ایزونیازید
Isoniazid (Isoniazid Tablets)
ایزونیازید

نام ژنریک

Isoniazid (INH)

شکل دارویی

اشكال دارويي:


Tablet: 100, 300mg


Injection: 100 mg/ml, 10ml


Tablet: (Isoniazid 75mg+Rifampin 150mg)


Tablet: Isoniazid 50mg + Pyrazinamide 300 mg + Rifampin 120mg

موارد مصرف

موارد و مقدار مصرف


الف) درمان اوليه بر عليه باسيل سل فعال به همراه ساير داروهاي ضدسل.


بزرگسالان و کودکان بالاي 15 سال: از راه خوراکي، يا تزريق عضلاني، مقدار mg/kg/day 5 تا mg/day 300 به صورت مقدار واحد و يا ( mg 900 ) mg/kg 15، 3-1 بار در هفته (در صورت کمپليانس مناسب) به مدت حداقل 6 ماه بسته به رژيم درماني مورد نظر.


نوزادان و کودکان: mg/kg 15-10 خوراکي به صورت تک دوز
(تا mg/day 300) يا mg/kg 30-20 (تا mg 900) دو بار در هفته به مدت حداقل 6 ماه بسته به رژيم درماني مورد نظر.


ب) پيشگيري در مقابل باسيل سل در افرادي که تماس نزديک داشته يا آزمون مثبت پوستي دارند.


بزرگسالان: از راه خوراکي، mg/kg 5 به صورت تک دوز تا mg/day 300 يا mg/kg 15 (تا mg 900) دو بار در هفته، به مدت حداقل 9 ماه مصرف مي‌شود.


شيرخواران و کودکان: از راه خوراکي، مقدار mg/kg/day 15-10 تا
mg/day 300 به صورت مقدار واحد يا mg/kg 30-20 (تا mg 900) دو بار در هفته به مدت حداقل 9 ماه مصرف مي‌شود.

موارد منع مصرف

تداخل دارويي


مصرف هر روزه الکل ممکن است خطر بروز حملات تشنجي و هپاتيت ناشي از مصرف INH را افزايش دهد.


مصرف همزمان با سيکلوسپورين خطر مسموميت CNS، خواب آلودگي و سرگيجه ناشي از سيکلوسپورين را افزايش مي‌دهد.


مهار متابوليسم و افزايش غلظت خوني ناشي از مصرف INH مسموميت ناشي از بنزوديازپينها (ديازپام)، فني توئين، وکاربامازپين را افزايش مي‌دهد.


مصرف همزمان INH و دي سولفيرام ممکن است منجر به اختلال تعادل و حملات سايکوز شود.


مصرف همزمان با ضداسيدها جذب خوراکي INH را کاهش دهد.


مصرف همزمان با کورتيکواستروئيدها ممکن است اثربخشي INH را کاهش دهد.


به علت توليد آنزيم القاکننده توسط ريفامپين، مصرف همزمان اين دارو با ريفامپين ممکن است متابوليسم INH را تسريع کرده و موجب تشکيل متابوليتهاي سمّي براي کبد شود.


مصرف همزمان INH با داروهاي ضدانعقادي ممکن است فعاليت ضدانعقادي را افزايش دهد.


مصرف همزمان استامينوفن باعث افزايش سميت کبدي مي‌شود.

عوارض جانبی دارو

ملاحظات اختصاصي


مصرف ايزونيازيد به عنوان پيشگيري در افراد داراي سابقه سل و بيماران مبتلا به ايدز به مدت حداقل 12 ماه توصيه مي‌شود.


در صورت اشکال در رعايت زمان مصرف، مصرف دو بار در هفته دارو ممکن است مؤثر باشد. مقدار توصيه شده براي بزرگسالان mg/kg 15 دو بار در هفته از راه خوراکي تا حداکثر 900 ميلي گرم است.


مصرف دارو با معده خالي جذب آن را به حداکثر مي‌رساند. در صورت بروز تحريکات گوارشي مي‌توان دارو را با غذا مصرف کرد.


ضداسيدهاي حاوي آلومينيم يا مسهل‌ها بايد يک ساعت بعد از ايزونيازيد مصرف شوند.


سميت کبدي وابسته به سن بيمار است و ممکن است باعث محدوديت مصرف دارو در موارد پروفيلاکسي گردد. مصرف الکل و يا بيماري کبدي وابسته به الکل باعث افزايش احتمالي سميت کبدي مي‌شود.


