abacavir

Brand: Ziagen, component of Epzicom, Triumeq, Trizivir

⚠ BBW Prototype: tenofovir-disoproxil-fumarate

Drug Class: nucleoside reverse transcriptase inhibitor (NRTI)

Drug Family: antiretroviral

Subclass: guanosine analog NRTI

Organ Systems: infectious-disease

Mechanism of Action

Intracellularly phosphorylated to carbovir triphosphate (not abacavir triphosphate); competes with deoxyguanosine triphosphate for incorporation into viral DNA; acts as a chain terminator.

HIV reverse transcriptase

Indications

HIV-1 infection (in combination ART) — particularly in patients who cannot tolerate tenofovir due to renal or bone disease

Contraindications

HLA-B*57:01 positive patients (hypersensitivity reaction — CONTRAINDICATED)
abacavir hypersensitivity (prior reaction)

Adverse Effects

Common

nausea
headache
fatigue

Serious

abacavir hypersensitivity reaction (ABCs: Abdominal pain, fever, Rash, Cough/dyspnea, constitutional Symptoms — occurs in ~5% of non-screened patients; potentially fatal on rechallenge)
lactic acidosis (class NRTI effect)
cardiovascular risk (association with MI risk at high doses — clinical significance debated)

Pharmacokinetics (ADME)

Absorption	83% oral bioavailability; not affected by food
Distribution	widely distributed; CSF penetration ~30% of plasma
Metabolism	hepatic (alcohol dehydrogenase and glucuronyl transferase); forms abacavir 5'-carboxylate and glucuronide metabolites
Excretion	renal (83% as metabolites); minor fecal
Half-life	1.5 hours (plasma); intracellular carbovir triphosphate: 20+ hours
Onset	rapid
Peak	0.7–1.7 hours
Duration	24 hours
Protein Binding	50%
Vd	moderate

Drug Interactions

Drug / Agent	Mechanism	Severity
alcohol	competitive inhibition of abacavir metabolism via ADH; increase abacavir AUC ~41%; ribavirin increases carbovir triphosphate	minor
ribavirin	ribavirin increases intracellular carbovir triphosphate levels (same metabolic pathway)	minor

Nursing Considerations

HLA-B*57:01 testing is MANDATORY before prescribing abacavir; patients testing positive must never receive abacavir — use an alternative NRTI (tenofovir preferred).
Counsel patients on the abacavir hypersensitivity reaction syndrome — symptoms within 6 weeks of initiation: fever, rash (not always present), GI symptoms, malaise, pharyngitis, and/or dyspnea.
If hypersensitivity is suspected, STOP abacavir immediately and NEVER rechallenge — rechallenge after hypersensitivity can be fatal within hours.
Educate patients never to restart abacavir without medical clearance even if they stopped for other reasons, as latent sensitization may exist.

Clinical Pearls

HLA-B*57:01 genotyping before abacavir prescription has been one of the most successful implementations of pharmacogenomics in clinical practice, reducing the incidence of abacavir hypersensitivity reaction from ~5% to near 0% in prospectively screened populations.
Abacavir is preferred over tenofovir DF in patients with significant renal disease or bone disease because it does not cause nephrotoxicity or decrease bone mineral density.

Safety Profile

Pregnancy use-with-caution

Lactation avoid

Renal Adjustment Not required

Hepatic Adjustment Required

TDM Not required

Concordance Terms

Cross-referenced clinical concepts — click any term to see all content where it appears.

HIV-1 Infection (in Combination ART) — Particularly In Patients Who Cannot Tolerate Tenofovir Due To Renal Or Bone Disease Nucleoside Reverse Transcriptase Inhibitor (NRTI)

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