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 The drug should be restarted in very small and gradually increasing doses and should be withdrawn immediately if there is any indication of recurrent liver involvement.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.
RIFAMATE is a combination capsule containing 300 mg rifampin and 150 mg isoniazid.
For pulmonary tuberculosis in which organisms are susceptible, and when the patient has been titrated on the individual components and it has therefore been established that this fixed dosage is therapeutically effective.
This fixed-dosage combination drug is not recommended for initial therapy of tuberculosis or for preventive therapy.
In the treatment of tuberculosis, small numbers of resistant cells, present within large populations of susceptible cells, can rapidly become the predominating type. Since rapid emergence of resistance can occur, culture and susceptibility tests should be performed in the event of persistent positive cultures.
This drug is not indicated for the treatment of meningococcal infections or asymptomatic carriers of
to eliminate meningococci from the nasopharynx.
Media Articles Related to Rifamate (Rifampin / Isoniazid)
Global rise of multidrug resistant tuberculosis threatens to derail decades of progress
Source: Respiratory / Asthma News From Medical News Today [2017.03.24]
New antibiotics are becoming available for the first time but without accurate diagnostics, clear treatment guidelines, and improved control efforts, their effectiveness could be rapidly lost...
Tuberculosis Deaths Fall in Europe
Source: Medscape HIV/AIDS Headlines [2017.03.21]
The number of people developing and dying from tuberculosis (TB) is falling in Europe, but among the most vulnerable - including migrants, prisoners and people who are HIV positive - there have been worrying increases, data showed on Monday.
Reuters Health Information
Old target, new mechanism for overcoming tuberculosis resistance
Source: Respiratory / Asthma News From Medical News Today [2017.03.20]
In strains of tuberculosis that have developed drug resistance mutations, researchers have identified a secondary pathway that can be activated to reinstate drug sensitivity.
Tuberculosis: Soil bacteria compound may yield potent new drug
Source: MRSA / Drug Resistance News From Medical News Today [2017.03.02]
Synthetic versions of a compound found in soil bacteria show promise as new drug candidates to fight TB, which is increasingly resisting current therapies.
Could a tuberculosis drug help treat autism?
Source: Autism News From Medical News Today [2017.01.27]
Researchers suggest that an antibiotic prescribed for the treatment of tuberculosis might help to reduce the social deficits seen in people with autism.
Published Studies Related to Rifamate (Rifampin / Isoniazid)
Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. [2004.08.15]
There is little published information regarding treatment completion, safety, and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection. In an open-label randomized trial at a university-affiliated respiratory hospital, consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were randomized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months...
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.
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.
Risk factors for rifampin-monoresistant tuberculosis: A case-control study. [1999.02]
Rifampin is the cornerstone of short-course chemotherapy for the treatment of tuberculosis (TB). Rifampin monoresistance (RMR) is less common than resistance to isoniazid alone or in combination with other antituberculous medications... Cases were frequently noncompliant with previous treatment for TB, had a history of incarceration, and had poor outcomes.
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 Rifamate (Rifampin / Isoniazid)
Wirelessly Observed Therapy in Comparison to Directly Observed Therapy for the Treatment of Tuberculosis [Recruiting]
This study uses an ingestion sensor and a wearable sensor (worn as a patch on the skin),
which are new Proteus Digital Health (PDH) technologies approved by the FDA, to collect
information about patients taking their TB medications. The wearable sensor records
information, which is uploaded wirelessly to a mobile device and then to a secure computer.
Together the sensors and the mobile device transmitting the information to the study
computer are called a digital health feedback system (DHFS), which gives healthcare
providers information about when patients have taken their TB medications. The advantage of
the DHFS is that patients can take their medication where and when it is convenient for
them, and do not have to wait for a nurse to directly observe them taking their medication.
The purpose of this study is to find out if using these new technologies works as well as
the standard method of observing in person when patients take their TB medications. This
study will also look at the costs of using a DHFS for TB medications, what patients and
healthcare providers think about using it, and other factors that can determine when one
approach works better than another.
This study has two parts. For the first part of the study (Step I), patients will have an
initial screening visit and then, in one two-week period, they will have 4 study visits at
the UCSD AntiViral Research Center (AVRC) and routine visits from Public Health Services
(PHS) workers. This part of the study is designed to confirm that the DHFS is working
correctly and is accurately collecting information about each dose of medication that
patients take, and to understand what patients and healthcare providers think about using
If patients are eligible for the second part of the study (Step II) and want to continue,
that will last another 8-14 weeks with an additional 4 study visits at the AVRC. In the
second part of the study, patients will be randomized into one of the following two groups.
Group 1: TB treatment is monitored by continued use of the DHFS
Group 2: TB treatment is monitored by the standard methods used by PHS (DOT)
The second part of the study is designed to compare these two methods of observing patients
taking their TB medications, what the relative costs of these methods are , and the
perception by patients and/or healthcare providers of the ease of use of the novel
Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation [Recruiting]
French guidelines currently recommend to initiate a 4-drug containing regimen associating
isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol
(EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind
routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of
primary resistance to INH. Hence, early detection of resistance to INH and RIF using
molecular testing in Mycobacterium tuberculosis could allow early adaptation of
antituberculosis treatment: i) start with a 3-drug containing regimen (i. e. INH, RIF, and
PZA); ii) early enforcement of treatment when resistance is suspected, pending in depth
the duration of treatment is 6 months or 12 months.
Patients Response to Early Switch To Oral:Osteomyelitis Study [Not yet recruiting]
Based on the current literature, investigators hypothesize that patients with osteomyelitis
who are treated with the standard approach of intravenous antibiotics for the full duration
of therapy will have the same clinical outcomes as patients treated with the experimental
approach of intravenous antibiotics with early switch to oral antibiotics.
The primary objective of this study is to compare patients with osteomyelitis treated with
the standard approach of intravenous antibiotics for the full duration of therapy versus
patients treated with intravenous antibiotics with an early switch to oral antibiotics in
relation to clinical outcomes at 12 months after discontinuation of antibiotic therapy.
Secondary objectives of the study include the evaluation of adverse events related to the
use of antibiotics as well as the cost of care evaluated from the hospital perspective.
Efficacy of Antituberculous Therapy in Management of Sarcoidosis [Completed]
From the time sarcoidosis has been described, there has always been a belief that the
disease is in some way related to tuberculosis. If indeed tuberculosis is a causal factor in
sarcoidosis, then the hypothesis can be further reinforced, if anti-tubercular therapy (ATT)
is useful in treatment of sarcoidosis. Very few trials have been conducted in the past but
the results of these trials have been discouraging. These trials were generally small
studies and limited by time bias and used older regimens based on isoniazid, amino-salicylic
acid and streptomycin. In our experience nearly one third of patients who are finally
diagnosed to have sarcoidosis, have received ATT for variable length of time, but its impact
of final outcome of sarcoidosis has not been studied. The aim of this prospective randomized
controlled trial (RCT) is to evaluate the efficacy and safety of Rifampicin and Isoniazid
along with prednisolone compared to prednisolone alone in treatment of Sarcoidosis.
A Bioequivalence Study Comparing A Fixed Dose Combination Formulation, Rin 150 And Individual Reference Drugs In Healthy Volunteers [Completed]
Page last updated: 2017-03-24