Abacavir

Last Updated June 10, 2016

Trade Names

• Abacavir: Ziagen; Aspen Abacavir; Cipla-Abacavir; Adco-Abacavir; Invertron; Sonke Abacavir; Kavimun Paed (Mylan);
• Zidovudine/lamivudine/abacavir: Trizivar, Sonke Abaclamid; 
• Lamivudine/abacavir: Kivexa, Dumiva (Mylan)

Drug Classification

Nucleoside reverse transcriptase inhibitor antiretroviral

Formulations

• Abacavir: 300 mg tablets; 20 mg/mL oral solution; 60 mg tablets
• Zidovudine/lamivudine/abacavir: 300/150/300 mg tablets
• Lamivudine/abacavir 300/600 mg tablets

Indications and Pharmacology

Indication: treatment of HIV infection in combination with other antiretrovirals.

Mechanism of action*: a guanosine analogue that is phosphorylated intracellularly to carbovir triphosphate, which interferes with HIV viral RNA–dependent DNA polymerase inhibiting viral replication.

Pharmacokinetics*: metabolized in the liver by alcohol dehydrogenase and glucuronyl transferase. 82% excreted in the urine. Half-life: serum = 1.5 hours; intracellular = 12-26 hours. Good cerebrospinal fluid penetration.

Dosage

Adult Dose: 300 mg twice daily or 600 mg once daily with or without food.

Use in Renal or Hepatic Insufficiency: 

• Reduce adult dose to 200 mg twice daily for mild liver impairment (Child-Pugh Class A).* Contraindicated in moderate or severe liver impairment.*
• No dose adjustments needed in renal insufficiency. Use with caution in patients receiving peritoneal dialysis.^‡

Use in Pregnancy and Breastfeeding: Category C. Excreted into breast milk. Infants of mothers receiving abacavir should not be breast-fed.

Use in Children:

• Safety and efficacy in neonates and infants < 3 months old is not established.
• 3 months to 12 years: oral 8 mg/kg twice daily or 16 mg/kg once daily up to 600 mg/day.
• > 12 years: use adult dosing.

Warnings

Contraindicated in patients with severe liver impairment or fructose intolerance (oral solution only) and in patients with HLA-B*5701 allele.

US Prescribing Information Boxed Warning*: serious and sometimes fatal hypersensitivity reactions have occurred. Patients testing positive for the HLA-B*5701 allele should not receive abacavir, and screening is recommended prior to initiating therapy. Although patients with the HLA-B*5701 allele are at higher risk for hypersensitivity reactions, they have also occurred in patients who do not carry the allele. The reaction usually occurs within 6 weeks of treatment. Two or more of the following symptoms usually occur: fever, rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (pharyngitis, dyspnea, cough), and gastrointestinal symptoms. If hypersensitivity occurs, abacavir should be discontinued immediately and the patient should not be rechallenged. In rare cases, severe reactions have occurred with abacavir reintroduction in patients without a history of abacavir hypersensitivity

US Prescribing Information Boxed Warning*: lactic acidosis/hepatomegaly with steatosis has been reported with the use of nucleoside analogues and other antiretroviral drugs with fatal cases reported. Use in caution with patients with risk factors for liver disease and suspend treatment if a patient develops signs and symptoms.

• Abacavir should be discontinued in any patient who develops lactic acidosis or pronounced hepatotoxicity.

Drug–Drug Interactions

No significant drug–drug interactions.

Considerations for Special Populations

See above for pregnancy and lactation

Adverse Effects

Generally very well tolerated. Potentially life-threatening hypersensitivity reaction may occur in the first 6 weeks of treatment (see Warnings). Rechallenge is contraindicated in any patient who has experienced symptoms of a hypersensitivity reaction to abacavir.

An increased risk of myocardial infarction has been seen in some but not all cohort studies, with the greatest risk in patients with risk factors for cardiovascular disease.*

Other adverse effects include sleep disorders, headache, lactic acidosis and hepatic steatosis (see Warnings), anemia, neutropenia, elevated creatine kinase, pancreatitis.

*Information from US prescribing information.
^‡Recommendation from South African Renal Society, 2008.