leon levin SAPRAA presentation Nov 2011

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PRactical Antiretroviral Medications
in Paediatrics
Dr Leon J. Levin
Head - Paediatric HIV Programmes
Right to Care
New Regimens for DOH and
Private Sector in SA
0-3 years
1st Line
2nd Line
>3years and >10 kg
Abacavir (ABC)
Lamivudine (3TC)
Kaletra®
Abacavir (ABC)
Lamivudine (3TC)
Efavirenz
Expert advice
Zidovudine (AZT)
DDI
Kaletra®
FIRST LINE
• 3TC/ABC/Kaletra
• 3TC/ABC/EFV
Abacavir +3TC Backbone
• Can’t use Tenofovir routinely in children
because of osteopaenia and nephrotoxicity
• Very good long term data from PENTA 5
• Spares Thymidine analogue for next regimen
• Volume of solution is same for both drugs eg
4ml bd
• Can be given once daily in > 3 years
IMPAACT P1060
• 452 children ages 2 to 35 months from India,
Malawi, South Africa, Tanzania, Uganda,
Zambia and Zimbabwe.
• Cohort 1: 164 children SD NVP at birth
• Cohort 2: 287 children who did not receive SDNVP
• Children in each cohort were randomly
selected to receive AZT/3TC/NVP or
AZT/3TC/LPV/r
IMPAACT P1060
Cohort 1 (SD-NVP)
• 2009, interim review showed that the LVP/r-based
regimen was more effective than the NVP-based
regimen in children previously exposed to SD-NVP.
Cohort 2 (No SD-NVP)
NEJM. 14 Oct 2010
• study defined failure occurred in :
– 40.1% of children taking the NVP-based regimen
– only 18.6% of children taking the LPV/r-based regimen
3TC,Lamivudine
Lamivudine
ADVERSE EFFECTS
 Headache
 Fatigue
 Nausea
 Diarrhoea
 Skin rash
 Abdominal Pain
 Pancreatitis
 Peripheral neuropathy
 Neutropaenia
 Elevated Liver enzymes
 Lactic acidosis
 Pure Red Cell Aplasia
Lamivudine
DRUG INTERACTIONS
 TMP/SMX increases 3TC levels
 3TC resistance delays or reverses ZDV resistance
 Do not administer together with FTC
SPECIAL INSTRUCTIONS
 Can be given with or without food
 Store at room temperature
Lamivudine
Lamivudine ( 3TC)
3TC
Previous DOSAGES
Neonates
2 mg/kg/dose 12 hourly
Paediatrics ( >1 month)
4mg/kg/dose 12 hourly
Adolescent/Adult
BW>50kg 150mg 12hrly
BW<50kg 4mg/kg/dose
12 hourly
Lamivudine
Lamividine
• At what weight should we change to adult
tabs?
• 150÷4=37.5kg
• WHO 25kg
• Some experts from 20kg
3TC dosage
• Don't know if lower exposure to 3TC in < 6yrs
is related to reduced virological activity of 3TC
containing ART
• Don't know effects of lower 3TC exposure on
intracellular concentrations
• Prudent to aim for higher dose especially in <6
years until more data
Can 3TC and Abacavir be given once daily?
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Standard adult dosage 3TC 300 mg once daily & Abacavir(ABC) 600mg once daily,
Few data regarding once-daily administration of 3TC & ABC in children.
PENTA-13 trial HIV-infected children 2 to 13 years of age
PENTA 15 trial children 3 to 36 months of age
Both trials were crossover design with doses of lamivudine of 8 mg/kg/once daily
or 4 mg/kg/twice daily and ABC 16mg/kg/dose once daily or 8mg/kg/dose bd.
Area under the curve (AUC)0-24 and clearance values were similar and most
children maintained an undetectable plasma RNA value after the switch.
