preloder

Abacavir sulfate


Abacavir sulfate

is a

medications

used to

prevent and treat

HIV

/

AIDS

. Similar to other

nucleoside analog reverse-transcriptase inhibitors

,

abacavir sulfate

is

used

together with other HIV

medications

, and is not recommended by itself.
Dosing
Adult 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 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 of

hypersensitivity reaction

.

Use is

contraindicated in patients who test positive for HLA-B*5701.

HIV infection

:

3 months or older,

oral solution

:

8 mg

/kg

ORALLY

twice daily

or

16 mg

/kg

ORALLY

once daily
Maximum

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 doses

20 kg to less than

25 kg

:

450 mg

ORALLY

once daily or

150 mg

in AM and

300

mg

in PM

25 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 and

300

mg

ORALLY

in PM

30 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

cellular

DNA

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 patients

Hypersensitivity

to

abacavir

or any other component of the product
Moderate 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 exposure

Methadone:
The addition of methadone has no clinically significant

effect on

the

pharmacokinetic

properties of

abacavir

. In a study of 11

HIV

-infected patients receiving methadone-maintenance therapy with

600 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 effect

Distribution:

Protein

binding,

plasma proteins

: Approximately 50%

Volume of Distribution

(Vd): 0.86 L/kg

Metabolism:
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% unchanged

Total body clearance

: 0.8 L/hour/kg

Elimination:
1.54 +/- 0.63 hours

Precaution
Cardiovascular:

Myocardial infarction

may occur; consider underlying risk of

coronary heart disease

and minimize modifiable risks (e.g.,

hypertension

,

hyperlipidemia

,

diabetes mellitus

, and

smoking

)

Endocrine and metabolic:

Lactic acidosis

including fatalities has been reported, with an increased risk in women and

obesity

; discontinue if suspected

Hepatic:
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 and

treatment

may be necessary

Autoimmune disorders (e.g.,

Graves’s disease

,

polymyositis

, and

Guillain-Barré syndrome

) have been reported in the setting of

immune 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

and

adolescents

:

viral

load: at baseline and with modification of

antiretroviral



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 every

6 months

for patients who are immunologically stable, adherent, and with suppressed

viral

loads for more than 2 years

Adults

and

adolescents

:

CD4 cell counts

: at baseline and with modification of ARV

treatment

, then every 3 to

6 months

during at least the first 2 years of

treatment

and if the CD4 counts are less than

300

cell

/mm(3) or viremia develops; after 2 years monitoring may be extended to every

12 months

for patients who are clinically stable with suppressed

viral

loads

Adults

and

adolescents

:

Hepatitis B

screening: baseline and with modification of ARV

treatment

; may repeat screening every

12 months

if

Hepatitis B

surface antigen or antibody are negative at baseline.

Adults

and

adolescents

:

Perform hepatitis C antibody testing prior to initiation or modification of ARV

treatment

; may repeat screening every

12 months

in high-risk patients if results are negative at baseline

Pediatrics:

viral

load: at baseline and with modification of ARV

treatment

, within 2 to 4 weeks, then every 3 to

4 months

thereafter

Pediatrics:
CD4 count/percentage: at baseline and with modification of ARV

treatment

, then every 3 to

4 months

; less frequent monitoring for children adherent to

treatment

who have remained clinically stable and have maintained

viral

suppression and CD4 counts above the threshold for opportunistic

infection

for more than 2 to 3 years

Pediatrics:
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 to

4 months

thereafter

Adults

and

adolescents

:

ALT, AST, and total bilirubin; at baseline and with modification of ARV

treatment

, at 2 to 8 weeks, then every 3 to

6 months



Adults

and

adolescents

:

Basic chemistry

including serum sodium,

potassium

,

bicarbonate

,

chloride

,

BUN

,

creatinine

, and creatinine-based estimated glomerular filtration rate; at baseline and with modification of ARV

treatment

, at 2 to 8 weeks, then every 3 to

6 months



Adults

and

adolescents

:

CBC with a differential; at baseline and with modification of ARV

treatment

,

6 months

thereafter or every 3 to

6 months

if

CD4

testing is done

Adults

and

adolescents

:

Fasting

blood

glucose

or HbA1c at baseline and with modification of ARV

treatment

, then every 3 to

6 months

in patients with abnormal values or every

12 months

in patients with normal values

Adults

and

adolescents

:

Fasting lipid profile at baseline and with modification of ARV

treatment

, then every

6 months

in patients with abnormal values or annually in patients with normal values

Adults

and

adolescents

:

Urinalysis; at baseline or modification of therapy, then annually

Adults

and

adolescents

:

Pregnancy test, in women of reproductive potential; prior to therapy initiation

Pediatrics:

Basic chemistry

including

creatinine

,

electrolytes

, and

glucose

; at baseline and with modification of ARV

treatment

, at 2 to 4 weeks after

treatment

initiation, then every 3 to

4 months

thereafter

Pediatrics:
CBC with differential; at baseline and with modification of ARV

treatment

, within 2 to 4 weeks, then every 3 to

4 months



Pediatrics:
Hepatic transaminases; at baseline and with modification of ARV

treatment

, then every 3 to

4 months

or more frequently if signs of

hepatotoxicity

develop

Pediatrics 2 years and older:
non-fasting lipid panel; at baseline and with modification of ARV

treatment

, then every 6 to

12 months

; patients with

lipid abnormalities

should have a fasting lipid panel every

6 months

or more frequently as clinically indicated

Pediatrics:
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 intact

tablets

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 uncoated

tablets

, NIOSH recommends

the 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 ML

Oral Tablet:

300

mg



Treatment
Management of Mild to Moderate Toxicity:
Supportive therapy remains the mainstay of care.

Benzodiazepines

or

antipsychotics

may be

used for

agitation or manic

symptoms

. 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 with

antiemetics

. 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 the

medications

.

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 by

infection

. Vasopressors may be necessary in cases with multi-organ failure. Withdrawal of the agent is imperative to improvement in severe adverse reactions.

Riboflavin

and

L-carnitine

may be useful in treating

nucleoside reverse-transcriptase inhibitors

(NRTI)-associated

lactic 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 with

nucleoside reverse-transcriptase inhibitors

(NRTIs).
Patient Counselling or Clinical Teaching
Instruct patient to immediately report

symptoms

of an

infection

.
Warn patient to immediately report

symptoms

of lactic acidosis or

hepatotoxicity

.
Side effects may include

nausea

,

vomiting

,

headache

,

fatigue

,

malaise

,

fever

,

chills

,

rash

, and dream or

sleep disorders

.
Advise patient to consult physician before resuming therapy if there is an interruption in therapy.












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