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  • Name: Ethambutol Hydrochloride, Pyrazinamide, Rifampicin and Isoniazid Tablets
  • Add time: 2015-05-14
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[Drug Name]
Generic Name:乙胺吡嗪利福异烟片
English name:Ethambutol Hydrochloride, Pyrazinamide, Rifampicin and Isoniazid Tablets
Pinyin:Yi’an Biqin Lifu Yiyan Pian
Ingredient product compound, each containing rifampicin 0.12g, isoniazid 0.12g, pyrazinamide 0.4g, ethambutol hydrochloride 0.25g.
【Properties】 film coated tablets, were removed after coating orange-red or dark red.
Indications This product is suitable for all types of adult tuberculosis. For new smear positive retreatment smear-positive patients or severe smear-negative patients with intensive treatment period.
Smear-positive patients: intensive treatment of 2H3R3Z3E3 / continuation phase 4H3R3
Retreatment smear-positive patients: intensive treatment of 2H3R3Z3E3S3 / continuation phase 6H3R3E3
Severe smear-negative patients: intensive treatment of 2H3R3Z3E3 / continuation phase 4H3R3
[Specification] each containing rifampicin 0.12g, isoniazid 0.12g, pyrazinamide 0.4g, ethambutol hydrochloride 0.25g.
This product is used smear positive retreatment smear positive patients (streptomycin plus) or severe smear-negative patients with intensive treatment period, each of the 2nd medication, a total of two months, the medication 30 times. Adult, weighing more than 50kg each patient fasting Dayton served this product 5, 50kg underweight patients under doctor's orders to reduce it. Take 1 hour before or 2 hours after meals Dayton clothing. Press the specification or compliance to the FDA, the treatment of the whole process can not be interrupted or unauthorized changes medication regimen. In the event of adverse reactions, shall obey the physician orders.
This product is used for smear positive retreatment smear-negative patients or critically ill patients with smear-positive intensive treatment period, namely the first 2 months of treatment. According to WHO recommendations and China TB control planning guide for the implementation, after this stage the need for maintenance phase treatment.
【Adverse reactions】
According to the literature as follows:
Frequency of occurrence:
Common adverse reactions:> 1/100
Not common adverse reactions: ≥1 / 1,000 and ≤1 / 100
Rare adverse reactions: ≥1 / 10,000 and ≤1 / 1,000
Adverse reactions very rare: <1 / 10,000
Rifampicin continuous and intermittent adverse reactions during treatment
Blood and lymphatic system disorders Rare: transient leukopenia, increased eosinophils. In a few cases, intermittent therapy than continuous treatment is more prone to thrombocytopenia, thrombocytopenic purpura symptoms. It has been reported that, if it continues in the event of purpura after taking rifampicin, will appear and the occurrence of cerebral hemorrhage to death. Hemolysis and hemolytic anemia.
Endocrine disorders rare: menstrual disorders (amenorrhea rare cases); caused Addison's disease patients crisis.
Insane insanity.
Nervous system disorders common: fatigue, drowsiness, headache, mild headache, dizziness. Rare: ataxia, muscle weakness.
Eye abnormalities common: jealous, and may cause permanent discoloration of contact lenses. Rare: visual disturbances. Severe symptoms, e.g., exudative conjunctivitis.
Gastrointestinal abnormalities Common: anorexia, nausea, abdominal pain and bloating. Rare: vomiting, diarrhea, erosive gastritis and pseudomembranous colitis.
Skin and subcutaneous tissue abnormalities common: flushing, itching, rash, urticaria. Rare: severe systemic allergic reactions, such as: exfoliative dermatitis, Lyell's syndrome, pemphigoid.
Hepatobiliary abnormalities Common: asymptomatic elevated liver drug metabolizing enzyme. Rare: hepatitis, jaundice, induction of porphyria.
Kidney and urinary system abnormalities rare: blood urea nitrogen, uric acid levels increased, acute renal failure caused hemoglobinuria, hematuria and chronic interstitial nephritis, glomerulonephritis, tubular necrosis.
Generally poor condition common: body fluids and secretions such as urine, saliva, tears, feces, sputum and sweat may be in orange. Rare: collapse, shock, edema.
