The Secretary of the 21st Expert Committee on the Selection and Use of Essential Medicines Department of Essential Medicines and Health Products World Health Organization 20 Avenue Appia CH-‐1211 Geneva 27 Switzerland
26 January 2017
Re: Statement of support for addition of fixed-‐dose combinations for tuberculosis to the World Health Organization Model List of Essential Medicines for Children
Dear Expert Committee, We are writing to express our support for the addition to the World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc) of two formulations critical to improving therapy for children with drug-‐sensitive tuberculosis (DS-‐TB): pediatric fixed-‐dose combinations (FDCs) of isoniazid, rifampin, and pyrazinamide (HRZ) and isoniazid and rifampin (HR). Access to appropriately dosed, water-‐dispersible FDCs simplifies treatment for children with TB and the providers who care for them. In 2010, the WHO recommended increased doses for first-‐line TB drugs in children, changing the required drug ratios for HRZ from 60/30/150 mg to 75/50/150 mg, and for HR from 60/30 mg to 75/50 mg. This important change unfortunately was not reflected in updated formulations, necessitating provider improvisation to achieve appropriate doses using single tablets and inappropriately dosed FDCs. In 2015, Macleods was the first manufacturer to introduce new pediatric FDCs of HRZ and HR with drug ratios aligned with the increased doses recommended by the WHO.1 Other companies, including Lupin, Sanofi, Sandoz, and Svizera, are at various stages of developing and introducing their own versions.2 When given for three to four months, the new pediatric FDC of HR, developed for use during the continuation phase of treatment for active TB disease, can also be used for prevention.3 This broadens the potential impact the pediatric FDCs beyond the one million children estimated to develop active TB each year, to the 67 million more estimated to be infected and at risk of developing active TB.4 The anti-‐tuberculosis medicines section of the 5th edition of the WHO EMLc includes language endorsing the use of fixed-‐dose combinations, but does not include information specific to the type of formulation or drugs and dosages contained therein. Given that appropriately dosed pediatric FDCs are now available, including for purchase through the Global Drug Facility (GDF), we encourage the Committee to include these important details in the 6th edition of the WHO EMLc.
Despite availability since December 2015, just 33 countries have placed orders for the new pediatric FDCs through the GDF.5 The addition of the new pediatric FDCs to the EMLc is critical to improving uptake and promoting equitable access for children to benefit from the treatment simplifying capabilities of these formulations. We ask the Committee to help pave the way for these formulations to become available to the children who desperately need them by approving the WHO’s application to add pediatric FDCs of HRZ and HR to the EMLc. We welcome the opportunity to discuss this issue further and ask you to please contact [email protected] with any questions. Sincerely, The Community Research Advisors Group (CRAG) Treatment Action Group (TAG) The Global TB Community Advisory Board (TB CAB) 1 World Health Organization. Guidance for national tuberculosis programs on the management of tuberculosis in children, 2nd ed. Geneva: World Health Organization; 2014. Available from: http://www.who.int/tb/publications/childtb_guidelines/en/. 2 McKenna L. The pediatric tuberculosis treatment pipeline: beyond pharmacokinetics and safety data. In: Clayden P, Collins S, Frick M, et al.; i-‐Base/Treatment Action Group. 2016 Pipeline Report. New York: Treatment Action Group; 15 July 2016; p. 181–195. Available from: http://www.pipelinereport.org/2016/tb-‐pediatric-‐treatment. 3 World Health Organization. Guidelines on the management of latent tuberculosis infection. Geneva, Switzerland: World Health Organization, 2015. Available from: http://www.who.int/tb/publications/ltbi_document_page/en/. 4 Dodd PJ, Sismanidis C, Seddon JA. Global burden of drug-‐resistant tuberculosis in children: a mathematical modelling study. Lancet Infect Dis, 2016. Published online June 21, 2016. http://dx.doi.org/10.1016/S1473-‐3099(16)30132-‐3. 5 Waning B. Global Drug Facility Update on New Pedi TB FDC Procurement. Presented at: 2nd Meeting of the TB Procurement & Market Shaping Action Team; 2016 December 6; Arlington, VA.