براي به حداقل رساندن مسموميت، آزمونهاي عملکرد کبد، کليه و خون قبل و طي درمان صورت گيرند. عملکرد بينايي به طور مرتب ارزيابي شود.


بيمار از نظر بروز عوارض جانبي، بخصوص اختلال عملکرد کبدي، مسموميت CNS، و نوريت عصب بينايي مورد مراقبت قرار گيرد و موازين ايمني، در صورت بروز کمي فشار خون وضعيتي رعايت گردند.


INH ممکن است از تثبيت غلظت سرمي گلوکز در بيماران مبتلا به ديابت جلوگيري کند.


شواهد بهبود بيماري معمولاً 3-2 هفته بعد از شروع درمان ظاهر مي‌شود.


بعضي از پزشکان تجويز خوراکي mg/kg 50 پيريدوکسين را براي جلوگيري از نوروپاتي محيطي ناشي از مصرف مقادير زياد INH توصيه مي‌کنند. اين مقدار پيريدوکسين ممکن است در بيماران در معرض خطر پيشرفت نوروپاتي محيطي (بيماران مبتلا به سوء تغذيه، ديابت و الکليسم) مفيد باشد. پيريدوکسين تا حد mg/day 200-50 براي درمان نوروپاتي ناشي از مصرف INH به کار رفته است.


از آنجايي که INH قابل دياليز است، در بيماران تحت همودياليز يا داليز صفاقي، ممکن است تنظيم مقدار مصرف آن ضروري باشد.


به نظر مي‌رسد مسموميت کبدي با سن بيمار رابطه داشته باشد و ممکن است مصرف دارو را به عنوان پيشگيري محدود سازد. مصرف اتانول و سابقه بيماري کبدي ناشي از مصرف آن نيز خطر مسموميت کبد را افزايش مي‌دهد.


افزايش آنزيم‌هاي کبدي در 15 % موارد رخ مي‌دهد که اکثراً خفيف و گذرا هستند ولي برخي تا پايان دوره درمان باقي مي‌مانند.

موارد قابل توجه

-

تداخل دارویی

اثر بر آزمايشهاي تشخيصي


ايزونيازيد ممکن است نتايج آزمون ادراري گلوکز با استفاده از روش سولفات مس (Benedict's reagent يا Clinitest) را تغيير دهد.


ايزونيازيد مي‌تواند باعث افزايش آنزيم‌هاي کبدي، قند، بيلي روبين و ائوزينوفيل شود و نيز مي‌تواند باعث کاهش کلسيم، فسفات، هموگلوبين، هماتوکريت، گرانولوسيت و پلاکت گردد.

مکانیزم اثر

اثر بر آزمايشهاي تشخيصي


ايزونيازيد ممکن است نتايج آزمون ادراري گلوکز با استفاده از روش سولفات مس (Benedict's reagent يا Clinitest) را تغيير دهد.


ايزونيازيد مي‌تواند باعث افزايش آنزيم‌هاي کبدي، قند، بيلي روبين و ائوزينوفيل شود و نيز مي‌تواند باعث کاهش کلسيم، فسفات، هموگلوبين، هماتوکريت، گرانولوسيت و پلاکت گردد.

فارماكوكینتیك

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت مفرط شناخته شده نسبت به دارو، سابقه بيماري کبدي حاد و يا سايرآسيب‌هاي کبدي ناشي از داروها.


موارد احتياط: سابقه بيماري کبدي يا کليوي مزمن، سابقه حملات تشنجي (بخصوص در کساني که فني توئين مصرف مي‌نمايند)، سالمندان، افرادي که بيماري کبدي شديد غيروابسته به ايزونيازيد دارند، مصرف مزمن الکل.


در مصرف همزمان با داروهاي ضد قند خوراکي و انسولين به علت ايجاد تداخل باعث بروز هيپرگليسمي خواهد شد.


در مصرف همزمان با SSRI‌ها احتمال بروز سندرم سروتونين وجود دارد.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: ايزونيکوتينيک اسيد هيدرازيد.


طبقه‌بندي درماني: ضد سل.


طبقه‌بندي مصرف در بارداري: رده C


نکات قابل توصيه به بيمار


1- دوره درمان را کامل کنيد.


2- بروز حساسيت مفرط و عوارض جانبي ديگر، بخصوص اختلالات بينايي و هر اثر غيرمعمول ديگر را به پزشک اطلاع دهيد.


3- از مصرف الکل خودداري کنيد، زيرا خطر مسموميت شديد CNS و افزايش خطر هپاتيت وجود دارد.


