Should Isoniazid Be Prescribed for a 73-Year-Old With a 10-Year History of a Positive PPD?

David R. Haburchak, MD, FACP


September 23, 2002


Should isoniazid (INH) be prescribed for this patient? He is a 73-year-old male with a positive purified protein derivative (PPD) test, probably first detected over 10 years ago. He is currently taking 9 drugs in the following amounts for a variety of conditions: Norvasc (amlodipine) 10 mg, HCTZ (hydrochlorothiazide) 25 mg, Accupril (quinapril) 40 mg, Pravachol (pravastatin) 40 mg, Flomax (tamsulosin) 0.4 mg, Proscar (finasteride) 5 mg, Celebrex (celecoxib) 200 mg, aspirin 81 mg, Prevacid (lansoprazole) 30 mg. CT of chest showed punctate calcifications consistent with granulomatous disease. The patient is asymptomatic.

Joseph Shube, MD

Response from David R. Haburchak, MD, FACP

Any clinical decision, particularly for drug therapy, should assess risk vs benefit for the proposed intervention. In the case of preventive therapy, the decision analysis becomes more complicated, because the benefit and the risk are both very dependent upon particular aspects of both the patient and the population in question. In the case of tuberculosis prevention, analysis should consider population and individual patient factors. For example, does the prevention not only prevent disease in the individual taking drug, but also in subsequent cases, such as in individuals residing in a nursing home?

The history of therapy for latent tuberculosis has been colored by a legacy of INH hepatotoxicity cases in the early 1970s, some of which included politically prominent individuals.[1] This led to the conservative use of INH in individuals older than 35 years of age who were at low risk of developing active tuberculosis. Subsequent studies confirmed increased risk of INH hepatitis in alcoholics, older patients, women, and those taking acetaminophen and other potentially hepatotoxic drugs.[2,3] Later studies indicated that the actual risk was lower than previously thought, because the prior incidence was based on chemical rather than clinical definitions. The results of subsequent studies, some using formal decision analysis, generally argued for more liberal use of INH prophylaxis, even for elderly individuals at low risk for active disease.[4,5,6]

The problem with such studies, and the guidelines[3] derived from these data, remains that the individual clinician has to explain the risks and benefits in terms of the individual patient sitting across the desk, in a way that both physician and patient can make a rational decision about treatment. The case described is a low-risk patient for both disease and toxicity from treatment.

Approximately 5% of latently infected patients will develop active tuberculosis within the first 2-3 years of skin test conversion. This represents approximately 50% of the lifetime risk of active disease in an infected patient.

This patient is at least 10 years out from time of initial exposure, and except for his use of Flomax, would appear reasonably free of risky diseases such as renal failure, diabetes, silicosis, HIV, or other immunosuppressive disease. His x-ray findings are also low-risk, since the lesions were punctate and calcified, rather than larger, fibronodular lesions.[3]

The risk of activation for this patient is about 0.095% per year or less.[6] The benefit of 9 months of INH therapy would be to lower this rate by 90%. The risk of 1 death from INH hepatitis would be 0.002% (these rates are for age > 40 years). Separate studies have indicated that patients over 65 would have a clinical hepatotoxicity rate of 0.28%,[5] and that as many as 17% of those over 65 years of age would not complete a course of observed INH therapy in nursing homes.[6] Even the most enthusiastic, pro-INH study indicated that the benefit for the individual patient over 70 years of age was small: life expectancy increased by 3.1 days, but at a "disutility" of 0.5 days for having to take the pill.[6] Even if your patient resided in a nursing home and infection in others were prevented, the cohort would have life expectancy increase of only 6 days. Unfortunately, this study, while extolling millions of dollars' savings to the population of the United States if everyone was treated, presented no analysis of the actual numbers of patients needed to be treated to clinically benefit 1 patient. I suspect it would be very high.

Being by nature conservative, I would therefore recommend that 2 fundamental medical laws be applied to this clinical situation: (1) primum non nocere (first of all do no harm); (2) "if things are going well, keep on watching the patient."


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