1. WHO - PSM 14/7/2005 Principles for selection of medicines Dr Mary R. Couper Quality Assurance and Safety of Medicines WHO

2. WHO - PSM 14/7/2005 Learning Objectives  The participants will learn the general principles for selection of medicines  The participants will learn about the HIV medicines used in the WHO treatment guidelines  The participants will learn major toxicities of ARVs

3. WHO - PSM 14/7/2005 Product selection

4. WHO - PSM 14/7/2005 Criteria for product selection  Prevalence of disease  Goals of treatment  Evidence of quality, efficacy and safety  Cost-effectiveness  Availability of products in the country

5. WHO - PSM 14/7/2005 Criteria for selection (cont.)  Special groups needing treatment  Stability in certain conditions  Need for special diagnostic or treatment facilities  Training and experience of available personnel

6. WHO - PSM 14/7/2005 Criteria for selection (cont.)  Fixed dose combination should be selected only when the combination has a proven advantage over single compounds  Important to use international nonproprietary names (INNs) instead of brand names

7. WHO - PSM 14/7/2005 Prevalence of HIV/AIDS

8. WHO - PSM 14/7/2005 Prevalence (cont.)  An estimated 6.4 million people are living with HIV/AIDS in South-East Asia in 2004; it is the second highest number of cases in the world after sub-Saharan Africa and is increasing rapidly.  In WPRO an estimated 1.135 million people are HIV-infected

9. WHO - PSM 14/7/2005 Goals in HIV/AIDS Treatment  Improved quality of life with effects for the individual, the family and the society  Reduction of HIV related morbidity and mortality  Restoration and preservation of immunology functions  Maximal and durable suppression of viral replication  Reduced need for medical intervention and support  Prevention/reduction of drug resistant strains of HIV and OI’s

10. WHO - PSM 14/7/2005 Efficacy, Quality and Safety  Efficacy –WHO Model List of Essential Medicines  Quality –WHO prequalification scheme  Safety –WHO Model List of Essential Medicines

11. WHO - PSM 14/7/2005 Cost-Effectiveness and Availability  When assessing cost-effectiveness, the cost of the total treatment, not just the unit cost of the medicines must be considered  The medicine must be available in the country

12. WHO - PSM 14/7/2005 Special Populations  Adults and adolescents  Pregnant women or women of child- bearing age  Children  People with TB & HIV Co-infection  Health and emergency workers after occupational exposure  Victims of sexual assault

13. WHO - PSM 14/7/2005 Other factors influencing selection  Adequate social support and patient care taker available  Adequate food supplies  Adequate health facilities nearby  Appropriate education for the patient re: adherence and side effect issues  Adequate testing and monitoring available

14. WHO - PSM 14/7/2005 Antiretrovirals on WHO ’ s Model List of Essential Medicines  N ucleoside reverse transcript inhibitors –abacavir (ABC) –didanosine (ddl) –didanosine (ddl) –lamivudine (3TC) –lamivudine (3TC) –stavudine (d4T) –stavudine (d4T) –zidovudine (ZDV or AZT)

15. WHO - PSM 14/7/2005 Antiretrovirals on WHO ’ s Model List of Essential Medicines  Non-nucleoside reverse transcriptase inhibitors  Non-nucleoside reverse transcriptase inhibitors –efavirenz (EFV or EFZ) –nevirapine (NVP) –nevirapine (NVP)

16. WHO - PSM 14/7/2005 Antiretrovirals on WHO ’ s Model List of Essential Medicines (cont.)  Protease inhibitors –indinavir (IDV) –lopinavir + ritonavir (LPV/r) –nelfinavir (NFV) –nelfinavir (NFV) –ritonavir ( r ) –ritonavir ( r ) –saquinavir (SQV) –saquinavir (SQV)