4- زمان و طريقه مصرف دارو را رعايت کنيد. INH را با معده خالي، حداقل يک ساعت قبل يا دو ساعت بعد از غذا، مصرف کنيد. در صورت بروز تحريکات گوارشي، دارو را با غذا مصرف کنيد.


5- دستورات پزشک را رعايت کنيد. مصرف دارو را بدون دستور پزشک قطع نکنيد. به طور مرتب به پزشک مراجعه کنيد.


6- INH معمولاً به مدت 18 ماه تا دوسال براي درمان سل فعال مصرف مي‌شود. مدت زمان لازم براي پيشگيري 12 ماه است. در صورت ترکيب INH و ريفامپين مدت زمان لازم 9 ماه خواهد بود.


7- از قطع درمان پرهيز کنيد تا از عود بيماري و انتشار عفونت جلوگيري شود.


مصرف در سالمندان: اين دارو در بيماران سالخورده بايد با احتياط تجويز شود. احتمال بروز عوارض کبدي اين دارو بعد از 35 سالگي افزايش مي‌يابد. INH به عنوان پيشگيري در بيماران سالخورده داراي آزمون مثبت PPD ممکن است مصرف نشود، زيرا خطر مسموميت کبدي وجود دارد.


مصرف در کودکان: شيرخواران و کودکان مقادير بيشتر دارو را تحمل مي‌کنند.


مصرف در شيردهي: ايزونيازيد در شير ترشح مي‌شود. مصرف اين دارو در شيردهي بايد با احتياط همراه بوده و شيرخواران را از نظر احتمال بروز مسموميت ناشي از INH تحت نظر داشت.


عوارض جانبي


اعصاب مرکزي : نوروپاتي محيطي، حملات تشنجي، ضعف حافظه، انسفالوپاتي سمّي، سايکوز.


چشم : نوريت عصب بينايي همراه با آتروفي.


دستگاه گوارش: تهوع، استفراغ، ناراحتي اپي گاستر.


خون: آگرانولوسيتوز، کم خوني هموليتيک، کم خوني آپلاستيک، ائوزينوفيلي، ترومبوسيتوپني، آنمي سيدروبلاستيک.


كبد: هپاتيت، يرقان، بيلي روبينمي.


متابوليک: زيادي قند خون، اسيدوز متابوليک، کمبود پيريدوکسين، هيپوفسفاتمي، هيپوکلسمي.


ساير عوارض: سندرم روماتيسمي و سندرم شبه لوپوس اريتماتوز سيستميک، واکنشهاي ناشي از حساسيت مفرط (تب، بثورات پوستي، لنفادنوپاتي، واسکوليت)، ژنيکوماستي.


مسموميت و درمان


تظاهرات باليني: علائم زودرس: تهوع، استفراغ، اختلال در تکلم، سرگيجه، تاري ديد، توهمات بينايي (طي 30 دقيقه تا سه ساعت بعد از مصرف خوراکي دارو ظاهر مي‌شوند). علائم مصرف بسيار زياد دارو: تضعيف پيشرونده CNS (از عدم هوشياري نسبي تا اغماء)، همراه با ديسترس تنفسي، حملات تشنجي مقاوم به درمان و مرگ.


درمان: شامل برقراري تهويه و کنترل حملات تشنجي با ديازپام است. پيريدوکسين با مقادير معادل با INH مصرف مي‌شود. مقدار اوليه پيريدوکسين 4-1 گرم به صورت تزريق وريدي و به دنبال آن، يک گرم هر 30 دقيقه تا مصرف کامل دارو است. بعد از کنترل حملات تشنجي، دارو را با شستشوي معده از بدن خارج کرده و با تزريق بيکربنات سديم اسيدوز تصحيح مي‌شود. با تزريق وريدي مايعات و مدرهاي اسموتيک ديورز برقرار شده و در صورت لزوم مي‌توان کليرانس دارو را با همودياليز يا دياليز صفاقي افزايش داد.

Isoniazid (Isoniazid Tablets)

Isoniazid
(isoniazid)
Tablets, USP

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 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. 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.

DRUG DESCRIPTION

Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. Each tablet also contains as inactive ingredients: colloidal silicon dioxide, lactose monohydrate, pregelatinized starch, povidone, and stearic acid.

Isoniazid is chemically known as isonicotinyl hydrazine or isonicotinic acid hydrazide. It has an empirical formula of C6H7N3O and a molecular weight of 137.14. It has the following structure:

Isoniazid structural formula illustration

Isoniazid is odorless, and occurs as a colorless or white crystalline powder or as white crystals. It is freely soluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform and in ether. Isoniazid is slowly affected by exposure to air and light.

