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U.S. Department of Health and Human Services


Core Curriculum on Tuberculosis, 2000

Chapter 7
Treatment of TB Disease


Adverse reactions to TB drugs are relatively rare, but in some patients they may be severe. Clinicians who treat TB should be familiar with the methods of monitoring for adverse reactions and response to treatment. In some situations (e.g., drug-resistant TB, pregnancy, HIV-positive patients), expert consultation may be required.

Adverse Reactions to First-Line TB Drugs
(See Tables 5 and 6)

Adults treated for TB should have baseline measurements of hepatic enzymes, bilirubin, and serum creatinine or blood urea nitrogen, as well as a complete blood and platelet count (or estimate). Serum uric acid should be measured if pyrazinamide is used, and a baseline examination of visual acuity should be obtained for patients for whom ethambutol is prescribed. Audiometry should be performed at the beginning of therapy for patients for whom streptomycin is prescribed. The purpose of these baseline tests is to detect any abnormality that would complicate therapy or require a modified regimen. For children, only baseline vision tests are necessary unless a child has other medical conditions that may complicate therapy.

Monitoring for adverse reactions to TB medications must be individualized. The type and frequency of monitoring should depend on the drugs used in a given regimen and the patient’s risk for adverse reactions ( e.g., age, alcohol use). At minimum, patients should be seen monthly during therapy and questioned by medical personnel concerning adverse reactions, even if no problems are apparent. Patients should be specifically instructed to look for symptoms associated with the most common reactions to the medications they are taking. They should also be instructed to seek medical attention immediately should these symptoms occur. If the symptoms suggest adverse reactions, appropriate laboratory testing should be performed.

All patients receiving isoniazid, rifampin, or pyrazinamide should be instructed to stop taking the medications and to immediately report any hepatitis-suggesting symptoms (nausea, loss of appetite, vomiting, persistently dark urine, yellowish skin, malaise, unexplained elevated temperature for more than 3 days, or abdominal tenderness).

Isoniazid. Peripheral neuropathy is associated with the use of isoniazid but is uncommon at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., diabetes, uremia, alcoholism, malnutrition, HIV infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (10–50 mg/day) with isoniazid. As little as 6 mg/day of pyridoxine has been shown to prevent isoniazid-associated neuropathy. 22,23 The interaction of isoniazid and phenytoin increases the serum concentration of both drugs. When these drugs are given concomitantly, the serum level of phenytoin should be monitored. (See Treatment for Latent TB Infection).

Rifampin. Rifampin may accelerate the clearance of drugs metabolized by the liver. These include methadone, coumarin derivatives, glucocorticoids, estrogens, oral hypoglycemic agents, digitalis, anticonvulsants, ketoconazole, fluconazole, cyclosporine, and protease inhibitors. For patients who are in a drug-treatment program, it may be necessary to increase the methadone dose by as much as 50%. 24 Rifampin may also reduce the efficacy of oral contraceptives and contraceptive implants (e.g., Norplant) by accelerating estrogen metabolism. Women using hormonal contraception and taking rifampin should supplement the contraception or use an alternative birth control method (i.e., barrier methods). Patients receiving rifampin should be monitored for possible manifestations of thrombocytopenia (bleeding tendency, easy bruising, blood in urine) or flu-like symptoms. Protease inhibitors and NNRTIs interact with rifamycin derivatives, such as rifampin and rifabutin. Of the rifamycins, rifampin has the most potent interactions; rifabutin has substantially fewer interactions.

Pyrazinamide. Hyperuricemia may occur in patients receiving pyrazinamide, but acute gout is uncommon. Asymptomatic hyperuricemia is not an indication for discontinuing the drug.

Streptomycin. Ototoxicity and neprotoxicity may occur in patients receiving streptomycin. Audiometry should be performed at periodic intervals during streptomycin therapy. If vertigo, dizziness, or ataxia occur in patients taking streptomycin, the drug should be discontinued immediately.

Ethambutol. Optic neuritis is the most frequent and serious adverse effect of ethambutol. Baseline and monthly tests of visual acuity and color vision should be conducted.

Current literature and package inserts should be consulted for other possible drug reactions.


Released October 2008
Centers for Disease Control and Prevention
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of Tuberculosis Elimination -

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