abacavir
Regulatory sources consulted
Approved indications
- Combination antiretroviral treatment of HIV-1 infection.
Contraindications
Absolute
- Positive HLA-B*57:01; prior or suspected abacavir hypersensitivity reaction; moderate or severe hepatic impairment.
Clinical warnings
- Boxed warning: it may cause fatal multiorgan hypersensitivity. Discontinue immediately if suspected and never rechallenge, even with negative HLA. — DailyMed, set_id 44fb1e25-ad03-4a7f-9f35-2e29f5025661
- It may cause lactic acidosis/hepatomegaly with steatosis; a possible cardiovascular risk should be assessed. — DailyMed, set_id 44fb1e25-ad03-4a7f-9f35-2e29f5025661
Drug interactions
- ModerateMethadone
Mechanism: Abacavir may increase methadone clearance.
Recommendation: Monitor withdrawal and adjust methadone if needed.
DailyMed, set_id 44fb1e25-ad03-4a7f-9f35-2e29f5025661
- HighRiociguat
Mechanism: Abacavir may increase riociguat exposure approximately threefold through CYP1A1 inhibition.
Recommendation: Riociguat dose reduction may be needed; follow its prescribing information.
DailyMed, set_id 44fb1e25-ad03-4a7f-9f35-2e29f5025661
Adverse events
Common (≥1%)
Nausea, vomiting, diarrhea, headache, fatigue, and rash
Rare but serious
Fatal hypersensitivity, lactic acidosis, hepatomegaly with steatosis, and pancreatitis
Pregnancy and lactation
Use during pregnancy within the antiretroviral regimen when indicated. Do not breastfeed if you have HIV and receive treatment.
Recent literature (PubMed)
Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing. The antivirals are a large and diverse group of agents
Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes. Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA. Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to <95%) or low (<85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA < 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (<95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF. Participants with suboptimal (<85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.