BOX WARNING
WARNING :
Severe and sometimes fatal hepatitis associated with isoniazid therapy has been reported and may occur or may develop even after many months of treatment. The risk of developing hepatitis is age related. Approximate case rates by age are: less than 1 per 1,000 for persons under 20 years of age, 3 per 1,000 for persons in the 20-34 year age group, 12 per 1,000 for persons in the 35-49 year age group, 23 per 1,000 for persons in the 50-64 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 involving 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. For persons 35 and older, in addition to monthly symptom reviews, hepatic enzymes (specifically, AST and ALT (formerly SGOT and SGPT, respectively)) should be measured prior to starting isoniazid therapy and periodically throughout treatment. Isoniazid-associated hepatitis usually occurs during the first three months of treatment. Usually, enzyme levels return to normal despite continuance of drug, but in some cases progressive liver dysfunction occurs. Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease and injection drug use. A recent report suggests an increased risk of fatal hepatitis associated with isoniazid among women, particularly black and Hispanic women. The risk may also be increased during the post partum period. More careful monitoring should be considered in these groups, possibly including more frequent laboratory monitoring. If abnormalities of liver function exceed three to five times the upper limit of normal, discontinuation of isoniazid should be strongly considered. Liver function tests are not a substitute for a clinical evaluation at monthly intervals or for the prompt assessment of signs or symptoms of adverse reactions occurring between regularly scheduled evaluations.
Patients should be instructed to immediately report signs or symptoms consistent with liver damage or other adverse effects. These include any of the following: unexplained anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever of greater than 3 days duration and/or abdominal tenderness, especially right upper quadrant discomfort. 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 who have hepatitis attributed to isoniazid 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.
Preventive treatment should be deferred in persons with acute hepatic diseases.
|
| |
ISONIAZID SUMMARY
ISONIAZID TABLETS, USP
Isoniazid is an antibacterial available as 100 mg or 300 mg tablets for oral administration.
Isoniazid is recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant antituberculosis medications to prevent the emergence of drug resistance. Single-drug treatment of active tuberculosis with isoniazid, or any other medication, is inadequate therapy.
Isoniazid is recommended as preventive therapy for the following groups, regardless of age. (Note: the criterion for a positive reaction to a skin test (in millimeters of induration) for each group is given in parenthesis):
1. Persons with human immunodeficiency virus (HIV) infection (≥ 5 mm) and persons with risk factors for HIV infection whose HIV infection status is unknown but who are suspected of having HIV infection.
Preventive therapy may be considered for HIV infected persons who are tuberculin-negative but belong to groups in which the prevalence of tuberculosis infection is high. Candidates for preventive therapy who have HIV infection should have a minimum of 12 months of therapy.
2. Close contacts of persons with newly diagnosed infectious tuberculosis (≥ 5 mm). In addition, tuberculin-negative (< 5 mm) children and adolescents who have been close contacts of infectious persons within the past 3 months are candidates for preventive therapy until a repeat tuberculin skin test is done 12 weeks after contact with the infectious source. If the repeat skin test is positive (> 5 mm), therapy should be continued.
3. Recent converters, as indicated by a tuberculin skin test (≥ 10 mm increase within a 2-year period for those < 35 years old; ≥ 15 mm increase for those ≥ 35 years of age). All infants and children younger than 4 years of age with a > 10 mm skin test are included in this category.
4. Persons with abnormal chest radiographs that show fibrotic lesions likely to represent old healed tuberculosis (≥ 5 mm). Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly.
5. Intravenous drug users known to be HIVseronegative (> 10 mm).
6. Persons with the following medical conditions that have been reported to increase the risk of tuberculosis (≥ 10 mm): silicosis; diabetes mellitus; prolonged therapy with adrenocorticosteroids; immunosuppressive therapy; some hematologic and reticuloendothelial diseases, such as leukemia or Hodgkin’s disease; end-stage renal disease; clinical situations associated with substantial rapid weight loss or chronic undernutrition (including: intestinal bypass surgery for obesity, the postgastrectomy state (with or without weight loss), chronic peptic ulcer disease, chronic malabsorption syndromes, and carcinomas of the oropharynx and upper gastrointestinal tract that prevent adequate nutritional intake). Candidates for preventive therapy who have fibrotic pulmonary lesions consistent with healed tuberculosis or who have pulmonary silicosis should have 12 months of isoniazid or 4 months of isoniazid and rifampin, concomitantly.
Additionally, in the absence of any of the above risk factors, persons under the age of 35 with a tuberculin skin test reaction of 10 mm or more are also appropriate candidates for preventive therapy if they are a member of any of the following high-incidence groups:
1. Foreign-born persons from high-prevalence countries who never received BCG vaccine.
2. Medically underserved low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans.
3. Residents of facilities for long-term care (e.g., correctional institutions, nursing homes, and mental institutions).
Children who are less than 4 years old are candidates for isoniazid preventive therapy if they have > 10 mm induration from a PPD Mantoux tuberculin skin test.
