the dose of disulfiram reduced.
Analgesics
Acetylsalicylic acid
Type of interaction - possible weakening of the effect of isoniazid.
Clinical Implication: Coadministration is not recommended.
Opioids (such as morphine, fentanyl, alfentanil, buprenorphine, methadone, codeine)
Type of interaction: isoniazid slows down the metabolism of opioids.
Clinical Implication: Monitor for side effects and adjust opioid dosage if necessary.
Paracetamol
Type of interaction - isoniazid increases the hepatotoxicity of paracetamol.
Clinical implications: Concomitant use is not recommended and monitoring of liver function is necessary.
Anesthetics
Isoflurane, enflurane
Type of interaction - isoniazid can increase the formation of potentially nephrotoxic inorganic fluorine as a metabolite of isoflurane and enflurane (especially in “fast acetylators”), increasing nephrotoxicity.
The clinical implication is monitoring of renal function, especially in “fast acetylators” after surgery.
General anesthetics
Type of interaction: increased hepatotoxicity of isoniazid is possible.
Clinical implication is monitoring of liver function.
Antiasthmatic drugs
Theophylline
Type of interaction: isoniazid slows down the metabolism of theophylline.
The clinical consequence is monitoring the concentration of theophylline in the blood serum, in particular after discontinuation of isoniazid, and adjusting the dose of theophylline.
Antibiotics
Cycloserine, terizidone
The type of interaction is increased toxicity to the central nervous system of cycloserine/terizidone. Clinical consequence - increased attention should be paid to side effects from the central nervous system, if necessary, dose adjustment of cycloserine/terizidone.
Pyrazinamide
The type of interaction is increased hepatotoxicity of isoniazid and pyrazinamide. Clinical implication is monitoring of liver function.
Rifampicin
The type of interaction is increased hepatotoxicity of isoniazid and rifampicin. Clinical implication is monitoring of liver function.
Ethionamide, prothionamide
The type of interaction is increased toxicity towards the central nervous system of isoniazid and ethionamide/prothionamide.
Clinical Implication: Increased attention should be paid to CNS side effects.
Antifungal agents
Itraconazole
The type of interaction is a decrease in the concentration of itraconazole in the blood.
The clinical consequence is treatment failure; co-administration is not recommended.
Ketoconazole
The type of interaction is a decrease in the concentration of ketoconazole in the blood.
Clinical consequence - monitoring of the effectiveness of ketoconazole is necessary, and if necessary, dose adjustment of ketoconazole.
Anticholinergics
Atropine
The type of interaction is increased toxicity of atropine.
Clinical Implication: Coadministration is not recommended.
Darifenacin
Type of interaction: Isoniazid may slow down the elimination of darifenacin.
Clinical consequence: the effect of darifenacin may be enhanced; if necessary, the dose of darifenacin should be adjusted.
Antidepressants
Citalopram
Type of interaction: isoniazid may slow down the elimination of citalopram.
Clinical consequence - increased cardiotoxicity, if necessary, dose adjustment of citalopram; hypokalemia and hypomagnesemia should be corrected before treatment and monitored regularly.
Hypoglycemic agents
Insulin and derivatives/Alpha-glucosidase inhibitors/Sulfonylurea derivatives, biguanides, glinides, incretin mimetics, DPP4 inhibitors
The type of interaction is a violation of the effect of hypoglycemic drugs.
Clinical consequence - monitoring of blood glucose concentration, possibly reducing or increasing the effectiveness of hypoglycemic drugs, if necessary - dose adjustment.
Antiepileptic drugs
Carbamazepine
Type of interaction: isoniazid slows down the metabolism of carbamazepine, possibly increasing hepatotoxicity.
Clinical consequence - clinical monitoring is required, monitoring carbamazepine concentrations and liver function, and, if necessary, adjusting the dose of carbamazepine.
Phenytoin
Type of interaction: isoniazid slows down the metabolism of phenytoin.
Clinical consequence - it is necessary to monitor side effects, determine the concentration of hydantoin in the blood, and, if necessary, adjust the dose of phenytoin; it is recommended to monitor the concentration of phenytoin after discontinuation of isoniazid.