What are the possible side effects of isoniazid ()?

If you experience any of the following serious side effects, stop taking isoniazid and seek emergency medical attention or contact your doctor immediately:

  • an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
  • unusual weakness or fatigue;
  • nausea, vomiting, or loss of appetite;
  • abdominal pain;
  • yellow skin or eyes;
  • dark urine;
  • numbness or tingling in your hands or feet;
  • seizures;
  • blurred vision; or
  • confusion or abnormal behavior.

Side effects...

Read All Potential Side Effects and See Pictures of Isoniazid Tablets »

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Isoniazid is recommended for all forms of tuberculosis in which organisms are susceptible. However, active tuberculosis must be treated with multiple concomitant anti-tuberculosis 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; ≥ 1 5 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 HIV-seronegative ( > 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

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.

For Treatment of Tuberculosis: Isoniazid is used in conjunction with other effective anti-tuberculous agents. Drug susceptibility testing should be performed on the organisms 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 Oral Dosage (depending on the regimen used):

Adults: 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

Children: 10-15 mg/kg up to 300 mg daily in a single dose; or 20-40 mg/kg up to 900 mg/day, two or three times/week

Patients with Pulmonary Tuberculosis Without HIV Infection

There are 3 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 2-3 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 visual acuity cannot be monitored.

Patients with Pulmonary Tuberculosis and HIV Infection

The response of the immunologically impaired host to treatment may not be as satisfactory as that of a person with normal host responsiveness. For this reason, therapeutic decisions for the impaired host must be individualized. Since patients co-infected 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 regimen is effective. Because of the insufficient data, miliary tuberculosis, bone/joint tuberculosis, and tuberculous 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 Pott's Disease. Corticosteriods 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 noncompliance 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 anti-tuberculosis 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, 20-30 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 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 of resistant organisms 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 Concomitant administration of pyridoxine (B6) is recommended in the malnourished and in those predisposed to neuropathy (e.g., alcoholics and diabetics)

HOW SUPPLIED

Isoniazid Tablets (isoniazid) , USP 100 mg: white, round, biconvex, scored on one side, and debossed with

E over and "4354" below the score. Available in opaque white bottles of 30, 100 and 1000

Isoniazid Tablets (isoniazid) , USP 300 mg: white, round, biconvex, scored on one side, and debossed with

E over and "4350" below the score. Available in opaque white bottles of 30, 100 and 1000

Storage: Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Protect from moisture and light.

References

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.

Sandoz Inc Princeton, NJ 08540. Rev. 12/06. FDA Rev date: NA

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The most frequent reactions are those affecting the nervous system and the liver.

Nervous System Reactions: Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics), and is usually preceded by paresthesias of the feet and hands. The incidence is higher in "slow inactivators".

Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment, and toxic psychosis.

Hepatic Reactions: See BOXED WARNING. Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice, and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise, and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10 to 20 percent of patients taking isoniazid. This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal, and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the isoniazid should be strongly considered. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.

Gastrointestinal Reactions: Nausea, vomiting, and epigastric distress.

Hematologic Reactions: Agranulocytosis; hemolytic, sideroblastic, or aplastic anemia, thrombocytopenia; and eosinophilia.

Hypersensitivity Reactions: Fever, skin eruptions (morbilliform, maculopapular, purpuric, or exfoliative), lymphadenopathy, and vasculitis.

Metabolic And Endocrine Reactions: Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis, and gynecomastia.

Miscellaneous Reactions: Rheumatic syndrome and systemic lupus erythematosus-like syndrome.

Read the Isoniazid Tablets (isoniazid) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Food: Isoniazid should not be administered with food. Studies have shown that the bioavailability of isoniazid is reduced significantly when administered with food. Tyramine- and histamine-containing foods should be avoided in patients receiving isoniazid. Because isoniazid has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (e.g., headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g., skipjack, tuna, other tropical fish).

Acetaminophen: a report of severe acetaminophen toxicity was reported in a patient receiving Isoniazid It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed. However current evidence suggests that isoniazid does induce P-450IIE1, a mixed-function oxidase enzyme that appears to generate the toxic metabolites, in the liver. Furthermore it has been proposed that isoniazid resulted in induction of P-450IIE1 in the patients liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites. Studies have demonstrated that pretreatment with isoniazid potentiates acetaminophen hepatotoxicity in rats1,2.

