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What is isoniazid, INH, and how does it work (mechanism of action)?
- Isoniazid is an anti-bacterial drug that has been used to prevent and to treat tuberculosis since 1952. Tuberculosis is an infectious disease caused by a bacterium. Once the infection is acquired, it usually remains dormant in the lungs for up to many years. 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 isoniazid alone for 9 months. Patients with active infection on chest X-ray are given isoniazid combined with other antituberculous drugs. The mechanism of action of isoniazid 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.
What are the uses for isoniazid, INH?
- Isoniazid is used to prevent active tuberculosis in persons who have an abnormal skin test for tuberculosis (latent tuberculosis) or in combination with other drugs for the treatment of active tuberculosis.
What brand names are available for isoniazid, INH?
Is isoniazid, INH available as a generic drug?
Do I need a prescription for isoniazid, INH?
What are the side effects of isoniazid, INH?
When isoniazid 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, isoniazid can cause important and even fatal liver injury (hepatitis) in approximately 1 out of every 100 patients. Isoniazid-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 isoniazid, 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 isoniazid-induced hepatitis (not just minor abnormalities of liver tests) is approximately 10%. In one U. S. Public Health Service Surveillance Study involving 13,838 persons taking isoniazid, 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. Because of the risk of hepatitis, patients taking isoniazid should have their blood liver tests monitored monthly and should notify their physicians immediately if symptoms or signs of hepatitis arise. These symptoms and signs include:
- Unexplained loss of appetite
- Dark urine
- Yellow skin or a yellowish tinge to the whites of the eyes
- Persistent fatigue
- Fever of greater than 3 days duration
- Abdominal tenderness or discomfort, especially in the right upper part of the abdomen
OTHER RARE :
Damage to nerves (peripheral neuropathy) may occur with isoniazid and cause numbness and tingling of the hands or feet (parethesia).
Other rare side effects related to the nervous system include:
- Encephalopathy (inflammation of the brain)
- Optic neuritis (inflammation of the nerve coming from the eye)
- Atrophy (degeneration) of the nerve coming from the eye
- Impaired memory
- Peripheral neuropathy
Pyridoxine (vitamin B6), 10-50 mg/day, decreases the risk of neural side effects.
The rate at which isoniazid is eliminated by the liver is race-dependent. Thus, 60% of African Americans and whites eliminate isoniazid slowly compared with only 10%-20% of Asians. Individuals who eliminate isoniazid slowly are more prone to develop hepatitis and neural side effects with long-term use of isoniazid.
Other important side effects of isoniazid include:
- Abdominal pain
- Dry skin
- Skin rashes and eruptions
- Swollen lymph nodes
- Reductions in white blood cells (which increases the risk of infection)
- Reductions in platelets (which increases the risk of bleeding)
- High blood sugar levels in the blood
- Gynecomastia (enlargement of the breasts in men)
- Ringing in the ears
- Urinary retention (difficulty passing urine)
- Blood disorders
- Hypersensitivity reactions
- Painful joints
What is the dosage for isoniazid, INH?
- The recommended dose for latent tuberculosis 300 mg daily for 9 months.
- Active tuberculosis is treated with 5 mg/kg up to 300 mg daily or 15 mg/kg up to 900 mg 1-3 times weekly.
- It is best to take isoniazid 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 isoniazid in the intestine and prevent its absorption.)
Which drugs or supplements interact with isoniazid, INH?
- Antacids containing aluminum (for example, Mylanta; Maalox, Gelusil; Amphojel; Alternagel) reduce the amount of isoniazid that is absorbed from the intestine, and this can result in reduced blood levels and effect of isoniazid. If aluminum-containing antacids must be taken, they should be taken at least one hour after the isoniazid to prevent binding.
- Isoniazid can increase the effectiveness of the blood thinner, warfarin (Coumadin) by interfering with the enzyme in the liver that eliminates warfarin.
- Isoniazid 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 isoniazid, can result in an increased risk of side effects from both carbamazepine and isoniazid. Isoniazid 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 isoniazid together increases the risk of liver toxicity to a level that is greater than with either drug alone.
What else should I know about isoniazid, INH?
What preparations of isoniazid, INH are available?
Tablets: 100 or 300 mg. Syrup: 50 mg per teaspoonful. Injection: 100 mg/ml.
How should I keep isoniazid, INH stored?
Tablets and syrup should be stored at room temperature, 15 C - 30 C (59 F - 86 F).
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Isoniazid is a medication prescribed to prevent active tuberculosis (TB) in individuals who have an abnormal skin test for TB, and is used in combination with other drugs to treat active TB. Side effects, drug interactions, and pregnancy and breastfeeding safety should be reviewed prior to taking this medication.
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