Primidon
Type of interaction: isoniazid slows down the metabolism of primidone.
Clinical consequence - monitoring of side effects is necessary, and dose adjustment if necessary.
Valproic acid
Type of interaction - the toxicity of isoniazid and valproic acid can be enhanced by mutual interaction.
Clinical consequence: monitoring of side effects is necessary, especially at the beginning and end of therapy, and, if necessary, dose adjustment of valproic acid.
Ethosuximide
Type of interaction: isoniazid slows down the metabolism of ethosuximide.
Clinical consequence - monitoring of side effects is necessary, and dose adjustment if necessary.
Anticoagulants
Warfarin and other coumarins/Indanedione derivatives
Type of interaction - isoniazid slows down the metabolism of anticoagulants and increases the tendency to bleeding.
Clinical consequence - with simultaneous use - monitoring of blood coagulation parameters, especially after cessation of isoniazid therapy, if necessary, dose adjustment of anticoagulants.
Antiparkinsonian drugs
Levodopa
The type of interaction is a decrease in the AUC (area under the pharmacokinetic curve) of levodopa, an increase in the risk of peripheral neuropathy due to levodopa and isoniazid.
Clinical consequence - loss of levodopa effectiveness, motor restlessness, tremor, general worsening of parkinsonian symptoms; If there are signs of peripheral neuropathy, therapy should be discontinued.
Antiprotozoal
Chloroquine
The type of interaction is an increased risk of peripheral neuropathy due to chloroquine and isoniazid.
Clinical implication: Monitoring for side effects is necessary, and if signs of peripheral neuropathy occur, therapy should be discontinued.
Halofantrine
The type of interaction is a decrease in the metabolism of halofantrine, an increase in the concentration of halofantrine in plasma.
Clinical implications: Monitoring for cardiac side effects and ECG monitoring before, during and after completion of therapy is necessary.
Beta blockers
Propranolol
Type of interaction: propranolol may reduce the plasma clearance of isoniazid.
Clinical consequence: Possible slight increase in isoniazid plasma concentrations; clinical significance probably low.
CCR5 chemokine receptor antagonists
Maraviroc
Type of interaction: Isoniazid may increase plasma concentrations of maraviroc.
The clinical consequence is to adjust the dose of maraviroc if necessary.
Glucocorticosteroids
Budesonide
Type of interaction: isoniazid may increase plasma concentrations of budesonide.
Clinical consequence: the effect of budesonide may be enhanced with long-term therapy.
Prednisolone
Type of interaction: Prednisolone can reduce plasma concentrations of isoniazid.
Clinical consequence - a decrease in the effect of isoniazid is possible; if necessary, dose adjustment of isoniazid is required.
Serotonin 5-HT3 receptor antagonists
Alosetron
The type of interaction is an increase in plasma concentrations of alosetron.
Clinical Implication: Coadministration is not recommended.
Immunomodulators
BCG vaccine
Type of interaction - loss of vaccine effect (including use in the treatment of bladder cancer).
Clinical Implication: Coadministration is not recommended.
Interferon beta-1a
The type of interaction is increased hepatotoxicity of isoniazid and interferon beta-1a.
Clinical consequence - monitoring of liver function is necessary, if ALT is 5 times > normal, a reduction in the dose of interferon beta-1a is recommended, which can be increased again after ALT normalization.
Immunosuppressants
Cyclosporine
Type of interaction: isoniazid may affect the concentration of cyclosporine in the blood plasma.
The clinical consequence is to monitor the concentration of cyclosporine in the blood plasma, and, if necessary, adjust the dose of cyclosporine.
Leflunomide/Teriflunomide
Type of interaction - increased risk of hepatotoxicity due to isoniazid and leflunomide/teriflunomide.
Clinical implications: Increased risk of hepatotoxicity; liver enzyme activity and bilirubin concentrations should be measured prior to initiation of leflunomide/teriflunomide therapy, then monthly for the first 6 months of therapy, and then every 6–8 months. Patients with liver failure or increased transaminase activity (ALT 2 times > normal) should not take leflunomide/teriflunomide. When ALT is 3 times > normal, it is necessary to discontinue therapy and remove the active metabolite of leflunomide using cholestyramine or activated carbon, weekly monitoring, and, if necessary, repeat the intake of adsorbents.