Recovery of adverse reactions after treatment intermittent therapy or withdrawal of rifampicin
When patients with rifampicin level, not by the daily routine of medication or treatment temporarily interrupted recovery after administration, the common "flu-like syndrome" occurs, probably due to the immune response induced pathology. Fever, tremors, headache, dizziness and muscle pain. Can occur even thrombocytopenia, purpura, dyspnea, asthma, hemolytic anemia, shock and acute renal failure. When rifampicin temporarily discontinued restore one dose (≥25mg / kg) when this serious syndrome may suddenly occur or rifampicin treatment administered weekly, without showing progress of "flu-like syndrome" in ʱ??
Adverse reactions Isoniazid
Blood and lymphatic system abnormalities rare: increased eosinophils, thrombocytopenia, anemia (blood insoluble anemia, iron deficiency anemia). Very rare: agranulocytosis.
Endocrine abnormalities rare: liver metabolism hormones interfere with the individual, leading to menstrual disorders, gynecomastia, Cushing's syndrome, uncontrolled diabetes, hyperglycemia, metabolic acidosis.
Mental disorders Rare: insane, over-excitement, euphoria, insomnia.
Nervous system abnormalities common: peripheral neuropathy (common in large doses, malnutrition, alcoholism, slow acetylation and diabetes) showed numbness, tingling. Rare: optic nerve damage, convulsions, dizziness, headache, viral encephalitis, large doses can increase the frequency of epileptic seizures.
Gastrointestinal abnormalities common: nausea, vomiting, abdominal pain.
Hepatobiliary abnormal common: liver dysfunction (serum transaminase levels usually mild or a transient increase), common prodromal symptoms are poor appetite, nausea, vomiting, fatigue, depression and weakness. Rare: hepatitis, severe hepatitis.
Generally poor condition common: allergy, rash and fever. Rare: allergy, dry mouth, heartburn, frequent urination, rheumatism, systemic lupus erythematosus disease, pellagra, vasculitis, lymphadenopathy, acne.
Adverse reactions pyrazinamide
Blood and lymphatic system abnormalities rare: thrombocytopenia, iron deficiency anemia, blood clotting disorders, splenomegaly.
Gastrointestinal abnormalities common: nausea, vomiting, anorexia, abdominal pain.
Hepatobiliary abnormal common: Early treatment of moderate or a serum transaminases transient increase, porphyria. Rare: severe dose-related hepatotoxicity, hepatomegaly, jaundice.
Kidney and urinary system abnormalities common: hyperuricemia (usually asymptomatic), gout. Rare: chronic interstitial nephritis, urinary retention.
Generally poor condition common: allergies, mild joint pain, muscle pain. Rare: allergy, rash, photosensitivity, urticaria, pruritus, fever, acne.
Adverse reactions ethambutol
Blood and lymphatic system abnormalities rare: thrombocytopenia, leukopenia.
Mental disorders Uncommon: hallucinations.
Nervous system abnormalities Uncommon: dizziness, disorientation, confusion, headache, malaise. Rare: peripheral neuropathy (numbness, tingling, burning, weakness).
Rare eye abnormalities: Dose-dependent retrobulbar optic neuritis (blurred vision, eye pain, color blindness, blindness).
Gastrointestinal abnormalities Uncommon: abdominal pain, loss of appetite, nausea, vomiting, anorexia.
Skin and subcutaneous tissue abnormalities uncommon: pruritus, urticaria, rash.
Kidney and urinary system abnormalities Uncommon: increased blood uric acid, causing gout (chills, joint pain, swelling, especially the thumb, ankle and knee).
Generally poor condition rare: hypersensitivity reactions (rash, fever, joint pain), allergic reactions.
1. Rifampin, pyrazinamide, isoniazid, ethambutol hydrochloride or any of the excipients allergies were banned;
2. Normal liver function, biliary obstruction, within 3 months pregnant, gout, mental illness, epilepsy, diabetes retinopathy who porphyria disabled;
3. disabled patients with severe renal insufficiency;
4. Taboo and voriconazole and protease inhibitors used in combination (see drug interactions).
Because of acetylation subtypes in the crowd, so the patient has the ability to fast or slow acetylation should take four drugs were so easy to adjust the dose of isoniazid.
