keyword :
分类
Products
  • Name: Rifampicin and Isoniazid Tablets
  • Add time: 2015-05-14
  • Views : 86

[Drug Name]
Generic Name:利福平异烟肼片
English name:Rifampicin and Isoniazid Tablets
Pinyin:Lifuping Yiyanjing Pian
Ingredient
This product is compound, each containing rifampicin (C43H58N4O12) 0.2g, isoniazid (C6H7N3O) 0.2g.
[Character]
This product is film-coated tablets, were removed after coating orange-red or dark red.
Indications
This product is applicable to all types of adult tuberculosis. For smear-positive, smear-negative patients with newly diagnosed smear-negative patients with severe or continue on with.
Chemotherapy:
Smear-positive patients: intensive treatment of 2H3R3Z3E3 / continuation phase 4H3R3
Smear female patients: intensive treatment of 2H3R3Z3E3 / continuation phase 4H3R3
Severe smear-negative patients: intensive treatment of 2H3R3Z3E3 / continuation phase 4H3R3
[Specification]
Each containing rifampicin (C43H58N4O12) 0.2g, isoniazid (C6H7N3O) 0.2g.
【Dosage】
Oral.
This product is used smear positive, smear-negative patients with previously untreated or severe smear-negative patients who continued on every medication on the 2nd, a total of four months, medication 60 times. Adult, weighing more than 50kg each patient fasting Dayton served this product three patients weighing less than 50kg according to doctor's orders to reduce it, one hour before meals or two hours after a meal 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.
【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.
Taboo
1. Rifampin and isoniazid allergies were banned;
2. Liver dysfunction, biliary obstruction, within 3 months pregnant, gout, mental illness, epilepsy, diabetes retinopathy who porphyria disabled.
3. Taboo and voriconazole and protease inhibitors used in combination (see drug interactions).
【Precautions】
1. Elderly and diabetic patients with caution. Alcoholism, liver dysfunction, optic neuritis, kidney dysfunction in patients with caution.
2. The diagnosis of interference: make blood urea nitrogen, serum alkaline phosphatase, serum alanine aminotransferase, aspartate aminotransferase, bilirubin and serum measurement results of serum uric acid concentration increased. Where rifampicin can cause direct antiglobulin test (Coombs test) positive; measured serum folate concentrations and interfere with the measurement results of serum vitamin B12 concentrations; make methyl bromide phthalocyanine sodium retention test false positive; can interfere with the use of a spectrophotometer or color changes were the result of the urine analysis test. Isoniazid urine determination of copper sulfate method showed a false positive reaction, but does not affect the results of the enzymatic assay. Isoniazid can increase serum bilirubin measurement results.
3. Cross-allergy: drug allergy patients B isonicotinoyl similar amines, nicotinic acid or other chemical structures may also allergic to the chemicals.
4. Since the product can make the serum uric acid concentration increased, causing gout. Therefore, in the course of treatment should be measured regularly.
5. During the treatment should be checked: eye, vision, vision, red-green discrimination, etc., before treatment, treatment of daily checks, optic neuritis symptoms, eye examination should be carried out immediately, and periodic review.
6. rifampicin
(1) baby, three months or more pregnant and lactating women with caution.
(2) rifampicin can cause liver dysfunction, jaundice associated deaths have been reported in patients with liver disease or when the original of this product with other hepatotoxic drugs with the service, and therefore the original patients with liver disease, only in case there is a clear indication below It can be used with caution, before the start of treatment, the treatment of close observation of changes in liver function, liver damage occur, immediate withdrawal.
(3) Department of hyperbilirubinemia liver cells and bile retention of mixed type, in patients with mild medication subside on their own weight are required to observe the withdrawal. Blood bilirubin may also be the result of competition rifampin and bilirubin excretion. Early treatment for 2 to 3 months should be closely monitored changes in liver function.
(4) rifampicin may cause neutropenia and thrombocytopenia and bleeding gums and lead to infection, delayed wound healing and the like. You should avoid tooth extraction surgery, and pay attention to oral hygiene, brushing and flossing are required to carefully until the blood return to normal. Peripheral blood should be checked regularly during the treatment.
(5) after taking the urine, saliva, sweat and other excretions could significantly orange. Interstitial nephritis may occur.
[Pregnant women and lactating women drug]
Rifampicin: can cross the placenta, pregnant women should be the FDA ban within three months, more than three months pregnant women should be used with caution. Although unproven in humans against the harmful effects of fetal, maternal drug use should remain fully weigh; by milk excretion, although not confirmed in humans there is a problem, but lactating women should still be fully weighed.
Isoniazid: can cross the placenta, causing fetal blood concentrations higher than the maternal plasma concentration in humans did not confirm there is a problem, but the application must be fully weighed against pregnant women; similar concentration in breast milk and blood drug concentration, although in humans not confirmed there is a problem, the application should be fully weigh during lactation.
Pediatric Use
This product is not for children.
[Geriatric medicine]
Unclear.
Drug interactions
Rifampicin:

1. Lifestyle usually taking rifampicin daily drinking can lead to increased incidence of liver toxicity, and increased metabolic rifampicin, the need to adjust the dose of rifampicin, and closely monitor patients with and without liver toxicity symptoms appear.
