Treatment Completion and Costs of a Randomized Trial of Rifampin for 4 Months versus Isoniazid for 9 Months

Abstract

There is little published information regarding treatment completion, safety, and efficacy of rifampin administered daily for 4 months-a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection. In an open-label randomized trial at a university-affiliated respiratory hospital, consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were randomized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months. Of 58 patients randomized to rifampin, 53 (91%) took 80% of doses, and 50 (86%) took more than 90% of doses within 20 weeks compared with 44 (76%) and 36 (62%) who took 80 and 90%, respectively, of doses of isoniazid within 43 weeks (relative risks: 80% of doses, 1.2 [95% confidence interval: 1.02, 1.4]; 90% of doses, 1.4 [1.1, 1.7]). Adverse events resulted in permanent discontinuation of therapy for two (3%) patients taking rifampin, and for eight (14%) patients taking isoniazid. Three patients developed druginduced hepatitis-all were taking isoniazid. Total costs of therapy were significantly higher for isoniazid. In conclusion, completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower. Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen. Keywords: latent tuberculosis infection; treatment of latent tuberculosis infection; tuberculosis preventionA major activity of many tuberculosis (TB) control programs in industrialized countries is the identification of persons with latent TB infection (LTBI), who have increased risk of development of active TB. Treatment of such individuals can provide individual (1-6) and public health (4-8) benefits. The current recommended standard therapy is 9 months of isoniazid (9INH). This has an efficacy of more than 90% (9) if taken properly. However, because of the long duration, only 64-67% of patients (10, 11) or fewer (12) complete therapy under routine program conditions. Another limitation of INH is the occurrence of druginduced hepatitis. Although rare, this can be fatal (13-17). The incidence of this complication appears to have diminished over the past three decades (10,18,19), but nevertheless this remains an important disadvantage of INH therapy. As well, the long duration, and need for close monitoring because of the possibility of serious adverse events, make this regimen relatively costly.

A Guide to the Management of Tuberculosis in Patients with Chronic Liver Disease

“…43 This may be transient and occurs early in treatment or in some individuals with preexisting liver disease. 44,45 Occasionally RIF can cause hepatocellular injury and can potentiate hepatotoxicity of other ATD. 43 In patients with primary biliary cirrhosis, in whom baseline transaminases were significantly elevated, clinically significant hepatitis was attributed to RIF in 7.3 and 12.5% of patients.…”

“…43 In patients with primary biliary cirrhosis, in whom baseline transaminases were significantly elevated, clinically significant hepatitis was attributed to RIF in 7.3 and 12.5% of patients. 45 RIF can cause hepatocellular changes such as centrilobular necrosis, associated with cholestasis. Histopathological findings range from spotty to diffuse necrosis with more or less complete cholestasis.…”

Completion Rates of Treatment for Latent Tuberculosis Infection in Quebec, Canada From 2006 to 2010

“…4 A four-month regimen with RMP seemed to be associated with better completion rates, ranging from 72% to 91%. [10][11][12] The aim of this study was to evaluate the proportion of adult patients who started LTBI treatment and completed it within 12 months of first prescription.…”

Tuberculosis in the Elderly

“…30 Sınırlı sayıda çalışmada RİF ile tedavide hepatotoksisite riskinin biraz daha düşük olduğu bildirilmiştir. 31 Yaşlı hastalarda İNH tedavisine bağlı hepatotoksisite daha yüksek oranda görülmektedir. Bir çalışmada, 20 yaş altında hiç görülmezken 50-64 yaş arası grupta %2,3 oranında olduğu saptanmıştır.…”