If the FDA severe acute allergic reaction should immediately stop, such as: thrombocytopenia, purpura, hemolytic anemia, dyspnea, and asthma-like symptoms, shock or renal failure, in rare use of rifampicin treatment of cases these adverse reactions may also occur when patients these adverse reactions should not be using this service again.
In any other allergy symptoms should also be disabled, such as: fever or skin reactions. For security reasons, we should continue to use or restore the FDA during treatment.
In patients using this treatment for vision defects, should pay more attention. Is recommended at the beginning and during use (especially when using higher doses) should have regular eye examination, including resolution, color discrimination and visual field examination. It should be recorded for each patient during treatment made by visual inspection, if there during the clinical treatment of vision disorders Patients should be advised to discontinue use.
This product medication precautions and rifampin, isoniazid, ethambutol and pyrazinamide various drugs use the same precautions.
We recommend that patients should be continuous treatment.
Damage to liver function, malnutrition, alcoholism
Rifampin, isoniazid, ethambutol, pyrazinamide, mainly in the liver metabolism, it is in the process of taking usually occurs transaminase elevation, above the upper limit of the normal range (ULN). In just a few weeks before the start of treatment of liver dysfunction may occur, but there is no interruption of treatment, in the first three months of treatment will naturally return to the normal range.
Lifestyle usually use, although often mild transaminase elevation, but extremely rare jaundice or hepatitis. While taking isoniazid and rifampicin patients, elevated alkaline phosphatase is mainly caused by rifampicin, but it may be caused by elevated transaminase isoniazid, rifampicin, pyrazinamide were caused, or It is caused by the combined effects of the three.
Patients with impaired liver function during therapy should be used with caution, and strict drug monitoring. In these patients, liver function should be carefully monitored, especially the emergence of serum glutamic pyruvic transaminase (SGPT / ALAT) and serum aspartate transaminase (SGOT / ASAT) when, before treatment and every week or every two weeks to monitor liver function ʱ?? If symptoms of liver damage should be immediately discontinued.
Bilirubin and / or moderately elevated transaminases without stopping the treatment; however, after repeated tests of liver function, should bilirubin and / or transaminase trends and linked to the physical condition of the patient's clinical judgment.
When patients with jaundice or transaminases exceeding the upper limit of its normal range (ULN) three times, it is recommended to stop the FDA. In order to facilitate the treatment of this clinical situation, it should replace complex drugs, and the use of rifampin, isoniazid, pyrazinamide, ethambutol, or a single component.
If hepatic function fails to return to normal or transaminases exceed 5 times the upper limit of the normal range, you should stop using this product. In order to facilitate treatment, should FDCs (the product) to replace a single component of a pharmaceutical formulation.
In the FDA for patients with chronic liver disease should be closely monitored. Isoniazid can cause serious, even fatal hepatitis, this situation may occur in use within a few months after their treatment. Although the use of isoniazid hepatotoxicity caused by reactions in patients around 20 years of age is rare, but its frequency of occurrence increases with age, occurred in 50 patients over the age of 3% chance. It will closely monitor liver function of liver cells reduced the incidence of toxicity. Patients should be monitored and precursory symptoms associated with hepatitis, such as: fatigue, weakness, malaise, anorexia, nausea, vomiting. Once these symptoms appear, or find liver damage, drug treatment should be stopped immediately. If the FDA should continue treatment might increase the degree of liver damage.
Patients with chronic liver disease in patients with chronic alcoholism and malnutrition as the FDA in the treatment of tuberculosis should minimize the damage to the liver this product. If TB treatment is required, then rifampin, isoniazid, pyrazinamide, ethambutol dose should be adjusted, but the product is not available for such patients.
Due to high doses of isoniazid make malnutrition or elderly patients generate insufficient vitamin B6, vitamin B6 and therefore may be necessary.
Renal damage
Patients with severe renal insufficiency, isoniazid, pyrazinamide, ethambutol eliminated slowly, so that the body of drug concentration, increased adverse reactions in patients with moderate renal impairment (creatinine clearance 30 ~ 60ml / min ) should be careful.
In patients with a history of gout should be the FDA should be cautious. During the taking regularly check blood uric acid. When patients with gouty arthritis should be discontinued.