2. adrenocorticotropic hormone (glucocorticoid, mineralocorticoid), anticoagulants, or indandione coumarin derivatives, oral hypoglycemic agents, corticotropin, dapsone, digitalis glycosides, disopyramide When amines, quinidine and rifampin, as the latter stimulating effect on the liver microsomal enzyme activity, can reduce the efficacy of these drugs, so in addition to dapsone digoxin and outside, with rifampicin flat front and the course of treatment of these drugs need to adjust the dose. When combined with coumarin or indane ketones daily or periodically measuring prothrombin time, to adjust the dose.
3. aminosalicylates may affect the absorption of rifampicin, resulting in reduced plasma concentration of rifampicin; for patients taking aminosalicylates and Lifestyle usual, separated by at least 6 hours between the two drugs.
4. Rifampicin can stimulate estrogen metabolism or decrease its enterohepatic circulation, reduce the role of oral contraceptives, resulting in irregular menstruation, menstrual bleeding and unplanned pregnancy period, usually patients taking rifampicin, should use other contraceptive methods ʱ??
5. rifampicin may induce hepatic microsomal enzymes, an increase of antineoplastic agents dacarbazine (dacarbazine), the metabolism of cyclophosphamide, an alkylating metabolites formed to promote leukocyte reduced, and therefore need to adjust the dose.
6. isoniazid and rifampin, or miconazole (intravenous), ketoconazole increase the risk of liver toxicity, especially liver dysfunction original fast and isoniazid acetylation patients. In addition, isoniazid or rifampicin and miconazole or ketoconazole, after both can reduce blood concentration, so this product and isoniazid should not be combined with imidazole.
7. rifampicin and diazepam (Valium) combined to increase the elimination of the latter, so that the plasma concentration decreased, so the need to adjust the dose.
8. rifampin and isoniazid amine B sulfur can be combined to aggravate the adverse reactions.
9. rifampicin increase levothyroxine degradation in the liver, so the dose of L-thyroxine should be increased when the two combined. Rifampin can increase methadone, mexiletine metabolized in the liver, causing methadone withdrawal symptoms mexiletine plasma concentrations reduced, so after two in combination require dose adjustment. Phenytoin rifampin may increase the metabolism in the liver, so the two combined phenytoin plasma concentrations should be measured and adjust the dosage.
10. probenecid can compete with rifampicin uptake by liver cells, so that increased plasma concentration of rifampicin and produce toxicity. But instability in the role, it is usually not added with probenecid to increase plasma concentrations of rifampicin.
11. rifampin trimethoprim may increase the elimination of increased metabolic xanthine, so eliminate the increase of theophylline.
Isoniazid:
1. while taking isoniazid daily drinking can lead to liver toxicity induced by isoniazid, isoniazid and accelerate metabolism, and therefore need to adjust the dose of isoniazid and closely observe signs of liver toxicity, the patient should be advised Avoid alcoholic beverages while taking this medicine.
2. The aluminum-containing antacids may delay and reduce the absorption of isoniazid after oral administration, the blood concentration reduced, it should be taken to avoid both, or prior to oral antacids for at least 1 hour before taking isoniazid.
3. anticoagulants (such as coumarin derivative or indandione) simultaneously with the application of isoniazid, due to inhibition of the enzyme metabolism of anticoagulants, so anticoagulation effects.
4. and cycloserine with taking the central nervous system to increase the side effects (such as dizziness or drowsiness), the need to adjust the dose, and closely observe the signs of central nervous system toxicity, especially in the need for higher working sensitivity patients.
5. rifampin and isoniazid in combination can increase the risk of liver toxicity, and in particular liver dysfunction or fast acetylation of isoniazid, so in the first three months whether the course should be closely followed signs of liver toxicity occurs.
6. isoniazid vitamin B6 antagonists, and increase the amount of vitamin B6 excreted by the kidneys, which may lead to peripheral neuritis, thus increasing requirement of vitamin B6 when combined with isoniazid.
7. When combined with adrenocorticotropic hormone (especially prednisolone), increase isoniazid in liver metabolism and excretion, causing the latter to reduce the plasma concentration affect efficacy in fast acetylation more significant, should appropriate dose adjustment.
8. When combined with alfentanil (alfentanil), due to liver enzyme inhibitors isoniazid, extend alfentanil role; with disulfiram (disulfiram) combined to increase the role of the central nervous system, resulting in dizziness, incoordination, irritability, insomnia; increase combined form of inorganic fluorine nephrotoxic metabolite and enflurane.
9. B sulfur isoniazid or other anti-TB drugs, adverse reactions may increase both. Increase the liver toxicity of this product in combination with other hepatotoxic drugs, and therefore should be avoided.
10. isoniazid not with ketoconazole or miconazole in combination, can reduce both due after the plasma concentration.
11. When combined with phenytoin inhibits the latter in the liver metabolism, which led to increased phenytoin plasma concentrations, it has both an application or combination, phenytoin dose should be adjusted appropriately.
