Expiration date: 02/2026
Dosage form
Tablets are white with a yellowish or creamy shade of color, round, flat-cylindrical, with a chamfer and a risk. The presence of "marbling" is allowed.
Composition
One tablet contains:
active ingredients: isoniazid - 150 mg, ethambutol hydrochloride - 400 mg, pyridoxine hydrochloride - 15 mg;
excipients: calcium hydrophosphate dihydrate, povidone, crospovidone, magnesium stearate.
Pharmacotherapeutic group
antituberculous agent combined
Pharmacodynamics
A combined anti-tuberculosis drug.
Isoniazid is an anti-tuberculosis agent; it acts bacteriostatically. It is a prodrug - mycobacterial catalase peroxidase metabolizes isoniazid to an active metabolite, which, by binding to enoyl-(acyl-transferring protein)-reductase of fatty acid synthase II, disrupts the conversion of delta2-unsaturated fatty acids into mycolic acid. The latter is a branched chain fatty acid, which, combining with arabinogalactan (polysaccharide), participates in the formation of components of the Mycobacterium tuberculosis cell wall. Isoniazid is also an inhibitor of mycobacterial catalase peroxidase, which reduces the protection of the microorganism against reactive oxygen species and hydrogen peroxide.
Isoniazid is also active against a small number of Mycobacterium kansasii strains (in infections caused by this pathogen, sensitivity to isoniazid must be determined before starting treatment).
Ethambutol acts bacteriostatically; penetrates into actively growing mycobacterium cells, inhibits RNA synthesis, disrupts cellular metabolism, causes the cessation of reproduction and death of bacteria. It is active only against intensively dividing cells. Inhibits the growth and reproduction of Mycobacterium tuberculosis resistant to streptomycin, isoniazid, PASC (aminosalicylic acid), ethionamide, kanamycin. The minimum suppressive concentration (MPC) is 0.78-2 mg/l. It does not work on non-tuberculosis pathogens.
Pyridoxine is vitamin B6, participates in metabolism; it is necessary for the normal functioning of the central and peripheral nervous system. Upon entering the body, it is phosphorylated, converted into pyridoxal-5-phosphate and is part of enzymes that perform decarboxylation, transamination and racemization of amino acids, as well as enzymatic conversion of sulfur-containing and hydroxylated amino acids.
Participates in tryptophan metabolism (participation in the serotonin biosynthesis reaction).
Pharmacokinetics
Isoniazid
It is quickly and completely absorbed when ingested, food reduces absorption and bioavailability. The effect of the "first pass" through the liver has a great influence on the bioavailability index. The time to reach the maximum concentration of isoniazid in blood plasma is 1-2 hours, the maximum concentration in blood plasma after ingestion of a single dose of 300 mg is 3-7 mcg / ml. The association with plasma proteins is insignificant - up to 10%. The volume of distribution is 0.57-0.76 l/kg. It is well distributed throughout the body, penetrating into all tissues and fluids, including cerebrospinal, pleural, ascitic; High concentrations are created in lung tissue, kidneys, liver, muscles, saliva and sputum. Penetrates through the placental barrier and into breast milk.
It is metabolized in the liver by acetylation to form inactive products. In the liver, it is acetylated by N-acetyltransferase to form
N-acetylisoniazide, which is then converted into isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by the formation of cytochrome P450 by the system during N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; people with "slow" acetylation have little N-acetyltransferase. It is an inducer of the CYP2E1 isoenzyme. Half-life (T1/2) for "fast acetylators" -
0.5-1.6 hours; for "slow" patients - 2-5 hours. Limited data indicate that the pharmacokinetics of isoniazid may vary in patients with liver failure. With renal insufficiency, the half-life can increase to 6.7 hours. The half-life for children aged 1.5 to 15 years is 2.3-4.9 hours, and in newborns - 7.8-19.8 hours (which is explained by the imperfection of acetylation processes in newborns). Despite the fact that the T1/2 index varies significantly depending on the individual intensity of the acetylation processes, the average T1/2 value is 3 hours (oral intake of 600 mg) and 5.1 hours (900 mg). With repeated prescriptions, the half-life is shortened to 2-3 hours.
