Core Curriculum on Tuberculosis, 2000
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
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.
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
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.