Blood disease
When prolonged treatment process, as well as the treatment of patients with liver dysfunction, should be done to check blood cells. Once purpura or thrombocytopenia should stop using this product immediately. Pyrazinamide may affect clotting time or vascular integrity should be advised of the symptoms of patients with hemoptysis.
It has been reported that diabetic patients taking isoniazid, will increase the difficulty of controlling the disease diabetes.
Since isoniazid and ethambutol have neurotoxic effects, so in the treatment of patients with a history of seizures should be closely observed.
Patients with peripheral or optic neuritis should be used with caution. When patients with history of alcohol abuse, you should have regular check nervous system. Vitamin B6 can delay or reduce the patient isoniazid nervous system damage, especially in elderly patients and malnutrition. Vitamin B6 dose should medication under the guidance of a medical practitioner.
In the process of applying rifampicin therapy should be used an additional non-hormonal method of contraception.
During the FDA should treatment, patients should stop drinking.
Laboratory examination
Before and during treatment should have regular complete blood count test, liver function tests (SGPT / ALAT, SGOT / ASAT), renal function tests and uric acid monitoring is also recommended to do visual inspection.
Combination therapy
Rifampicin is an effective inducer of cytochrome P450 system, can promote the combination therapy drug metabolism, so that the plasma concentration decreased efficacy weakened. If you have the ability to monitor in the liver metabolism of drugs and dose adjustment, the drug can still be used in combination with rifampin.
This product is not suitable for combination with the following drugs: nevirapine, simvastatin, oral contraceptives and ritonavir (when low doses of medication, will be significantly reduced plasma concentration).
This product will slightly affect the medication's ability to drive and use machines capabilities. Ethambutol induced insanity, disorientation, hallucinations, dizziness, discomfort and visual disorders, medication side effects that may affect the ability to drive and use machines.
Pregnant women and lactating women drug]
Contraindicated in pregnancy before three months pregnant.
If the product can be able to benefit patients, the regimen should be considered. Only when the potential benefits to the mother outweigh the potential risk to the fetus, to the FDA.
Limited clinical data on use during pregnancy published in the show, will not increase the likelihood of fetal teratogenicity. Rifampicin through the placenta. In the last few weeks of pregnancy can lead to the use of rifampicin postpartum maternal and neonatal bleeding. Animal studies have shown that the dose ≥150mg / kg, reproductive toxicity occurs.
According to the limited data, congenital teratogenicity isoniazid unexpected occurs. Isoniazid can, for infants through the placenta to produce neurotoxic effects, animal studies show reproductive toxicity.
No reproductive toxicity studies on animals pyrazinamide, pregnant women taking pyrazinamide whether there is damage to the fetus, not yet confirmed.
Ethambutol through the placenta and may cause fetal blood concentration of 30% of the parent's. Limited clinical data suggest that ethambutol does not increase the likelihood of fetal body teratogenic. Animal studies have shown that there is a potential teratogenic risk.
Recommended in the last month of pregnancy, the mother and the newborn after delivery of oral vitamin K, because rifampicin can lead to maternal and neonatal bleeding.
Since isoniazid for young children may have neurotoxic effects, need vitamin supplements during pregnancy B6.
Rifampin, isoniazid, pyrazinamide and ethambutol can enter the milk, but not yet observed adverse reactions in nursing infants. But given isoniazid and ethambutol theoretically have neurotoxic effects in medication during breastfeeding is not recommended.
Pediatric Use of this product is not for children.
[Geriatric medicine]
The elderly often accompanied by physiological renal dysfunction, renal function should therefore adjust the dosage or doctor.
Drug interactions
Effect of other drugs on this product
Antacids can reduce rifampin, isoniazid, ethambutol bioavailability. To avoid such situations, the product should be taken at least 1 hour before taking antacids. Corticosteroids can reduce the plasma concentration by promoting the metabolism of isoniazid and / or increased renal clearance.