Thalidomide
Type of interaction - risk of peripheral neuropathy due to thalidomide and isoniazid.
Clinical implications: monthly monitoring of side effects in the first 3 months of treatment, electrophysiological tests before and after 6 months of treatment, possible discontinuation of therapy if signs of neuropathy appear.
Lipid-lowering drugs
Fluvastatin/Simvastatin/Pravastatin/Atorvastatin
The type of interaction is an increased risk of peripheral neuropathy due to isoniazid and fluvastatin, simvastatin, pravastatin and atorvastatin.
Clinical consequence: if signs of peripheral neuropathy occur, therapy should be discontinued.
MAO inhibitors
Tranylcypromine/Moclobemide
Type of interaction: isoniazid reduces the metabolism of tranylcypromine and moclobemide (clinically significant only in “slow acetylators”).
Clinical consequence - it is possible to increase the effectiveness of tranylcypromine and moclobemide in “slow acetylators”, monitoring side effects.
Muscle relaxants
Tizanidine
Type of interaction: isoniazid can slow down the metabolism of tizanidine and increase plasma concentrations of tizanidine.
Clinical consequence - combined use is not recommended, increased cardiotoxicity and CNS toxicity, increased effect of tizanidine.
Chlorzoxazone
The type of interaction is a decrease in clearance, an increase in plasma, and an increase in AUC (about 125%) of chlorzoxazone.
Clinical consequence: Monitoring of side effects is necessary and, if necessary, dose adjustment of chlorzoxazone.
Neuroleptics
Haloperidol
Type of interaction: isoniazid may slow down the metabolism of haloperidol.
Clinical consequence: monitoring of the neurological status is necessary, and, if necessary, dose adjustment of haloperidol.
Pimozide
Type of interaction: isoniazid can slow down the metabolism of pimozide and increase plasma concentrations of pimozide.
Clinical consequence: Concomitant use is not recommended, severe cardiac side effects.
Nonnucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz
The type of interaction is an increased risk of hepatotoxicity due to efavirenz and isoniazid.
Clinical Implication: Liver function testing before and during treatment is necessary.
Nucleoside reverse transcriptase inhibitors (NRTIs)
Didanosine/Stavudine
The type of interaction is an increased risk of peripheral neuropathy due to isoniazid, didanosine and stavudine.
Clinical consequence: Monitoring for side effects is necessary; if signs of peripheral neuropathy occur, therapy should be discontinued or the dose of isoniazid, didanosine or stavudine reduced.
Zalcitabine
Type of interaction: increased clearance of isoniazid by 2 times.
Clinical Implication: Monitoring of isoniazid efficacy is necessary.
Opioid receptor antagonists
Naltrexone
The type of interaction is an increased risk of hepatotoxicity due to naltrexone and isoniazid.
Clinical Implication: Coadministration should be avoided and liver function testing is warranted.
Phosphodiesterase inhibitors
Roflumilast
Type of interaction: Isoniazid may increase the bioavailability of roflumilast and roflumilast N-oxide.
The clinical implication is that the efficacy of roflumilast may be increased.
Selective estrogen receptor modulators (SERMs)
Torymifene
Type of interaction: isoniazid may increase plasma concentrations of toremifene.
Clinical implications include regular electrolyte measurements, complete blood count, and liver function testing.
Antispasmodics
Tolterodine
Type of interaction: Isoniazid may increase plasma concentrations of tolterodine.
Clinical consequence: If necessary, reduce the dose of tolterodine when used concomitantly with CYP3A4 inhibitors such as isoniazid (1 mg tolterodine twice daily), clinical monitoring is necessary.
Sympathomimetics
Adrenaline/Norepinephrine
The clinical consequence is increased side effects.
Platelet aggregation inhibitors
Clopidogrel
Type of interaction: isoniazid reduces bioactivation by inhibiting CYP2C19 and thereby reduces the effect of clopidogrel.
Clinical consequence: Concomitant use is not recommended and monitoring of clopidogrel effectiveness is necessary.
