Transcript Module IV Session 5 Prescribing ARVs

Prescription and Use of
Paediatric Antiretroviral
Drugs (ARVs) for the
Treatment of HIV in Children
Prescribing ARVs
Key Questions:
• How do we select the appropriate regimen?
• How do we select the most effective ARV
formulations?
• How do we prescribe appropriate doses of
each formulation based on the child’s weight?
Three Steps to Prescribing Ped ARVs
Once a child has been identified as eligible for
ART and prepared to initiate treatment, there
are three steps to prescribing ARVs:
1. Identify the proper regimen to prescribe
based on National Guidelines and clinical condition of the child
2. Select which ARV formulations to use
based on the regimen selected
3. Use the Paediatric ARV Dosing Chart to prescribe
the proper amount of each formulation
based on the child’s weight
Review of Regularly Used ARVs
Drug Class
Drug Name
Abbreviation
NRTI
Zidovudine
AZT
Abacavir
ABC
Stavudine
d4T
Lamivudine
3TC
Nevirapine
NVP
Efavirenz
EFV
Lopinavir +
Ritonavir
LVP/r
NNRTI
Protease
Inhibitor (PI)
Step 1: Identify the right regimen
Recommended ART Regimens
Select the appropriate
regimen based on the
for Children
national ART
1st Line Therapy
guidelines:
Preferred
AZT + 3TC + (NVP or EFV)*
AZT based
regimen should
always be used
to initiate
children on 1st
line, unless the
child is anemic
1st Alternative
ABC + 3TC + (NVP or EFV)*
2nd Alternative
d4T + 3TC + (NVP or EFV)*
2nd Line Therapy
If AZT or d4T used in 1st
Line
ABC + 3TC + LPV/r
If ABC used in 1st Line
(AZT or d4T) + 3TC + LPV/r
* For all infants exposed to NVP in PMTCT, LPV/r
should be substituted into 1st line for NVP or EFV
Step 2: Choose the right formulations
• Pediatric ARVs are available in three kinds of
formulations:
1. Oral suspensions
i.e. AZT syrup
2. Single drug tablets
i.e. 3TC 150mg
3. Fixed-dose combination tablets
i.e. Triomune Baby
(d4T 6mg + 3TC 30mg + NVP 50mg)
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Step 2: Choose the right formulations
Many different products are available to choose from…
Single Drug
Formulations
AZT
ABC
d4T
3TC
NVP
EFV
LPV/r
• AZT
syrup
• ABC
syrup
• d4T
syrup
• 3TC
syrup
• NVP
syrup
• EFV
syrup
• LPVr
syrup
• AZT
100mg
• ABC
60mg
• d4T
15mg
• 3TC
150mg
• NVP
200mg
• EFV
200mg
• LPVr
125mg
• EFV
100mg
• LPVr
250mg
• AZT
300mg
-
• d4T
20mg
-
-
AZT / 3TC / NVP 60/30/50mg
AZT / 3TC 60/30mg
Fixed-Dose
Combinations
ABC / 3TC 60/30mg
d4T / 3TC / NVP 6/30/50mg
d4T / 3TC / NVP 12/60/100mg
d4T / 3TC 6/30mg
d4T / 3TC 12/60mg
Step 2: Choose the right formulations
However, fixed-dose combinations should always be
used when possible due to their many advantages
over oral suspensions and single tabs:
•Easier to dose, as you do not have to give instructions for
multiple drugs
•Better control in administration than oral solutions
•More versatile – can be crushed, dispersed in food or
water, or swallowed as a tablet
•More neutral taste
•Lower tablet burden/volumes
•Easier to check adherence
•Easier to transport/store with no need for refrigeration
•Easier to order due to reduced number of formulations
Step 2: Choose the right formulations
Fixed-dose combinations can and should be used to
build every recommended regimen:
Recommended
Regimen
Regimen using fixed-dose combinations
AZT + 3TC + NVP
• AZT/3TC/NVP 60/30/50mg
AZT + 3TC + EFV
• AZT/3TC 60/30mg + EFV (200mg or 100mg)
AZT + 3TC + LPVr
• AZT/3TC 60/30mg + LPVr (solution / 125mg)
ABC + 3TC + NVP
• ABC/3TC 60/30mg + NVP (solution / 200mg)
ABC + 3TC + EFV
• ABC/3TC 60/30mg + EFV (200mg or 100mg)
ABC + 3TC + LPVr
• ABC/3TC 60/30mg + LPVr (solution / 125mg)
d4T + 3TC + NVP
• d4T/3TC/NVP 6/30/50mg
d4T + 3TC + EFV
• d4T/3TC 6/30mg + EFV (200mg or 100mg)
d4T + 3TC + LPVr
• d4T/3TC 6/30mg + LPVr (solution / 125mg)
Fixed-dose combination tablets can be split, crushed,
and most of them dispersed in water:
Formulation
Can be split?