The impact of the product on other drugs
Rifampicin strong cytochrome P450 system (CYP450) induction of cytochrome P450 system mainly consists of two subfamilies CYP3A and CYP2C, representing the cytochrome P450 isoenzyme system 80%. When combined with medication, can accelerate the metabolism of rifampin combination of drugs, while taking these drugs part or all of the two isoenzymes through metabolism. But also induction of rifampicin uridine-5'-diphosphate - glucuronide transferases (which is another enzyme drug metabolism), which causes the plasma concentration of other drugs at the same time the application of sub-therapeutic dose The plasma concentration, increase or reduce the effect of adverse reactions. Isoniazid can inhibit the metabolism of these drugs lead to its increased blood concentration.
Moreover, rifampicin and isoniazid may affect some drugs antagonism, such as: phenytoin, warfarin and theophylline. The net effect of unpredictable and may change over time.
Mainly metabolized by the liver eliminate drugs, if we can monitor their blood concentration or adverse reactions, and can adjust their dosage, and the product can still be combined. Stop taking this period and in 2 to 3 weeks after treatment should be checked regularly.
Rifampicin role in enzyme induction, within ten days to reach the peak, and gradually reduced to two weeks after withdrawal, the FDA's process if other drug use increased dose, these factors need to be considered disabled.
If you want to consider the compatibility with the goods on the drug concentration is affected, refer to the following:
Interaction rifampicin
The product with the following drugs is strictly prohibited while using: voriconazole and protease inhibitors, but except ritonavir 600mg twice daily dose or adequate dose.
This product should not be used simultaneously with the following drugs: nevirapine, simvastatin, oral contraceptives and ritonavir (when low doses of medication, will be significantly reduced plasma concentration).
When this product with the following medicines at the same time, you need to be monitored for some specific parameters or clinical monitoring, such as: calcium antagonists, Ia antiarrhythmic drugs (quinidine, disopyramide), oral anticoagulants, pyrrole antifungal agents (except voriconazole), buspirone, carvedilol (because of its insufficiency and the low therapeutic window in cardiac symptoms), immunosuppressants (such as cyclosporine, tacrolimus, sirolimus), clozapine, corticosteroids, gestrinone, combined estrogen and progestin hormone replacement therapy, haloperidol, thyroid hormones, methadone, morphine, efavirenz, propafenone, terbinafine Finland, tiagabine, zidovudine, zolpidem, zaleplon, carbamazepine, phenytoin, theophylline, diazepam, digitalis, dapsone, atovaquone, repaglinide and sulfur ureide class of oral diabetes drugs, β receptor antagonists (such as by the hepatic metabolism of metoprolol, propranolol), chloramphenicol, clarithromycin, telithromycin, tricyclic antidepressants, amino water salicylic acid, cimetidine, mexiletine, nevirapine, fluvastatin, rofecoxib, imidapril, Topsy dragon.
Isoniazid Interaction
When this product with the following medicines at the same time, we need to be monitored for some specific parameters or clinical monitoring, such as: anesthetics, corticosteroids, ketoconazole, phenytoin, pyrazinamide, stavudine, carbamazepine, diazepam Pan, ethosuximide, theophylline.
Interaction pyrazinamide
When this product with the following medicines at the same time, we need to be monitored for some specific parameters or clinical monitoring, such as: probenecid, sulfinpyrazone.
Rifampicin can reduce the effects of oral contraceptives, so that patients using this treatment approach should use non-hormonal contraception. At the same time the use of antibiotics may make oral typhoid vaccine inactivation.
Should avoid food rich in tyrosine and histidine food. Isoniazid may inhibit monoamine oxidase and diamine oxidase. Food containing tyrosine (such as cheese, red wine) or containing histidine (such as tuna) food can cause headaches, palpitations, flushing and other symptoms.
Radiological examination in the gallbladder, rifampicin may delay the secretion of bile. During use of rifampicin, microbiological methods can not be used to determine folate and cyanocobalamin acid (vitamin B12) plasma concentrations, because rifampicin and bilirubin and BSP will compete. To avoid false positive reactions in the morning before taking rifampin BSP test should be carried out.
Poisoning: Infants (1-4 years) Oral 100mg / kg rifampicin appear typical skin symptoms; severe poisoning adults taking 15g, 12g taking moderate poisoning, take 60g can produce extremely serious poisoning.
Symptoms: gastrointestinal discomfort, vomiting, sweating, difficulty breathing, seizures, kidney failure, liver failure, confusion, generalized itching, skin and urine was orange, facial edema, pulmonary swelling.