It is mainly excreted by the kidneys: 75-95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites - N-acetylisoniazide and isonicotinic acid. At the same time, the content of N-acetylisoniazide in "fast acetylators" is 93%, and in "slow" ones - no more than 63%. Small amounts are excreted in the faeces. The drug is removed from the blood during hemodialysis; 5 hours of hemodialysis allows up to 73% of the drug to be removed from the blood.
Ethambutol
Absorption is high; bioavailability is 75-80%. After oral administration of a dose of 25 mg, the maximum concentration is reached in 2-4 hours, the maximum concentration of ethambutol in plasma is 1-5 mcg /ml. The bond with plasma proteins is 20-30%.
It penetrates well into tissues and organs, as well as into biological fluids, with the exception of ascitic and pleural (into cerebrospinal fluid only in meningitis). The highest concentrations are created in the kidneys, lungs, saliva, and urine. Penetrates into breast milk. It does not pass through the intact blood-brain barrier. It is partially metabolized in the liver (15%) with the formation of inactive metabolites. The half-life from plasma is 3-4 hours, with impaired renal function - 8 hours. It is excreted by the kidneys - 80-90% (50% - unchanged, 15% - in the form of inactive metabolites) and with feces - 10-20% (unchanged). It is excreted during hemodialysis and peritoneal dialysis.
Pyridoxine
It is absorbed rapidly throughout the small intestine, a larger amount is absorbed in the jejunum. It is metabolized in the liver to form pharmacologically active metabolites (pyridoxal-5-phosphate and pyridoxaminophosphate). Pyridoxal-5-phosphate binds to plasma proteins by 90%. It penetrates well into all tissues; accumulates mainly in the liver, less in the muscles and central nervous system. It penetrates through the placenta and is secreted with breast milk. The plasma half-life is 15-20 days. It is excreted by the kidneys, as well as during hemodialysis.
Indications
Treatment and prevention of all forms of tuberculosis caused by M.tuberculosis sensitive to isoniazid and ethambutol as part of combination therapy.
It is necessary to take into account the current official guidelines on the rules for the use of antibacterial drugs.
Contraindications
Phtizoethamum® B6 is contraindicated in children under 12 years of age, patients with hypersensitivity to isoniazid, ethambutol or any other component of the drug; in epilepsy and other diseases accompanied by a tendency to seizures, uncontrolled hypertension, severe coronary insufficiency, cirrhosis of the liver, drug hepatitis and / or other severe adverse reactions that developed against the background of previous treatment with the drug containing isoniazid in the composition, acute liver diseases, severe liver failure; myxedema, optic neuritis, cataracts, diabetic retinopathy, bronchial asthma, psoriasis, hyperuricemia, acute gout, gastric ulcer, duodenal ulcer, pregnancy and lactation.
With caution
Alcoholism, liver failure of mild to moderate severity, liver dysfunction in the anamnesis or chronic liver dysfunction, renal failure, seizures, age over 35 years, prolonged use of other potentially hepatotoxic drugs, withdrawal of therapy with isoniazid in the anamnesis, peripheral neuropathy, HIV infection, decompensated diseases of the cardiovascular system (chronic heart failure, angina pectoris, arterial hypertension), hypothyroidism, diabetes mellitus, exhaustion, a history of mental illness, "slow acetylators", female.
Method of administration and dosage
Inside, after eating, once a day.
Treatment
The drug Phtizoethamum® B6 is administered orally, after meals, once a day. Dosage of Phtizoethamum® B6 is carried out according to isoniazid: 5-10 mg / kg of patient weight. The drug is used daily during the intensive care period (3-4 months), and subsequently every other day. The total course dose of Phtizoethamum® B6 for each patient is individual and depends on the nature of the disease, the effectiveness of treatment and tolerability.