Tranquilizers
Benzodiazepines (such as diazepam, midazolam, triazolam)
Type of interaction: isoniazid may slow down the metabolism of benzodiazepines.
Clinical consequence - monitoring of side effects is necessary, and if necessary, dose adjustment of benzodiazepines.
Vitamins
Vitamin B6
Type of interaction: isoniazid enhances the excretion of pyridoxine.
Clinical Implication: Prophylactic administration of pyridoxine during isoniazid therapy is recommended.
Vitamin D
Type of interaction: isoniazid reduces plasma concentrations of vitamin D.
Clinical consequence: when taking medications containing vitamin D, monitoring of serum calcium concentration, serum phosphate concentration, and renal function is necessary, and, if necessary, dose adjustment of vitamin D.
A nicotinic acid
Type of interaction - isoniazid reduces the concentration of nicotinic acid (inhibition of the incorporation of nicotinic acid into nicotinamide adenine dinucleotide).
Clinical consequence - no.
Cytostatics
Bendamustine
Type of interaction - isoniazid increases the concentration of bendamustine in plasma.
Clinical Implication: The effect of bendamustine should be closely monitored for signs of toxicity such as leukopenia, infection, thrombocytopenia, bleeding, anemia and neutropenia, and the dose of bendamustine adjusted if necessary.
Clofarabine
The type of interaction is increased hepatotoxicity of clofarabine and isoniazid. Clinical Implication: Coadministration should be avoided and liver function monitoring is necessary.
Gefitinib
Type of interaction: Isoniazid may slow down the metabolism of gefitinib.
Clinical consequence: Monitoring of side effects is necessary and, if necessary, dose adjustment of gefitinib.
Methotrexate
The type of interaction is increased hepatotoxicity of methotrexate and isoniazid.
Clinical implications: Coadministration should be avoided and liver function tests should be monitored.
Pazopanib
Type of interaction: Isoniazid may slow down the metabolism of pazopanib.
Clinical implications: Monitoring for side effects, electrolyte measurements, ECG, liver function tests before and during treatment is necessary, and pazopanib dose adjustment is necessary if necessary.
Thioguanine
The type of interaction is increased hepatotoxicity of thioguanine and isoniazid.
Clinical implications—liver function testing.
Antacids
Antacids (especially those containing aluminum)
The type of interaction is a decrease in absorption and concentration of isoniazid in the blood.
Clinical consequence: Concomitant use should be avoided, and antacids should be taken no earlier than 1 hour after taking isoniazid.
Other
Chenodeoxycholic acid
Type of interaction: metabolism (acetylation) and excretion of isoniazid may be increased.
Clinical Implication: Coadministration is not recommended.
Interaction with food and drink
Ethanol increases the hepatotoxicity of isoniazid and accelerates its metabolism.
Absorption of isoniazid worsens after eating, especially carbohydrates.
During treatment, you should avoid eating cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack), since when they are consumed simultaneously with isoniazid, reactions may occur (skin flushing, itching, sensations of heat or cold, palpitations, increased sweating, chills, headache, dizziness) associated with suppression of the activity of monoamine oxidase (MAO) and diamine oxidase and leading to disruption of the metabolism of tyramine and histamine contained in fish and cheese.
Effect on laboratory parameters
Isoniazid may cause false-positive blood glucose results using a copper reagent; does not affect enzymatic tests for glucose determination.
Pyrazinamide:
Pyrazinamide is combined with other anti-tuberculosis drugs.
The likelihood of developing hepatotoxic effects of pyrazinamide increases when used together with rifampicin.
When used simultaneously with drugs that block tubular secretion, their excretion may be reduced and toxic reactions may increase.
Strengthens the antituberculosis effect of lomefloxacin.
Hypoglycemia may develop in patients with diabetes mellitus.
When used simultaneously with probenecid, a decrease in excretion and, as a result, increased toxic reactions are possible.
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;
- pregnancy period;
- breast-feeding;
- individual intolerance to the components of the drug.
Caution should be exercised when prescribing Fthisopyram tablets to patients with chronic renal failure, impaired liver function, malnutrition, and chronic alcohol dependence.
