WHO - PSMWHO - PSM

Principles for selection of Principles for selection of medicinesmedicines

Dr Mary R. CouperDr Mary R. CouperQuality Assurance and Safety of Quality Assurance and Safety of

MedicinesMedicinesWHOWHO

WHO - PSMWHO - PSM

Learning ObjectivesLearning Objectives

The participants will learn the general The participants will learn the general principles for selection of medicinesprinciples for selection of medicines

The participants will learn about the HIV The participants will learn about the HIV medicines used in the WHO treatment medicines used in the WHO treatment guidelines guidelines

The participants will learn major toxicities of The participants will learn major toxicities of ARVsARVs

WHO - PSMWHO - PSM

Product selectionProduct selection

WHO - PSMWHO - PSM

Criteria for product selectionCriteria for product selection

Prevalence of diseasePrevalence of disease Goals of treatmentGoals of treatment Evidence of quality, efficacy and safetyEvidence of quality, efficacy and safety Cost-effectivenessCost-effectiveness Availability of products in the countryAvailability of products in the country

WHO - PSMWHO - PSM

Criteria for selection (cont.)Criteria for selection (cont.)

Special groups needing treatmentSpecial groups needing treatment Stability in certain conditionsStability in certain conditions Need for special diagnostic or treatment Need for special diagnostic or treatment

facilitiesfacilities Training and experience of available Training and experience of available

personnelpersonnel

WHO - PSMWHO - PSM

Criteria for selection (cont.)Criteria for selection (cont.)

Fixed dose combination should be Fixed dose combination should be selected only when the combination has selected only when the combination has a proven advantage over single a proven advantage over single compoundscompounds

Important to use international Important to use international nonproprietary names (INNs) instead of nonproprietary names (INNs) instead of brand namesbrand names

WHO - PSMWHO - PSM

Prevalence of HIV/AIDSPrevalence of HIV/AIDS

WHO - PSMWHO - PSM

Prevalence (cont.)Prevalence (cont.)

An estimated 6.4 million people are living An estimated 6.4 million people are living with HIV/AIDS in South-East Asia in 2004; it with HIV/AIDS in South-East Asia in 2004; it is the second highest number of cases in is the second highest number of cases in the world after sub-Saharan Africa and is the world after sub-Saharan Africa and is increasing rapidly.increasing rapidly.

In WPRO an estimated 1.135 million people In WPRO an estimated 1.135 million people are HIV-infectedare HIV-infected

WHO - PSMWHO - PSM

Goals in HIV/AIDS TreatmentGoals in HIV/AIDS Treatment Improved quality of life with effects for the Improved quality of life with effects for the

individual, the family and the societyindividual, the family and the society Reduction of HIV related morbidity and mortalityReduction of HIV related morbidity and mortality Restoration and preservation of immunology Restoration and preservation of immunology

functionsfunctions Maximal and durable suppression of viral Maximal and durable suppression of viral

replicationreplication Reduced need for medical intervention and Reduced need for medical intervention and

supportsupport Prevention/reduction of drug resistant strains of Prevention/reduction of drug resistant strains of

HIV and OI’sHIV and OI’s

WHO - PSMWHO - PSM

Efficacy, Quality and SafetyEfficacy, Quality and Safety

Efficacy Efficacy – WHO Model List of Essential MedicinesWHO Model List of Essential Medicines

QualityQuality– WHO prequalification schemeWHO prequalification scheme

SafetySafety– WHO Model List of Essential MedicinesWHO Model List of Essential Medicines

WHO - PSMWHO - PSM

Cost-Effectiveness and AvailabilityCost-Effectiveness and Availability

When assessing cost-effectiveness, the cost When assessing cost-effectiveness, the cost of the total treatment, not just the unit cost of of the total treatment, not just the unit cost of the medicines must be consideredthe medicines must be considered

The medicine must be available in the The medicine must be available in the countrycountry