Prevention
Inside, 5-10 mg / kg / day, the maximum daily dose is 600 mg.
Doses and duration of administration should be determined according to the official current federal guidelines on tuberculosis.
Patients with renal insufficiency
Recommended doses and frequency of administration for patients with creatinine clearance less than 30 ml / min and with hemodialysis - 300 mg once daily.
Patients with liver failure
Phthisoetham® B6 has a hepatotoxic effect, therefore, in patients with moderate and mild liver dysfunction, it is prescribed with strict monitoring of "liver" enzymes and the use of hepatoprotectors (also see the section "Special instructions"). The use of Phtizoethamum® B6 is contraindicated in patients with severe hepatic insufficiency.
In severe pulmonary heart failure, severe atherosclerosis, coronary heart disease and hypertension, doses of more than 10 mg / kg should not be prescribed.
Side effects
Isoniazid
Isoniazid-related adverse events mainly depend on age and dose and are more pronounced in "slow acetylators".
The following adverse events noted with the use of isoniazid are distributed by frequency according to the following gradation: very common (≥ 1/10), common (≥ 1/100 to 1/10), infrequent (≥ 1/1000 to 1/100), rare (≥ 1/10000 to 1/1000), very rare (1/10000), frequency unknown (it is impossible to estimate based on the available data).
Disorders of the blood and lymphatic system: the frequency is unknown − eosinophilia, bone marrow depression, granulocytopenia, thrombocytopenia, agranulocytosis, sideroblastic anemia, hemolytic or megaloblastic anemia, pyridoxine deficiency anemia, coagulopathy, aplastic anemia.
Disorders of the immune system: the frequency is unknown - exanthema (including acne, especially in young patients), exfoliative dermatitis, Stevens-Johnson syndrome, photosensitization, fever, asthma, myalgia and arthralgia, anaphylactic reactions, anaphylactic shock, systemic lupus erythematosus, lupus-like syndrome, lymphadenopathy.
Endocrine disorders: the frequency is unknown - mainly reversible hyperfunction of the adrenal cortex (Cushing's syndrome) and the anterior pituitary gland (with menstrual disorders in women or gonadotropic disorders/gynecomastia in men).
Metabolic and nutritional disorders: - very rare - hypoglycemia; frequency unknown - hyperglycemia, metabolic acidosis, pellagra (nicotine deficiency
acids). Nicotinic acid deficiency may be associated with pyridoxine deficiency caused by isoniazid, which affects the conversion of tryptophan into nicotinic acid
Mental disorders: the frequency is unknown - mental disorders (irritability, anxiety), decreased concentration, depression, psychoses (manifest, catotonic or paranoid), euphoria.
Disorders of the nervous system: often - peripheral polyneuropathy with paresthesia, sensory disturbances, headache, dizziness; frequency unknown - convulsions, drowsiness, lethargy. Hyperreflexia occurs more often at doses of 10 mg/ kg of body weight. The development of peripheral neuropathy is especially possible in elderly patients, pregnant women, patients with hypotrophy, patients with diabetes mellitus, as well as in patients with chronic liver diseases, including alcoholic etiology. To prevent peripheral neuropathy, it is recommended to take pyridoxine.
Visual organ disorders: rarely - optic nerve atrophy; frequency unknown - optic neuritis, diplopia, strabismus.
Hearing disorders and labyrinthine disorders: the frequency is unknown - deafness, tinnitus, vertigo. These effects have been reported in patients with end-stage renal failure. Vertigo occurs more often at doses of 10 mg/ kg of body weight.
Cardiac disorders: the frequency is unknown - arrhythmia, increased or decreased blood pressure.
Disorders of the respiratory system, chest and mediastinal organs: the frequency is unknown - acute respiratory distress syndrome, interstitial lung disease.
Disorders of the gastrointestinal tract: often - gastrointestinal disorders (diarrhea, constipation, regurgitation, bloating, vomiting); frequency unknown - pancreatitis (see section "Special instructions"), dry mouth.
