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Isoniazid Injection USP 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.
Intramuscular administration is intended for use whenever administration by the oral route is not possible.
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):
- 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.
- 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.
- 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.
- 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.
- Intravenous drug users known to be HIV-seronegative (>10 mm).
- 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 Hodgkins 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:
- Foreign-born persons from high-prevalence countries who never received BCG vaccine.
- Medically underserved low-income populations, including high-risk racial or ethnic minority populations, especially blacks, Hispanics, and Native Americans,
- 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 to 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 to 6) and on an individual basis in situations where there is likelihood of serious consequences to contacts who may become infected.
DOSAGE AND ADMINISTRATION
(See also INDICATIONS)
NOTE: For preventive therapy of tuberculous infection and treatment of tuberculosis, it is recommended that physicians be familiar with the following publications: (1) the recommendations of the Advisory Council for the Elimination of Tuberculosis, published in the MMWR: vol 42; RR-4, 1993 and (2) Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children, American Journal of Respiratory and Critical Care Medicine: vol 149; 1359-1374, 1994.
Isoniazid Injection USP is used in conjunction with other effective antituberculous agents.
For Treatment of Tuberculosis
Drug susceptibility testing should be performed on the organism initially isolated from all patients with newly diagnosed tuberculosis. If the bacilli becomes resistant, therapy must be changed to agents to which the bacilli are susceptible.
Usual Parenteral Dosage (Depending On the Regiman Used)
5 mg/kg up to 300 mg daily in a single dose; or 15 mg/kg up to 900 mg/day, two or three times/week
10 to 15 mg/kg up to 300 mg daily in a single dose; or 20 to 40 mg/kg up to 900 mg/day, two or three times/week
Patients with Pulmonary Tuberculosis Without HIV Infection
There are three regimen options for the initial treatment of tuberculosis in children and adults:
Option 1: Daily isoniazid, rifampin, and pyrazinamide for 8 weeks followed by 16 weeks of isoniazid and rifampin daily or 2 to 3 times weekly.
Ethambutol or streptomycin should be added to the initial regimen until sensitivity to isoniazid and rifampin is demonstrated. The addition of a fourth drug is optional if the relative prevalence of isoniazid-resistant Mycobacterium tuberculosis isolates in the community is less than or equal to four percent.
Option 2: Daily isoniazid, rifampin, pyrazinamide and streptomycin or ethambutol for 2 weeks followed by twice weekly administration of the same drugs for 6 weeks, subsequently twice weekly isoniazid and rifampin for 16 weeks.
Option 3: Three times weekly with isoniazid, rifampin, pyrazinamide and ethambutol or streptomycin for 6 months.
*All regimens given twice weekly or 3 times weekly should be administered by directly observed therapy (see also Directly Observed Therapy).
The above treatment guidelines apply only when the disease is caused by organisms that are susceptible to the standard antituberculous agents. Because of the impact of resistance to isoniazid and rifampin on the response to therapy, it is essential that physicians initiating therapy for tuberculosis be familiar with the prevalence of drug resistance in their communities. It is suggested that ethambutol not be used in children whose vital acuity cannot be monitored.
Patients with Pulmonary Tuberculosis and HIV Infection
The response of the immunologically impaired host to treatment may not be satisfactory as that of a person with normal host responsiveness.
For this reason, therapeutic decisions for the impaired host must be individualized. Since patients coinfected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB.
Patients with Extra Pulmonary Tuberculosis
The basic principles that underlie the treatment of pulmonary tuberculosis also apply to Extra pulmonary forms of the disease. Although there have not been the same kinds of carefully conducted controlled trials of treatment of Extra pulmonary tuberculosis as for pulmonary disease, increasing clinical experience indicates that a 6 to 9 month short-course regimens are effective. Because of the insufficient data, miliary tuberculosis, bone/joint tuberculosis, and tuberculosis meningitis in infants and children should receive 12 month therapy.
Bacteriologic evaluation of Extra pulmonary tuberculosis may be limited by the relative inaccessibility of the sites of disease. Thus, response to treatment often must be judged on the basis of clinical and radiographic findings.
The use of adjunctive therapies such as surgery and corticosteroids is more commonly required in Extra pulmonary tuberculosis than in pulmonary disease. Surgery may be necessary to obtain specimens for diagnosis and to treat such processes as constrictive pericarditis and spinal cord compression from Potts Disease. Corticosteroids have been shown to be of benefit in preventing cardiac constriction from tuberculous pericarditis and in decreasing the neurologic sequelae of all stages of tuberculosis meningitis, especially when administered early in the course of the disease.
Pregnant Women with Tuberculosis
The options listed above must be adjusted for the pregnant patient. Streptomycin interferes with in utero development of the ear and may cause congenital deafness. Routine use of pyrazinamide is also not recommended in pregnancy because of inadequate teratogenicity data. The initial treatment regimen should consist of isoniazid and rifampin. Ethambutol should be included unless primary isoniazid resistance is unlikely (isoniazid resistance rate documented to be less than 4%).
Treatment of Patients with Multi-Drug Resistant Tuberculosis (MDRTB)
Multiple-drug resistant tuberculosis (i.e., resistance to at least isoniazid and rifampin) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. In such cases, consultation with an expert in tuberculosis is recommended.
Directly Observed Therapy (DOT)
A major cause of drug-resistant tuberculosis is patient non-compliance with treatment. The use of DOT can help assure patient compliance with drug therapy. DOT is the observation of the patient by a health care provider or other responsible person as the patient ingests antituberculosis medications. DOT can be achieved with daily, twice weekly or thrice weekly regimens, and is recommended for all patients.
For Preventative Therapy of Tuberculosis
Before isoniazid preventive therapy is initiated, bacteriologically positive or radiographically progressive tuberculosis must be excluded. Appropriate evaluations should be performed if Extra pulmonary tuberculosis is suspected.
Adults over 30 Kg: 300 mg per day in a single dose.
Infants and Children: 10 mg/kg (up to 300 mg daily) in a single dose.
In situations where adherence with daily preventative therapy cannot be assured, 20 to 30 mg/kg (not to exceed 900 mg) twice weekly under the direct observation of a health care worker at the time of administration8.
Continuous administration of isoniazid for a sufficient period of time is an essential part of the regimen because relapse rates are higher if chemotherapy is stopped prematurely. In the treatment of tuberculosis, resistant organisms may multiply and the emergence during the treatment may necessitate a change in the regimen.
For following patient compliance: the Potts-Cozart test9, a simple colorimetric6 method of checking for isoniazid in the urine, is a useful tool for assuring patient compliance, which is essential for effective tuberculosis control. Additionally, isoniazid test strips are also available to check patient compliance.
Isoniazid Injection USP is available for intramuscular use in 10 mL vials providing 100 mg isoniazid per mL NDC 0781-3056-70.
Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature). Protect from light.
Isoniazid Injection USP may crystallize at low temperatures. If this occurs, warm the vial to room temperature before use to redissolve the crystals.
6. American Thoracic Society/Centers for Disease Control: Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children. Amer. J. Respir Crit Care Med. 1994; 149: p1359-1374.
8. Committee on infectious Diseases American Academy of Pediatrics: 1994, Red Book: Report of the Committee on Infectious Diseases; 23 edition; p487.
9. Schraufnagel, DE; Testing for Isoniazid; Chest (United States) 1990, August: 98 (2) p314-316.
Manufactured in Canada by: Sandoz Canada Inc. for: Sandoz Inc., Princeton, NJ 08540This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 7/25/2016
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