WHO - PSMWHO - PSM

Special PopulationsSpecial Populations

Adults and adolescentsAdults and adolescents Pregnant women or women of child-Pregnant women or women of child-

bearing agebearing age ChildrenChildren People with TB & HIV Co-infectionPeople with TB & HIV Co-infection Health and emergency workers after Health and emergency workers after

occupational exposure occupational exposure Victims of sexual assaultVictims of sexual assault

WHO - PSMWHO - PSM

Other factors influencing selectionOther factors influencing selection

Adequate social support and patient care Adequate social support and patient care taker availabletaker available

Adequate food suppliesAdequate food supplies Adequate health facilities nearbyAdequate health facilities nearby Appropriate education for the patient re: Appropriate education for the patient re:

adherence and side effect issues adherence and side effect issues Adequate testing and monitoring availableAdequate testing and monitoring available

WHO - PSMWHO - PSM

Antiretrovirals on WHO’s Model List of Antiretrovirals on WHO’s Model List of Essential MedicinesEssential Medicines

NNucleoside reverse transcript ucleoside reverse transcript inhibitorsinhibitors

– abacavir (ABC)abacavir (ABC)

– didanosine (ddl)didanosine (ddl)    

– lamivudine (3TC)lamivudine (3TC)    

– stavudine (d4T)stavudine (d4T)    

– zidovudine (ZDV or AZT)zidovudine (ZDV or AZT)

WHO - PSMWHO - PSM

Antiretrovirals on WHO’s Model List Antiretrovirals on WHO’s Model List of Essential Medicinesof Essential Medicines

Non-nucleoside reverse Non-nucleoside reverse transcriptase inhibitors transcriptase inhibitors 

–efavirenz (EFV or EFZ)efavirenz (EFV or EFZ)

–nevirapine (NVP)nevirapine (NVP)    

WHO - PSMWHO - PSM

Antiretrovirals on WHO’s Model List Antiretrovirals on WHO’s Model List of Essential Medicines (cont.)of Essential Medicines (cont.)

Protease inhibitorsProtease inhibitors

– indinavir (IDV)indinavir (IDV)

– lopinavir + ritonavir (LPV/r)lopinavir + ritonavir (LPV/r)

–nelfinavir (NFV)nelfinavir (NFV)    

–ritonavir ( r )ritonavir ( r )    

–saquinavir (SQV)saquinavir (SQV)    

WHO - PSMWHO - PSM

Considerations that informed the choice of Considerations that informed the choice of First-Line ARV RegimensFirst-Line ARV Regimens

PotencyPotency Side effect profileSide effect profile Laboratory monitoring requirementsLaboratory monitoring requirements Potential for maintenance of future optionsPotential for maintenance of future options Predicted adherencePredicted adherence Coexistent medical conditions Coexistent medical conditions Pregnancy or risk thereof Pregnancy or risk thereof Concomitant medications (drug interactions)Concomitant medications (drug interactions) Potential for infections with resistant viral strainPotential for infections with resistant viral strain Cost and availabilityCost and availability

WHO - PSMWHO - PSM

WHO Recommended First and Second-Line ARV WHO Recommended First and Second-Line ARV Regimens for HIV Treatment in Adults/AdolescentsRegimens for HIV Treatment in Adults/Adolescents

* NFV in places without cold chain

protease inhibitor: protease inhibitor:

lopinavir + ritonavir (LPV/r) or lopinavir + ritonavir (LPV/r) or saquinavir +ritonavir (SQV/r) *saquinavir +ritonavir (SQV/r) *

nevirapine (NVP) or nevirapine (NVP) or efavirenz (EFZ)efavirenz (EFZ)

PlusPlusPlusPlus

didanosine (ddI)didanosine (ddI)lamivudine (3TC)lamivudine (3TC)

PlusPlusPlusPlus

abacavir (ABC)abacavir (ABC)stavudine (d4T) or stavudine (d4T) or zidovudine (ZDVzidovudine (ZDV

Second-Line RegimenSecond-Line RegimenFirst-Line RegimenFirst-Line Regimen

WHO - PSMWHO - PSM

WHO Recommended First and Second-Line ARV WHO Recommended First and Second-Line ARV Regimens for Treatment in ChildrenRegimens for Treatment in Children