Disorders of the liver and biliary tract: very often - increased activity of "hepatic" transaminases; infrequently - hepatitis; frequency unknown - acute liver failure, liver damage, jaundice, acute hepatitis (including fatal).
Disorders of musculoskeletal and connective tissue: often - muscle tremor; frequency unknown - rheumatic syndrome, rhabdomyolysis.
Disorders of the kidneys and urinary tract: the frequency is unknown - glomerulonephritis (mostly reversible), dysuria.
Disorders of the skin and subcutaneous tissues: rarely - toxic epidermal necrolysis, drug rash with eosinophilia and systemic manifestations (DRESS syndrome).
Vascular disorders: the frequency is unknown - vasculitis.
Ethambutol
Disorders of the digestive system: decreased appetite, nausea, vomiting, gastralgia, increased activity of "liver" transaminases.
Disorders of the nervous system: weakness, headache, dizziness,
blurred consciousness, disorientation, hallucinations, paresis, peripheral neuritis (tingling in the extremities, numbness, itching).
Sensory disorders: optic neuritis (decreased acuity vision, color blindness, scotoma).
Allergic reactions: dermatitis, itching, arthralgia, fever, anaphylaxis.
Other: hyperuricemia.
Overdose
Symptoms of overdose: nausea, vomiting, abdominal pain, jaundice, increased
liver enzymes, acute pulmonary edema, impaired consciousness, coma, seizures, respiratory disorders, hyperglycemia, metabolic ketoacidosis.
Treatment: gastric lavage with oral administration of activated charcoal, forced diuresis, general measures to maintain vital functions, hemodialysis.
Drug interaction
Isoniazid
Simultaneous administration of isoniazid with certain medications may lead to an increase or decrease in the effect.
Isoniazid inhibits the isoenzymes CYP2C19, CYP1A2, CYP2A6, CYP2E1 and CYP3A
the cytochrome P450 system of the liver, which can lead to a slowdown in the excretion of drugs metabolized by these enzymes.
The administration of other drugs may affect the metabolism of isoniazid.
In "slow acetylators" and in patients using aminosalicylic acid at the same time, tissue concentrations of isoniazid may be increased and the frequency of side effects increased.
Possible interactions are presented below:
Alpha - 1- adrenoblockers
Alfuzozin
The type of interaction is an increase in the concentration of alfuzosin in the blood.
The clinical consequence is monitoring of hemodynamics at the beginning 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 of 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 should be reduced.
Analgesics
Acetylsalicylic acid
Type of interaction - possible weakening of the effect of isoniazid.
The clinical consequence is that joint use is not recommended.
Opioids (such as morphine, fentanyl, alfentanyl, buprenorphine, methadone, codeine)
Type of interaction - isoniazid slows down the metabolism of opioids.
Clinical consequence - monitoring of side effects is necessary, if necessary, correction of the dose of opioids.
Paracetamol
Type of interaction - isoniazid enhances the hepatotoxicity of paracetamol.
Clinical consequence - joint use is not recommended, monitoring of liver function is necessary.
Anesthetics
Isoflurane, Enflurane
The type of interaction - isoniazid can increase the formation of potentially nephrotoxic inorganic fluorine as a metabolite of isoflurane and enflurane (especially in "fast acetylators"), increased nephrotoxicity.
The clinical consequence is the control of kidney function, especially in "fast acetylators" after surgery.
General anesthetics
Type of interaction - possible increased hepatotoxicity of isoniazid.
The clinical consequence is monitoring of liver function.
Anti-asthmatic agents
Theophylline
Type of interaction - isoniazid slows down the metabolism of theophylline.
The clinical consequence is to control the concentration of theophylline in the blood serum, in particular after discontinuation of isoniazid, dose adjustment 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 an increase in the hepatotoxicity of isoniazid and pyrazinamide.
The clinical consequence is monitoring of liver function.
Rifampicin
The type of interaction is an increase in the hepatotoxicity of isoniazid and rifampicin.