Finally, persons under the age of 35 who a) have none of the above risk factors (1-6); b) belong to none of the high-incidence groups; and c) have a tuberculin skin test reaction of 15 mm or more, are appropriate candidates for preventive therapy.
The risk of hepatitis must be weighed against the risk of tuberculosis in positive tuberculin reactors over the age of 35. However, the use of isoniazid is recommended for those with the additional risk factors listed above (1-6) and on an individual basis in situations where there is likelihood of serious consequences to contacts who may become infected.
|
NEWS HIGHLIGHTSMedia Articles Related to Isoniazid
Arthritis Drug Raises Risk of Tuberculosis
Source: MedicineNet Ankylosing Spondylitis Specialty [2009.07.10]
Title: Arthritis Drug Raises Risk of Tuberculosis
Category: Health News
Created: 7/10/2009 7:00:00 AM
Last Editorial Review: 7/10/2009
Tuberculosis
Source: MedicineNet Erythema Nodosum Specialty [2008.01.17]
Title: Tuberculosis
Category: Diseases and Conditions
Created: 12/31/1997
Last Editorial Review: 1/17/2008
Extensively Drug-Resistant Tuberculosis (XDR TB)
Source: MedicineNet ICU Psychosis Specialty [2007.05.30]
Title: Extensively Drug-Resistant Tuberculosis (XDR TB)
Category: Diseases and Conditions
Created: 5/30/2007
Last Editorial Review: 5/30/2007
Opinions: Fighting TB; Currency Transaction Tax
Source: Health News from Medical News Today [2009.11.19]
Innovation, Coordination Needed To 'Bring TB Research Into The 21st Century' Though tuberculosis "is one of the world's leading killers … few citizens, scientists and policymakers are demanding more attention to TB research, treatment and prevention.
Global Fund Approves $2.4B For Ninth Round Grants
Source: HIV / AIDS News From Medical News Today [2009.11.16]
During its recent board meeting in Addis Ababa, Ethiopia, the Global Fund to Fight AIDS, Tuberculosis and Malaria approved $2.4 billion for the three diseases, PlusNews reports. The money is for the fund's "ninth round of grants, bringing the total amount of approved funding since its inception in 2001 to $18.4 billion," according to the publication.
Published Studies Related to Isoniazid
Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. [2009.08.01]
RATIONALE: Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. OBJECTIVES: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB... CONCLUSIONS: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity.
Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial. [2008.11.18]
BACKGROUND: Treatment of latent tuberculosis infection with isoniazid for 9 months is complicated by poor patient adherence and the need for close follow-up of side effects, especially hepatotoxicity. Shorter and safer regimens are needed. OBJECTIVE: To compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection... CONCLUSION: Treatment of latent tuberculosis with 4 months of rifampin leads to fewer serious adverse events and better adherence than 9 months of isoniazid. These findings justify a large-scale trial to compare the efficacy of rifampin with that of isoniazid.
Completion of isoniazid preventive therapy among HIV-infected patients in Tanzania. [2008.09]
SETTING: Isoniazid preventive therapy (IPT) has not been widely implemented due to questions about acceptance, adherence and side effects. OBJECTIVE: To examine factors related to completion of IPT among human immunodeficiency virus (HIV) infected subjects in Tanzania... CONCLUSIONS: HIV-infected subjects provided with counseling, monthly follow-up and travel reimbursement have high rates of IPT completion with minimal side effects.
Efficacy of isoniazid prophylaxis in renal allograft recipients. [2006.09]
The efficacy of isoniazid (INH) prophylaxis in renal allograft recipients who are on long-term immunosuppression in a region highly prevalent for tuberculosis (TB) was studied. INH (300 mg/d in patients weighing more than 35 kg and 5 mg/kg/d in patients with <35 kg body weight) together with Pyridoxine 50 mg/d for 1 year was started in randomly assigned renal allograft recipients...
Weekly rifapentine/isoniazid or daily rifampin/pyrazinamide for latent tuberculosis in household contacts. [2006.04.15]
RATIONALE: Treatment of latent tuberculosis (TB) infection with weekly rifapentine and isoniazid is a potentially effective alternative to current therapies. OBJECTIVES: To compare the efficacy of weekly rifapentine/isoniazid to daily rifampin/pyrazinamide in preventing TB in household contacts of patients with pulmonary TB in Brazil... CONCLUSIONS: Rifapentine/isoniazid was better tolerated than rifampin/pyrazinamide and was associated with good protection against TB. Rifapentine/isoniazid weekly for 12 wk is likely a promising therapy for latent TB infection.
