abacavir (Rx)

>10%

Nausea (17-19%)

Headache (9-13%)

Malaise/Fatigue (12%)

Nausea & vomiting (10%)

1-10%

Hypersensitivity reaction (2-8%)

Diarrhea (5-7%)

Musculoskelatal pain (5-7%)

Hypertriglyceridemia (6%)

Hepatic: AST Increased (6%)

Depression (4-6%)

Fever/chills (3-6%)

Viral respiratory infections (5%)

Ear/nose /throat infections (4-5%)

Rash (4-5%)

Anxiety (3-5%)

Thrombocytopenia (1%)

<1%

Anaphylactoid reaction

Pulmonary hypertension

Erythema multiforme

Redistribution/accumulation of body fat

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Pancreatitis

GGT increased

Hepatic steatosis

Heptaomegaly

Hepatotoxicity

Lactic acidosis

MI

Contraindications

Prior hypersensitivity reaction to abacavir

Presence of HLA-B*5701 allele

Moderate or severe hepatic impairment

Cautions

Increased risk of serious or fatal hypersensitivity reactions; patients with human leukocyte antigen allele, HLA-B*5701 are at a higher risk; do not restart abacavir following hypersensitive reaction; may cause hypotension, multiorgan failure, and/or death (see Contraindications and Black Box Warnings)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with nucleoside analogues, including abacavir; a majority of these cases have been in women; female gender and obesity may be risk factors; suspend dosing in those who develop clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity

Immune reconstitution syndrome reported with combination ART; during the initial treatment phase, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis); autoimmune disorders (eg, Grave disease, polymyositis, and Guillain-Barré syndrome) have also been reported

Use has been associated with increased risk of myocardial infarction in observational studies, but not in a meta-analysis of 26 randomized trials; caution with risks for coronary heart disease and minimizing modifiable risk factors, including smoking, hypertension, and hyperlipidemia, prior to use

Drug interaction overview

• Methadone

  • In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with abacavir 600 mg BID (twice the currently recommended dose), PO 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

Pregnancy

Healthcare Providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

Available data from the APR show no difference in the overall risk of birth defects for abacavir compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population

In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose; however, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose

Lactation

Abacavir is present in human milk; there is no information on effects of abacavir on breastfed infant or effects of drug on milk production; because of potential for (1) HIV-1 transmission (in HIV-negative infants), (2) developing viral resistance (in HIV- positive infants), and (3) serious adverse reactions in breastfed infant, instruct mothers not to breastfeed if they are receiving abacavir

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Guanosine analog that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which in turn inhibits viral replication

Pharmacokinetics

Absorption: Rapid & extensive absorption

Vd: 0.86 L/kg

Protein Bound: 50%

Metabolism: hepatic via alcohol dehydrogenase & glucuronyl transferase to inactive carboxylate & glucuronide metabolites

Bioavailability: 83%

Half-life elimination: 1.5 hr

Peak Plasma Time: 0.7-1.7 hr

Excretion: Urine (80%); feces (16%)

Absorption

Rapid and extensive PO absorption

Bioavailability: 83%

Peak plasma concentration: 3 mcg/mL (300 mg); 4.26 mcg/mL (600 mg)

AUC: 6.02 mcg·h/mL (300 mg); 11.95 mcg·h/mL (600 mg)

Distribution

Vd: 0.86 L/kg

Protein Bound: 50%

Metabolism

Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites

Elimination

Half-life: 1.5 hr

Peak Plasma Time: 0.7-1.7 hr

Excretion: Urine (80%); feces (16%)

Pharmacogenomics

Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction

Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended

For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended

Genetic testing laboratories

• The following companies provide genetic testing for HLA variants
• Kashi Clinical Laboratories (www.kashilab.com)
• LabCorp (http://www.labcorp.com/)
• Specialty Laboratories (http://www.specialtylabs.com)
• Quest (http://www.questdialgnotics.com)

Oral Administration

May take with or without food