The clinical consequence is monitoring of liver function.
Ethionamide, protionamide.
The type of interaction is an increase in toxicity against CNM isoniazid and ethionamide/protionamide.
The clinical consequence is that increased attention should be paid to side effects from the central nervous system.
Antifungal agents
Itraconazole
The type of interaction is a decrease in the concentration of itraconazole in the blood.
The clinical consequence is the ineffectiveness of treatment, joint use is not recommended.
Ketoconazole
The type of interaction is a decrease in the concentration of ketoconazole in the blood.
Clinical consequence - it is necessary to monitor the effectiveness of ketoconazole, if necessary, adjust the dose of ketoconazole.
Anticholinergic drugs
Atropine
The type of interaction is an increase in the toxicity of atropine.
The clinical consequence is that joint use is not recommended.
Darifenacin
The type of interaction - isoniazid can slow down the elimination of darifenacin.
Clinical consequence - it is possible to enhance the effect of darifenacin, if necessary, adjust the dose of darifenacin.
Antidepressants
Citalopram
The type of interaction - isoniazid can slow down the excretion of citalopram.
The clinical consequence is increased cardiotoxicity, if necessary, dose adjustment of citalopram; hypokalemia and hypomagnesemia should be corrected before starting treatment and monitored regularly.
Hypoglycemic agents
Insulin and derivatives / Alpha-glucosidase inhibitors / Sulfonylurea derivatives, biguanides, glinides, incretinomimetics, DPP4 inhibitors.
The type of interaction is a violation of the effect of hypoglycemic drugs.
The clinical consequence is monitoring the concentration of glucose in the blood, it is possible to reduce or increase the effectiveness of hypoglycemic drugs, if necessary, dose adjustment.
Antiepileptic drugs
Carbamazepine.
Type of interaction - isoniazid slows down the metabolism of carbamazepine, possibly increased hepatotoxicity.
Clinical consequence - clinical monitoring is necessary, control of carbamazepine concentration and liver function, if necessary, correction of carbamazepine dose.
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, if necessary, adjust the dose of phenytoin, it is recommended to monitor the concentration of phenytoin after the withdrawal of isoniazid.
Primidon.
Type of interaction - isoniazid slows down the metabolism of primidone.
Clinical consequence - monitoring of side effects is necessary, if necessary, dose adjustment.
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 at the end of therapy, if necessary, dose adjustment of valproic acid.
It is a suximide.
Type of interaction - isoniazid slows down the metabolism of ethosuximide.
Clinical consequence - monitoring of side effects is necessary, if necessary, dose adjustment.
Anticoagulants
Warfarin and other coumarins/Indandion derivatives.
Type of interaction - isoniazid slows down the metabolism of anticoagulants, increases the tendency to bleeding.
The clinical consequence is the simultaneous use of blood coagulation monitoring, especially after discontinuation of isoniazid therapy, if necessary, dose adjustment of anticoagulants.
Antiparkinsonian drugs
Levodopa.
Type of interaction - reduction of AUC (area under the pharmacokinetic curve)
levodopa, increased risk of peripheral neuropathy due to levodopa and isoniazid.
The clinical consequence is loss of effectiveness of levodopa, motor restlessness, tremor, general worsening of Parkinsonism symptoms; with signs of peripheral neuropathy, therapy should be discontinued.
Antiprotozoal
Chloroquine.
The type of interaction is an increase in the risk of peripheral neuropathy due to chloroquine and isoniazid.
Clinical consequence - monitoring of side effects is necessary, if signs
peripheral neuropathy therapy should be discontinued.
Halophantrin.
The type of interaction is a decrease in halophantrin metabolism, an increase in concentration
halophantrine in plasma.
Clinical consequence - monitoring of side effects from the heart, ECG monitoring before, during and after the end of therapy is necessary.
Beta blockers
Propranolol.
The type of interaction - propranolol can reduce the plasma clearance of isoniazid.
