Transcript PSM - World Health Organization

Principles for selection of
medicines
Dr Mary R. Couper
Quality Assurance and Safety of
Medicines
WHO
14/7/2005
WHO - PSM
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
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Product selection
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Criteria for product selection
 Prevalence of disease
 Goals of treatment
 Evidence of quality, efficacy and safety
 Cost-effectiveness
 Availability of products in the country
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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
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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
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Prevalence of HIV/AIDS
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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
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Goals in HIV/AIDS Treatment
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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
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Efficacy, Quality and Safety
 Efficacy
– WHO Model List of Essential Medicines
 Quality
– WHO prequalification scheme
 Safety
– WHO Model List of Essential Medicines
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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
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Special Populations
 Adults and adolescents
 Pregnant women or women of childbearing age
 Children
 People with TB & HIV Co-infection
 Health and emergency workers after
occupational exposure
 Victims of sexual assault
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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
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Antiretrovirals on WHO’s Model List of
Essential Medicines
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Nucleoside reverse transcript
inhibitors
– abacavir (ABC)
– didanosine (ddl)
– lamivudine (3TC)
– stavudine (d4T)
– zidovudine (ZDV or AZT)
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Antiretrovirals on WHO’s Model List
of Essential Medicines
 Non-nucleoside reverse
transcriptase inhibitors
–efavirenz (EFV or EFZ)
–nevirapine (NVP)
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Antiretrovirals on WHO’s Model List
of Essential Medicines (cont.)
 Protease inhibitors
–indinavir (IDV)
–lopinavir + ritonavir (LPV/r)
–nelfinavir (NFV)
–ritonavir ( r )
–saquinavir (SQV)
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Considerations that informed the choice of
First-Line ARV Regimens
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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
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WHO Recommended First and Second-Line ARV
Regimens for HIV Treatment in Adults/Adolescents
First-Line Regimen
Second-Line Regimen
stavudine (d4T) or
zidovudine (ZDV
abacavir (ABC)
Plus
Plus
lamivudine (3TC)
didanosine (ddI)
Plus
Plus
nevirapine (NVP) or
efavirenz (EFZ)
protease inhibitor:
lopinavir + ritonavir (LPV/r) or
saquinavir +ritonavir (SQV/r) *
* NFV in places without cold chain
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WHO Recommended First and Second-Line ARV
Regimens for Treatment in Children
First-Line Regimen
Second-Line Regimen
stavudine (d4T) or
zidovudine (ZDV)
abacavir (ABC)
Plus
Plus
lamivudine (3TC)
didanosine (ddi)
Plus
Plus
nevirapine (NVP) or
efavirenz (EFZ)
Protease inhibitor:
lopinavir + ritonavir (LPV/r) or
nelfinavir (NFV),
or saquinavir+ ritonavir (SQV/r) if
wt >25 kg
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Factors influencing choice
ARV
regimen
stavudine
lamivudine
nevirapine
zidovudine
lamivudine
nevirapine
stavudine
lamivudine
efavirenz
zidovudine
lamivudine
efavirenz
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Use in
Use in TB
women (of
coinfection
childbearing
age or
pregnant)
Yes
Yes but
caution with
rifampicin
Yes
Yes but
caution with
rifampicin
No
Yes
Availability
Laboratory
as 3-drug
monitoring
combination
No
Yes
Yes
No
Yes
Yes
No
No
No
Yes
WHO - PSM
SIMPLIFIED GUIDELINES FOR ARV
TREATMENT (HIV-1 INFECTION)
Substitute
If severe
anemia
ZDV to
d4T
If severe CNS
symptoms or pregnancy
1st Line Regimen
Substitute
ZDV/3TC + EFV
If severe anemia
and neuropathy or
pancreatitis
EFV to NVP
If hepatitis or
severe rash
Therapeutic
Failure
Substitute
EFV to NFV
Substitute ZDV
to ddI (or ABC)
Substitute
If renal
failure
TDF to
ABC
If severe
dislipidemia
TDF + ddI + LPV/r
TB/HIV
Substitute
LPV/r to SQV/r
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2nd Line Regimen
Substitute
LPV/r to NFV
(or ATV/r)
If severe GI intolerance
DISTRICT/REGIONAL
LEVEL
Substitute ddI to ABC
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LOCAL LEVEL
Factors influencing change
 Toxicity
 Treatment failure
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Prescription
Dr A. Who
31 December 2005
Re: Mr Joseph Bloggs
R/
1)
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)
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abacavir + lamivudine + zidovudine 1 BD
sildenafil
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Common side effects and
HAART…
 Diabetes
 Hypertension
 Raised cholesterol, decreased HDL, raised
LDL
 Endothelial dysfunction
 Lipodystrophy, with increased intraabdominal fat
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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
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Nucleoside Reverse Transcripatse
Inhibitors
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Marrow suppression, particularly zidovudine
Neuropathy, particularly stavudine
Pancreatitis, particularly didanosine
Lactic acidosis, particularly stavudine
Myopathy, particularly zidovudine
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Protease Inhibitors
 Lipodystrophy
– Fat redistribution
– Raised triglycerides and cholesterol
– Elevated blood sugar
 Metabolic disorders
 Nephrolithiasis (Indinavir >30%)
 Hepatic disorders
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