ZIAGEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZIAGEN (ZIAGEN).
Abacavir is a nucleoside reverse transcriptase inhibitor (NRTI). It is converted intracellularly to carbovir triphosphate, which competes with dGTP for incorporation into viral DNA, causing chain termination and inhibition of HIV reverse transcriptase.
| Metabolism | Abacavir is metabolized primarily by alcohol dehydrogenase and glucuronyl transferase to form 5'-carboxylic acid and 5'-glucuronide metabolites. It is not significantly metabolized by CYP450 enzymes. |
| Excretion | Renal (approximately 82% as unchanged drug and metabolites via glomerular filtration and active tubular secretion); biliary/fecal (minor, <2%) |
| Half-life | Terminal elimination half-life: 1.5–2 hours (mean 1.7 h); intracellular triphosphate half-life: 12–15 hours, supporting once-daily dosing |
| Protein binding | Approximately 50% bound to human plasma proteins (primarily albumin) over a concentration range of 0.5–10 µg/mL |
| Volume of Distribution | Apparent Vd: 0.83 L/kg (mean 0.86 L/kg), indicating distribution into total body water and intracellular spaces, including penetration into CSF (CSF-to-plasma ratio ~0.3–0.5) |
| Bioavailability | Oral: 83% (with high interindividual variability, range 60–90%); not affected by food |
| Onset of Action | Oral: Peak plasma concentration at ~1.0–1.5 hours; antiviral effect begins with intracellular phosphorylation |
| Duration of Action | Plasma levels decline rapidly; intracellular carbovir triphosphate persists with a half-life of ~12–15 hours, allowing once-daily dosing |
600 mg orally once daily, or 300 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for creatinine clearance ≥30 mL/min; insufficient data for <30 mL/min or hemodialysis, use with caution. |
| Liver impairment | Child-Pugh Class A: 600 mg daily. Child-Pugh Class B: 300 mg daily. Child-Pugh Class C: contraindicated. |
| Pediatric use | 3 months to 12 years: 8 mg/kg orally twice daily (max 300 mg twice daily). 12 years and older: same as adult. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline, as per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZIAGEN (ZIAGEN).
| Breastfeeding | Recommended against breastfeeding due to potential for HIV transmission and adverse effects in infant. Abacavir is excreted in human breast milk; M/P ratio not established. |
| Teratogenic Risk | Pregnancy Category C. Human data limited; animal studies show no evidence of teratogenicity at subtoxic doses. First trimester: no increased risk of major malformations in Antiretroviral Pregnancy Registry. Second/third trimesters: no specific fetal toxicity identified; use only if benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
Hypersensitivity reactions: Serious, sometimes fatal hypersensitivity reactions have occurred with abacavir. Symptoms may include fever, rash, fatigue, gastrointestinal symptoms, and respiratory symptoms. Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out. HLA-B*5701 allele screening is recommended prior to initiation; abacavir is contraindicated in patients with the HLA-B*5701 allele.
| Serious Effects |
["Prior hypersensitivity reaction to abacavir","HLA-B*5701 allele positive","Moderate or severe hepatic impairment"]
| Precautions | ["Hypersensitivity reactions: Fatal hypersensitivity can occur; monitor closely and discontinue permanently if suspected.","Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported.","Immune reconstitution syndrome may occur.","Myocardial infarction: Some studies suggest an increased risk; use with caution in patients with cardiovascular risk factors.","Hepatic impairment: Dose adjustment may be necessary in mild impairment; not recommended in moderate/severe impairment.","Pancreatitis: Has been reported, especially in pediatric patients."] |
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| Maternal: Liver function tests, LFTs at baseline and periodically (risk of hepatotoxicity); HIV RNA and CD4+ count every 1-3 months. Fetal: No specific fetal monitoring; consider ultrasound for growth if prolonged use. |
| Fertility Effects | No evidence of impaired fertility in animal studies. No human data on fertility effects with abacavir. |