Arrow Trial substudy. 41 children 3 to 12 years of age (median age 7.6 years) in
Uganda Stable on twice-daily 3TC and ABC- switch to once-daily3TC & ABC, with
median follow-up of 1.15 year.
Equivalent (AUC)0-24 and good clinical outcome (disease stage and CD4 cell count)
after a switch
All three studies enrolled only patients who had low viral load or were “clinically
stable” on twice-daily 3TC & ABC before changing to once-daily dosing
Therefore, some experts support switching to once-daily dosing of 3TC & ABC in
clinically stable patients with undetectable viral load and stable CD4 cell count,
(USA)
Others support the use of once daily 3TC ABC from age 3 years (PENTA)
Antivir Ther.
Antivir Ther. 2010;15(3):297-305., Antivir Ther. 2010;15(8):1115-1124.
2005;10(2):239-
Lamivudine
DOSAGE
Neonates
Lamivudine ( 3TC)
3TC
2 mg/kg/dose 12 hourly
Paediatrics ( >1 month) 4-6 mg/kg/dose 12 hourly
(aim for higher dose)
From 3 years can give
8-12mg/kg/dose once daily
Change to full adult dose at
25kg (some say at 20kg)
Adolescent/Adult
150mg 12hrly
Or 300mg OD
Abacavir
Abacavir
ADVERSE EFFECTS
 Nausea and vomiting
 Fever
 headache
 Diarrhoea
 Hypersensitivity Reaction
 Lactic Acidosis
 Pancreatitis
 Liver enzymes
 Blood glucose
 Triglycerides
Abacavir Hypersensitivity
Reaction
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What is a Hypersensitivity Reaction?
An Allergy
Has anyone ever died of Penicillin Allergy?
Do we still use penicillin?
Has anyone ever died of Abacavir Hypersensitivity
Reaction?
• No
• But there have been deaths from rechallenging
with Abacavir after a reaction
Abacavir Hypersensitivity
Reaction
• Therefore
• If you stop Abacavir for a suspected
Hypersensitivity reaction, you can NEVER give the
patient Abacavir again
Abacavir Hypersensitivity
Reaction
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Fever
Malaise, Aches
Rash
Vomiting
Diarrhoea
Abdominal pain
Cough
Dyspnoea
Sore throat
Symptoms
• Multi system disorder
• Usually occurs within 6 weeks of starting ABC
Abacavir Hypersensitivity
Reaction
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Differential Diagnosis
Measles
Influenza
Pneumonia
Streptococcal Pharyngitis
Scarlet Fever
TB
IRIS
Abacavir Hypersensitivity
Reaction
Incidence
• Hypersensitivity linked to HLA B*5701
• HLA B*5701 rare in Black population
• HSR 5% in whites, 0.2% in Blacks
Abacavir
DRUG INTERACTIONS
 No significant interactions with other ARVs
 Ethanol ABC levels
SPECIAL INSTRUCTIONS
 Can be given without regard to meals
 Warn patient about Hypersensitivity Reaction
 Don’t stop ABC until discussed with HCW
 Do NOT rechallenge with ABC after Hypersensitivity
Reaction
 Therapy should not be interrupted and then restarted
Abacavir
• At what weight should we change to adult
tabs?
