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Who Model List of Essential Medicines Application 1 WHO MODEL LIST OF ESSENTIAL MEDICINES APPLICATION Information to be included with an application for inclusion, change or deletion of a medicine in the WHO Model List of Essential Medicines: 1. Name of the focal point in WHO submitting or supporting the application: ................................................. 3 2. Name of the organization(s) consulted and/or supporting the application: ................................................... 3 3. International Nonproprietary Name (INN, generic name) of the medicine: .................................................. 3 4. Dosage form or strength proposed for inclusion: ............................................................................................. 3 5. International availability - sources, if possible manufacturers:.......................................................................... 3 6. Whether listing is requested as an individual medicine or as an example of a therapeutic group:................. 3 7. Information supporting the public health relevance ......................................................................................... 3 7.1. Epidemiological information on disease burden: ...................................................................................... 3 7.2. Assessment of current use: ......................................................................................................................... 4 7.3. Target population:........................................................................................................................................ 5 8. Treatment details .................................................................................................................................................. 5 8.1. Reference to existing WHO and other clinical guidelines: ....................................................................... 5 8.2. Dosage regimen, duration: .......................................................................................................................... 5 9. Summary of comparative effectiveness in a variety of clinical settings: ........................................................... 6 9.1. Fixed-dose Combinations ........................................................................................................................... 7 9.2. Dispersibility ................................................................................................................................................ 7 9.3. Scored tablets ............................................................................................................................................... 7 10. Summary of comparative evidence on safety: .................................................................................................... 7 10.1. Estimate of total patient exposure to date ................................................................................................. 7 10.2. Description of adverse effects/reactions ................................................................................................... 8 10.3. Identification of variation in safety due to health systems and patient factors ...................................... 9 10.4. Special Populations ...................................................................................................................................... 9 10.5. Drug Interactions .......................................................................................................................................10 11. Summary of available data on comparative cost1 and cost-effectiveness within the pharmacological class or therapeutic group: ..........................................................................................................................................11 11.1. Range of costs of the proposed medicine................................................................................................11 11.2. Comparative cost-effectiveness presented as range of cost per routine outcome ...............................11 12. Summary of regulatory status of the medicine .................................................................................................11 13. Availability of pharmacopoeial standards (British Pharmacopoeia, International Pharmacopoeia, United States Pharmacopoeia) .......................................................................................................................................11 14. Proposed (new/adapted) text for the WHO Model Formulary .....................................................................11 1 WHO MODEL LIST OF ESSENTIAL MEDICINES APPLICATION Summary statement of the proposal for inclusion, change or deletion: This document proposes the inclusion of the dispersible, scored tablet formulation of Abacavir (as sulfate)/Lamivudine (ABC/3TC) 120mg/60mg for treatment of HIV-1 infection among children living with HIV/AIDS in the WHO Essential Medicines List for Children (EMLc). Both the adult formulation of ABC/3TC 600mg/300mg and a lower strength pediatric formulation ABC/3TC 60mg/30mg are already listed in the EML. The principal reasons for requesting this inclusion are as follows: Children living with HIV infection in resource-limited settings presently have limited treatment options for their infection. Since 2013 WHO Guidelines have recommended Abacavir/Lamivudine (ABC/3TC) as the preferred NRTI backbone in first-line ART in children ages 3-10years and as one of two preferred NRTI backbones for first line in infants and children ages 0-3 years. The WHO’s Interagency Task Team on Prevention and Treatment (IATT) Pediatric Working Group includes the dispersible, scored formulation of ABC+3TC 120mg/60mg as “Optimal” for pediatric treatment of HIV on its Optimized Pediatric ARV list. In comparison to syrups, dispersible solid formulations offer many advantages: More convenient for active pharmaceutical ingredients with insufficient stability in water; More easily transportable and they generate less handling and transportation costs for the same amount of active ingredient (less volume, less weight); Easier to produce and the production costs are less, which makes them more affordable than standard liquid formulations; Can still be used in very young children (0 – 6 months) and can be dispersed in breast milk; Are easy to dispense and they require minimal manipulation by health professionals and parents prior to use which minimizes the risk of errors; and Dispersible with only a small amount of water for administration. Antiretroviral therapy generally requires the use of three or more drugs. This often requires taking a large number of tablets/capsules each day. Fixed-dose combinations (FDCs) of ARV drugs may: Allow for once- or twice-daily dosing using one or two pills, reducing the pill-burden; Increase patient adherence to treatment; Delay the development of resistance; Lower the total cost, including production, storage, transport, dispensing and other health system costs; and Reduce the risk of medication errors by prescribers, dispensers or patients themselves. 2 WHO MODEL LIST OF ESSENTIAL MEDICINES APPLICATION 1. Name of the focal point in WHO submitting or supporting the application: Martina Penazzato, MD, DTMH, MSC, PHD, Paediatric Focal Point for the HIV Department of WHO 2. Name of the organization(s) consulted and/or supporting the application: Clinton Health Access Initiative, Inc. (CHAI) 3. International Nonproprietary Name (INN, generic name) of the medicine: Abacavir (as sulfate)/Lamivudine, ATC code : J05AR02 4. Dosage form or strength proposed for inclusion: Each dispersible, scored tablet contains abacavir (as sulfate) 120mg and lamivudine 60mg (WHO supported). 5. International availability - sources, if possible manufacturers: Abacavir (as sulfate)/Lamivudine 120mg/60mg dispersible, scored tablets are manufactured at: Mylan Laboratories Limited (formerly Matrix Laboratories Limited) H-12 & H-13, MIDC, Waluj, Aurangabad, 431136, Maharashtra India 6. Whether listing is requested as an individual medicine or as an example of a therapeutic group: Since ABC and 3TC are nucleoside reverse transcriptase inhibitor, in this case as a combined product, inclusion within ‘FIXED-DOSE COMBINATIONS’ (6.4.2) is requested. 7. Information supporting the public health relevance 7.1. Epidemiological information on disease burden: Despite an impressive reduction in mother to child transmission of HIV in recent years, 150,000 new pediatric infections occurred in 2015. There are now 1.8 million children living with HIV, the vast majority in sub-Saharan Africa. Evidence shows that in the absence of antiretroviral treatment (ART), over 50% of HIV-infected infant’s progress to AIDS and death by the age of 2 years1, but the introduction of pediatric ART has changed HIV infection in children from a life-threatening illness to a chronic but manageable infection. Despite recognition of the advantages of early treatment, pediatric treatment coverage still only reaches 49% of children eligible for treatment and in 2015 an estimated 110,000 HIV/AIDS related deaths occurred in children <15 years of age2. However, with increasing evidence about the beneficial effects of earlier ART initiation and the release of the 2016 WHO Consolidated Guidelines, new recommendations stress the need for early testing and treatment for all infants and children living with HIV. The global community, led by UNAIDS, now has a target to end the AIDS epidemic by 2030
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