Overdosage
Rifampicin:
Poisoning: Infants (1-4 years) Oral 100mg / kg rifampicin typical skin symptoms appear; adults take 15 g of severe poisoning, take 12g 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: a gastric lavage, because patients often experience nausea, vomiting, should then induce vomiting; give activated charcoal paste after gastric lavage to absorb the remnants of rifampicin in the gastrointestinal tract; severe nausea and vomiting antiemetic agent. 2. Give diuretics promote drug excretion. 3. severe liver damage for 24 to 48 hours or more may be considered for biliary drainage. If necessary, hemodialysis.
Isoniazid:
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, 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.
Handling: 1 to maintain airway patency; 2 using short-acting barbiturate within preparations and intravenous administration of vitamin B6, vitamin B6 dose of isoniazid with each 1mg 1mg, followed by gastric lavage, gastric lavage should be taking isoniazid. performed within 2-3 hours after; 3. Determination of immediate blood gas analysis, dielectric, urea nitrogen, blood sugar; 4 immediate intravenous administration of sodium bicarbonate, correction of metabolic acidosis, repeated administration as needed; 5 using penetration diuretics, and continue to apply after the clinical symptoms have improved, promote excretion of isoniazid to prevent recurrence; when 6 severe poisoning patients should be early with blood, ready to do hemodialysis, can not be hemodialysis, peritoneal dialysis can be performed while combined with a diuretic; 7 to take effective measures to prevent hypoxia, hypotension and aspiration pneumonia.
Pharmacology and Toxicology
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.
【Pharmacokinetics】
Rifampicin: Good oral absorption, after taking 1.5 to 4 hours of peak plasma concentration. After the adult oral 600mg peak plasma concentration (Cmax) of 7 ~ 9mg / L, 6 months to 5 years old children an oral 10mg / kg, peak plasma concentration (Cmax) of 11mg / L. After rifampicin diffuse systemic absorption of most tissues and body fluids, including cerebrospinal fluid, when there is inflammation of the meninges increase in drug concentration in the cerebrospinal fluid; in saliva can achieve effective therapeutic concentrations; can cross the placenta. The apparent volume of distribution (Vd) is 1.6L / kg. Protein binding rate of 80% to 91%. Medication after eating can reduce by 30% the absorption of drugs, the drug blood elimination half-life (t1 / 2) is 3 to 5 hours, after repeated administration has been shortened, from 2 to 3 hours. Rifampicin in the liver may be self-induced microsomal oxidase rapid action of deacetylation, become metabolites having antimicrobial activity 25- desacetyl rifampicin, inactive metabolites formed after hydrolysis from urine. Rifampicin the biliary and intestinal excretion, may enter the enterohepatic circulation, but its active metabolite deacetylation no enterohepatic circulation. 60% to 65% of the dose through the feces, 6% to 15% of the drug to the prototype, 15% of active metabolites excreted in the urine, 7% places no active 3-formyl derivative discharged. Also excreted through breast milk. Patients with renal dysfunction in this product is no accumulation; due to its induction of hepatic microsomal oxidase, taking rifampicin 6 to 10 days after its excretion rate increased; After high doses due to saturation biliary excretion, excretion may be delayed ʱ?? Rifampicin not clear by hemodialysis or peritoneal dialysis.
Isoniazid: After oral rapidly absorbed from the gastrointestinal tract and distributed in body tissues and fluids, including cerebrospinal fluid, pleural effusion, ascites, skin, muscle, milk and cheese-like tissue. You can cross the placental barrier. Protein binding rate 0 to 10%. Orally 1 to 2 hours up to the peak plasma concentration, but 4 to 6 hours after the plasma concentration of acetylated according to the patient rather than the speed of a fast acetylation, t1 / 2 0.5 to 1.6 hours, slow acetylation of 2 to 5 hours, liver and kidney dysfunction may be extended. Metabolism acetylation mainly in the liver from an inactive metabolites, some of which have liver toxicity. The rate of acetylation is determined by heredity. Liver often slow acetylation N- acetyltransferase enzyme deficiency, acetylation of isoniazid may not be part of the combination. Isoniazid mainly by renal excretion (approximately 70%), discharge within 24 hours, mostly inactive metabolites. Fast acetylation of 93% to acetylation excreted in the urine, slow acetylation of 63%. Fast acetylation of isoniazid 7% in the urine in free or combined form, and slow compared to 37 percent who Acetylating. Isoniazid easily through the blood brain barrier, also discharged from the milk, a small amount of self saliva, sputum and feces. A considerable amount of isoniazid may be hemodialysis and peritoneal dialysis.
[Storage]
Sealed, in a cool dark dry place (dark and not more than 20 ℃) to save.
[Packaging]
(1) blister packaging, 9 / plate; composite film packaging, 5 boards / bag; carton packaging, bag / box.
(2) blister packaging, 9 / plate; composite film packaging, 5 boards / bag; carton packaging, 2 bags / boxes.
(3) blister packaging, 9 / plate; composite film packaging, 5 boards / bag; carton packaging, 4 bags / box.
[Validity]
18 months
[Executive standard]
State Food and Drug Administration standards YBH05602009
【Approval Number】
Zhunzi H20090223
[manufacturer]
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