The clinical consequence is a slight increase in the concentration of isoniazid in blood plasma, the clinical significance is probably low.
Antagonists of CCR5 chemokine receptors
Maravirok.
The type of interaction - isoniazid can increase the plasma concentrations of maraviroc.
The clinical consequence is, if necessary, correction of the dose of maraviroc.
Glucocorticosteroids
Budesonides.
The type of interaction - isoniazid can increase plasma concentrations of budesonide.
The clinical consequence is that the effect of budesonide may be enhanced with long-term therapy.
Prednisone.
The type of interaction - prednisone can reduce plasma concentrations of isoniazid.
The clinical consequence is a possible decrease in the effect of isoniazid, if necessary, correction of the dose of isoniazid is required.
Antagonists of serotonin 5-HT3 receptors
Alosetron.
The type of interaction is an increase in the concentration of alosetron in plasma.
The clinical consequence is that joint use is not recommended.
Immunomodulators
BCG vaccine.
The type of interaction is the loss of the effect of the vaccine (including use in the treatment of bladder cancer).
The clinical consequence is that joint use is not recommended.
Interferon beta - 1a.
The type of interaction is an increase in the hepatotoxicity of isoniazid and interferon beta - 1a.
Clinical consequence - monitoring of liver function is necessary, if ALT is 5 times higher than normal, it is recommended to reduce the dose of interferon beta-1a, which may again be
increased after ALT normalization.
Immunosuppressants
Cyclosporine.
The type of interaction - isoniazid can affect the concentration of cyclosporine in blood plasma.
The clinical consequence is monitoring the concentration of cyclosporine in blood plasma, if necessary, correction of the dose of cyclosporine.
Leflunomide/Teriflunomide.
The type of interaction is an increased risk of hepatotoxicity due to isoniazid and leflunomide/teriflunomide.
The clinical consequence is an increased risk of hepatotoxicity, the activity of "liver" enzymes and bilirubin concentration should be measured before starting therapy with leflunomide /teriflunomide, then monthly during the first 6 months of therapy, and then every 6-8 months. Patients with hepatic insufficiency or increased transaminase activity (ALT 2 times > normal) should not take leflunomide / teriflunomide. With ALT 3 times > normal, it is necessary to cancel therapy and remove the active metabolite of leflunomide with colestyramine or activated charcoal, weekly monitoring, if necessary, repeat the intake of adsorbents.
Thalidomide.
The type of interaction is the risk of peripheral neuropathy due to thalidomide and isoniazid.
The clinical consequence is monthly monitoring of side effects in the first 3
months of treatment, electrophysiological tests before and after 6 months of treatment, it is possible to cancel therapy if signs of neuropathy appear.
Hypolipidemic agents
Fluvastatin/Simvastatin/Pravastatin/Atorvastatin.
The type of interaction is an increase in the risk of peripheral neuropathy due to isoniazid and fluvastatin, simvastatin, pravastatin and atorvastatin.
The clinical consequence is that with signs of peripheral neuropathy, 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").
The clinical consequence is a possible increase in the effectiveness of tranylcypromine and moclobemide in "slow acetylators", monitoring of side effects.
Muscle relaxants
Tizanidine.
Type of interaction - isoniazid can slow down the metabolism of tizanidine, increase the concentration of tizanidine in plasma.
Clinical consequence - joint use is not recommended, increased cardiotoxicity and toxicity to the central nervous system, 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, if necessary, dose adjustment of chlorzoxazone.
Neuroleptics
Haloperidol.
The type of interaction - isoniazid can slow down the metabolism of haloperidol.
Clinical consequence - monitoring of the neurological status is necessary, if necessary, correction of the dose of haloperidol.
Pimozide.
Type of interaction - isoniazid can slow down the metabolism of pimozide, increase the concentration of pimozide in plasma.
Clinical consequence - joint use is not recommended, severe side effects from the heart.
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
Efavirenz.
The type of interaction is an increased risk of hepatotoxicity due to efavirenz and isoniazid.