Carbamazepine: Isoniazid is known to slow the metabolism of carbamazepine and increase its serum levels. Carbamazepine levels should be determined prior to concurrent administration with isoniazid signs and symptoms of carbamazepine toxicity should be monitored closely, and appropriate dosage adjustment of the anticonvulsant should be made3.

Ketoconazole: Potential interaction of Ketoconazole and Isoniazid may exist. When Ketoconazole is given in combination with isoniazid and rifampin the AUC of ketoconazole is decreased by as much as 88% after 5 months of concurrent Isoniazid and Rifampin therapy4.

Phenytoin: Isoniazid may increase serum levels of phenytoin. To avoid phenytoin intoxication appropriate adjustment of the anticonvulsant should be made5,6.

Theophylline: A recent study has shown that concomitant administration of isoniazid and theophylline may cause elevated plasma levels of theophylline, and in some instances a slight decrease in the elimination of isoniazid. Since the therapeutic range of theophylline is narrow, theophylline serum levels should be monitored closely, and appropriate dosage adjustments of theophylline should be made7.

Valproate: A recent case study has shown a possible increase in the plasma level of valproate when co-administered with isoniazid. Plasma valproate concentration should be monitored when isoniazid and valproate are co-administered, and appropriate dosage adjustments of valproate should be made5

References

1. Murphy, R., et al: Annuals of Internal Medicine; 1990: November 15; volume 113: 799-800

2. Burke, R.F., et al: Res Commun Chem Pathol Pharmacol; 1990: July; vol. 69: 115-118

3. Fleenor, M. F., et al: Chest (United States) Letter; 1991; June; 99 (6): 1554

4. Baciewicz, A.M. and Baciewicz, Jr. F.A.: Arch Int Med 1993: September; volume 153: 1970-1971

5. Jonviller, A.P, et al:European Journal of Clinical Pharmacol (Germany), 1991: 40 (2) p198

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

7. Hoglund P., et al: European Journal of Respir Dis (Denmark) 1987: February; 70 (2) p110-116.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

See the BOXED WARNING

PRECAUTIONS

General

All drugs should be stopped and an evaluation made at the first sign of a hypersensitivity reaction. If isoniazid therapy must be reinstituted, the drug should be given only after symptoms 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 hypersensitivity reaction Use of isoniazid should be carefully monitored in the following:

  1. Daily users of alcohol. Daily ingestion of alcohol may be associated with a higher incidence of + isoniazid hepatitis.
  2. Patients with active chronic liver disease or severe renal dysfunction
  3. Age > 35.
  4. Concurrent use of any chronically administered medication
  5. History of previous discontinuation of isoniazid
  6. Existence of peripheral neuropathy or conditions predisposing to neuropathy
  7. Pregnancy.
  8. Injection drug use
  9. Women belonging to minority groups, particularly in the postpartum period
  10. HIV seropositive patients.

Laboratory Tests

Because there is a higher frequency of isoniazid associated hepatitis among certain patient groups including Age > 35, daily users of alcohol, chronic liver disease, injection drug use and women belonging to minority groups, particularly in the post-partum period, transaminase measurements should be obtained prior to starting and monthly during preventative therapy, or more frequently as needed. If any of the values exceed three to five times the upper limit of normal, isoniazid should be temporarily discontinued and consideration given to restarting therapy.

Carcinogenesis and Mutagenesis

Isoniazid has been shown to induce pulmonary tumors in a number of strains of mice. Isoniazid has not been shown to be carcinogenic in humans. (Note: a diagnosis of mesothelioma in a child with prenatal exposure to isoniazid and no other apparent risk factors has been reported). Isoniazid has been found to be weakly mutagenic in strains TA 100 and TA 1535 of Salmonella typhimurium (Ames assay) without metabolic activation.

Pregnancy

Teratogenic effects: Pregnancy Category C: Isoniazid has been shown to have an embryocidal effect in rats and rabbits when given orally during pregnancy. Isoniazid was not teratogenic in reproduction studies in mice, rats and rabbits. There are no adequate and well-controlled studies in pregnant women. Isoniazid should be used as a treatment for active tuberculosis during pregnancy because the benefit justifies the potential risk to the fetus. The benefit of preventive therapy also should be weighed against a possible risk to the fetus. Preventive therapy generally should be started after delivery to prevent putting the fetus at risk of exposure; the low levels of isoniazid in breast milk do not threaten the neonate. Since isoniazid is known to cross the placental barrier, neonates of isoniazid treated mothers should be carefully observed for any evidence of adverse effects.