• 300÷8=37.5kg
• WHO 25kg
• Some experts from 20kg
DOSAGE
Abacavir
0-3 months
No data
Paediatrics/Adolescents
>3 months
8-10mg/kg/dose bd
(max 300mg bd)
16-20mg/kg/dose once daily
in > 3years
(Max 600mg daily)
Adult dose from 25kg (some
say from 20kg)
300mg bd or 600mg daily
Adult dose
Kivexa
®
• Fixed dose Combination tablet 3TC &
Abacavir
• 300mg 3TC/600mg Abacavir per tablet
• Dose: 1 tablet once a day
• Very large tablet
• Use from 20kg if child can swallow it
• Expensive
Stavudine
Stavudine
ADVERSE EFFECTS
 Headache, GI disturbance, Skin Rashes
Peripheral neuropathy, Pancreatitis, Lactic Acidosis
LIPOATROPHY
SPECIAL INSTRUCTIONS
 Can be administered with or without food
 Decrease dose with renal impairment
 Oral solution needs refrigeration
 Oral solution stable in fridge for 30 days
 Powder from capsules stable in water for 24 hours
 Do not administer together with ZDV
Stavudine
(d4T)
Zerit
BMS
DOSAGE
Neonatal birth to 13 days 0.5mg/kg/dose 12 hourly
Paediatrics > 14 days
(up to 30 kg)
1mg/kg/dose 12 hourly
Adolescent/Adult
30mg 12 hourly
Lopinavir/ritonavir
Lopinavir/ritonavir
PREPARATION
Adult dose
Oral solution
80mg LPV & 20mg RTV per ml
Aluvia 200/50
200mg LPV and 50mg RTV per
capsule
2 tabs bd
Aluvia 100/25
100mg LPV and 25mg RTV per
capsule
4 tabs bd
Lopinavir/ritonavir
DRUG INTERACTIONS
 Numerous interactions due to potent inhibition of
Cytochrome P450 CYP3A4 by RTV
 Check every drug that patient is on for interactions with
LPV/RTV
 Interactions as for Ritonavir
 EFV & NVP serum concentrations of LPV/RTV.
dose
of LPV/RTV .
 Interactions with other PIs. Appropriate doses not
established.
 Solution contains 42% alcohol. Avoid Disulphuram or
metronidazole.
What is the Dose of Kaletra®/Aluvia®
• Ideally Children < 2 years should receive a
dose of LPV of 300mg/m2
• Some paediatricians use a dose of LPV of
300mg/m2 in all paediatric patients
• Dont don't exceed 400mg LPV (unless on
concomitant NNRTI (not > 500mg LPV))
• WHO recommends 230-350mg/m2/dose bd
• Rather aim for upper end of range especially
in younger children
Infants < 6 months of Age
Infants < 6 months of Age
300/75 mg/m2/dose LPV/r provides similar
exposure to that seen in older children, albeit
slightly less than seen in adults
No data in infants < 14 days of age
AIDS 2008, 22:249–255
What about premature infants?
What about premature infants?
• Kaletra oral solution contains 356.3 mg/mL (42% v/v)
ethanol and 152.7 mg/mL propylene glycol.
• LPV is metabolized by CYP3A; both ethanol and propylene
glycol are initially metabolized by alcohol dehydrogenase.
• Reduced hepatic metabolism and renal clearance in
newborns, especially preterm infants, can lead to
accumulation of all 3 ingredients.
• Propylene glycol toxicity can cause bradycardia and cardiac
arrhythmias, central nervous system (CNS) depression,
acute renal failure, and lactic acidosis.
• Acute ethanol toxicity can lead to AV block, cardiac
arrhythmias, CNS depression, and lactic acidosis.
• LPV has been associated with cases of heart block, and PR
and QT interval prolongation.
• Cases of toxicity in neonates, mostly premature, have been
reported to FDA.
CROI 2011. Poster 708
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What about premature infants?
Methods:
Searched the FDA Adverse Event Reporting System (AERS) for all reports of toxicity
in children ≤2 years of age after administration of Kaletra oral solution.
Results:
Found 10 cases in neonates, 8 of whom were premature.
The gestational age was between 28 and 35 weeks in infants born prematurely.
Documented events included cardiac toxicity (bradycardia, complete AV block,
bundle branch block, or cardiac failure; n = 7), acute renal failure (n = 5), increased
serum creatinine (n = 1), elevated serum lactate level (n = 2), hyperkalemia (n = 4),
respiratory failure (n = 2), hypotonia (n = 1), abnormal EEG (n = 1), and CNS
depression (n = 1).
Acute overdoses were described in 2 cases, 1 resulting in death.
