Access to Pediatric Formulations in Developing Countries David J Woods School of Pharmacy, University of Otago, Dunedin, New Zealand Pharminfotech Consultancy

Problem Statement: Oral liquid preparations for administration of doses to children are not freely available in developing countries. Consequently, pharmacists frequently must modify solid-dose forms. Information on the stability of these formulations is often lacking, difficult to find, inconsistent, or only applicable for use in a handful of developed countries. Objective: To gather some preliminary data on the availability of oral liquid preparations and related pharmacy practices in developing countries, and to suggest strategies for making improvements. Design: Phase 1: A prospective analysis of pediatric formulation questions received by Phase 2: (still in progress) A survey of product availability in specific countries or regions. Setting and Population: Phase 1: Pharminfotech Ltd. (NZ) developed an information database on more than 80 oral liquid formulations. The database is available on CD-ROM and on the Web. From April 2001, the CD has been distributed to more than 40 countries, free of charge to developing countries. The main recipients of the CD were hospital pharmacists, community pharmacists and academic institutions. Each mailing included a letter inviting comments on country-specific problems and information requests. Phase 2: Specific developing countries are being targeted for a more detailed analysis of problems and practices. Outcome Measures: Phase 1: The requests for formulation information on pediatric liquids were collated and a comparison made between requests received from developing and developed countries. In phase 2 more specific information is being gathered from selected countries to ascertain if access to pediatric formulations is compromised and possible reasons for this.. Results: Phase 1: Data were collated for the period April 2001–March A total of 269 information requests were received from 28 countries. The requests involved more than 30 different drugs. Important general and country-specific problems have been identified. Lack of commercial products and information on extemporaneous formulations are contributing to suboptimal treatment in many countries. One problem found was the common practice of compounding of antiretroviral liquids from tablets despite the lack of data on stability; many practitioners in developing countries must compound liquids for treatment of tuberculosis, malaria, HIV/AIDS, and cardiovascular disease without guarantee of effectiveness. Commercially manufactured products are widely available in developed countries. Preliminary data from phase 2 suggests that availability of pediatric formulations in developing countries may be hindered by high costs and the reluctance of companies to register and make products available in uneconomic markets. Conclusion: Many developing countries have poor access to commercially manufactured pediatric formulations. Practices for compounding are inconsistent, and the problems are exacerbated by lack of ingredients and information. Strategies to improve the situation include international guidelines, increased availability of information, practitioner education, and improved product availability. ABSTRACT

Background Oral liquid preparations for the administration of doses to children are not freely available. Consequently, pharmacists frequently have to modify solid dose forms. Information on the stability of these formulations is often lacking, difficult to find, inconsistent, or only applicable for use in a handful of developed countries. Information on the situation in developing countries is lacking, but anecdotally it has been ascertained that the use of substandard preparations for the treatment of tuberculosis, HIV/AIDS, and malaria is widespread. Objectives T o gather some preliminary data on the availability of oral liquid preparations and related pharmacy practices in developing countries, and to suggest strategies for making improvements.

Methods 1 Phase 1: A prospective analysis of pediatric formulation questions received by . Pharminfotech Ltd. Developed an information database on more than 80 oral liquid formulations. The database is available on CD-ROM and on the Web. From April 2001, the CD has been distributed to more than 40 countries, free of charge to developing countries. Each mailing included a letter inviting information requests and comments on country-specific problems. Pharmacists were invited to request information about formulations not included in the database. Enquiries received were categorized according to country of origin, drug and therapeutic use. Requests were collated and a comparison made between requests from developed and developing countries.

Methods 2 Phase 2: (still in progress) A survey of product availability in specific countries or regions to see if access to pediatric medicines is compromised. Analysis is being performed on the possible reasons for inter-country variations in access to pediatric formulations.

Results 1 Phase 1: Data were collated for the period April 2001 – March A total of 269 information requests were received from 28 countries. These involved more than 30 different drugs. Requests from developing countries (Fig.1) frequently involved liquid formulations for the treatment of infectious disease including TB, malaria and HIV. There were also requests involving antibiotic mixtures and cardiovascular drugs. The majority of these preparations are commercially available. Requests from developed countries (Fig.2) tended to involve formulations not commercially available or more specific information on the use of bases or preservatives. There were also requests for information on specialist formulations for the treatment of metabolic disease in neonates and the use of sildenafil (Viagra) for infant pulmonary hypertension.

Results 2 Phase 2: Information has been partially collected from the Caribbean, Nepal, Vanuatu and Kenya but most country specific surveys are still pending. Examples of problems identified are: Compounding of antiretroviral liquids from tablets is a common practice, even though data on stability are lacking. Commercially available liquid formulations are often not available in developing countries Many practitioners in developing countries have to compound liquids for the treatment of malaria, TB, cardiovascular disease (e.g. digoxin) without guarantee of effectiveness. These preparations are freely available in developed countries. Availability in developing countries may be hindered by high costs and the reluctance of companies to make products available in uneconomic markets.

Conclusions Many developing countries have poor access to commercially manufactured pediatric preparations Practices for compounding are inconsistent, and the problems are exacerbated by lack of ingredients and information Strategies to improve the situation include international guidelines, increased availability of information, practitioner education and improved product availability.

eMixt CD-ROM The complete database is now available free of charge on the Internet. Further development is planned in response to requests for information and feedback.