Treatment for latent tuberculosis infection (LTBI) during methadone maintenance therapy: Patients who receive methadone maintenance therapy are less likely to complete LTBI treatment and more likely to develop withdrawal symptoms if treated for LTBI with a rifapentine-containing regimen Open Access

Sheehan, Deirdre (2015)

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Previous studies have shown that shorter regimens to treat latent tuberculosis infection (LTBI) have higher completion rates. Effectiveness of a 3-month weekly regimen of rifapentine plus isoniazid (3HP) is equal to that of standard 9-month daily isoniazid (9H) and 6-month daily isoniazid (6H) regimens, and treatment completion of 3HP is higher than that of 9H and of 6H (4, 25). Rifapentine belongs to the rifamycin drug class, which has been shown to interact with and decrease activity of methadone. Therefore, in patients concomitantly receiving methadone maintenance therapy and 3HP, methadone has the potential to hinder LTBI treatment completion rates. This analysis aims to determine (a) the effect of concomitant methadone maintenance therapy on the completion of a rifapentine-containing LTBI treatment regimen and (b) the effect of a rifapentine-containing treatment regimen on the development of withdrawal symptoms. The analysis used data from a clinical trial in which subjects were randomized to receive either 3HP or 9H. This analysis included 6242 subjects, 137 (2.19%) of whom were concomitantly receiving methadone maintenance therapy. Overall, 79% of subjects completed LTBI treatment, but completion rates were differential by treatment regimen and by methadone maintenance therapy. Among subjects not receiving methadone, 3HP was associated with significantly higher odds of treatment completion compared to 9H (OR=1.809, p<0.001), but subjects receiving 3HP during methadone maintenance therapy were significantly less likely to complete treatment than subjects receiving 3HP alone (OR=0.539, p=0.026). Among subjects concomitantly receiving methadone maintenance therapy, 38 of 137 (27.7%) developed methadone withdrawal, and 19 of these 38 (50%) were unable to complete LTBI treatment. The rifapentine-containing 3HP treatment regimen was associated with odds of developing withdrawal 5.6 times those of the 9H treatment regimen (p<0.001). In conclusion, clinicians should give careful consideration to prescribing rifapentine-containing regimens to treat LTBI in those who currently receive methadone maintenance therapy and should monitor patients for the appearance of early withdrawal symptoms during treatment to increase likelihood of treatment completion and to minimize risk of permanent discontinuation of the LTBI regimen due to development of withdrawal syndrome.

Table of Contents

Treatment for Latent Tuberculosis Infection 1
Methadone-rifampin drug interaction 1
Importance of LTBI treatment completion for patients receiving methadone maintenance therapy 3
Factors associated with LTBI treatment completion 5
Factors associated with methadone withdrawal 5
Study design 6
Definitions 9
Statistical analysis 10
Subjects 11
Treatment Completion 12
Development of methadone withdrawal 14
Limitations 18

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