Treatment: gastric lavage, given after gastric lavage activated charcoal to absorb the remnants of rifampicin in the gastrointestinal tract; symptomatic treatment; renal failure requiring dialysis.
Poisoning: Alcohol can induce toxicity. Lethal dose infant is 80 ~ 150mg / kg; 15-year-olds taking 5 g fatal poisoning; 8-year-old children taking 900mg moderate poisoning; 3-year-old children taking 2 ~ 3 g serious poisoning; 15-year-olds taking 3g, adults take 5 ~ 7.5g can produce extremely serious poisoning.
Symptoms: Typical symptoms are seizures and metabolic acidosis, ketone, hyperglycemia; orbital myoclonus, dizziness, tinnitus, tremor, hyperreflexia, confusion, hallucinations; respiratory depression, apnea; tachycardia, arrhythmia, hypertension ; nausea, vomiting, fever, rhabdomyolysis, disseminated intravascular coagulation, hyperglycemia, hyperkalemia, liver damage. Isoniazid doses greater than 10mg / kg may affect the peripheral nervous system, damage to the patient's ability to drive or operate machinery.
Remedy: No history of seizures in patients with gastric lavage, gastric lavage after administration of isoniazid residue activated carbon adsorption. Blood samples were collected from blood gas measurement should be done immediately, ions, blood urea nitrogen, blood sugar levels. Seizures and metabolic acidosis, per gram of isoniazid given vitamin B61 g; seizures and isoniazid dose of uncertainty, with 5 grams of vitamin B6 intravenously; no seizures, prevent giving vitamin B6 2 ~ 3 grams intravenously. To reduce the vascular stimulation, vitamin B6 diluted before use, and the drug using an infusion pump or a syringe pump into the body within 30min, repeated administration of vitamin B6 if necessary. Stability and enhance the role of vitamin B6, use of high doses of diazepam alone treat seizures. Severe cases have respiratory depression, timely rescue; correction of metabolic acidosis and ion imbalance; diuresis, when severe intoxication hemodialysis; symptomatic treatment.
Liver dysfunction, hyperuricemia.
Loss of appetite, gastrointestinal disorder, fever, headache, dizziness, confusion, hallucinations.
Pharmacology and Toxicology
This product is compound rifampin, isoniazid, pyrazinamide, ethambutol hydrochloride thereof. among them
Rifampicin: a broad-spectrum antimicrobial activity against gram positive and negative bacteria have good antibacterial effect; Mycobacterium tuberculosis, and some non-tuberculous mycobacteria, Mycobacterium leprae have significant bactericidal effect.
Isoniazid: Mycobacterium tuberculosis to various growth states have a strong bactericidal effect, is a wholly-potent bactericidal drug, Kansas mycobacteria are also inhibitory effect in a variety of non-tuberculous mycobacteria.
Pyrazinamide: This nicotinamide derivatives, and interference by replacing nicotinamide dehydrogenase, preventing dehydrogenation impede tuberculosis oxygen utilization, and affect the normal metabolism of bacteria, Mycobacterium people better antibacterial effect. 5.5 This product pH5 ~, sterilization strongest.
Ethambutol: growth and reproduction of various states have a role TB, strains resistant to isoniazid and streptomycin resistance is also effective, combination of isoniazid, rifampicin, pyrazinamide can delay and reduce tuberculosis resistant to its effects it produces, with no cross-resistance to other anti-TB drugs.
Fasting absorption, medication after eating can reduce the rate and extent of drug absorption. 2h plasma concentration peak, is widely distributed in the body after absorption; In addition to meningitis, cerebrospinal fluid drug concentration is low. The apparent volume of distribution is about 55L, protein binding rate of 80%. After deacetylation reaction, become active metabolite deacetylation rifampin. Rifampicin and its metabolites mainly by biliary excretion and enterohepatic circulation there. Approximately 10% of unchanged drug excreted in the urine.
The plasma elimination half-life of rifampicin 3 ~ 5h, shortened half-life after multiple dosing, is 2 ~ 3h. Because of its hepatic drug metabolizing enzyme induction, rifampicin dose 6 to 10 days after the elimination of the rate increase. Large doses, since biliary excretion reaches saturation, excretion may be delayed.
