Dr. Saltiel received his Pharm.D. from the University of California, San Francisco, in 1980, following undergraduate work at UCLA. At UCSF, he was the recipient of the Outstanding Service Award and the Bowl of Hygeia Award. He completed a residency in clinical pharmacy practice at the University of Illinois, in Chicago.
Jay W. Marks, MD, is a board-certified internist and gastroenterologist. He graduated from Yale University School of Medicine and trained in internal medicine and gastroenterology at UCLA/Cedars-Sinai Medical Center in Los Angeles.
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 approximately 10%. 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.
Because of the risk of hepatitis, patients taking INH 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, nausea, vomiting, dark urine, yellow skin or a yellowish tinge to the whites of the eyes, persistent fatigue, weakness or fever of greater than 3 days duration, or abdominal tenderness or discomfort, especially in the right upper part of the abdomen.
Damage to nerves (peripheral neuropathy)) may occur with INH and cause numbness and tingling of the hands or feet. Other rare side effects of 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, seizures, impaired memory, psychosis. Pyridoxine (vitamin B6), 10-50 mg/day, decreases the risk of neural side effects.
The rate at which INH is eliminated by the liver is race-dependent. Thus, 60% of African Americans and whites eliminate INH slowly compared with only 10-20% of Asians. Individuals who eliminate INH slowly are more prone to develop hepatitis and neural side effects with chronic use of INH.
Other side effects of INH include nausea, vomiting, abdominal pain, dry skin, fever, skin rashes and eruptions, swollen lymph nodes, reductions in while blood cells (which increases the risk of infection), platelets (which increases the risk of bleeding), anemia, high blood sugar levels in the blood, gynecomastia (enlargement of the breasts in men), ringing in the ears, urinary retention (difficulty passing urine), and painful joints.
Liver disease can be cause by a variety of things including infection (hepatitis), diseases such as gallstones, high cholesterol or triglycerides, blood flow obstruction to the liver, and toxins (medications and chemicals). Symptoms of liver disease depends upon the cause; however, common symptoms may include nausea, vomiting, upper right abdominal pain, and jaundice. Treatment depends upon the cause of the liver disease.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis bacteria. Symptoms include weakness, fever, weight loss, night sweats and in worse cases, chest pain, shortness of breath, and coughing up blood. A person with an active infection (a positive TB skin test, abnormal chest x-ray and TB bacteria in their sputum) requires treatment with izoniazid, rifampin, ethambutol and pyrazinaide.
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