Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related. Approximate case rates by age are: 0 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20 to 34 year age group, 12 per 1,000 for persons in the 35 to 49 year age group, 23 per 1,000 for persons in the 50 to 64 year age group, and 8 per 1,000 for persons over 65 years of age. The risk of hepatitis is increased with daily consumption of alcohol. Precise data to provide a fatality rate for isoniazid-related hepatitis is not available; however, in a U.S. Public Health Service Surveillance Study of 13,838 persons taking isoniazid, there were 8 deaths among 174 cases of hepatitis.
Therefore, patients given isoniazid should be carefully monitored and interviewed at monthly intervals. Serum transaminase concentration becomes elevated in about 10% to 20% of patients, usually during the first few months of therapy, but it can occur at any time. Usually enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Patients should be instructed to report immediately any of the prodromal symptoms of hepatitis, such as fatigue, weakness, malaise, anorexia, nausea, or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.
Patients with tuberculosis should be given appropriate treatment with alternative drugs. If isoniazid must be reinstituted, it should be reinstituted only after symptoms and laboratory abnormalities have cleared. The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement. Treatment should be deferred in persons with acute hepatic diseases.
RIFATER (rifampin/isoniazid/pyrazinamide) tablets are combination tablets containing 120 mg rifampin, 50 mg isoniazid, and 300 mg pyrazinamide for use in antibacterial therapy.
RIFATER is indicated in the initial phase of the short-course treatment of pulmonary tuberculosis. During this phase, which should last 2 months, RIFATER should be administered on a daily, continuous basis (see DOSAGE AND ADMINISTRATION section).
Following the initial phase and treatment with RIFATER, treatment should be continued with rifampin and isoniazid (eg, RIFAMATE) for at least 4 months. Treatment should be continued for a longer period of time if the patient is still sputum or culture positive, if resistant organisms are present, or if the patient is HIV positive.
In the treatment of tuberculosis, the small number of resistant cells present within large populations of susceptible cells can rapidly become the predominant type. Since resistance can emerge rapidly, susceptibility tests should be performed in the event of persistent positive cultures during the course of treatment. Bacteriologic smears or cultures should be obtained before the start of therapy to confirm the susceptibility of the organism to rifampin, isoniazid, and pyrazinamide and they should be repeated throughout therapy to monitor response to the treatment. If test results show resistance to any of the components of RIFATER and the patient is not responding to therapy, the drug regimen should be modified.
Media Articles Related to Rifater (Rifampin / Isoniazid / Pyrazinamide)
Tuberculosis and HIV co-infection
Source: Respiratory / Asthma News From Medical News Today [2016.10.19]
The HIV virus increases the potency of the tuberculosis bacterium (Mtb) by affecting a central function of the immune system.
Study suggests antibodies may offer protection against tuberculosis
Source: Respiratory / Asthma News From Medical News Today [2016.09.23]
Antibodies are one of the body's first lines of defense against infection, but their role in tuberculosis (TB) has gone largely unstudied.
Is Tuberculosis (TB) Contagious?
Source: MedicineNet Tuberculosis Skin Test (PPD Skin Test) Specialty [2016.08.16]
Title: Is Tuberculosis (TB) Contagious?
Category: Diseases and Conditions
Created: 8/24/2015 12:00:00 AM
Last Editorial Review: 8/16/2016 12:00:00 AM
HIV is not a super-spreader of drug-resistant tuberculosis
Source: HIV / AIDS News From Medical News Today [2016.08.11]
While the human immunodeficiency virus (HIV) pandemic fuels tuberculosis (TB) outbreaks, it does not drive the development and transmission of multidrug-resistance in TB patients as previously...
Source: MedicineNet Neutropenia Specialty [2016.06.02]
Title: Tuberculosis (TB)
Category: Diseases and Conditions
Created: 12/31/1997 12:00:00 AM
Last Editorial Review: 6/2/2016 12:00:00 AM
Published Studies Related to Rifater (Rifampin / Isoniazid / Pyrazinamide)
Initial experience on rifampin and pyrazinamide vs isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong. [2003.12]
CONCLUSION: A higher incidence of hepatotoxicity was associated with rifampin plus pyrazinamide than isoniazid in the treatment of latent tuberculosis infection among patients with silicosis in Hong Kong.
Fixed-dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two-year follow-up. [2002.11]
SETTING: Veterans General Hospital-Taipei, Taiwan. OBJECTIVE: To assess the efficacy and safety of a fixed-dose combination (FDC) of Rifater (RFT)/Rifinah (RFN) in the treatment of newly diagnosed smear-positive pulmonary tuberculosis... CONCLUSION: This study suggests that the two regimens had similar effectiveness in the treatment of smear-positive pulmonary tuberculosis. However, the fewer adverse drug events among those patients treated with the FDC regimen suggests that it has a better safety profile.
Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group. [2000.03.15]
CONTEXT: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed. OBJECTIVE: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection... CONCLUSIONS: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs.
Assessment of a combined preparation of isoniazid, rifampicin and pyrazinamide (Rifater) in the initial phase of chemotherapy in three 6-month regimens for smear-positive pulmonary tuberculosis: a five-year follow-up report. [1999.02]
SETTING: Singapore Tuberculosis Service. OBJECTIVE: To assess the acceptability, efficacy and relapse rate of a combined formulation of three drugs--isoniazid, rifampicin and pyrazinamide (Rifater)--given in the initial phase of chemotherapy in three 6-month regimens (2SHRZ/4H3R3, 1SHRZ/5H3R3 and 2HRZ/4H3R3) under direct observation for all patients... CONCLUSION: A combined formulation of three drugs given daily in the initial phase of 6-month short-course therapy, followed by intermittent treatment with isoniazid and rifampicin given three times a week under direct observation for all patients, appears to be less effective than treatment with the component drugs given as separate formulations.
Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids. [1999.01]
STUDY OBJECTIVES: Determine the intrasubject and intersubject variability in, and the effects of food or antacids on, the pharmacokinetics of rifampin (RIF)... CONCLUSIONS: These changes in Cmax, Tmax, and AUC0-infinity can be avoided by giving RIF on an empty stomach whenever possible.
Clinical Trials Related to Rifater (Rifampin / Isoniazid / Pyrazinamide)
Pharmacokinetic Study for Anti-tuberculosis Drugs [Recruiting]
The purpose of this study is to evaluate the effect of food on pharmacokinetic profile of
multiple doses orally administered first-line anti-tuberculosis drugs in subjects with
The Incidence and Risk Factors of Side Effects During the Initial Phase of Rifater Therapy - a Prospective Study [Recruiting]
Tuberculosis remains one of the largest health problems in the world today. Multidrug
therapy is necessary to cure tuberculosis patients and to prevent the selection of
drug-resistant mutants, however, which may increase the incidence of side effects during the
course of treatment. These side effects may be mild as well as fatal. A severe side effect
against one of the anti-TB drugs, which influences drug compliance, may lead to the
discontinuation of that drug. At the same time, the risk of treatment failure and relapse
are higher. Therefore monitoring the rate of anti-TB drugs induced adverse effects and the
related risk factors is crucial. Awareness of the risk groups may decrease the incidence of
serious drug-related side effects and medical cost.
The fixed-dose combinations (FDCs) of tablets against tuberculosis is now being recommended
by WHO, which simplify the prescription of drugs and prevent the development of drug
resistance. However, the FDC regimen is not consistent with the dosages that are usually
given, the higher risk of drug toxicity and adverse reactions should be considered. To our
knowledge, there was no report to assess the adverse effects of FDC anti-TB drugs in Taiwan.
The aim of the present study is to investigate the current incidence of side effects and the
risk factors related to FDC drugs for side effects during the initial phase of therapy.
Study of Rifampicin in Multiple System Atrophy [Terminated]
The purpose of this study was to determine whether Rifampicin was effective in slowing or
reversing the progression of multiple system atrophy (MSA). Research studies indicate that
there is an abnormality in protein synthesis and structure in parts of the brain responsible
for MSA (protein misfolding) and the drug Rifampicin could potentially prevent or reverse
this protein alteration. The study was done on participants with early MSA. The study
consisted of taking the drug 2 times a day for 12 months. Participants underwent an
evaluation of symptoms and function and will underwent a neurologic examination at the
beginning of the study, at 6 months and at 12 months. They were also be contacted at 3 and
9 months by telephone. Studies were done at 10 participating sites.
Adverse Reactions and Efficacy of Fixed-dose Combination Anti-tuberculosis (TB) Drugs [Completed]
The fixed-dose combinations (FDC) with two or more antituberculous drugs in one capsule or
tablet are available to prevent the development of drug resistance. However, the fixed-dose
combination regimen is not consistent with the dosages that are usually given. The present
available FDC chemotherapy (Rifater) for pulmonary tuberculosis that is used in Taiwan has a
higher ratio of isoniazid to rifampin and pyrazinamide. The higher risk of drug toxicity and
adverse reactions when using fixed-dose combinations regimen should be considered. The aim
of the present study is to compare the toxicity between using FDC regimen (Rifater/Rifinah)
in Taiwan and single drugs in the treatment of newly diagnosed pulmonary tuberculosis. The
investigators also evaluate the efficacy of two regimens and determine the incidence of
discontinuation of TB drugs and the predisposed factors between two regimens.
Reports of Suspected Rifater (Rifampin / Isoniazid / Pyrazinamide) Side Effects
Cytolytic Hepatitis (9),
Drug Rash With Eosinophilia and Systemic Symptoms (7),
Renal Failure (3),
Mouth Ulceration (2), more >>
Page last updated: 2016-10-19