17. WHO - PSM 14/7/2005 Considerations that informed the choice of First-Line ARV Regimens  Potency  Side effect profile  Laboratory monitoring requirements  Potential for maintenance of future options  Predicted adherence  Coexistent medical conditions  Pregnancy or risk thereof  Concomitant medications (drug interactions)  Potential for infections with resistant viral strain  Cost and availability

18. WHO - PSM 14/7/2005 WHO Recommended First and Second-Line ARV Regimens for HIV Treatment in Adults/Adolescents * NFV in places without cold chain protease inhibitor: lopinavir + ritonavir (LPV/r) or saquinavir +ritonavir (SQV/r) * nevirapine (NVP) or efavirenz (EFZ) PlusPlus didanosine (ddI) lamivudine (3TC) PlusPlus abacavir (ABC) stavudine (d4T) or zidovudine (ZDV Second-Line Regimen First-Line Regimen

19. WHO - PSM 14/7/2005 WHO Recommended First and Second-Line ARV Regimens for Treatment in Children Protease inhibitor: lopinavir + ritonavir (LPV/r) or nelfinavir (NFV), or saquinavir+ ritonavir (SQV/r) if wt >25 kg nevirapine (NVP) or efavirenz (EFZ) PlusPlus didanosine (ddi) lamivudine (3TC) PlusPlus abacavir (ABC) stavudine (d4T) or zidovudine (ZDV) Second-Line Regimen First-Line Regimen

20. WHO - PSM 14/7/2005 Factors influencing choice

21. WHO - PSM 14/7/2005 SIMPLIFIED GUIDELINES FOR ARV TREATMENT (HIV-1 INFECTION) 1 st Line Regimen ZDV/3TC + EFV 2 nd Line Regimen TDF + ddI + LPV/r If severe CNS symptoms or pregnancy Substitute ZDV to d4T Substitute EFV to NVP If severe anemia Substitute ZDV to ddI (or ABC) If severe anemia and neuropathy or pancreatitis If hepatitis or severe rash Substitute EFV to NFV Therapeutic Failure Substitute LPV/r to NFV (or ATV/r) Substitute TDF to ABC If renal failure If severe dislipidemia If severe GI intolerance Substitute ddI to ABC Substitute LPV/r to SQV/r TB/HIV DISTRICT/REGIONAL LEVEL LOCAL LEVEL

22. WHO - PSM 14/7/2005 Factors influencing change  Toxicity  Treatment failure

23. WHO - PSM 14/7/2005 Prescription Dr A. Who 31 December 2005 Re: Mr Joseph Bloggs R/ 1) abacavir + lamivudine + zidovudine 1 BD 2) atenolol 100 mg/d 3) acetylsalicylic acid 150mg/d 4) simvastatin 10 mg/d 5) bezafibrate 200 mg/d 6) metformin 500 mg/d 7) fluoxetine 50 mg/d 8) sildenafil

24. WHO - PSM 14/7/2005 Common side effects and HAART…  Diabetes  Hypertension  Raised cholesterol, decreased HDL, raised LDL  Endothelial dysfunction  Lipodystrophy, with increased intra- abdominal fat

25. WHO - PSM 14/7/2005 Non Nucleoside Reverse Transcriptase Inhibitors  Nevirapine and Efavirenz - Rash  Common - up to 20%  Stevens Johnson Syndrome -Liver Toxicity : up to 20% of pts on NVP, 2x higher in females, can be fatal. LFTs must be done -Rash -Neuropsychiatric

26. WHO - PSM 14/7/2005 Nucleoside Reverse Transcripatse Inhibitors  Marrow suppression, particularly zidovudine  Neuropathy, particularly stavudine  Pancreatitis, particularly didanosine  Lactic acidosis, particularly stavudine  Myopathy, particularly zidovudine

27. WHO - PSM 14/7/2005 Protease Inhibitors  Lipodystrophy –Fat redistribution –Raised triglycerides and cholesterol –Elevated blood sugar  Metabolic disorders  Nephrolithiasis (Indinavir >30%)  Hepatic disorders