Nonteratogenic effects: Since isoniazid is known to cross the placental barrier, neonates of isoniazid- treated mothers should be carefully observed for any evidence of adverse effects.

Nursing Mothers

The small concentrations of isoniazid in breast milk do not produce toxicity in the nursing newborn; therefore, breast feeding should not be discouraged. However, because levels of isoniazid are so low in breast milk, they can not be relied upon for prophylaxis or therapy of nursing infants.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Signs and Symptoms: Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision, and visual hallucinations (including bright colors and strange designs) are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma, are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria, and hyperglycemia are typical laboratory findings.

Treatment: Untreated or inadequately treated cases of gross isoniazid overdosage, 80 mg/kg - 150 mg/kg, can cause neurotoxicity6 and terminate fatally, but good response has been reported in most patients brought under adequate treatment within the first few hours after drug ingestion.

For the Asymptomatic Patient: Absorption of drugs from the GI tract may be decreased by giving activated charcoal. Gastric emptying should also be employed in the asymptomatic patient. Safeguard the patient's airway when employing these procedures. Patients who acutely ingest > 80 mg/kg should be treated with intravenous pyridoxine on a gram per gram basis equal to the isoniazid dose. If an unknown amount of isoniazid is ingested, consider an initial dose of 5 grams of pyridoxine given over 30 to 60 minutes in adults, or 80 mg/kg of pyridoxine in children.

For the Symptomatic Patient: Ensure adequate ventilation, support cardiac output, and protect the airway while treating seizures and attempting to limit absorption. If the dose of isoniazid is known, the patient should be treated initially with a slow intravenous bolus of pyridoxine, over 3 to 5 minutes, on a gram per gram basis, equal to the isoniazid dose. If the quantity of isoniazid ingestion is unknown, then consider an initial intravenous bolus of pyridoxine of 5 grams in the adult or 80 mg/kg in the child. If seizures continue, the dosage of pyridoxine may be repeated. It would be rare that more than 10 grams of pyridoxine would need to be given. The maximum safe dose for pyridoxine in isoniazid intoxication is not known. If the patient does not respond to pyridoxine, diazepam may be administered. Phenytoin should be used cautiously, because isoniazid interferes with the metabolism of phenytoin.

General: Obtain blood samples for immediate determination of gases, electrolytes, BUN, glucose, etc.; type and cross-match blood in preparation for possible hemodialysis.

Rapid control of metabolic acidosis: Patients with this degree of INH intoxication are likely to have hypoventilation. The administration of sodium bicarbonate under these circumstances can cause exacerbation of hypercarbia. Ventilation must be monitored carefully, by measuring blood carbon dioxide levels, and supported mechanically, if there is respiratory insufficiency.

Dialysis: Both peritoneal and hemodialysis have been used in the management of isoniazid overdosage. These procedures are probably not required if control of seizures and acidosis is achieved with pyridoxine, diazepam and bicarbonate.

Along with measures based on initial and repeated determination of blood gases and other laboratory tests as needed, utilize meticulous respiratory and other intensive care to protect against hypoxia, hypotension, aspiration, pneumonitis, etc.

CONTRAINDICATIONS

Isoniazid is contraindicated in patients who develop severe hypersensitivity reactions, including drug- induced hepatitis; previous isoniazid-associated hepatic injury; severe adverse reactions to isoniazid such as drug fever, chills, arthritis; and acute liver disease of any etiology

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Within 1 to 2 hours after oral administration, isoniazid produces peak blood levels which decline to 50 percent or less within 6 hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70 percent of a dose of isoniazid is excreted in the urine in 24 hours.

Isoniazid is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50 percent of Blacks and Caucasians are "slow inactivators" and the rest are "rapid inactivators"; the majority of Eskimos and Orientals are "rapid inactivators." The rate of acetylation does not significantly alter the effectiveness of isoniazid. However, slow acetylation may lead to higher blood levels of the drug and, thus, to an increase in toxic reactions. Pyridoxine (vitamin B6) deficiency is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.

Mechanism of Action

Isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.

Isoniazid resistant Mycobacterium tuberculosis bacilli develop rapidly when isoniazid monotherapy is administered.

Microbiology

Two standardized in vitro susceptibility methods are available for testing isoniazid against Myco- bacterium tuberculosis organisms. The agar proportion method (CDC or NCCLS M24-P) utilizes middlebrook 7H10 medium impregnated with isoniazid at two final concentrations, 0.2 and 1.0 mcg/mL. MIC99, values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug ≥ 1% of the control indicates resistance.

