An assessment of nucleic acid amplification testing for active mycobacterial infection

Drug / regimen	Discontinuation of treatment (overall)	Hepatitis	Simple elevation of transaminases	Dermato-logical	Gastro-intestinal	Hyper-sensitivity
Neuro-logical*
INH	7%	0.4%	11%	1%	2%	0.1–17%	1–3%
RIF	2%	1%	3–9%	0.5–3%	1–8%	Yes	No
PZA	5%	1–5%	NA	2–5%	1%	NA	No
EMB	0.2–0.3%	Rare	No	Rare	No	No	0.2–0.3%
SM	3%	No	No	2%	No	Rare	Yes
RIF-PZA	8%	8%	6%	4%	6%	0.3%	0.1–3%
PZA-Q	67–88%	18%	4–88%	−	−	−	−
HR+	5%	3%	15%	3%	2%	2%	3–7%
HRZ+	4%	3%	22%	12%	12%	1–4%	7%
HRS+	6%	2%	3–51%	11%	16%	1–4%	14%

Median rate given for values representing ≥ 4 studies; range given for values representing ≤ 3 studies

^a Includes vestibular toxicity and optic neuritis

NA = not available; INH = isoniazid; Q = quinolone; RIF = rifampicin; PZA = pyrazinamide; EMB = ethambutol; SM = streptomycin; HR+ = regimens containing INH, RIF and any other drug, but not PZA or SM; HRZ+ = regimens containing INH, RIF, PZA and any other drug, but not SM; HRS+ = regimens containing INH, RIF and SM and any other drug

Source: Forget and Menzies (2006)

Adverse reactions in children (0–18 years)

A review by Frydenberg and Graham (2009) was identified that discussed toxicity of first-line anti-TB regimens in children. On discussion of recommended doses for children, it was noted that the dosage level of isoniazid should depend on whether the child is a fast, intermediate or slow acetylator, as determined by the N-acetyltransferase 2 genotype. The slow acetylator genotype is associated with more AEs (Possuelo et al. 2008; Tostmann et al. 2008). Once again, the attribution of side effects to individual drugs was found to be difficult when the majority of treatments are multidrug regimens. Incidence of AEs attributed to individual drugs are summarised in Table , stratified according to dose/regimen. In some cases the data from a number of studies using the same dose were combined. Reports of adverse reactions for mono-therapeutic use of rifampicin and pyrazinamide are scarce as they are most commonly used in multi-therapies. Furthermore, a large proportion of the included mono-therapy data in children comes from prophylactic use of anti-TB drugs.

The AEs reported in treatment trials of multidrug regimens in children are summarised in Table . For comparative studies the arm in which the AE occurred was not reported by Frydenberg and Graham (2009). The AEs of two Indian trials assessing more serious forms of TB in children are shown in Table . One of the trials compared a treatment regimen containing streptomycin for more severe TB with a regimen without streptomycin for children with less-severe disease. A second trial treated children with tuberculous meningitis.

Table Incidence of adverse reactions to TB drugs in children