Abacavir sulfate
is amedications
used to
prevent and treat HIV/AIDS. Similar to othernucleoside analog reverse-transcriptase inhibitors
,abacavir
sulfate isused
together with other HIVmedications
, and is not recommended by itself.Dosing
Adult Dose:Important Note:
Perform HLA-B*5701 testing prior to initiation or reinitiating of
abacavir
(unless patients have a previously documented HLA-B*5701 al≤ assessment) to reduce the risk of hypersensitivity reaction.Use is
contraindicated in patients who test positive for HLA-B*5701.HIV infection
:300 mg ORALLY twice daily or 600 mg ORALLY once daily
Pediatric dosing:
Important Note:
Perform HLA-B*5701 testing prior to initiation or reinitiating of
abacavir
(unless patients have a previously documented HLA-B*5701 al≤ assessment) to reduce the risk ofhypersensitivity reaction
.Use is
contraindicated in patients who test positive for HLA-B*5701.HIV infection
:3 months or older,
oral solution
:8 mg
/kgORALLY
twice daily
or16 mg
/kgORALLY
once dailyMaximum
600 mg
/day (manufacturer dose)3 months or older, tablets:
14 to less than 20 kg:
300
mg
ORALLY
once daily or in 2 divided doses20 kg to less than
25 kg
:450 mg
ORALLY
once daily or150 mg
in AM and300
mg
in PM25 kg
or greater:600 mg
ORALLY
once daily or in 2 divided doses (manufacturer dose)3 months or older,
tablets
:14 to 21 kg,
150 mg
ORALLY
twice daily
Greater than 21 to less than
30 kg
:150 mg
ORALLY
in AM and300
mg
ORALLY
in PM30 kg or greater:
300 mg ORALLY twice daily (Guideline dose)
3 months or older, with undetectable viral load and stable CD4 cell counts for more than 24 weeks, oral solution or tablets, 16 to 20 mg/kg ORALLY once daily up to Maximum 600 mg/day (guideline dose)
Indications
FDA-Labeled Indications:HIV infection
Mechanism of Action
abacavir
is a carbocyclic synthetic nucleoside analogue.abacavir
is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA. The lack of a 3′-OH group in the incorporated nucleotide analogue prevents the formation of the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. CBV-TP is a weak inhibitor of cellularvDNA polymerases α, β, and γ.Adverse Effect
Common:Dermatologic:
Rash (7%)
Gastrointestinal:
Nausea (7% to 19%)
Vomiting
Neurologic:
Headache (7% to 13%)
Sleep disorder (10%)
Respiratory:
Upper respiratory infection (5%)
Other:
Fatigue (7% to 12%)
Fever (6% to 9%)
Serious:
Cardiovascular:
Disorder of cardiovascular system
Myocardial infarction
Dermatologic:
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Endocrine metabolic:
Lactic acidosis
Hepatic:
Hepatomegaly (Severe)
Hepatotoxicity
Steatosis of liver
Immunologic:
hypersensitivity reaction (8%)
Contraindication
HLA-B*5701 al≤-positive patientsHypersensitivity to abacavir
or any other component of the productModerate or severe hepatic impairment
Interaction
Ethanol:abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the
elimination of abacavir
causing an increase in overall exposureMethadone:
The addition of methadone has no clinically significant
effect on
thepharmacokinetic properties of abacavir
. In a study of 11 HIV-infected patients receiving methadone-maintenance therapy with600 mg of abacavir
twice daily(twice the currently recommended dose), oral methadone clearance increased. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.Phamacokinetics
Absorption:Time of Maximum Plasma Concentration
(Tmax
):Oral: 0.7 to 1.7 hours
Bioavailability
, oral: 83%Effects of food
: No significant effectDistribution:
Protein
binding,plasma proteins
: Approximately 50%Volume of Distribution
(Vd): 0.86 L/kgMetabolism:
CYP450 independent, alcohol dehydrogenase, glucuronyl transferase
Metabolites:
Active: Carbovir triphosphate
Inactive: 5′-carboxylic acid
Inactive: 5′-glucuronide
Excretion:
Fecal
: 16%Renal
: 81% changed; 1.2% unchangedTotal body clearance
: 0.8 L/hour/kgElimination:
1.54 +/- 0.63 hours
Precaution
Cardiovascular:Myocardial infarction