The clinical consequence is that liver function testing is necessary before and during treatment.
Nucleoside Reverse transcriptase inhibitors (NRTIs)
Didanosine/Stavudin.
The type of interaction is an increase in the risk of peripheral neuropathy due to isoniazid, didanosine and stavudine.
Clinical consequence - monitoring of side effects is necessary, with signs of peripheral neuropathy, therapy should be discontinued or doses of isoniazid, didanosine or stavudine should be reduced.
Zalcitabine.
The type of interaction is an increase in the clearance of isoniazid by 2 times.
The clinical consequence is that monitoring of the effectiveness of isoniazid is necessary.
Opioid receptor antagonists
Naltrexone.
The type of interaction is an increased risk of hepatotoxicity due to naltrexone and isoniazid.
Clinical consequence - joint use should be avoided, liver function testing is necessary.
Phosphodiesterase inhibitors
Roflumilast.
Type of interaction - isoniazid may increase the bioavailability of roflumilast and
N- oxide of roflumylast.
The clinical consequence is a possible increase in the effectiveness of roflumilast.
Selective Estrogen Receptor Modulators (SERM)
Torimifene.
The type of interaction - isoniazid can increase the concentration of toremifene in plasma.
The clinical consequence is regular measurement of electrolytes, a general blood test, and checking liver function.
Antispasmodics
Tolterodine.
The type of interaction - isoniazid can increase plasma concentrations of tolterodine.
The clinical consequence is, if necessary, a reduction in the dose of tolterodine when used concomitantly with CYP3A4 inhibitors such as isoniazid (1 mg tolterodine 2 times a day), clinical monitoring is necessary.
Sympathomimetics
Adrenaline rush/Norepinephrine.
The clinical consequence is an increase in side effects.
Inhibitors of platelet aggregation
Clopidogrel.
Type of interaction - isoniazid reduces bioactivation by inhibiting CYP2C19 and thereby reduces the effect of clopidogrel.
Clinical consequence - joint use is not recommended, monitoring of the effectiveness of clopidogrel is necessary.
Tranquilizers
Benzodiazepines (such as diazepam, midazolam, triazolam).
Type of interaction - isoniazid can slow down the metabolism of benzodiazepines.
Clinical consequence - monitoring of side effects is necessary, if necessary, dose adjustment of benzodiazepines.
Vitamins
Vitamin B6.
The type of interaction - isoniazid enhances the elimination of pyridoxine.
Clinical consequence - prophylactic administration of pyridoxine during isoniazid therapy is recommended.
Vitamin D.
The type of interaction - isoniazid reduces the plasma concentration of vitamin D.
Clinical consequence - in the case of taking drugs containing vitamin D, it is necessary to monitor the serum concentration of calcium, serum concentration of phosphates, as well as kidney function, if necessary, dose adjustment of vitamin D.
Nicotinic acid.
Type of interaction - isoniazid reduces the concentration of nicotinic acid (inhibition of the inclusion of nicotinic acid in nicotinamide adenine dinucleotide).
The clinical consequence is not.
Cytostatics
Bendamustine.
The type of interaction - isoniazid increases the concentration of bendamustine in plasma.
Clinical consequence - the effect of bendamustine should be carefully monitored for signs of toxicity, such as leukopenia, infections, thrombocytopenia, bleeding, anemia and neutropenia, if necessary, dose adjustment of bendamustine.
Clofarabine.
The type of interaction is an increase in the hepatotoxicity of clofarabine and isoniazid.
Clinical consequence - joint use should be avoided, 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, if necessary, dose adjustment of gefitinib.
Methotrexate.
The type of interaction is an increase in the hepatotoxicity of methotrexate and isoniazid.
The clinical consequence is to avoid joint use, it is necessary to monitor liver function indicators.
Pazopanib.
Type of interaction - isoniazid may slow down the metabolism of pazopanib.
Clinical consequence - monitoring of side effects, measurement of electrolytes, ECG, liver function tests, before and during treatment, if necessary, dose adjustment of pazopanib.