Therapy was initiated on the day of birth in 7 neonates, day after birth in 1, day 34
in 1, and unknown in 1. Onset of symptoms occurred within 1 to 6 days (n = 8);
discontinuation of Kaletra resulted in clinical improvement within 1 to 5 days (n =
6).
Conclusions:
This case series shows that premature neonates are at increased risk of LPV,
ethanol, and/or propylene glycol toxicity associated with Kaletra oral solution
administration.
CROI 2011. Poster 708
What about premature infants?
• RECOMMENDATION: The use of Kaletra oral
solution should be avoided in premature babies
until 14 days after their due date, or in full-term
babies younger than 14 days of age unless a
healthcare professional believes that the benefit
of using Kaletra oral solution to treat HIV
infection immediately after birth outweighs the
potential risks. In such cases, FDA strongly
recommends monitoring for increases in serum
osmolality, serum creatinine, and other signs of
toxicity.
Can Kaletra be given once daily in
children
• Adult data conflicting
• Some studies suggest only effective in PI naive
patients with low viral loads
• Adults – only use if < 3 LPV mutations
• Paeds- PI says dont use once daily
CROI 2008. Poster 775; 11th European AIDS Conference, Madrid, 2007.
[Abstract LBPS7/5] ; 11th European AIDS Conference, Madrid, 2007
[Abstract LBPS7/4]
Can Kaletra given once daily in
Children
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Sample sizes have been small
Awaiting KONCERT trial
High viral load issue not fully resolved
Vomiting seems to be a problem early on
Probably best if not done routinely until more
data
• In selected cases may be appropriate
Lopinavir/ritonavir
ADVERSE EFFECTS
• Diarrhoea,headache,asthenia,nausea & vomiting
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Cholesterol & Triglycerides, pancreatitis,hyperglycaemia, hepatitis,
Lipodystrophy
• Arrythmias
SPECIAL INSTRUCTIONS
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Administer solution with food
Dose solution in ml not mg and Aluvia in tablets not mg
Aluvia can be given with or without food (food may enhance tolerabilty)
Do NOT crush or halve Aluvia tablets
Give ddI 1 hour before or 2 hours after LPV/RTV
Solution.Refrigerate. Stable for 6 weeks at room temperature
Give a drink straight after dose of solution.
Aluvia does not require refrigeration
Do not administer to premature babies or infants < 14 days old
Once daily dosing generally not recommended
DOSAGE
Lopinavir/ritonavir
Prematures
Avoid till 2 weeks after due date
Neonates
No data < 14 days. Avoid
Paediatrics
230mg/m2/dose of LPV component
12 hrly
Patients > 6 months not on NVP or
EFV
Paediatrics
Infants < 6 months
Patients on NVP or EFV Or PI exp
300mg/m2/dose of LPV component
12 hrly
Or some say all paediatric patients
Adult/Adolescent
400mg of LPV component 12 hrly
Patients not on NVP or EFV
Adult/Adolescent
Patients on NVP or EFV or PI
experienced
500mg of LPV component 12 hrly
Ritonavir
Ritonavir
SPECIAL INSTRUCTIONS
 Only used as a booster or in addition to Kaletra with TB Rx
 Should never be used as a sole PI
 High incidence of resistance and cross resistance if used as
sole PI
 Check every drug that patient is on for interactions with RTV
 If child can swallow capsules give capsule even if dose is high
 Administer with food
 Give ddI and RTV 1-2 hours apart
 Keep oral solution at room temperature
 Oral solution has 6 month shelf life
 Terrible taste can be disguised by giving RTV with milk,
chocolate milk, vanilla or chocolate pudding, or ice
cream.Coating mouth with peanut butter. Give maple
syrup,cheese or chewing gum after dose.