The radiometric broth method employs the BACTEC 460 machine to compare the growth index from untreated control cultures to cultures grown in the presence of 0.2 and 1.0 mcg/mL of isoniazid. Strict adherence to the manufacturer's instructions for sample processing and data interpretation is required for this assay.

Mycobacterium tuberculosis isolates with an MIC99 ≤ 0.2 mcg/mL are considered to be susceptible to isoniazid. Susceptibility test results obtained by the two different methods discussed above cannot be compared unless equivalent drug concentrations are evaluated.

The clinical relevance of in vitro susceptibility for mycobacterium species other than M. tuberculosis using either the BACTEC or the proportion method has not been determined.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

Isoniazid
(isoniazid)
Tablets, USP

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 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. 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.

DRUG DESCRIPTION

Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. Each tablet also contains as inactive ingredients: colloidal silicon dioxide, lactose monohydrate, pregelatinized starch, povidone, and stearic acid.

Isoniazid is chemically known as isonicotinyl hydrazine or isonicotinic acid hydrazide. It has an empirical formula of C6H7N3O and a molecular weight of 137.14. It has the following structure:

Isoniazid structural formula illustration

Isoniazid is odorless, and occurs as a colorless or white crystalline powder or as white crystals. It is freely soluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform and in ether. Isoniazid is slowly affected by exposure to air and light.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

Isoniazid
(isoniazid)
Tablets, USP

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 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. 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.

DRUG DESCRIPTION

Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. Each tablet also contains as inactive ingredients: colloidal silicon dioxide, lactose monohydrate, pregelatinized starch, povidone, and stearic acid.

Isoniazid is chemically known as isonicotinyl hydrazine or isonicotinic acid hydrazide. It has an empirical formula of C6H7N3O and a molecular weight of 137.14. It has the following structure:

Isoniazid structural formula illustration

Isoniazid is odorless, and occurs as a colorless or white crystalline powder or as white crystals. It is freely soluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform and in ether. Isoniazid is slowly affected by exposure to air and light.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

Isoniazid
(isoniazid)
Tablets, USP

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 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. 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.

DRUG DESCRIPTION

Isoniazid is an antibacterial available as 100 mg and 300 mg tablets for oral administration. Each tablet also contains as inactive ingredients: colloidal silicon dioxide, lactose monohydrate, pregelatinized starch, povidone, and stearic acid.

Isoniazid is chemically known as isonicotinyl hydrazine or isonicotinic acid hydrazide. It has an empirical formula of C6H7N3O and a molecular weight of 137.14. It has the following structure:

Isoniazid structural formula illustration

Isoniazid is odorless, and occurs as a colorless or white crystalline powder or as white crystals. It is freely soluble in water, sparingly soluble in alcohol, and slightly soluble in chloroform and in ether. Isoniazid is slowly affected by exposure to air and light.

Last reviewed on RxList: 1/11/2008
This monograph has been modified to include the generic and brand name in many instances.

Isoniazid Tablets Patient Information Including Side Effects

Brand Names:

Generic Name: isoniazid (Pronunciation: eye so NYE a zid)

What is isoniazid ?

Isoniazid is an antibiotic. It prevents tuberculous bacteria from multiplying in the body.

Isoniazid is used to treat and to prevent tuberculosis (TB).

Isoniazid may also be used for purposes other than those listed in this medication guide.

Isoniazid 100 mg-VER

round, white, imprinted with WestWard, 260

Isoniazid 100 mg-BAR

round, white, imprinted with b, 066 100

Isoniazid 300 mg-BAR

oval, white, imprinted with b, 071 300

Isoniazid 300 mg-VER

round, white, imprinted with WestWard 261

What are the possible side effects of isoniazid ?

If you experience any of the following serious side effects, stop taking isoniazid and seek emergency medical attention or contact your doctor immediately:

  • an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);
  • unusual weakness or fatigue;
  • nausea, vomiting, or loss of appetite;
  • abdominal pain;
  • yellow skin or eyes;
  • dark urine;
  • numbness or tingling in your hands or feet;
  • seizures;
  • blurred vision; or
  • confusion or abnormal behavior.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the Isoniazid Tablets (isoniazid) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about isoniazid ?

Take all of the isoniazid that has been prescribed for you even if you begin to feel better. Your symptoms may begin to improve before the infection is completely treated.

Avoid alcohol while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid treatment.

Contact your doctor immediately if you experience numbness or tingling in the hands or feet, weakness, fatigue, loss of appetite, nausea and vomiting, yellowing of the skin or eyes, or darkening of the urine.