Side effects
- from the hepatobiliary system: liver dysfunction (including jaundice), more often with malnutrition, previous liver diseases, in the elderly patient;
- from the digestive system: metallic taste in the mouth, abdominal pain, nausea, vomiting, loss of appetite, diarrhea, exacerbation of peptic ulcers;
- from the nervous system: increased excitability, headache, sleep disturbances, dizziness, depression; rarely – insomnia, irritability, psychosis, euphoria; sometimes - peripheral neuropathy (more often in old age, pregnancy, malnutrition, diabetes mellitus, chronic liver diseases, alcoholism); in some cases – convulsions, hallucinations, confusion; in patients with epilepsy - increased frequency of seizures;
- from the cardiovascular system: increased blood pressure (BP), palpitations, angina pectoris;
- from the hemostatic system and hematopoietic organs: increased blood coagulation, thrombocytopenia, porphyria, sideroblastic anemia, splenomegaly, vacuolization of red blood cells;
- from the urinary system: interstitial nephritis, dysuria;
- from the musculoskeletal system: myalgia, arthralgia;
- allergic reactions: skin itching, rash, urticaria, photosensitivity;
- other: hyperthermia, hyperuricemia, acne, increased serum iron levels, gouty arthritis; very rarely - gynecomastia, menorrhagia.
special instructions
The use of alcohol and ethanol-containing medications is contraindicated throughout the entire course of treatment with the drug.
It is recommended to regularly monitor liver function tests and complete blood count in patients with impaired liver function or when long-term therapy is required. 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, for its prevention and treatment, simultaneous administration of pyridoxine (vitamin B6) is recommended.
The effect of pyrazinamide on blood clotting time should be taken into account when prescribing Fthisopyram to patients with hypoplastic anemia.
It is recommended to evaluate liver function monthly and monitor plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.
If there is an asymptomatic transient increase in the level of liver enzymes, you should not stop taking Fthisopyram. If the level of ALT or AST exceeds the upper limit of normal by more than 3 times, discontinuation of isoniazid is required. The drug should also be discontinued if acute or chronic forms of hepatitis develop; in the latter case, isoniazid therapy cannot be resumed.
It should be taken into account that isoniazid can increase the excretion of zinc ions, reducing their concentration in the blood.
Impact on the ability to drive vehicles and complex mechanisms
When taking high doses of Ftisopyram, peripheral neuropathy and other adverse effects from the nervous system may develop, which have a negative impact on the patient’s ability to drive vehicles or operate complex mechanisms.
PHTIZOPYRAM: DOSAGE
The drug Ftisopyram is administered orally after meals, 1 time/day. Dosing of Fthisopyram is carried out according to isoniazid at the rate of 5-10 mg/kg of the patient’s weight.
The drug is used daily during the period of intensive therapy (3-4 months), and subsequently every other day. The total course dose of Ftisopyram for each patient is individual and depends on the nature of the disease, the effectiveness of treatment and tolerability.
Drug interactions
Possible drug interactions during simultaneous use of Ftisopyram:
- 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, increasing the side effects of the latter;
- disulfiram: simultaneous use with isoniazid contributes to the development of mental disorders, so this combination should be avoided;
- ketoconazole, cyclosporine: may reduce their concentration in the blood and reduce their effectiveness;
- antacids: help reduce the absorption of isoniazid;
- glipizide, tolbutamide, oral contraceptives, theophylline, tolazamide: in combination with isoniazid they reduce their therapeutic effectiveness;
- 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 because it increases the concentration of uric acid in the blood serum (in this situation, increasing the dose of anti-gout drugs should be considered);
- vitamin B1: isoniazid increases the excretion of vitamin B1, reducing its effectiveness.
pharmachologic effect
Isoniazid is a specific anti-tuberculosis drug that has a pronounced bactericidal effect, mainly against rapidly proliferating populations of Mycobacterium tuberculosis. Isoniazid inhibits the synthesis of mycolic acid, which is necessary for the formation of the cell wall of mycobacteria.
Pyrazinamide, a nicotinamide derivative, has high anti-tuberculosis activity. Its effect can be both bactericidal and bacteriostatic, depending on the concentration of the drug and the sensitivity of microorganisms.