Ritonavir
ADVERSE EFFECTS
 Nausea, Vomiting , Diarrhoea & abd pain
 Headache
 anorexia
 circumoral paresthesias

Liver enzymes
 Pancreatitis
 Cholesterol and Triglycerides
 Hyperglycaemia
 Lipodystrophy
(RTV)
Norvir
Ritonavir
Abbott
DOSAGE
With comcommitant TB Rx- ¾ Kaletra volume
As PI booster-Depends on PI being boosted
Generally 100mg bd or daily
If child can swallow capsules give capsule even
if overdose
Efavirenz
Adverse effects
Efavirenz
 Skin Rash
 CNS effects
• Insomnia,somnolence,nightmares,confusion,
amnesia, hallucinations,agitation,euphoria
 Raised Liver enzymes
 Teratogenic in monkeys (and humans)
 Lipomastia
SPECIAL INSTRUCTIONS
 Supposed to be given on empty stomach but can generally be
taken with or without food providing it is tolerated well.
 Avoid high fat meals ( Absorption)
 Capsules may be opened and added to soft foods. (Peppery
taste)
 Tablets cannot be crushed. Use generic capsules if child cant
swallow tablets
 Bedtime dosing especially 1st 2-4 weeks
 No data in children < 3 years and < 10kg
Efavirenz
DRUG INTERACTIONS
• mixed inducer/inhibitor of Cytochrome P450 CYP3A4 (More
Inhibitor)
• concentrations of concomitant drugs can be increased or
decreased depending on the specific enzyme pathway involved.
There are multiple drug interactions with efavirenz.
• Before efavirenz is administrated, the patient’s medication
profile should be carefully reviewed for potential drug
interactions with efavirenz.
 Contra-indicated ,terfenadine,midazolam,triazolam,,cisapride,
ergot alkaloids
 Monitor carefully. Warfarin, ethinyl oestradiol
 Rifampicin, phenobarb, phenytoin may decrease EFV levels.
Significance unknown Can still use EFV with TB treatment
 EFV deceases Clarithromycin levels & increases its metabolite.
Rather use Azithromycin with EFV
 PI’s .EFV decreases levels of LPV and ATV. Therefore increase
dose of LPV and only use RTV boosted ATV
Efavirenz
EFV
Stocrin
MSD
DOSAGE
Paediatric Dose
(> 3 years)
Adult /Adolescent dose
15mg/kg/dose nocte
or
10- <15kg 200mg nocte
15- <20kg 250mg nocte
20- <25kg 300mg nocte
25-<32.5kg 350mg nocte
32.5-<40kg 400mg nocte
>= 40kg
600mg nocte
600mg nocte
Efavirenz
EFV
Stocrin
MSD
New WHO DOSAGE
Paediatric Dose
(> 3 years and > 10kg)
10- <15kg 200mg nocte
15- <25kg 300mg nocte
25-<35kg 400mg nocte
> 35kg
600mg nocte
Adult /Adolescent dose
600mg nocte
Weight based vs Body Surface Area
BSA based
• Some drugs weight based eg 3TC,ABC,EFV
• Some drugs BSA based eg LPV/r,NVP,AZT
• BSA dosages more accurately follow growth of
child
• Weight based dosage Charts reasonably
accurate and very convenient
• Use weight based dosages except in special
circumstances eg 3rd line, resistant virus, pt on
rifampicin
Weight Base Dosage Chart
Weight Base Dosage Chart
Advantages
• Only requires weight
• Doses rounded off
Disadvantages
• Developed for Western
Cape – not necessarily ideal
for rest of SA
• Not that accurate for BSA
dosed drugs
• Different doses morning
and evening may impact on
adherence
• Not all dosage forms
catered for e.g. tabs and
syrup
Weight Base Dosage Chart
• Needs work
• Use should be encouraged especially with
inexperienced nurses and doctors
• Meeting of DOH and HIV Clinicians Society 2
December to discuss
Conclusion
• Keep things simple
• Accurate doses vs simplicity and ease of use
• With post marketing research very often
Package insert doses are no long reliable
• Things aren't always as clear as they seem