Side Effects Centers

Isoniazid Tablets Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking isoniazid ?

Before taking this medication, tell your doctor if you have

  • ever had an allergic reaction to isoniazid,
  • kidney disease, or
  • liver disease.

You may not be able to take isoniazid, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

It is not known whether isoniazid will be harmful to an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant or could become pregnant during treatment.

It is not known whether isoniazid will be harmful to a nursing baby. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

How should I take isoniazid ?

Take isoniazid exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass (8 ounces) of water.

Take isoniazid on an empty stomach 1 hour before or 2 hours after meals.

If nausea occurs, ask your doctor if you can take isoniazid with food.

Take all of the isoniazid that has been prescribed for you even if you begin to feel better. Your symptoms may begin to improve before the infection is completely treated.

It is important to take isoniazid regularly to get the most benefit.

Your doctor may also want you to take a supplemental vitamin B6 (pyridoxine) tablet daily during treatment to prevent numbness and tingling caused by low levels of this vitamin.

Your doctor may want you to have blood tests or other medical evaluations during treatment with isoniazid to monitor progress and side effects.

Store this medication at room temperature away from moisture and heat.

Side Effects Centers

Isoniazid Tablets Patient Information including If I Miss a Dose

What happens if I miss a dose ?

Take the missed dose as soon as you remember. If it is almost time for the next regularly scheduled dose, skip the missed dose and take the next one as directed. Do not take a double dose of this medication.

What happens if I overdose ?

Seek emergency medical attention if an overdose is suspected.

Symptoms of an isoniazid overdose include nausea, vomiting, dizziness, slurring of speech, blurred vision, visual hallucinations, seizures, coma, and death.

What should I avoid while taking isoniazid ?

Avoid alcohol while taking isoniazid. Alcohol will increase the risk of damage to the liver during treatment with this medication.

Use caution with the foods listed below. They can interact with isoniazid and cause a reaction that includes a severe headache, large pupils, neck stiffness, nausea, vomiting, diarrhea, flushing, sweating, itching, irregular heartbeats, and chest pain. A reaction will not necessarily occur, but eat these foods with caution until you know if you will react to them. Call your doctor immediately if you experience any of these symptoms.

Eat the following foods with caution:

  • cheeses, including American, Blue, Boursault, Brick, Brie, Camembert, Cheddar, Emmenthaler, Gruyere, Mozzarella, Parmesan, Romano, Roquefort, Stilton, and Swiss;
  • sour cream and yogurt;
  • beef or chicken liver, fish, meats prepared with tenderizer, bologna, pepperoni, salami, summer sausage, game meat, meat extracts, caviar, dried fish, herring, shrimp paste, and tuna;
  • avocados, bananas, figs, raisins, and sauerkraut;
  • soy sauce, miso soup, bean curd, and fava beans;
  • yeast extracts;
  • ginseng;
  • chocolate;
  • caffeine (coffee, tea, cola, etc.); and
  • beer (alcoholic and nonalcoholic), red wine (especially Chianti), sherry, vermouth, and other distilled spirits.

What other drugs will affect isoniazid ?

Before taking isoniazid, tell your doctor if you are taking any of the following drugs:

  • antacids. Aluminum salts will decrease the action of isoniazid. Do not take antacids that contain aluminum for 1 to 2 full hours before or after taking a dose of isoniazid.
  • ketoconazole (Nizoral) and itraconazole (Sporanox). Isoniazid may decrease the actions of these antifungal medicines. Therefore, a fungal infection may not be adequately treated.
  • rifampin (Rimactane, Rifadin) or rifabutin (Mycobutin).
  • disulfiram (Antabuse). Unusual behavior and coordination difficulties may occur if these medicines are taken together.

Isoniazid may increase the effects of the following medicines:

  • warfarin (Coumadin);
  • carbamazepine (Tegretol);
  • cycloserine (Seromycin);
  • phenytoin (Dilantin), ethotoin (Peganone), and mephenytoin (Mesantoin);
  • meperidine (Demerol);
  • benzodiazepines such as alprazolam (Xanax), diazepam (Valium), lorazepam (Ativan), and temazepam (Restoril);
  • theophylline (Theo-Dur, Theochron, Theolair, Elixophyllin, Slo-Phyllin, others);
  • ethionamide (Trecator-SC).

You may require a dosage adjustment or special monitoring if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with isoniazid. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

Where can I get more information?

Your pharmacist has additional information about isoniazid written for health professionals that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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