If both first-line regimens are not tolerated, not feasible or contraindicated, the following regimens can be considered as alternatives. Regimens are listed in order of preference.
3.2.1. Isoniazid daily for nine months (9H)
The efficacy of INH has been established in a variety of populations (both HIV-positive and-negative) and settings.3,26–28 The recommended duration of nine months is based on a reanalysis of data from trials among Alaskan Inuit.29 Disadvantages of this regimen include: the longer duration, with lower rate of treatment completion compared to 3HP and 4 R,9 and greater adverse effects, particularly hepatotoxicity, which in rare circumstances (<0.1%) can result in a liver transplant or death.30–32 The risk of INH-associated hepatotoxicity increases with older age.25,33–37 We suggest pyridoxine (Vitamin B6) 25 mg daily given at each dose to minimize the risk of neuropathy.
Recommendation
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We strongly recommend that, when rifamycin-based regimens cannot be used because they are not tolerated, not feasible, or are contraindicated, the 9-month daily isoniazid regimen (9H) for tuberculosis preventive treatment be used (good evidence).
3.2.2. Isoniazid daily for six months (6H)
6H might be required when 9H is considered if a patient is unwilling or unable to complete more than 6 months of therapy. This regimen has demonstrated efficacy in preventing active TB compared to placebo in RCTs and network meta-analyses RCTs.9,10,38,39 Nonetheless, efficacy in these trials was modest (65-67%),38,39 providing a rationale for extending treatment to 9 months whenever possible. However, 6H likely carries a lower risk of hepatotoxicity compared to longer durations of INH monotherapy,39 results in better completion rates.9
Recommendation
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We strongly recommend that, when the 9-month isoniazid regimen (9H) cannot be used, the 6-month daily isoniazid regimen (6H) for tuberculosis preventive treatment be used (good evidence).
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