Rapid oral absorption, absorption rate and extent taken after eating were decreased. 1 ~ 2h after the plasma concentration peak. After absorption of isoniazid is widely distributed in body fluids and tissues, the apparent volume of distribution is about 43 L; low protein binding, only 0-10%. By N- acetyltransferase acetylation into acetyl isoniazid, then biotransformation isonicotinic and single acetohydrazide, single acetohydrazide liver toxicity. Effect of isoniazid acetylation speed by genetic factors, often slow acetylation liver N- acetyltransferase enzyme deficiency, about 50 percent of Caucasians and African Indians belong slow metabolizers; the vast majority of Eskimos and Japan, China, Vietnam and other Asian belonging fast metabolizers.
The half-life of isoniazid is usually 1 ~ 4h, but because of the different speeds of acetylation, which may be in the range 0.5 ~ 6h. Nearly 75% to 95% within 24 h of isoniazid excreted by the kidneys, mostly inactive metabolite N- acetyl isoniazid and isonicotinic acid.
After oral administration in the gastrointestinal tract rapidly and completely absorbed, eating no effect on absorption. Adult 1 ~ 2h after the peak plasma concentration, children Tong Dafeng time of 3h. Pyrazinamide by microsomal deaminase hydrolysis of an active metabolite - pyrazine acid, followed by a xanthine oxidase into 5- hydroxylated pyrazine hydroxy acid. Pyrazinamide mainly in the form of metabolites excreted by the kidneys, only 3% of the urine is discharged in the form of prototype drug. Plasma half-life is about 10 h.
Good oral absorption, bioavailability of nearly 80%, eating does not affect its absorption. 2 ~ 4h peak plasma concentration, widely distributed in body tissues and fluids (except for the cerebrospinal fluid), but the drug concentration in the cerebrospinal fluid of patients with tuberculous meningitis in up treatment values. Drug concentration of red blood cells may be a plasma drug concentration of 2 to 3 times, low protein binding, only 20% to 30%, apparent volume of distribution is about 20L. Ethambutol mainly by the liver metabolism, approximately 15% metabolized to inactive metabolites. Half-life of 3 ~ 4 h, but in patients with renal insufficiency, the half-life of up to 8 h. Approximately 80% within 24 h (at least 50% of the parent drug and nearly 15% inactive metabolites) excreted by the kidneys, excreted in the feces about 20%.
Special Populations
Patients with renal insufficiency, daily 600mg (10mg / kg) allows the elimination half-life of drugs, resulting in drug accumulation. Rifampicin can not be eliminated by hemodialysis.
In patients with liver dysfunction, plasma drug concentration increased, the elimination half-life.
Slow acetylation metabolic patients with renal insufficiency, isoniazid drug accumulation may occur. Isoniazid blood concentration should be monitored and, if necessary, reduce the dose. Patients with hepatic dysfunction, the elimination half-life of isoniazid.
Cirrhotic patients was significantly reduced clearance rate, half-life, pyrazine acid (the main metabolite) of AUC increase threefold. Patients with renal insufficiency drug metabolism have not been reported, can be cleared by hemodialysis.
In patients with renal insufficiency prolonged elimination half-life, we need to adjust the dose. Not by hemodialysis.
[Storage] sealed and kept in a cool dark dry place (dark and not more than 20 ℃).
[Packaging] Blister packaging, 5 / plate; composite film packaging, 5 boards / bag; carton packaging, 2 bags / boxes;
Blister packaging, 5 / plate; composite film packaging, 5 boards / bag; carton, 3 bags / box;
Blister packaging, 10 / plate; composite film packaging, 5 boards / bag; carton packaging, 2 bags / boxes;
Blister packaging, 10 / plate; composite film packaging, 5 boards / bag; carton, 3 bags / boxes.
[Validity] 24 months
[Executive standard] China Food and Drug Administration standards YBH01352014
[Approval No.] H20090219 Zhunzi
Company Name: Shenyang Hongqi Pharmaceutical Co., Ltd.
Production Address: Shenyang Hunnan New District envelope Street on the 6th
Postal Code: 110179
Telephone number: 024-23786260 024-23786261
Fax: 024-23786263


The above is for reference
If you have questions can contact the manufacturer