Thioguanine.
The type of interaction is an increase in the hepatotoxicity of thioguanine and isoniazid.
Clinical consequences - liver function testing.
Antacids
Antacids (especially aluminum-containing ones).
The type of interaction is a decrease in the absorption and concentration of isoniazid in the blood.
Clinical consequence - concomitant use should be avoided, antacids should be taken no earlier than 1 hour after taking isoniazid.
Other
Henodeoxycholic acid.
The type of interaction - metabolism (acetylation) and excretion of isoniazid may be increased.
The clinical consequence is that joint use is not recommended.
Interaction with food and drinks.
Ethanol increases the hepatotoxicity of isoniazid and accelerates its metabolism.
The absorption of isoniazid worsens after eating, especially carbohydrates.
During treatment, cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack) should be avoided, since when used simultaneously with isoniazid, reactions may occur (skin hyperemia, itching, feeling hot or cold, palpitations, increased sweating, chills, headache, dizziness) associated with by suppressing the activity of monoamine oxidase (MAO) and diamine oxidase and leading to a violation of the metabolism of tyramine and histamine contained in fish and cheese.
Effect on laboratory parameters
Isoniazid can lead to false-positive blood glucose determination results using a copper reagent; it does not affect enzymatic glucose determination tests.
Ethambutol
Simultaneous administration of ethambutol and drugs with neurotoxic effects may increase the likelihood of developing optic neuritis and peripheral neuritis.
Special instructions
Isoniazid should be prescribed with caution to patients with convulsive disorders, exhaustion, diabetes mellitus, alcoholism and psychosis in the anamnesis, impaired liver and kidney function and patients taking other potentially hepatotoxic drugs.
During treatment with the drug, patients should refrain from drinking alcohol.
Patients who are intolerant to ethionamide, pyrazinamide nicotinic acid or other substances similar in chemical structure may have intolerance to isoniazid.
In some cases, especially in patients with a history of gout attacks, it is recommended to periodically monitor the level of uric acid in the blood serum.
Ethambutol can have a negative effect on vision. Vision usually returns to normal after timely withdrawal of ethambutol. In rare cases, normalization of vision can occur for a year or more. It is necessary to check the visual acuity of each eye individually and both eyes together; visual acuity is checked before starting treatment and periodically during treatment. In case of any change in visual acuity, patients should immediately consult a doctor. If a decrease in acuity is detected
of course, ethambutol is being canceled.
In patients with renal insufficiency, it may be necessary to reduce the dose of ethambutol.
In some cases, fatal drug hepatitis develops during treatment, which can occur even after several months of termination of use. The risk increases with age (the highest frequency in the 35-64 age group), especially with daily ethanol consumption. Therefore, liver function must be monitored monthly in all patients, and liver function is additionally examined in persons over 35 years of age before starting treatment. In addition to the use of ethanol, additional risk factors are chronic liver diseases, female gender, "slow acetylators", exhaustion, HIV infection, parenteral use of any medications and the postpartum period. With an increase in the activity of "hepatic" transaminases (ALT, AST) by 4 or more times or an increase in the concentration of bilirubin in the blood, treatment with isoniazid should be discontinued.
With the development of acute or chronic hepatitis, isoniazid should be discontinued, in
in the latter case, isoniazid therapy cannot be resumed.
When taken in high doses, adverse reactions from the nervous system (peripheral neuropathy) may develop, which affects the ability to drive a car and work with complex equipment.
At the risk of developing peripheral neuropathy (patients over 65 years of age, patients with diabetes mellitus, pregnant women, patients with chronic renal failure, alcoholism, eating disorders, concomitant anticonvulsant therapy), it is recommended to prescribe 10-25 mg / day of pyridoxine.
Influence on the ability to drive vehicles, mechanisms
Taking into account the side effects of the drug, you should refrain from performing these types of activities.
Storage temperature
from 2℃ to 25℃
