Could the WHO Model List of Essential Medicines do more for the Rational and Safe Use of Injections?

1. Could the WHO Model List of Essential Medicines do more for the Rational and Safe Use of Injections? Logez S, Hutin Y, Holloway K, Robin G, Hogerzeil H

2. Problem Statement: A national drug policy addressing the rational and safe use of injections is an important element in preventing overuse and unsafe use of injections. Over the past 25 years the WHO model list of essential medicines has led to a global acceptance of the concept of essential medicines as one crucial element to ensure access and rational use of medicines. Because the model list is a keystone of national drug policies, we examined the way it addresses injection practices. • Objectives: To examine opportunities to build the safe and rational use of injections into national drug policies, we reviewed the eleventh model list to describe the injectable medicines that it includes and to examine how it addresses the issue of safe and rational use of injectable medicines. • Design: Descriptive analysis through the development of a database of all injectable medicines included in the model list. We reviewed the injectable medicines included in the eleventh WHOmodel list of essential medicines (revised December 1999) to identify how the model list may better promote injection safety and more rational use of injections. We presented the results to the 2002 WHO Expert Committee for the selection and use of essential medicines. • Outcome Measures: Proportion of injectable medicines and their characteristics in the model list; proportion of injectables that need diluents; estimated needs of syringes for injectable medicines; estimated price for injectable medicines on the model list. • Results: Of 306 active ingredients on the list, 135 (44%) are listed as injectable medicines in 173 instances. Of these, 41 (30%) need diluents for reconstitution. The results of the analysis suggests that the model list could address more clearly the need to use injections safely and rationally. First, it includes many injectable medicines, some of which may not be justified. Second, there is no clear mention that of the injectable medicines that need to be reconstituted, single-dose diluent vials are needed. Finally, the model list makes no clear reference of the need to procure safe injection devices and safety boxes to administer injectable medications safely. • Conclusions: The main results were presented to the Expert Committee in 2002, which agreed to recommend that a review of all injectables on the model list be carried out. The aim of such a revision would be to reduce the number of injectable formulations on the basis of evidence. This is now in process. In addition, the committee recommended that when injectable mediations are being supplied, the necessary injectable devices should also be supplied. Abstract

3. 16 thousand million injections are administered in developing and transitional countries each year, 90% of these for curative purpose. • Worldwide, unsafe injections may account for: • 30% of new HBV infections • 41% of new HCV infections • 5% of new HIV infections • Most medications used in primary care can be administered orally • WHO Model List of essential medicines is one crucial element to ensure medicines access and rational use of medicines. • In 1999, 156 (81%) WHO Member States had a national list of essential medicines. Background

4. Examine opportunities to build the safe and rational use of injections into national medicine policies • Describe the injectable medicines included in the WHO 11th model list of essential medicines • Examine how the model list addresses the issue of safe and rational use of injectable medicines. Study Aims

5. Construction a database of injectable medicines included in the WHO 11th model list: • type of essential medicines • therapeutic section • joint presence of an equivalent oral form • indicated dosage forms and strengths • presentation and the diluent requirement • Inclusion of information on: • documented routes of administration • expected size of syringes needed • median price per unit of the injectable medicine Methods

6. WHO model list includes 306 active ingredients • 135 (44%) active ingredients are in injectable form. Of these : • 29 (21%) come in various dosages and volumes for a total of 171 injectable formulations; • 46 (34%) contain active ingredients also included as an oral form; • 41 (30%) are mentioned as a powder for injection that needs to be reconstituted with a diluent. • The list includes 7 (5%) active ingredients present in multi-dose vial presentation (including anaesthetics) Results

7. Number % Injectables on the ML 135 44% “Essential” 116 86% “Complementary” 14 10% “Reserved” 5 4% With oral form in the ML 46 34% Diluents required 41 30% Solely IM-formulation 24 18% Solely IV-formulation 63 46% Both IM- and IV-formulation 49 36% SC-formulation 14 10.3% Solely spinal formulation 3 2.2% Characteristics of Injectable Medicines of the Model List (ML)

8. Characteristics of Injectable Medicines on the Model List Model List Injectables 10% Complementary 44% Injectables Others 86% Essential 4% Reserved Injectables with oral equivalent on model list 34% Injectables which require diluents 30%

9. No mention of the need to procure diluents, single use injection devices and safety boxes to administer injectable medicines safely • Of the 97 formulations with indication of the volume: • 7% would require 1 ml syringes, • 51% would require 2 ml syringes, • 19% would require 5 ml syringes, • 11% would require 10 ml syringes, • 4% would require 20 ml syringes, • 8% would require a perfusion placement set • Impossible to estimate the type of syringes needed for 74 (43%) of the 171 formulations. • 8 formulations are only available as multi-dose vials in the different price indicator guides Estimated Needs of Syringes for Injectable Medicines

10. For 104 (61%) formulations, the median price was US$ 0.5 (Mean: US$ 2.8, range US$ 0.023 - 27.5) • A median international price could not be estimated for 67 (39%) because: • size or volume indicated was not available in the price indicator guides (n=4, 2%), • dosage indicated was not available (n=7, 4%) • formulations were not listed in the price indicators of the main international low-cost procurement agencies (n=56, 33%). Estimated Price for Injectable Medicines on WHO Model List

11. The model list could address more clearly the need to use injections safely and appropriately. • Many injectable medicines are included, some of which may not be justified • No mention that single-dose diluent vials were needed for injectable medicines that need to be reconstituted • Some injectable medicines are solely available in the international market as multi-dose vials Discussion

12. No clear reference of the need to procure single use injection devices and safety boxes to administer injectable medications safely • Insufficient information regarding the volume of vials which made the forecasting of single use injection devices needs more difficult. Discussion

13. High number of injectables on the model list: • re-examine, based on evidence, if 86% of injectables are “essential” • Evidence should be generated of which injectable medicines could be replaced by an oral alternative • List should state where diluents are required • Volume of injectable vials and size of syringes should be specified • Inclusion of multi-dose vials should be discouraged • Need for matching supplies of sterile injection devices and sharps boxes should be stated Recommendations