Adverse effects of oral second-line antituberculosis drugs in children

ABSTRACT

Introduction: Increasing numbers of children with drug-resistant tuberculosis are accessing second-line antituberculosis drugs; these are more toxic than first-line drugs. Little is known about the safety of new antituberculosis drugs in children. Knowledge of adverse effects, and how to assess and manage these, is important to ensure good adherence and treatment outcomes.

Areas covered: A Pubmed search was performed to identify articles addressing adverse effects of second-line antituberculosis drugs; a general search was done for the new drugs delamanid and bedaquiline. This review discusses adverse effects associated with oral second-line antituberculosis drugs. The spectrum of adverse effects caused by antituberculosis drugs is wide; the majority are mild or moderate, but these are important to manage as it could lead to non-adherence to treatment. Adverse effects may be more common in HIV-infected than in HIV-uninfected children.

Expert opinion: Although children may experience fewer adverse effects from oral second-line antituberculosis drugs than adults, evidence from prospective studies of the incidence of adverse events in children is limited. Higher doses of second-line drugs, new antituberculosis drugs, and new drug regimens are being evaluated in children: these call for strict pharmacovigilance in children treated in the near future, as adverse effect profiles may change.

KEYWORDS:

• Adverse effects
• antituberculosis drugs
• children
• multidrug-resistant
• tuberculosis

Article highlights

• The number of children accessing second-line antituberculosis drugs is increasing and new antituberculosis drugs are entering the child tuberculosis treatment armamentarium

• There is a lack of high quality prospective data on the safety and tolerability of second-line antituberculosis treatment in children

• Health care providers managing children with drug-resistant tuberculosis should have detailed knowledge of possible adverse effects of second-line antituberculosis drugs

• In designing new multidrug-resistant tuberculosis regimens for children, the safety of component drugs must be a key consideration

• Some adverse effects, such as hypothyroidism, are more common in HIV-infected children compared to HIV-uninfected children

• Mild to moderate adverse events, such as abdominal disturbance, pruritis and skin rash are common, and may lead to non-adherence. However, severe adverse events, such as severe cutaneous adverse drug effects and hepatotoxicity leading to interruption or permanent discontinuation of drugs, are relatively rare

This box summarizes key points contained in the article.

Declaration of interest

HS Schaaf is an employee of the Government of the Western Cape (South Africa) and Stellenbosch University. The university receives grants from NIH for pharmacokinetic studies of second-line antituberculosis drugs in children from which some references were used, HS Schaaf is a co-principal investigator on one and co-investigator on the other of these two grant, he is also co-investigator on a study of delamanid pharmacokinetics and safety in children for which the university receives a grant from Otsuka. AJ Garcia-Prats and AC Hesseling are principal investigator/co-investigator on the same studies mentioned with the lead author above for which the university receives grants. L van der Laan is co-investigator on NIH grant PK and safety studies of second-line antituberculosis drugs in children. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper received no funding.