brand name | preparation | manufacturer | route | form | dosage^ | cost* |
Ziagen | Abacavir (ABC) | GlaxoSmithKline | oral | tablet | 300 mg | $11.17 per tab |
oral | solution | 20 mg/mL | $0.73 (per mL) | |||
Abacavir (generic) | ABC | Mylan Pharmaceuticals | oral | tablet | 300 mg | $9.64 - 10.06 per tab |
oral | solution | 20 mg/mL | $0.65 (per mL) | |||
Trizivir | GlaxoSmithKline | oral | tablet | ABC 300 mg + AZT 300 mg + 3TC 150 mg | $32.19 per tab | |
Abacavir, Zidovudine, and Lamivudine (generic) | ABC + AZT + 3TC | Lupin | oral | tablet | ABC 300 mg + AZT 300 mg + 3TC 150 mg | $28.97 per tab |
Epzicom | ABC + 3TC | GlaxoSmithKline | oral | tablet | ABC 600 mg + 3TC 300 mg | $51.67 per tab |
Abavavir and Lamivudine (generic) | ABC + 3TC | Teva | oral | tablet | ABC 600 mg + 3TC 300 mg | $46.45 per tab |
Kivexa (brand name available in Europe) | ABC + 3TC | GlaxoSmithKline | oral | tablet | ABC 600 mg + 3TC 300 mg | variable |
*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.
Pill burden: 2 pills/d (Ziagen, Trizivir) or 1 pill/d (Epzicom, Kivexa)
Usual dose
No data-Usual dose likely
No data-Usual dose likely
No renal dosage adjustment is necessary.
Rates of adverse reactions are defined during combination therapy with other antiretrovirals.
Not a substrate, inducer, or inhibitor of CYP3A4. No interaction is likely with PIs, NNRTIs, MVC, and RAL. ABC metabolized by alcohol dehydrogenase and glucoronyl transferase.
Drug | Effect of Interaction | Recommendations/Comments |
3TC AUC decreased by 15%. | Not clinically significant. Use a standard dose. | |
Alcohol | ABC AUC increased by 41%. | Clinical significance is unknown. No dose adjustment recommended. |
No significant interaction. | Use a standard dose. | |
Food | ABC AUC was decreased by 5%(NS). | Administer ABC with or without food. |
Methadone clearance increased by 23%; | Monitor for methadone withdrawal, but dose adjustment unlikely to be necessary. | |
Decreased EVR to HCV treatment. | Avoid co-administration | |
Suboptimal virologic suppression when ABC/TDF/3TC once daily was used as a triple nucleoside regimen without PIs or NNRTIs. However, preliminary analysis of ABC/AZT/3TC with TDF as a nucleoside regimen did not show similar suboptimal results and no evidence of drug interaction. | Do not co-administer ABC/TDF/3TC once-daily as a triple nucleoside regimen. Minimal data on the use of this combination with a 4th agent. | |
Decreased ABC AUC by 40%. | Clinical significance is unknown. Active intracellular carbovir triphosphate not measured. Use a standard dose. |
Intracellular phosphorylation to active carbovir triphosphate, which competitively inhibits HIV DNA polymerase.
Well absorbed with 83% oral bioavailability.
81% metabolized by alcohol dehydrogenase and glucuronyl transferase with renal excretion of metabolites; 16% recovered in stool and 1% unchanged in urine.
50%
Mean steady-state Cmax=3mcg/mL; AUC=6 mcg hr/mL. Intracellular levels of carbovir triphosphate 100 FM/million cells.
Serum: 1.5 hrs; intercellular (carbovir triphosphate):-12-20hrs.
Usual dose or 200 mg twice daily (limited clinical data).
Category C: rodent studies demonstrated placental passage. Teratogenic in rodent studies resulting in anasarca, skeletal malformation at 1000 mg/kg dose (35x human therapeutic levels) during organogenesis. However, rabbit studies using 8.5x human therapeutic levels did not result in fetal malformation. No adequate human data, placental passage was 32-66%.
No human data. Breastfeeding is not recommended in the U.S in order to avoid post-natal transmission of HIV to the child, who may not yet be infected.
Comment:
Current DHHS HIV Guidelines. "What Not to Use Section" describes the recommendation against triple NRTI therapy for the management of HIV infection.
Comment:
Current DHHS HIV Guidelines. "What Not to Use Section" describes the recommendation against triple NRTI therapy for the management of HIV infection.
Comment: The study helped establish the drug as a potential incorporation into a once-daily regimen due to its long half-life.
Comment: The randomized controlled trial compared TDF/FTC and ABC/3TC in combination with EFV or boosted ATV. At a median follow-up of 60 weeks, among pts with VL >100K c/mL, the time to virologic failure was significantly shorter in the ABC/3TC group than in the TDF/FTC group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P< 0.001), 57 virologic failures (14%) were observed in the ABC/3TC group versus 26 (7%) in the TDF/FTC group. In pts with VL < 100K c/mL, there was no significant difference in time to virological failure between groups.
