ABACAVIR SULFATE
Clinical safety rating: caution
Abacavir sulfate is a nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral agent used in combination therapy for the treatment of HIV-1 infection. It is a carbocyclic synthetic nucleoside analogue that inhibits HIV reverse transcriptase.
Abacavir sulfate is a nucleoside reverse transcriptase inhibitor (NRTI). It is phosphorylated intracellularly to carbovir triphosphate, which competes with deoxyguanosine triphosphate for incorporation into viral DNA by HIV reverse transcriptase. Once incorporated, it causes chain termination, inhibiting viral DNA synthesis.
| Metabolism | Abacavir is primarily metabolized by alcohol dehydrogenase and glucuronyl transferase. It is also a substrate for UDP-glucuronosyltransferase (UGT) enzymes, including UGT2B7. Minor metabolism via cytochrome P450 isoenzymes (CYP) occurs; it does not significantly inhibit or induce CYP enzymes. |
| Excretion | Renal: approximately 83% as unchanged drug and metabolites (5'-carboxylic acid and glucuronide conjugate); fecal: <5%. |
| Half-life | Terminal elimination half-life: approximately 1.5 hours; intracellular carbovir triphosphate half-life: 12-26 hours (supports twice-daily dosing). |
| Protein binding | Approximately 50% bound to human plasma proteins, predominantly albumin. |
| Volume of Distribution | Vd/F approximately 0.86 L/kg (range 0.62-1.11 L/kg), indicating distribution into total body water and tissues. |
| Bioavailability | Oral: approximately 83% (range 64-96%) with no significant food effect. |
| Onset of Action | Oral: Antiviral effect begins within 4-6 hours; intracellular carbovir triphosphate levels approach steady-state in 4 days. |
| Duration of Action | Dosing interval 12 hours; intracellular triphosphate persists >12 hours maintaining antiviral suppression. |
300 mg twice daily or 600 mg once daily (as part of combination antiretroviral therapy).
| Dosage form | TABLET |
| Renal impairment | For CrCl <30 mL/min: avoid use; no specific dose for dialysis. For CrCl 30-49 mL/min: no dose adjustment. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. No dose adjustment for mild impairment (Child-Pugh class A) but use with caution. |
| Pediatric use | Approved for children ≥3 months of age; dosing based on weight (8 mg/kg twice daily up to 300 mg twice daily or 16 mg/kg once daily up to 600 mg once daily). |
| Geriatric use | No specific dose adjustments; use with caution due to age-related renal/hepatic decline and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Abacavir use in pregnancy has limited human data; animal studies showed no teratogenicity. It is recommended when benefit outweighs risk, with preference for alternatives in women of childbearing potential if HLA-B*5701 positive.
| Placental transfer | Abacavir crosses the placenta in animal studies and is expected to cross in humans based on its molecular properties. |
| Breastfeeding | Abacavir is excreted into human breast milk. The milk-to-plasma ratio is approximately 0.8. There is potential for HIV transmission and adverse effects in the infant. The CDC recommends that HIV-infected women in the US not breastfeed to avoid transmission. Therefore, breastfeeding is contraindicated. |
■ FDA Black Box Warning
Hypersensitivity reactions, which can be fatal, occur in about 5-8% of patients. These reactions are characterized by symptoms such as fever, rash, fatigue, gastrointestinal symptoms, and respiratory symptoms. Rechallenge is contraindicated and can cause more severe reactions within hours. Genetic screening for HLA-B*5701 allele is recommended before initiation; abacavir should not be used in individuals who carry this allele.
| Common Effects | Nausea, Headache, Fatigue, Diarrhea, Rash, Fever, Vomiting, Insomnia |
| Serious Effects | Hypersensitivity reaction (potentially fatal), lactic acidosis, severe hepatomegaly with steatosis, immune reconstitution syndrome, pancreatitis, myocardial infarction risk (in some studies). |
["Known hypersensitivity to abacavir or any component of the formulation","Positive HLA-B*5701 allele status (absolute contraindication due to high risk of hypersensitivity)","Moderate to severe hepatic impairment (Child-Pugh Class B or C)"]
| Precautions | ["Hypersensitivity reactions: screen for HLA-B*5701 prior to initiation; avoid use in positive patients; monitor for symptoms and permanently discontinue if hypersensitivity suspected; do not rechallenge.","Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, reported with NRTIs, especially in women and obese patients.","Immune reconstitution syndrome: may occur during initial treatment, requiring evaluation for opportunistic infections.","Myocardial infarction: increased risk reported in some studies; use with caution in patients with cardiovascular risk factors.","Hepatotoxicity: monitor liver function tests, especially in patients with underlying hepatic disease or risk factors."] |
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| Teratogenic Risk | Abacavir is classified as FDA Pregnancy Category C. Animal studies have shown fetal toxicity at high doses, but no adequate and well-controlled studies in pregnant women. There is no evidence of increased risk of major birth defects based on limited human data. Use only if benefit outweighs potential risk. First trimester: theoretical risk based on animal data; second/third trimesters: no known fetal harm. |
| Fetal Monitoring | Monitor maternal HIV RNA and CD4 count regularly during pregnancy. Assess for hypersensitivity reactions (especially early in treatment). Fetal monitoring includes ultrasound for growth and anomalies as clinically indicated. Perform HIV viral load at delivery to determine mode of delivery. |
| Fertility Effects | No significant adverse effects on fertility in animal studies. In humans, no evidence of impaired fertility. HIV infection itself may affect fertility; antiretroviral therapy may improve fertility outcomes by improving overall health. |
| Food/Dietary | No significant food interactions. Abacavir can be taken with or without food. Avoid high-fat meals if taking combination tablets with other drugs (e.g., dolutegravir) as they may affect absorption of other components. No specific dietary restrictions. |
| Clinical Pearls | ["Screen for HLA-B*5701 allele before initiation; ABC is contraindicated if positive due to risk of hypersensitivity reaction.","Do not rechallenge after suspected hypersensitivity; even mild symptoms (fever, rash, GI upset) require permanent discontinuation.","Use with caution in patients with moderate hepatic impairment (Child-Pugh B); contraindicated in Child-Pugh C.","ABC has limited CNS penetration; consider alternative if CNS viral escape is suspected.","Twice-daily dosing is rarely used; once-daily (600 mg) is standard for most patients."] |
| Patient Advice | Take abacavir exactly as prescribed, once daily with or without food. · Call your doctor immediately if you experience fever, rash, nausea, vomiting, diarrhea, abdominal pain, extreme tiredness, aches, or sore throat — these may be signs of a serious allergic reaction. · Do not restart abacavir if you stop taking it, especially if you had a prior allergic reaction; permanent discontinuation is required. · Avoid alcohol; abacavir may increase the risk of liver problems when combined with alcohol. · Use effective contraception during treatment as HIV transmission is still possible despite viral suppression. · Do not run out of medication; missing doses can lead to viral resistance. |