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 |
| Molecular Weight | 286.33 |
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 | Limited human data; no increased risk of major birth defects observed in prospective studies. Use if benefit outweighs risk. |
| 2nd trimester | Limited human data; no evidence of fetal harm. Monitor maternal HIV viral load. |
| 3rd trimester | Limited human data; no evidence of fetal harm. Monitor maternal HIV viral load and consider potential for neonatal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for ZIAGEN (ZIAGEN).
| Placental transfer | Abacavir crosses the placenta in humans, with cord blood concentrations approximately 70% of maternal plasma levels. Transfer is via passive diffusion. |
| Breastfeeding | Abacavir is excreted into human breast milk at low concentrations. The levels are insufficient to treat HIV infection and may lead to viral resistance in the infant. In settings where formula feeding is feasible, breastfeeding is not recommended. In resource-limited settings, consider risks and benefits. |
■ 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 |
Hypersensitivity to abacavir or any component of the formulationPresence of HLA-B*5701 allele (increased risk of hypersensitivity reaction)Moderate to severe hepatic impairment (Child-Pugh Class B or C)
| 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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| Lactation Rating | L3 (Moderately Safe) - limited data but unlikely to cause harm at low doses; however, breastfeeding is generally not recommended due to risk of viral resistance. |
| 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 | 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. |
| Food/Dietary |
| No clinically significant food interactions. Abacavir can be taken with or without food. Avoid alcohol as it may increase the risk of liver toxicity. |
| Clinical Pearls | ZIAGEN (abacavir sulfate) carries a Black Box Warning for hypersensitivity reactions, which can be fatal. Testing for HLA-B*5701 allele is mandatory before initiation; if positive, abacavir is contraindicated. Symptoms of hypersensitivity include fever, rash, nausea, vomiting, abdominal pain, and respiratory symptoms. Rechallenge is contraindicated due to risk of severe hypotension and death. Monitor for lactic acidosis and hepatomegaly with steatosis, especially in women with obesity or prolonged nucleoside exposure. |
| Patient Advice | Discontinue and seek immediate medical attention if you develop two or more of the following: fever, rash, nausea, vomiting, abdominal pain, extreme tiredness, or sore throat. · Never restart ZIAGEN or any abacavir-containing product after a hypersensitivity reaction, as a life-threatening allergic reaction can occur within hours. · Carry an Alert Card with you at all times that lists your allergy to abacavir. · Take ZIAGEN exactly as prescribed; do not miss doses. · Report any signs of liver problems: dark urine, light-colored stools, yellowing of skin or eyes. · ZIAGEN does not cure HIV or prevent transmission to others. |