Comment: A retrospective review of D:A:D observational cohort for cardiovascular disease risks associated with NRTI use included 33,347 pts (157,912 pt-yrs of follow-up). There were 517 MIs, including 192 in pts receiving ABC-containing regimens. After adjusting for confounding risk factors, the relative risk for ABC use within the last 6 months was 1.9 (95% CI 1.5-2.5). There was also increased risk associated with ddI treatment, but not d4T or AZT. Greatest risk (and greatest increased risk) in pts with risk factors for cardiovascular disease. The pathophysiologic mechanism of this effect, if real, has not been identified. Other studies have not shown this risk, but they may have been underpowered to show a risk of infrequent toxicity. However, the usual caveats with observational studies apply.
Comment: Continuation of ACTG 5095 compared AZT/3TC/EFV to AZT/ABC/3TC/EFV in ART-naive pts. No significant differences between 3vs 4-drug regimens; approximately 80% of pts had VL < 50 through 3 yrs. 10% treated with AZT/3TC/ABC/EFV had ABC HSR, vs. 7% on AZT/3TC/EFV.
Comment: A high rate of virologic failure in the TDF+ABC+3TC arm, with 49% experiencing virologic failure compared to 5.4% of pts taking EFV. Among TDF-treated pts for whom virologic data are available, 64% had both the K65R and M184V mutations and 36% had M184V alone. TDF/ABC/3TC is not recommended as a triple-NRTI regimen, and data minimal for use with a 4th agent.
Comment: EFV + once- or twice-daily ABC as part of an ABC/3TC backbone were equivalent, with 66% and 68% of pts achieving VL <50, respectively.
Comment: The PENTA 13 cross-over PK study evaluated ABC 8mg/kg BID vs. 16mg/kg QD in 24 HIV infected children ages 2-13 years old who had undetectable/low viral loads and stable CD4 counts. Although AUC (0-24) was comparable between QD and BID dosing, Cmin of QD ABC was lower in younger children (2-6 y/o).
Comment: ABC/3TC + EFV was non-inferior to AZT/3TC + EFV in a randomized, double-blind study involving 649 naive pts. Response rate (< 50) through wk 48 was 70% and 69% in ABC and AZT group, respectively. Pts on ABC/3TC had less nausea, vomiting, fatigue, and anemia than pts taking AZT, but more HSR. ABC/3TC associated with a greater increase in CD4 (209 vs 155) and CD4%.
Comment: Compared triple-NRTI regimen of AZT/3TC/ABC with 2 EFV-containing regimens, AZT/3TC + EFV and AZT/3TC/ABC + EFV. The triple-NRTI arm was stopped early because of a higher rate of virologic failure vs. EFV-based regimens (21% vs 10%, p < 0.001). Triple NRTI regimens should only be used as an alternative in pts who cannot take PI or NNRTI-based regimens.
Comment: This study found an extraordinary association between the presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 alleles and HSR to ABC (OR 822 [43-15675], p< 0.0001). The authors concluded that if ABC was withheld in the presence of these alleles, the prevalence of HSR would decrease from 9-5% to 2.5%. Positive predictive value for HSR 100%, negative predictive value 97%.
Comment: AZT/3TC + ABC was equivalent to AZT/3TC + unboosted IDV, with 51% in both groups achieving VL < 400 at 48 wks. Trend favoring IDV-based regimen in pts with baseline VL >100,000, with 45% vs 31% achieving < 50 (a treatment difference -14% (95% CI, -27% to 0%). Although this trial demonstrated equivalency at < 400 endpoints, the decreased potency at high VL suggests lower potency overall.
Comment: A 24-week randomized double-blind trial compared the safety of NVP or ABC when combined with zidovudine/lamivudine in 599 ARV-naive patients in Uganda. 6 (2%) on ABC and 14 (4.7%) on NVP developed a serious adverse reaction (HR = 0.41; 95% CI 0.16-1.08; log-rank p = 0.06). 19/20 of these SAR were consistent with a hypersensitivity reaction. Grade 4 toxicities were more common in the NVP treated group (64 ABC vs 91 NVP, p=0.008), but the majority of these were due to bone marrow suppression. 8 patients (all NVP) developed grade 4 LFTs elevation.
Comment: Study randomized 1956 ABC-naive patients to the standard of care or screening with the HLA-B*5701 test before starting ABC. Incidence of both clinically diagnosed and immunologically confirmed HSR significantly lower in screening arm vs. control arm. No cases of immunologically confirmed HSR observed in the prospective screening arm. HLA-B*5701 had a 100% sensitivity.
Comment: A retrospective review of 2752 pts enrolled in continuous treatment arm of SMART evaluated cardiovascular (CV) disease risks associated with NRTI components of ARV regimens. CV risk factors comparable between groups: the median age of 40, 73% males, 39% smokers, 7% had diabetes, and 4% with prior CV disease. Use of ABC associated with increased risk of MI (AHR = 4.3), CV-related death (AHR = 1.8), with significantly increased risk seen in those with 5 or more CV risk factors.