HomeThere are three different treatment regimens in regular use in Canada for TB preventive treatment in children and teens: (1) 3HP:12 weekly doses of INH and rifapentine (note that rifapentine can only be used in children ≥2 years old); (2) 4 R: four months of daily RMP; and (3) 9H: nine months of daily INH. (These regimens and their efficacy and safety profiles are also described in Chapter 6: Tuberculosis Preventive Treatment in Adults.) Parental and child preference should be strongly considered when choosing a TB preventive treatment regimen. The following information should be made available to the family to aid in decision-making: total pill burden per dose; frequency of doses; duration of treatment; need for treatment support with intermittent regimens; local public health supports; side effect profile; drug-drug interactions; and availability of liquid suspensions. In addition to these considerations, rifapentine is not currently available in many jurisdictions in Canada.
For children ≥2 years, the 3HP regimen or the 4 R regimen are the regimens of choice, as these are as effective as 9 months of INH and have higher completion rates, with no increase in adverse event rates.107–109 However, the use of rifamycins may be contraindicated in certain pediatric subpopulations due to significant drug interactions (ie, adolescents on hormonal contraceptive agents). In these cases, 9 months of INH is a reasonable alternative.
For children <2 years, the preferred treatment option is 4 R, because of tolerability and total duration of therapy of the treatment options available. It should be noted, however, that 9 months of INH has been the most studied regimen and historically the most widely used in children in this age group and can also be considered. Children in this age group do not have the same rates of hepatotoxicity with INH as adults. When choosing between regimens, this information should be considered in addition to the evidence available about completion rates and adverse events that favor the use of 4 R in older children and adults. In some countries, 3 months of daily INH and RMP is used because it is available as a combination, dispersible tablet with no age restrictions.
Treatment support should be available to those prescribed intermittent regimens or where adherence issues are a concern, given the commonly encountered practical difficulties, including (but not limited to) spitting out medicines, parental anxiety and taste issues with liquid suspension or crushed tablets. Routine baseline lab investigations are not required in otherwise healthy children who do not have any underlying conditions predisposing them to hepatotoxicity. Regular follow-up visits, either by public health staff or clinicians, should focus both on adherence to treatment and adverse event monitoring. Questions should focus on the early warning signs of drug-induced hepatitis: persistent nausea, vomiting, fatigue, anorexia or abdominal pain. Jaundice and scleral icterus are late signs of severe liver injury. If any of these symptoms are observed by the caregivers, they should be told to stop treatment immediately and report this to their health care team, followed by prompt assessment for hepatotoxicity.
Children with both TB infection and HIV should begin TB preventive treatment as soon as possible, which may happen concurrently with initiation of antiretroviral therapy. The preferred regimen in young children with HIV who cannot swallow pills is INH for 9 months, as it can be used with any antiretroviral therapy regimen without need for dose adjustment.110,111 While shorter-course regimens with rifamycins may be considered, their practical use is limited by numerous drug-drug interactions and overlapping toxicities that may compromise their effectiveness in young children.112,113
If a child is exposed to, and/or confirmed to have, TB infection following a contact with an INH mono-resistant source case, then RMP is the treatment of choice. When TB preventive treatment is being considered for contacts of a confirmed multidrug-resistant (ie, resistant to INH and RMP) source case, then consultation with a local expert is recommended. The choice should always be guided by the susceptibility results of the source case and should never be empiric. If the source case has a fluoroquinolone-susceptible isolate, there are several case series showing that preventive therapy with a fluoroquinolone is effective.114,115 Currently there are 2 randomized controlled trials in progress that are evaluating the efficacy of levofloxacin compared to placebo that are enrolling pediatric participants.
Recommendations
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We strongly recommend that, in children ≥2 years old, TB infection be treated with either 12 weeks of once-weekly isoniazid and rifapentine (3HP, where available) or 4 months of daily rifampin (good evidence).
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We strongly recommend that, in children <2 years old, 9 months of daily isoniazid be an acceptable alternative given its historical use (good evidence).
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We conditionally recommend that, in children <2 years old, 4 months of daily rifampin (4R) be prescribed for TB preventive therapy (poor evidence).
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