GENERIC NAME: Isoniazid, INH
BRAND NAME: Nydrazid, Laniazid
DRUG CLASS AND MECHANISM: Isoniazid, or INH, is an anti-bacterial drug that has been used to prevent and to treat tuberculosis since 1952. Tuberculosis is an infectious diseased caused by a bacterium. Once the infection is acquired, it usually remains dormant in the lungs. Later, the infection may become active in the lungs and sometimes spreads throughout the body. Patients with a tuberculosis skin test that has recently become abnormal (demonstrating recent infection with tuberculosis) but a normal chest x-ray (demonstrating inactive infection) are given INH alone for 6-9 months. Patients with active infection on chest x-ray are given INH combined with other antituberculous drugs.
The mechanism of action of INH is not known, but it is thought to work through its effects on lipids (fats) and DNA within the tuberculosis bacterium. It is very selective for the tuberculosis bacteria, that is, it has few if any effects on other bacteria.
PRESCRIPTION: yes
GENERIC AVAILABLE: yes
PREPARATIONS: INH is available as 100 mg or 300 mg tablets and as a syrup (50 mg per teaspoonful).
STORAGE: Tablets and syrup should be stored at room temperature, 15-30°C (59-86°F).
PRESCRIBED FOR: INH is used to prevent active tuberculosis in persons who have an abnormal skin test for tuberculosis or in combination with other drugs for the treatment of active tuberculosis.
DOSING: INH is most commonly taken once daily. When used for the treatment of active tuberculosis, some physicians prefer using a high dose twice weekly. It is best to take INH on an empty stomach for maximum absorption into the body, but if it causes abdominal discomfort, it may be taken with food or with a non-aluminum antacid such as Tums or Titralac. (Aluminum-containing antacids bind to the INH in the intestine and prevent its absorption.)
DRUG INTERACTIONS: Antacids containing aluminum (e.g. Mylanta; Maalox, Gelusil; Amphojel; Alternagel) reduce the amount of INH that is absorbed from the intestine, and this can result in reduced blood levels and effect of INH. If aluminum-containing antacids must be taken, they should be taken at least one hour after the INH to prevent binding.
INH can increase the effectiveness of the blood thinner, warfarin (Coumadin) by interfering with the enzyme in the liver that eliminates warfarin.
INH can increase the effect of certain benzodiazepines, such as diazepam (Valium), triazolam (Halcion), and others, by interfering with the enzymes in the liver that eliminate benzodiazepines. This may result in excessive sedation.
Carbamazepine (Tegretol) taken at the same time as INH, can result in an increased risk of side effects from both carbamazepine and INH.
INH can decrease the rate at which the liver eliminates phenytoin (Dilantin), which can raise the blood levels and result in side effects of phenytoin.
Because rifampin can be toxic to the liver, the use of rifampin and INH together increases the risk of liver toxicity to a level that is greater than with either drug alone.
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PREGNANCY: INH has not been shown to cause birth defects in humans or animals; however, studies in rats and rabbits have shown that it may increase the risk of fetal death. Nevertheless, tuberculosis is a very serious infection, and many women have been treated with isoniazid during pregnancy with no problems in their infants. Ultimately, the physician and the pregnant patient must evaluate the risks and benefits of INH.
NURSING MOTHERS: INH is secreted into breast milk, however, it has not been reported to cause problems in nursing babies. Ultimately, the physician and the nursing mother must evaluate the risks and benefits of INH.
SIDE EFFECTS: When INH is broken down by the liver, one of the products is acetylhydrazine, a potent toxin for the liver. When taken over a long period of time at standard doses, INH can cause important and even fatal liver injury (hepatitis) in approximately 1 out of every 100 patients. INH-associated hepatitis usually occurs during the first three months of treatment but can occur at any time during therapy or even many months after starting treatment. Elevated blood liver tests occur in between 1 in 20 and 1 in 10 patients. Usually, enzyme levels return to normal despite continuation of the INH, but in some cases progressive liver damage and even death occurs.
The risk of developing hepatitis is age-related. It occurs in less than 1 per 1,000 patients under 20 years of age, 3 per 1,000 patients 20-34 years of age, 12 per 1,000 patients 35-49 years of age, 23 per 1,000 patients 50-64 years of age, and 8 per 1,000 patients over 65 years of age. The risk of hepatitis is increased by daily consumption of alcohol.
Among individuals who complete a full course of prophylaxis (prevention of tuberculosis), the hepatitis-related death rate (mortality) is 23-58 patients per 100,000 patients, far lower than the frequency of hepatitis. The mortality rate among individuals who develop symptoms of INH-induced hepatitis (not just minor abnormalities of liver tests) is approximately10%. In one U. S. Public Health Service Surveillance Study involving 13,838 persons taking INH, there were 8 deaths among 174 cases of hepatitis, a mortality rate of 5%. There seems to be an increased risk of fatal hepatitis among women, particularly African-American and Hispanic women. The risk also may be increased during postpartum or immediately after pregnancy.
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