• Consult a recent good guideline
Zidovudine
Zidovudine
AZT,ZDV) - Retrovir
GlaxoSmithKline
DOSAGE
Premature infants <35 1.5mg/kg/dose(ivi) or 2mg/kg/dose po 12
hourly. Inc to 8hrly at 2 weeks(> 30
weeks
weeks) or 4 weeks (<30 weeks)
Neonates (< 6 weeks) 2mg/kg/dose po 6hrly or
4mg/kg/dose 12 hourly
Paediatrics
180-240mg/m2 /dose 12 hrly
Adolescent/Adult
300mg 12 hourly
Didanosine
Didanosine
SPECIAL INSTRUCTIONS
Buffered Tablets
 Tablets can be chewed or dispersed in 30ml of water or clear apple juice
 Administer tablets on empty stomach ½ hour before or 1 hour after a
meal
 Tablets contain Buffer. Always give at least 2 tablets together to get the
right dose of buffer
 Give Lopinavir/ritonavir 1 hour after or 2 hours before ddI
 Limited data for once daily dosing in children but does aid adherence
Solution
 Oral solution needs to be reconstituted with antacid. Shake well. Is stable
for 30 days in Fridge
EC capsules
 Must still be given on empty stomach
 Can be given together with Aluvia tablets on an empty stomach
 Kaletra solution must still be separated from Videx EC by 1-2 hours
Didanosine
DRUG INTERACTIONS
ddI serum concentrations are increased
when ddI is coadministered with TDF. Avoid
this combination if possible
 Mitochondrial toxicity increased if given with d4TAVOID
 Absorption of Tetracyclines & Fluoroquinolines.
Separate by 2 hours
 ddI Absorption of Protease Inhibitors. Separate
by 1-2 hours or use EC ddI
DOSAGE
Didanosine
(ddI)
Videx
BMS
Neonates (2 weeks to <3
months)
50mg/m2/dose 12hourly
Infants 3 months to 8 months
100 mg/m2/dose 12hourly
Paediatrics
90–150mg /m2/dose 12
hourly
Some experts give 180300 mg/m2/dose once
daily
Adolescent/Adult
BW>60kg 400mg once
daily
BW<60kg 250mg once
daily
Tenofovir
ADVERSE EFFECTS
Osteopaenia
Renal toxicity
Tenofovir
• FDA USA and WHO advocate using TDF from
12 years and 35kg
• USA DHHS guidelines age 12 and > Tanner
stage IV
• SA package insert- from 18 years
• Most experts are reluctant to use it routinely
in children so young.
• Best to reserve for patients with resistance or
Hep B > 12years or routinely from 18 years
NNRTIS
Nevirapine
Nevirapine
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, SPECIAL INSTRUCTIONS
Can be administered with or without food
Can be given concurrently with ddI
Rash normally occurs in 1st 6 weeks
If rash occurs, do not increase dose until rash resolves
Discontinue with severe rash or constitutional
symptoms
• Monitor liver functions 2 weekly for the first 8 weeks
and 3 monthly thereafter
• If child reaches 8years, don’t decrease the dose. Let the
child grow into the correct dose
• If NVP dosing is interrupted for more than 7 days,
restart with once-daily dosing for 14 days and increase
if rash resolved
Nevirapine
DRUG INTERACTIONS
 Induces Cytochrome P450 CYP3A Therefore numerous
potential interactions
 Before nevirapine is administered, the patient’s medication
profile should be carefully reviewed for potential drug
interactions with nevirapine
 Rifampicin -lowers NVP levels significantly. Don’t use
together
 Anticonvulsants – monitor levels
 Oral contraceptives –use other means of birth control
 Don’t use NVP together with Atazanavir boosted or
unboosted
Nevirapine
DOSAGE
Neonates prophylaxis
Paediatrics > 15 days
Adolescent/Adult
BW <2.5kg
BW> 2.5kg
1ml daily
1.5ml daily
Age < 8 year
200mg /m2 /dose 12 hrly
Age >8 year 120-150mg
/m2 bd .