may occur; consider underlying risk ofcoronary heart disease
and minimize modifiable risks (e.g.,hypertension
,hyperlipidemia
,diabetes mellitus
, andsmoking
)Endocrine and metabolic:
Lactic acidosis
including fatalities has been reported, with an increased risk in women andobesity
; discontinue if suspectedHepatic:
Severe hepatomegaly with steatosis including fatalities has been reported, with an increased risk in women and obesity; discontinue if suspected
Mild hepatic impairment (Child-Pugh score 5 to 6); dosage adjustment necessary
Immunologic:
Immune reconstitution syndrome
has been reported; further evaluation andtreatment
may be necessaryAutoimmune disorders (e.g.,
Graves’s disease
,polymyositis
, andGuillain-Barré syndrome
) have been reported in the setting ofimmune reconstitution syndrome
Pregnancy Category
Fetal risk cannot be ruled out.Breast Feeding
Infant risk cannot be ruled out.Monitoring
Adults
,adolescents
, and pediatrics:HLA-B*5701 testing: prior to initiation of
therapy
Adults
andadolescents
:viral
load: at baseline and with modification ofantiretroviral
ARV:
Treatment, at 2 to 8 weeks; then every 4 to 8 weeks until values are below the limit of detection (less than 200 copies/mL), then every 3 to
4 months
; monitoring may be extended to every6 months
for patients who are immunologically stable, adherent, and with suppressedviral
loads for more than 2 yearsAdults
andadolescents
:CD4 cell counts
: at baseline and with modification of ARVtreatment
, then every 3 to6 months
during at least the first 2 years oftreatment
and if the CD4 counts are less than300
cell
/mm(3) or viremia develops; after 2 years monitoring may be extended to every12 months
for patients who are clinically stable with suppressedviral
loadsAdults
andadolescents
:Hepatitis B
screening: baseline and with modification of ARVtreatment
; may repeat screening every12 months
ifHepatitis B
surface antigen or antibody are negative at baseline.Adults
andadolescents
:Perform hepatitis C antibody testing prior to initiation or modification of ARV
treatment
; may repeat screening every12 months
in high-risk patients if results are negative at baselinePediatrics:
viral
load: at baseline and with modification of ARVtreatment
, within 2 to 4 weeks, then every 3 to4 months
thereafterPediatrics:
CD4 count/percentage: at baseline and with modification of ARV
treatment
, then every 3 to4 months
; less frequent monitoring for children adherent totreatment
who have remained clinically stable and have maintainedviral
suppression and CD4 counts above the threshold for opportunisticinfection
for more than 2 to 3 yearsPediatrics:
clinical history, physical exam, and evaluation of adherence: at baseline at 1 to 2 weeks and 2 to 4 weeks following initiation or modification of ARV
treatment
, then every 3 to4 months
thereafterAdults
andadolescents
:ALT, AST, and total bilirubin; at baseline and with modification of ARV
treatment
, at 2 to 8 weeks, then every 3 to6 months
Adults
andadolescents
:Basic chemistry
including serum sodium,potassium
,bicarbonate
,chloride
,BUN
,creatinine
, and creatinine-based estimated glomerular filtration rate; at baseline and with modification of ARVtreatment
, at 2 to 8 weeks, then every 3 to6 months
Adults
andadolescents
:CBC with a differential; at baseline and with modification of ARV
treatment
,6 months
thereafter or every 3 to6 months
ifCD4
testing is doneAdults
andadolescents
:Fasting
blood
glucose
or HbA1c at baseline and with modification of ARVtreatment
, then every 3 to6 months
in patients with abnormal values or every12 months
in patients with normal valuesAdults
andadolescents
:Fasting lipid profile at baseline and with modification of ARV
treatment
, then every6 months
in patients with abnormal values or annually in patients with normal valuesAdults
andadolescents
:Urinalysis; at baseline or modification of therapy, then annually
Adults
andadolescents