Can be
crushed?
Can be
dispersed in
water?
AZT/3TC/NVP
60/30/50mg
AZT/3TC 60/30mg
X
ABC/3TC 60/30mg
X
d4T/3TC/NVP 6/30/50mg
d4T/3TC 6/30mg
Step 2: Choosing the right formulation
Fixed-dose combination tablets can be split, crushed,
and most of them dispersed in water:
Formulation
Can be split?
Can be
crushed?
Can be
dispersed in
water?
AZT/3TC/NVP
60/30/50mg
AZT/3TC 60/30mg
X
ABC/3TC 60/30mg
X
d4T/3TC/NVP 6/30/50mg
d4T/3TC 6/30mg
Exercise 1 – Administering FDC
tablets
• Take three fixed dose
combination tablets:
• Split the first one in half
• Crush the second with a
spoon
• Put the third in a cup and add
a few MLs of water—watch it
dissolve in the water
Which was difficult to do?
Which is easiest to teach to a mother of an HIV+ child?
Step 2: Choose the right formulation
When using fixed-dose combinations, you only require
the following pediatric formulations at your facility:
Fixed-dose combinations
Single formulations
1. AZT/3TC/NVP 60/30/50mg
6. EFV 200mg
2. AZT/3TC 60/30mg
7. EFV 100mg
3. ABC/3TC 60/30mg
8. NVP solution
(for use with ABC)
4. d4T/3TC/NVP 6/30/50mg
9. LPVr solution
5. d4T/3TC 6/30mg
10. LPVr 125mg
* Will also need NVP 200mg, but that is also used for adults so should be readily
available
Step 3: Prescribe the right dose
• The first step in dosing ARVs for children is determining
the weight of the child—doses need to be increased as
the child grows
• There are 6 major weight ranges to use when dosing:
• 3 – 5.9kg
• 6 – 9.9kg
• 10 – 13.9kg
• 14 – 19.9kg
• 20 – 24.9kg
• 25kg and above
You must weigh a child each time he/she comes to the clinic
to check if he/she has reached the next weight range
Step 3: Prescribe the right dose
Dosing of fixed-dose combinations is harmonized across
drug types…
Weight ranges (kg)
3-5.9
6-9.9
1013.9
1419.9
2024.9
2529.9
• AZT 3TC NVP
(60/30/50mg)
• AZT/3TC
(60/30mg)
1
1.5
2
2.5
3
1
adult
tab
• ABC/3TC
(60/30mg)
1
1.5
2
2.5
3
1
adult
tab
• d4t 3TC NVP
(6/30/50mg)
• d4t/3TC
(6/30mg)
1
1.5
2
2.5
3
1
adult
tab
The number of tablets included in the
table above is given twice daily
Step 3: Prescribe the right dose
Dosing aide provides number of tablet to give for each formulation
(including CTX) across all weight ranges:
Exercise 2:Use your Paediatric ARV Dosing Chart to
answer the following about dosing FDCs:
1. For a 9kg child on the regimen AZT + 3TC + NVP:
a. Which formulation would you use for this child?
Triple FDC
b. What is the average daily dose of this formulation?
1.5 BD
c. How many tablets should you dispense for 30 days?
90 tablets
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Exercise 2: Dosing Ped FDCs (continued)
2. For a 16kg child on the regimen ABC + 3TC + EFV:
a. Which formulations would you use for this child?
Dual FD of ABC + 3TC, and single dose tablet of EFV
b. What is the average daily dose of these
formulations?
ABC/3TC 2.5 BD, 300mg of EFV
c. How many tablets of each formulation should you
dispense for 30 days?
ABC + 3TC = 150 tablets
For EFV, first need to decide on the best formulation
for the patient. Is there a 300 mg tablet? NO.
Exercise 3 – Dosing syrups vs FDCs
You have a patient who weighs 5 kg.
You prescribe a regimen of AZT/3TC/NVP.
1st: Calculate the AM and PM dose if you were to use syrups.
What is the total volume needed for a 30-day supply?
AZT = 360 ml, 3TC = 180 ml , NVP = 300 ml
2nd: Calculate the AM and PM dose if you were to use FDCs.
What is the total number of tablets needed for a 30-day supply?
FDC = 60 tablets
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We need to consider what the patient
will have to go home with…
Using FDCs for lead-in NVP dosing
•Current recommendation for any patient initiating
NVP-based ART for the first time is to dose the NVP
once daily for the first two weeks to reduce risk of
associated rash
•During 2 week lead in period, children should get the
appropriate triple FDC as the AM dose, and the
equivalent dual FDC for the PM dose
Morning
Evening
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AZT/3TC/NVP
AZT/3TC
Exercise 4 – Lead-in dosing with FDCs
4 year old child
Weight 12.5kg
Eligible for ART
Formulation?