Start daily X 14 days then
increase to full dose
200 mg daily X 14 days ,
then 200mg 12 hrly
Protease Inhibitors (PIs)
Atazanavir
Drug interactions
Atazanavir
• ATV is both a substrate and an inhibitor of the CYP3A4 enzyme system and
has significant interactions with drugs highly dependent on CYP3A4 for
metabolism.
• There is potential for multiple drug interactions with atazanavir. .
• Before atazanavir is administered, the patient’s medication profile should
be carefully reviewed for potential drug interactions with atazanavir.
• Tenofovir decreases atazanavir plasma concentrations. Only ritonavirboosted atazanavir should be used in combination with tenofovir.
• NNRTIs: Efavirenz, etravirine, and nevirapine decrease atazanavir plasma
concentrations significantly. Nevirapine and etravirine should not be
coadministered to patients receiving ATV . Efavirenz should not be
coadministered with atazanavir in treatment-experienced patients but
may be used in combination with atazanavir 400 mg plus ritonavir
boosting in treatment-naive adults.
• Atazanavir absorption is dependent on low gastric pH. When atazanavir is
administered with medications that alter gastric pH, dosage adjustment is
indicated
Special Instructions
Atazanavir
• Generally only use boosted with RTV esp in children< 13 years
• Administer ATV with food to enhance absorption.
• Use ATV with caution in patients with pre-existing cardiac
conduction system disease or with other drugs known to prolong
the PR interval (e.g., calcium channel blockers, beta-blockers,
digoxin, verapamil).
• ATV absorption is dependent on low gastric pH; therefore, when
ATV is administered with medications that alter gastric pH, special
dosing information is indicated
• Give ATV at least 2 hours before or 1 hour after antacid or ddI
tablet administration.
• Only RTV-boosted ATV should be used in combination with TDF or
EFV
• Nevirapine and etravirine should not be coadministered to patients
receiving atazanavir (with or without ritonavir
Atazanavir
Dosages
AGE
weight
Dosage given with food
Neonates
Dont administer to neonates because of risks
associated with hyperbilirubinemia (kernicterus)
Paediatric: 6 - 18 years
205 mg/m2 OD
Adolescent (≥18–21
years of age)/adult
dose:
15 - <25 kg
ATV 150mg + RTV 80 mg OD
25 - <32 kg
ATV 200mg + RTV 100 mg OD
32 - <35 kg
ATV 300mg + RTV 100 mg OD
>35 kg
ATV 300 mg+ RTV 100 mg OD
Antiretroviral-naive patients:
ATV 300 mg + RTV 100 mg OD or ATV 400 mg OD
Antiretroviral-experienced patients:
ATV 300 mg + RTV 100 mg OD
ATV +EFV adults in therapy-naive patients only:
ATV 400 mg + RTV 100 mg + EFV 600 mg OD
Conclusion
• Keep things simple
• Accurate doses vs simplicity and ease of use
• With post marketing research very often
Package insert doses are no long reliable
• Things aren't always as clear as they seem
• Consult a recent good guideline
Practical Resources
• SA HIV Clinicians Society
– http://www.sahivsoc.org/
– sahivsoc@gomail.co.za
• Right to Care Paediatric ARV Helpline
– 0823526642
• Dr Leon Levin leon.levin@righttocare.org
• SA HIV Clinicians Paeds Guidelines
http://www.sajhivmed.org.za/index.php/sajhivmed
• American Guidelines www.aidsinfo.nih.gov
• PENTA (European) Guidelines www.ctu.mrc.ac.uk/PENTA
• WHO Guidelines www.who.int
DOH Guidelines http://www.doh.gov.za/docs/hiv-f.html
• Liverpool drug interactions Website:
www.hiv-druginteractions.org
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