Composition, form of production and packaging
The tablets covered with a cover of white color, round, biconcave, with risk on one party and a stamp "300" - on another.
isoniazid 300 mg
pyridoxine hydrochloride 60 mg
Excipients: microcrystalline cellulose - 30 mg, macrogol 6000 - 6 mg, copolyvidone - 12 mg, crospovidone - 6 mg, talc - 4 mg, calcium hydrophosphate - 2 mg.
Sheath composition: hypromellose (hydroxypropylmethylcellulose) - 3.4 mg, titanium dioxide (E171) - 1.8 mg, macrogol 6000 - 1.8 mg.
100 pieces. - polypropylene containers (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the print edition of 2007.
[I] - Instruction on medical use approved by the Pharmacological Committee of the Ministry of Health of the Russian Federation
Isoniazid acts bactericidal, inhibits the synthesis of mycolic acids, which are an important component of the cell wall of mycobacteria. It is especially active against rapidly multiplying microorganisms (including those located intracellularly).
Pyridoxine plays an important role in the metabolism; is necessary for the normal functioning of the central and peripheral nervous system. In phosphorylene form, pyridoxine is a coenzyme of a large number of enzymes acting on a non-oxidative exchange of amino acids. It plays an important role in the exchange of histamine.Promotes the normalization of lipid metabolism.
Isoniazid quickly and completely absorbed when ingested, food reduces absorption and bioavailability. But the indicator of bioavailability is greatly influenced by the effect of the "first passage" through the liver. T max - 1-2 hours, C max after oral intake of a single dose of 300 mg - 3-7 Ојg / ml. The connection with proteins is insignificant - up to 10%. The volume of distribution is 0.57-0.76 l / kg. Well distributed throughout the body, penetrating all tissues and fluids, including cerebrospinal, pleural, ascites; high concentrations are created in the 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 with the formation of inactive products. The liver is acetylated with N-acetyltransferase to form N-acetylisoiniazide, which is then converted to isonicotinic acid and monoacetylhydrazine, which has a hepatotoxic effect by forming a mixed oxidase system of cytochrome P450 upon N-hydroxylation of the active intermediate metabolite. The rate of acetylation is genetically determined; in people with slow acetylation, there is little N-acetyltransferase. It is an inhibitor of the enzyme system CYP2C9 and CYP3A2E1 in the liver. E 1/2 for "fast acetylators" - 0.5 -1.6 h; for slow - 2-5 hours. In case of renal insufficiency, T 1/2 can increase up to 6.7 hours. Despite the fact that the T 1/2 index varies considerably depending on the individual intensity of the acetylation processes, the average value of T 1/2 is 3 h (intake of 600 mg) and 5.1 h (900 mg). With repeated appointments, T 1/2 is shortened to 2-3 hours.
It is excreted mainly by the kidneys: 75-95% of the drug is excreted within 24 hours, mainly in the form of inactive metabolites - N-acetylisiniazide and isonicotinic acid. At the same time, "fast acetylators" contain N-acetylisiniazide content of 93%, while "slow" - not more than 63%. Small amounts are excreted with feces. The drug is removed from the blood during hemodialysis; 5 h hemodialysis allows you to remove from the blood to 73% of the drug.
- tuberculosis of any localization in adults and children: treatment and prevention, including as part of combination therapy.
Inside. Isozid Comp. should be taken on an empty stomach, without chewing and washing down with a small amount of water.
The daily dose of adults is 5 mg (3-8 mg) of isoniazid per kilogram of the patient's body weight daily. On average, this corresponds to a daily dose of 300 mg. In the intermittent, intermittent form of treatment, the dose is 15 mg / kg body weight per week.
Children isoniazid is prescribed at a rate of 20 mg / m 2 body surface, or approximately 10 mg / kg body weight.
On the part of the digestive system: nausea, vomiting, constipation, a rapidly increasing activity of "liver" transaminases in the blood plasma during the first month of treatment, gastralgia, toxic hepatitis. Rarely - persistent increase in enzyme activity.
From the side of the central nervous system: headache, dizziness, rarely - unusual fatigue or weakness, irritability, euphoria, mood change, depression. Epileptic patients may experience seizures. When using high doses of isoniazid - peripheral neuropathy, manifested paresthesia of the skin of the hands; hyperreflexia, tremor, convulsions, toxic encephalopathy, psychosis, insomnia; Neuritis and optic atrophy
From the cardiovascular system: palpitation, angina pectoris, increased blood pressure.