AZT/3TC/NVP
60/30/50mg
Dose?
2 am / 2 pm
Lead-in?
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28 tabs of triple
FDC, 28 tabs of
dual FDC
Initiate leadin for 2
weeks
120 tabs of
triple FDC
Initiate full
ART
120 tabs of triple
FDC until weight
increases to 15kg
Follow up
Case Study Practice
• Let’s examine a few real cases and correctly determine:
– What regimen should they be given?
– What formulations should you use?
– How much would you prescribe of each formulation?
Case 1 Osofia is 3 month old and weighs 5 kg. She was given
single dose NVP for PMTCT but went on to get HIV infected.
Currently you don’t have kaletra syrup at your facility.
Initiate the patient on treatment in the recommended way.
• What regimen should she be given?
AZT/3TC/NVP
• What formulations should you use?
Triple FDC of AZT/3TC/NVP and Duo fixed dose AZT/3TC
• How much would you prescribe of each formulation?
Triple FDC AZT/3TC/NVP-1 od and AZT/3TC 1 od
• If you are giving them a 14-day supply, how many tablets
should you give them of each formulation?
AZT/3TC/NVP 14 tablet and AZT/3TC -14 tablets
Case 2 IBU is a 6 month old infant who is HIV
positive. He received NVP syrup for prophylaxis.
He is not anemic and the weight is 6 kg. You
have all the drugs available in the facility.
• What regimen should they be given?
AZT/3TC/Kaletra
• What formulations should you use?
FDC- AZT/3TC and Syrup for kaletra
• How much would you prescribe of each formulation?
AZT/3TC- 1.5 BD and Kaletra 1.5 mls BD
• If you are giving them a 30-day supply, how many
tablets should you give them of each formulation?
AZT/3TC 90 tablets and Kaletra 90mls for 30 days
Case 3Mary is 4 years old and weighs 15 kg. She was diagnosed with HIV. She is
anemic and you don’t have abacavir in your facility.
• What criteria would you use to determine if Mary is eligible for ARVs?
CD4 %- less than 25% or CD count <750 or WHO clinical stage 3 or 4
If she is eligible for ARVs
• What regimen should she be given?
D4T/3TC/NVP
• What formulations should you use?
Triple FDC of D4T/3TC/NVP baby and Duo FDC D4T/3TC baby
•
How much would you prescribe of each formulation?
D4T/3TC/NVP 2.5 A.M. and D4T/3TC 2.5 P.M.
•
If you are giving her a 14-day supply, how many tablets should you give her of
each formulation?
D4T/3TC/NVP 35 tablets and D4T/3TC 35 tablets
•
If she comes back for after 14 days as she has tolerated the drugs what
formulation would you give, what dose and how many tablets would you dispense
for 30 days?
D4T/3TC/NVP baby , 2.5 BD and 150 mg
Case 4 Aki is a 7 year old HIV positive boy. He is anemic and is eligible
to start ARV’s. You have abacavir in you facility. He is 18 kg.
• What regimen should they be given?
ABC/3TC/NVP or ABC/3TC/EFV
• What formulations should you use?
Duo FDC for ABC/3TC and single tablets NVP
or
Duo FDC ABC/3TC and single tablet EFV
• How much would you prescribe of each formulation?
ABC/3TC 2.5 BD and Tab NVP 1 in morning and 0.5 in Evening
Or
ABC/3TC 2.5 BD and Tab EFV(600mg) 0.5 mg od
• If you are giving them a 30-day supply, how many tablets should
you give them of each formulation?
ABC/3TC 150 tablets and NVP 45 tablets
Or
ABC/3TC 150 tablets and EFV 15 tablets
• Case 5
Popo is a 9 year old boy who is HIV+. He is not on ARVs
and was diagnosed with TB. His weight is 21kg.
He is eligible to start ARVs.
• When would you start him on ARVs
2-8 weeks after initiation of anti TB treatment
• What regimen should they be given?
AZT/3TC/EFV
• What formulations should you use?
Dou FDC AZT/3TC and single tablet EFV
• How much would you prescribe of each formulation?
AZT/3TC 3BD and EFV (600mg) 0.5 od
• If you are giving them a 30-day supply, how many
tablets should you give them of each formulation?
AZT/3TC 180 tablets and EFV(600mg) 15 tablets
Summary
• Use the national ART guidelines to select
which regimen to use
– Always check for anemia to determine if AZT is
acceptable
• When selecting formulations, always use fixed-dose
combinations where possible
– Easier to dose and better for the patient
• Always take the child’s weight, and use the
Ped ARV dosing chart to determine how
much to prescribe of each formulation