:Pregnancy test, in women of reproductive potential; prior to therapy initiation
Pediatrics:
Basic chemistry
includingcreatinine
,electrolytes
, andglucose
; at baseline and with modification of ARVtreatment
, at 2 to 4 weeks aftertreatment
initiation, then every 3 to4 months
thereafterPediatrics:
CBC with differential; at baseline and with modification of ARV
treatment
, within 2 to 4 weeks, then every 3 to4 months
Pediatrics:
Hepatic transaminases; at baseline and with modification of ARV
treatment
, then every 3 to4 months
or more frequently if signs ofhepatotoxicity
developPediatrics 2 years and older:
non-fasting lipid panel; at baseline and with modification of ARV
treatment
, then every 6 to12 months
; patients withlipid abnormalities
should have a fasting lipid panel every6 months
or more frequently as clinically indicatedPediatrics:
Urinalysis; at baseline, then every 6 to
12 months
How to Take or Administration
General Information:The National Institute for Occupational Safety and Health (NIOSH) recommends
the use of
single gloves by anyone handling intacttablets
or capsules or administering from a unit-dose package.In the preparation of
tablets
or capsules, including cutting, crushing, or manipulating, or the handling of uncoatedtablets
, NIOSH recommendsthe use of
double gloves and a protective gown. Prepare in a ventilated control device, if possible.Use
respiratory protection if not prepared in a control device. During administration, wear single gloves, and wear eye/face protection if the formulation is hard to swallow or if the patient may resist, vomit, or spit up.NIOSH recommends
the use of
double gloves and a protective gown by anyone handling a hazardous oral liquid or any hazardous drug via a feeding tube. Prepare in a control device, if possible.Use
respiratory, eye, and face protection if not done in a control device. During administration, eye/face protection is needed if the patient may resist, or if there is potential to vomit or spit up.Oral:
Take with or without food.
Dosage Form
Oral Solution:20 mg
/1 MLOral Tablet:
300
mg
Treatment
Management of Mild to Moderate Toxicity:Supportive therapy remains the mainstay of care.
Benzodiazepines
orantipsychotics
may beused for
agitation or manicsymptoms
. Mild transaminitis can be monitored, discontinuation of therapy is not usually necessary. Therapy should be changed for persistently rising transaminases or evidence of hepatic synthetic dysfunction. Nausea and vomiting should be treated withantiemetics
. Peripheral neuropathies are generally reversible with drug withdrawal and can be treated with pain management as needed. Asymptomatic elevation of lactic acid without systemic acidemia does not require discontinuation of themedications
.Management of Severe Toxicity:
Supportive care is the mainstay of care. Aggressive fluid resuscitation should be initiated for severe
lactic acidosis
. Granulocyte colony stimulating factor may be considered for patients with agranulocytosis complicated byinfection
. Vasopressors may be necessary in cases with multi-organ failure. Withdrawal of the agent is imperative to improvement in severe adverse reactions.Riboflavin
andL-carnitine
may be useful in treatingnucleoside reverse-transcriptase inhibitors
(NRTI)-associatedlactic acidosis
.Toxicology
A full month supply of many of these agents has been ingested in overdose without clinical effects, though toxicity can occur at therapeutic doses withnucleoside reverse-transcriptase inhibitors
(NRTIs).Patient Counselling or Clinical Teaching
Instruct patient to immediately reportsymptoms
of aninfection
.Warn patient to immediately report
symptoms
of lactic acidosis orhepatotoxicity
.Side effects may include
nausea
,vomiting
,headache
,fatigue
,malaise
,fever
,chills
,rash
, and dream orsleep disorders
.Advise patient to consult physician before resuming therapy if there is an interruption in therapy.