From the hemopoietic system: hemolytic, sideroblastic and aplastic anemia; thrombocytopenia, eosinophilia.
From the side of the system of homeostasis: acidosis.
Allergic reactions: "lupus-like" syndrome, skin rash, purpura, lymphadenopathy, vasculitis, itching, hyperthermia, arthralgia.
Other: very rarely - gynecomastia, menorrhagia, tendency to bleeding and hemorrhage.
Associated with pyridoxine:
With an irregular reception or with the resumption of treatment after a break, flu-like syndrome (fever, chills, headache, dizziness, myalgia), skin reactions, hemolytic anemia, thrombocytopenic purpura, acute renal failure are possible.
- epileptic syndrome;
- poliomyelitis (including in the anamnesis);
- bronchial asthma;
- chronic renal failure;
- cirrhosis of the liver;
With caution: severe form of heart failure, arterial hypertension, ischemic heart disease, widespread atherosclerosis, nervous system disease, hypothyroidism, pregnancy (not prescribed in a dose above 10 mg / kg).
Simultaneous use of alcohol contributes to the intensification of hepatotoxic reactions.
PREGNANCY AND LACTATION
Precautions should be taken during pregnancy (do not administer in a dose above 10 mg / kg).
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated cirrhosis of the liver, hepatitis.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated: chronic renal failure.
APPLICATION FOR CHILDREN
Dosage for children:
Isoniazid is taken at a rate of 20 mg per m 2 body surface, or approximately 10 mg per kg body weight.
To slow the development of microbial resistance is prescribed together with other antituberculous drugs.
In connection with the different metabolic rate before the use of isoniazid, it is expedient to determine the rate of its inactivation by the content of the active substance in the blood and urine.
With rapid inactivation, isoniazid is used in higher doses.
During the treatment, cheese (especially Swiss or Cheshire), fish (especially tuna, sardinella, skipjack) should be avoided, since when combined with isoniazid, reactions such as skin hyperemia, itching, heat or cold sensation, palpitations, increased sweating, chills, headache, dizziness associated with suppression of MAO activity and diaminoxidase and leading to a disruption of the metabolism of tyramine and histamine contained in fish and cheese.
It should be borne in mind that isoniazid can cause hyperglycemia with secondary glucosuria; tests with the recovery of Cu 2+ can be false positive, and the enzyme tests for glucose drug does not affect.
Laboratory indicators - ALT, ACT, serum bilirubin concentration can transiently increase without clinical manifestations.
When there are signs of toxic hepatitis the drug is canceled.
Isoniazid. When combined with paracetamol, hepato- and nephrotoxicity increases; isoniazid induces a cytochrome P450 system, which increases the metabolism of paracetamol to toxic products.
Ethanol increases the hepatotoxicity of isoniazid and speeds up its metabolism.
Reduces the metabolism of theophylline, which can lead to an increase in its concentration in the blood.
Reduces metabolic transformations and increases the concentration in the blood of alfentanil.
Cycloserine and disulfiram increase the adverse central effects of isoniazid.
Increases hepatotoxicity of rifampicin.
Combination with pyridoxine reduces the risk of peripheral neuritis.
Caution should be combined with potentially neuro-, hepato- and nephrotoxic drugs because of the risk of side effects.
Strengthens the action of coumarin and indanedione derivatives, benzodiazepines, carbamazepine, theophylline, as it reduces their metabolism by activating the cytochrome P450 system.
Glucocorticosteroids accelerate metabolism in the liver and reduce active concentrations in the blood.
It suppresses the metabolism of phenytoin, which leads to an increase in its concentration in the blood and an increase in the toxic effect (correction of the dosing regimen of phenytoin may be necessary, especially in patients with slow acetylation of isoniazid).
Pyridoxine. Strengthens the action of diuretics; weakens the activity of levodopa. Isonicotin hydrazide, penicillamine, cycloserine and estrogen-containing oral contraceptives weaken the effect of pyridoxine.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
In a dry, dark place, out of the reach of children, at a temperature of no higher than 25 В° C.
Shelf life - 4 g. Do not use after the expiration date indicated on the package.