Isoniazid + Pyrazinamide + Rifampicin
When ATH:
J04AM05
Characteristic.
Anti-tuberculosis combined tool.
Pharmacological action.
Antiphthisic, Antibacterial, bactericide.
Application.
Tuberculosis (any location, in the first period of intensive treatment).
Contraindications.
Hypersensitivity, jaundice, acute liver disease of various origins, pulmonary heart disease II-III art., hyperuricemia, gout, purpura, pregnancy (I trimester), lactation.
Restrictions apply.
Liver disease, kidney, Saint Martin's evil, elderly and debilitated patients, pregnancy (II–III trimesters), childhood.
Pregnancy and breast-feeding.
Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)
Side effects.
From the nervous system and sensory organs: headache, dizziness, sleep disturbance, hypererethism, depression, ataxia, disorientation, reduced visual acuity; rarely — excessive fatigue or weakness, irritability, euphoria, paraesthesia, numbness, optic neuritis, polyneuropathy, psychosis, mood lability, depression, hallucinations, convulsions, confusion; in patients with epilepsy may be more frequent seizures.
Cardio-vascular system and blood (hematopoiesis, hemostasis): heartbeat, angina, increased blood pressure, leukopenia, thrombocytopenia, sideroblastnaya anemia, vacuolation of erythrocytes, hypercoagulation, tendency to bleed and hemorrhage, splenomegaly.
From the digestive tract: nausea, vomiting, gastralgia, diarrhea, metallic taste in mouth, abnormal liver function (decreased appetite, increase in liver transaminases, liver tenderness, gepatomegaliya, jaundice, yellow atrophy of the liver, giperʙiliruʙinemija, hepatitis, incl. toxic hepatitis), aggravation of peptic ulcers, erosive gastritis, pseudomembranous enterocolitis.
On the part of the musculoskeletal system: arthralgia, myalgia, myasthenia.
With the genitourinary system: gynecomastia, menorragija, dysmenorrhoea, dizurija, nefronekroz, interstitial nephritis.
Allergic reactions: skin rash, itch, hives, eozinofilija, hyperthermia, bronchospasm, angioedema.
Other: porphyria, hyperuricemia, worsening of gout, acne, photosensitivity, increasing the concentration of serum iron.
When taking an irregular or resumption of treatment after interruption possible flu-like symptoms (fever, chills, headache, dizziness, myalgia), skin reactions, gemoliticheskaya anemia, trombotsitopenicheskaya purpura, acute renal failure.
Cooperation.
Antacids, Opiates, anticholinergic drugs ketoconazole and reduce the bioavailability of rifampicin. Preparations Pasco, soderzhashtie bentonite (hydrous aluminum), appointed later 4 h after administration of rifampicin. Rifampicin increases the rate of excretion bromsulfaleina. Rifampicin causes induction of the liver enzyme systems, It speeds up metabolism. Rifampicin reduces the activity of oral anticoagulants, oral hypoglycemic drugs, hormonal contraceptives, Digitalis preparations, antiarrhythmic drugs (disopyramide, pirmenol, quinidine, mexiletine, tokainid), glюkokortikoidov, dapsone, phenytoin, geksoʙarʙitala, nortriptyline, benzodiazepines, hormones, teofillina, chloramphenicol, ketoconazole, itraconazole, Cyclosporin A, beta-blockers, BCC, Enalapril, cimetidine. Antacids reduce the absorption of isoniazid. Isoniazid increases the concentration of phenytoin in the blood, reduces the effectiveness of oral contraceptive drugs combined, Glipizide, tolʙutamida, teofillina, tolazamida, tiamina; increases the side effects of phenytoin; inhibits the excretion of triazolam; reduces the content of Zn2+ in blood, increases the excretion. Isoniazid and / or pyrazinamide increased incidence and severity of liver dysfunction in combination with rifampicin in patients with a history of liver disease.
Overdose.
Isoniazid. Symptoms: dizziness, dysarthria, slackness, disorientation, hyperreflexia, peripheral polyneuropathy, abnormal liver function, metabolic acidosis, giperglikemiâ, glycosuria, ketonwrïya, convulsions (1-3 hours after treatment), coma.
Treatment: When peripheral polyneuropathy-B vitamins6, B1, B12, ATP, glutamic acid, nicotinamide, massage, physiotherapy; cramps-in/m vitamin B6 - 200-250 mg, I / 40% solution of dextrose — 20 ml, / m 25% a solution of magnesium sulfate — 10 ml, diazepam; If any of the liver-methionine, thioctic acid, ATP, vitamin B12.
Rifampicin. Symptoms: pulmonary edema, lethargy, confusion, convulsions.
Treatment: simptomaticheskaya therapy, gastric lavage, appointment of activated carbon, diurez.
Pyrazinamide. Symptoms: abnormal liver function, increased severity of side effects from the CNS.
Treatment: simptomaticheskaya therapy.
Dosing and Administration.
Inside, for 1-2 hours before meals in one step. When body weight less than 50 kg - 3 Table. (150 mg rifampicin, 100 mg isoniazid, 350 mg pyrazinamide), more 50 kg - 4 Table. Children 10-15 mg/kg/day in terms of rifampicin, but not more 600 mg / day. A course of treatment - 2 Months, with continued administration of combinations of isoniazid and rifampicin or isoniazid and ethambutol.
Precautions.
Severe and sometimes fatal hepatitis, associated with isoniazid therapy, It may develop even after many months of treatment. The risk of hepatitis depends on the age; sampling frequency: 0/1000 People under the age of 20 years, 3/1000 in the age group 20-34 years, 12/1000 in the age group 35-49 years, 23/1000 in the age group 50-64 years, 8/1000 the age 65 years. The risk of hepatitis is increased with daily alcohol consumption. Precise data on the percentage of fatalities in the isoniazid-induced hepatitis is not, but, According to U.S. Public Health Service Surveillance Study (PDR, 2005), among 13838 patients, poluchavshikh isoniazid, It was recorded 8 deaths from 174 cases of hepatitis. Therefore patients, poluchayushikh isoniazid, should be carefully examined on a monthly basis. Increased serum transaminases observed in approximately 10-20% of patients, usually within the first few months of treatment. Despite continued therapy, parameters return to normal, but in some cases developed progressive liver dysfunction. Patients should be instructed to immediately appeal to the doctor when you see any «symptom of hepatitis (fatigue, weakness, malaise, anorexia, nausea or vomiting). If signs and symptoms of liver dysfunction (incl. increase in liver transaminases) found, drug immediately overturned, tk. while continuing to receive perhaps more serious liver damage. Renew treatment after normalization.
Before treatment and every 2-4 weeks define the content of glutamatacetattransaminazy and glutamatoksaloacetattransaminazy.
Pyrazinamide worsens for gout and diabetes mellitus, requires monitoring kidney function and uric acid. In the case of persistent hyperuricemia and exacerbation of gouty arthritis treatment hereof. During the period of treatment is not applied microbiological methods for determining the concentration of folic acid and vitamin B12 serum. The treatment should not apply bromsulfaleinovyj test (false positive results). In the long admission control functions of the liver, kidney, picture peripheral blood and examination by an ophthalmologist. It is prohibited to use ethanol. During treatment recommended an additional intake of vitamin D to prevent violations of calcium and phosphorus.
At the time of appointment in the last weeks of pregnancy is possible post-partum haemorrhage in the mother and the newborn bleeding (treatment is vitamin k). Women during the treatment it is recommended to use non-hormonal methods of contraception. Rifampicin okrashivaet a shell, sputum, sweat, mud, lacrimal fluid, urine, soft contact lenses in an orange-red.