Protease inhibitor: Protease inhibitor:

lopinavir + ritonavir (LPV/r) or lopinavir + ritonavir (LPV/r) or nelfinavir (NFV), nelfinavir (NFV),

or saquinavir+ ritonavir (SQV/r) if or saquinavir+ ritonavir (SQV/r) if wt wt >>25 kg25 kg

nevirapine (NVP) or nevirapine (NVP) or efavirenz (EFZ)efavirenz (EFZ)

PlusPlusPlusPlus

didanosine (ddi)didanosine (ddi)lamivudine (3TC)lamivudine (3TC)

PlusPlusPlusPlus

abacavir (ABC)abacavir (ABC)stavudine (d4T) or stavudine (d4T) or zidovudine (ZDV)zidovudine (ZDV)

Second-LineSecond-Line RegimenRegimenFirst-Line RegimenFirst-Line Regimen

WHO - PSMWHO - PSM

Factors influencing choiceFactors influencing choice ARV regimen

Use in women (of childbearing age or pregnant)

Use in TB coinfection

Availability as 3-drug combination

Laboratory monitoring

stavudine lamivudine nevirapine

Yes Yes but caution with rifampicin

Yes No

zidovudine lamivudine nevirapine

Yes Yes but caution with rifampicin

Yes Yes

stavudine lamivudine efavirenz

No Yes No No

zidovudine lamivudine efavirenz

No Yes No Yes

WHO - PSMWHO - PSM

SIMPLIFIED GUIDELINES FOR ARV SIMPLIFIED GUIDELINES FOR ARV TREATMENT TREATMENT (HIV-1 INFECTION)(HIV-1 INFECTION)

1st Line Regimen

ZDV/3TC + EFV

2nd Line Regimen

TDF + ddI + LPV/r

If severe CNS symptoms or pregnancySubstitute

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

WHO - PSMWHO - PSM

Factors influencing changeFactors influencing change

ToxicityToxicityTreatment failureTreatment failure

WHO - PSMWHO - PSM

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

 

WHO - PSMWHO - PSM

Common side effects and Common side effects and HAART…HAART…

DiabetesDiabetes HypertensionHypertension Raised cholesterol, decreased HDL, raised Raised cholesterol, decreased HDL, raised

LDLLDL Endothelial dysfunctionEndothelial dysfunction Lipodystrophy, with increased intra-Lipodystrophy, with increased intra-

abdominal fatabdominal fat

WHO - PSMWHO - PSM

Non Nucleoside Reverse Non Nucleoside Reverse Transcriptase InhibitorsTranscriptase Inhibitors

Nevirapine and EfavirenzNevirapine and Efavirenz- Rash- Rash

Common - up to 20%Common - up to 20% Stevens Johnson SyndromeStevens Johnson Syndrome

- Liver Toxicity : Liver Toxicity : up to 20% of pts on NVP, 2x up to 20% of pts on NVP, 2x higher in females, can be fatal. LFTs must be higher in females, can be fatal. LFTs must be donedone

- RashRash- NeuropsychiatricNeuropsychiatric

WHO - PSMWHO - PSM

Nucleoside Reverse Transcripatse Nucleoside Reverse Transcripatse InhibitorsInhibitors

Marrow suppression, particularly zidovudineMarrow suppression, particularly zidovudine Neuropathy, particularly stavudineNeuropathy, particularly stavudine Pancreatitis, particularly didanosinePancreatitis, particularly didanosine Lactic acidosis, particularly stavudineLactic acidosis, particularly stavudine Myopathy, particularly zidovudineMyopathy, particularly zidovudine

WHO - PSMWHO - PSM

Protease InhibitorsProtease Inhibitors

LipodystrophyLipodystrophy– Fat redistributionFat redistribution– Raised triglycerides and cholesterolRaised triglycerides and cholesterol– Elevated blood sugarElevated blood sugar

Metabolic disordersMetabolic disorders Nephrolithiasis (Indinavir >30%)Nephrolithiasis (Indinavir >30%) Hepatic disordersHepatic disorders