Abacavir

Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI) used in combination with other antiretrovirals for HIV-1 treatment. It is a component of the widely prescribed fixed-dose combination Triumeq (Dolutegravir/abacavir/lamivudine). Abacavir is most notable for its potentially fatal hypersensitivity reaction linked to the HLA-B*5701 allele — one of the best-established pharmacogenomic associations in medicine.[1]

Administration

  • Type: Nucleoside reverse transcriptase inhibitor (NRTI)
  • Dosage Forms: 300 mg scored tablets; 20 mg/mL oral solution
  • Routes of Administration: Oral
  • Common Trade Names: Ziagen; also in fixed-dose combinations: Triumeq (abacavir/dolutegravir/lamivudine), Epzicom (abacavir/lamivudine), Trizivir (abacavir/lamivudine/zidovudine)

Adult Dosing

  • 600 mg PO daily, given as either 300 mg twice daily or 600 mg once daily[1]
  • May take with or without food
  • Must screen for HLA-B*5701 before initiating (see Contraindications/Comments)[1]

Pediatric Dosing

  • Approved for patients ≥3 months[1]
  • 8 mg/kg PO twice daily or 16 mg/kg PO once daily (max 600 mg/day)
  • Scored tablets may be used for children ≥14 kg; oral solution for younger/smaller children

Special Populations

Pregnancy Rating

  • Formerly Category C; no adequate controlled studies in pregnant women[1]
  • Crosses the placenta; no increased birth defect rate observed in registry data
  • Antiretroviral Pregnancy Registry: 1-800-258-4263

Lactation risk

  • Unknown whether excreted in human milk; women with HIV should not breastfeed (risk of HIV transmission)[1]

Renal Dosing

  • Adult: No dose adjustment needed (primarily hepatically metabolized; ~2% unchanged drug in urine)[1]
    • Not known if removed by dialysis
  • Pediatric: No specific data

Hepatic Dosing

  • Adult:[1]
    • Mild impairment (Child-Pugh A): 200 mg PO twice daily (reduced dose; use oral solution to enable this)
    • Moderate or severe impairment (Child-Pugh B or C): Contraindicated
  • Pediatric: Not studied

Contraindications

  • Allergy to class/drug
  • HLA-B*5701-positive patients[1]
  • Prior hypersensitivity reaction to abacavir (NEVER rechallenge)[1]
  • Moderate or severe hepatic impairment (Child-Pugh B or C)[1]

Adverse Reactions

Serious

  • Hypersensitivity reaction (Boxed Warning): Multi-organ syndrome occurring in ~8% without HLA screening (~1% with screening). Median onset 9 days (range: within first 6 weeks, though can occur any time). Presents with ≥2 of the following symptom groups:[1][2]
    • Group 1: Fever
    • Group 2: Rash (maculopapular or urticarial)
    • Group 3: GI (nausea, vomiting, diarrhea, abdominal pain)
    • Group 4: Constitutional (malaise, fatigue, body aches)
    • Group 5: Respiratory (dyspnea, cough, pharyngitis)
    • Symptoms worsen with each subsequent dose and resolve within 72 hours of stopping
    • Rechallenge after hypersensitivity can cause fatal hypotension, multi-organ failure, and death within hours[1]
  • Lactic acidosis with hepatic steatosis (NRTI class effect; including fatal cases)[1]
  • Immune reconstitution inflammatory syndrome (IRIS)

Common

  • Nausea, headache, malaise, fatigue, diarrhea, loss of appetite (each ≥10%)[1]
  • Insomnia, abnormal dreams

Pharmacology

  • Half-life: ~1.5 hours (plasma); intracellular carbovir triphosphate half-life ~21 hours (supports once-daily dosing)[1]
  • Metabolism: Hepatic via alcohol dehydrogenase and glucuronyltransferase; not a CYP450 substrate and does not significantly inhibit or induce CYP enzymes[1]
  • Excretion: ~83% urine (as metabolites; ~2% unchanged), ~16% feces[1]

Mechanism of Action

Abacavir is a guanosine analog that is intracellularly phosphorylated to its active metabolite, carbovir triphosphate. Carbovir triphosphate competes with the natural substrate deoxyguanosine triphosphate (dGTP) for incorporation by HIV-1 reverse transcriptase. Once incorporated into viral DNA, it acts as a chain terminator due to the absence of a 3'-hydroxyl group, halting proviral DNA synthesis.[1]

Comments

  • HLA-B*5701 screening is mandatory before starting any abacavir-containing product — this includes Triumeq, Epzicom, and Trizivir. ~6% of Caucasians and ~2–3% of African Americans carry this allele[2]
  • Hypersensitivity recognition: A patient on abacavir presenting with a multi-system illness (fever + rash + GI + respiratory symptoms) should be treated as a suspected abacavir hypersensitivity reaction until proven otherwise. Discontinue abacavir immediately — do not wait for confirmatory testing. Symptoms classically worsen with each dose and improve within 72 hours of stopping[1]
  • NEVER rechallenge: Restarting abacavir after a hypersensitivity reaction — even after resolution — can cause fatal anaphylaxis within hours (hypotension, renal failure, death). This applies regardless of HLA-B*5701 status[1]
  • Mimics of other diagnoses: Abacavir hypersensitivity can be misdiagnosed as pneumonia, flu, gastroenteritis, or drug reaction to other agents. If in doubt, stop abacavir and consult HIV/ID
  • Ethanol interaction: Alcohol decreases elimination of abacavir (competition for alcohol dehydrogenase) — increases abacavir exposure by ~41%. No dose adjustment recommended, but be aware in heavy drinkers[1]
  • Low drug interaction profile: Abacavir is not metabolized by CYP450 and does not significantly affect other drug levels — one of the safest NRTIs from an interaction standpoint when prescribing in the ED
  • Cardiovascular risk: Some observational data suggested increased MI risk with abacavir use; this remains controversial and has not been confirmed in randomized trials. The FDA has not added a cardiovascular warning[1]
  • Overdose: No specific antidote; supportive care. Not known if removed by dialysis[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 Ziagen (abacavir) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2020.
  2. ↑ 2.0 2.1 Abacavir Therapy and HLA-B*57:01 Genotype. Medical Genetics Summaries. NCBI Bookshelf. Updated 2025.
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