Clinical Trials Related to Isoniazid
Short-Course Isoniazid and Rifampin Compared With Isoniazid for Latent Tuberculosis Infection [Terminated]
The objective of the study was to compare the compliance and the side effects of a short
course to treatment of latent tuberculosis infection during 3 months(isoniazid plus
rifampin)group I, with the standard course for 6 months(isoniazid)group II .Prospective,
comparative, randomized and open trial of patients with positive TST and the suitable
criteria for treatment, in accordance with the guidelines of the CDC, excluding HIV
infection. 105 patients were included. In Conclusion, a short course with isoniazid plus
rifampin during 3 months shown better compliance with a lower percentage of abandonment that
the course 6H. Tolerance is similar in the two courses.
TBTC Study 24: Intermittent Treatment of TB With Isoniazid Resistance or Intolerance [Active, not recruiting]
This study is a prospective, open-label, nonrandomized trial using a largely-intermittent,
six-month tuberculosis treatment regimen among patients who will not receive isoniazid due to
the presence of initial isoniazid resistance or intolerance. Subjects are enrolled after
resistance or intolerance to isoniazid has been documented, and are treated for a total of
six months (nine months if baseline chest x-ray shows cavitation and 2-month sputum culture
is positive) with twice weekly or thrice weekly rifampin, ethambutol, and pyrazinamide.
TBTC Study 23A: Pharmacokinetics of Intermittent Isoniazid and Rifabutin in HIV-TB [Completed]
Primary Objectives:
1) To determine the proportion of patients with HIV-related tuberculosis who have abnormal
pharmacokinetic parameters for isoniazid and rifabutin.
Secondary Objectives:
1. To determine risk factors for abnormal pharmacokinetic parameters for isoniazid and
rifabutin.
2. To evaluate the correlation between pharmacokinetic parameters of isoniazid and
rifabutin and the occurrence of toxicity attributed to antituberculous therapy.
3. To evaluate the correlation between pharmacokinetic parameters of isoniazid and
rifabutin and the efficacy of TB therapy.
4. To define and correlate phenotypic INH acetylator status with the results of genotypic
acetylator data obtained in the parent trial.
High-Dose Isoniazid Adjuvant Therapy for Multidrug Resistant Tuberculosis [Completed]
The need for a standardized treatment protocol for multidrug resistant tuberculosis (MDR-TB)
in resource-limited countries is being increasingly recognized. This single center, double
blind, randomized controlled trial was designed to compare the time required for sputum
culture conversion and extent of radiological improvement in cases of MDR pulmonary
tuberculosis when isoniazid was included (both at a regular dose and at a high dose) as an
adjuvant to the standardized second line of treatment. The study was designed to test the
hypothesis that inclusion of high-dose isoniazid will enhance the effectiveness of the second
line of treatment in cases of MDR-TB without significantly increasing the toxicity.
A Pilot Study of Methodology to Rapidly Evaluate Drugs for Bactericidal Activity, Tolerance, and Pharmacokinetics in the Treatment of Pulmonary Tuberculosis Using Isoniazid and Levofloxacin [Completed]
To evaluate the methodology for rapidly determining the early bactericidal activity (EBA),
tolerance, and pharmacokinetics of isoniazid and levofloxacin in the treatment of pulmonary
tuberculosis (TB).
Traditionally, in trials for treatment of TB, a new drug is administered in combination with
two or more other antituberculous agents of known effectiveness over a long period of time.
In this setting, it is difficult to determine the effect of any single drug or dose level.
Development of new agents for the treatment of TB may be accelerated by a methodology in
which a new agent could be evaluated for activity by administering it as a single agent over
a short time period. This study utilizes a method to measure the amount of bacteria present
each day in the lungs.
|
PATIENT REVIEWS / RATINGS / COMMENTSBased on a total of 1 ratings/reviews, Isoniazid has an overall score of 7. The effectiveness score is 10 and the side effect score is 10. The scores are on ten point scale: 10 - best, 1 - worst.
| | Isoniazid review by 28 year old female patient | | | Rating |
| Overall rating: | |   |
| Effectiveness: | | Highly Effective |
| Side effects: | | No Side Effects | | |
Treatment Info |
| Condition / reason: | | Tuberculosis |
| Dosage & duration: | | 150 mg taken 1/day for the period of 6 months |
| Other conditions: | | none |
| Other drugs taken: | | None | | |
Reported Results |
| Benefits: | | While I did not have active Tuberculosis, I had tested positive. Taking Isoniazid will prevent a future case of Tuberculosis from developing. |
| Side effects: | | None, although liver screenings were required, and I could not drink alcohol. I also was encouraged to take B12 supplements. |
| Comments: | | After testing positive for Tuberculosis, my Dr. prescribed a 6 month course of Isoniazid. |
|
|
|
Page last updated: 2009-11-19
|
