Abacavir is a guanosine analog that is well absorbed following oral administration (83%) and is unaffected by food. The serum half-life is 1.5 hours. The drug undergoes hepatic glucuronidation and carboxylation. Dosage reduction is recommended in mild hepatic impairment; no data are available for patients with moderate or severe liver disease. Since the drug is metabolized by alcohol dehydrogenase, serum levels of abacavir may be increased with concurrent alcohol (ie, ethanol) ingestion. Cerebrospinal fluid levels are approximately one-third those of plasma. Abacavir is one of the NRTI agents recommended for use in pregnancy (Table 49–5).
Hypersensitivity reactions, occasionally fatal, have been reported in up to 8% of patients receiving abacavir and may be more severe in association with once-daily dosing. Symptoms, which generally occur within the first 6 weeks of therapy, include fever, fatigue, nausea, vomiting, diarrhea, and abdominal pain. Dyspnea, pharyngitis, and cough, and elevations in serum aminotransferase or creatine kinase levels may also be present, with skin rash in ~50% of patients. Rechallenge is contraindicated. Screening for HLA-B*5701 before initiation of abacavir therapy is important to identify patients with an increased risk for abacavirassociated hypersensitivity reaction (see Table 5–4). Although the positive predictive value of this test is only about 50%, it has a negative predictive value approaching 100%.
Rash occurs in approximately 5% of patients, typically in the first 6 weeks of treatment. Less frequent adverse events are fever, nausea, vomiting, diarrhea, headache, dyspnea, fatigue, and pancreatitis. In some studies but not in others, abacavir has been associated with an increased risk of myocardial infarction. The class effects of mitochondrial toxicity and disorders of lipid metabolism seem to be less common with abacavir than with other nucleoside analogs.
TABLE 49–3 Currently available antiretroviral agents.
Abacavir NRTI1 300 mg bid or 600 mg qd Test to rule out the presence Rash, hypersensitivity Avoid alcohol. of the HLA-B5701 allele prior reaction, nausea; to initiation of therapy. possible increase in
Atazanavir PI2 400 mg qd or 300 mg qd with ritonavir Take with food. Avoid Nausea, rash, myalgia, See footnote 4. Avoid elvitegravir/ 100 mg qd or cobicistat 150 mg qd; adjust concomitant antacids. indirect hyperbilirubinemia, cobicistat, etravirine, fosamprenavir, dose in hepatic insufficiency Separate dosing acid-diarrhea, ↑ liver enzymes, nevirapine, tipranavir. Avoid in severe reducing agents by ≥10 h. prolonged PR interval hepatic insufficiency. The oral powder contains phenylalanine.
Darunavir PI2 Treatment-naïve: 800 mg qd with ritonavir Take with food. Diarrhea, headache, nausea, See footnote 4. Avoid elvitegravir/ 100 mg qd or cobicistat 150 mg qd rash, hyperlipidemia, ↑ liver cobicistat and simeprevir. Avoid in enzymes, ↑ serum amylase patients with sulfa allergy.
Treatment-experienced: 600 mg bid with ritonavir 100 mg bid