Abacavir Sulfate

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE Abacavir tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus (HIV-1) infection. Abacavir tablets, a nucleoside analogue human immunodeficiency virus (HIV-1) reverse transcriptase inhibitor, are indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Before initiating abacavir, screen for the HLA-B*5701 allele. ( 2.1 ) Adults: 600 mg daily, administered as either 300 mg twice daily or 600 mg once daily. ( 2.2 ) Pediatric Patients Aged 3 Months and Older: Administered either once or twice daily. Dose should be calculated on body weight (kg) and should not exceed 600 mg daily. ( 2.3 ) Patients with Hepatic Impairment: Mild hepatic impairment – 200 mg twice daily. ( 2.4 ) 2.1 Screening for HLA-B*5701 Allele Prior to Starting Abacavir Screen for the HLA-B*5701 allele prior to initiating therapy with abacavir [see , Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage for Adult Patients The recommended dosage of abacavir tablets for adults is 600 mg daily, administered orally as either 300 mg twice daily or 600 mg once daily, in combination with other antiretroviral agents. 2.3 Recommended Dosage for Pediatric Patients The recommended dosage of abacavir oral solution in HIV-1–infected pediatric patients aged 3 months and older is 8 mg per kg orally twice daily or 16 mg per kg orally once daily (up to a maximum of 600 mg daily) in combination with other antiretroviral agents. Abacavir is also available as a scored tablet for HIV-1–infected pediatric patients weighing greater than or equal to 14 kg for whom a solid dosage form is appropriate. Before prescribing abacavir tablets, children should be assessed for the ability to swallow tablets. If a child is unable to reliably swallow abacavir tablets, the oral solution formulation should be prescribed. The recommended oral dosage of abacavir tablets for HIV-1–infected pediatric patients is presented in Table 1. Table 1. Dosing Recommendations for Abacavir Scored Tablets in Pediatric Patients Weight (kg) Once-Daily Dosing Regimen Data regarding the efficacy of once-daily dosing is limited to subjects who transitioned from twice-daily dosing to once-daily dosing after 36 weeks of treatment [see Clinical Studies (14.2)] . Twice-Daily Dosing Regimen AM Dose PM Dose Total Daily Dose 14 to < 20 1 tablet (300 mg) ½ tablet (150 mg) ½ tablet (150 mg) 300 mg ≥ 20 to < 25 1½ tablets (450 mg) ½ tablet (150 mg) 1 tablet (300 mg) 450 mg ≥ 25 2 tablets (600 mg) 1 tablet (300 mg) 1 tablet (300 mg) 600 mg 2.4 Recommended Dosage for Patients with Hepatic Impairment The recommended dose of abacavir in patients with mild hepatic impairment (Child-Pugh Class A) is 200 mg twice daily. To enable dose reduction, abacavir oral solution (10 mL twice daily) should be used for the treatment of these patients. The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment; therefore, abacavir is contraindicated in these patients. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues. ( 5.2 ) Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. ( 5.3 ) 5.1 Hypersensitivity Reactions Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment [see Adverse Reactions (6.1) ] . Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA-B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making. Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir: All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir or reinitiation of therapy with abacavir, unless patients have a previously documented HLA-B*5701 allele assessment. Abacavir is contraindicated in patients with a prior hypersensi