Abacavir

Brand Names: Abacavir

Drug Class: General Prescription

Overview

11 DESCRIPTION Abacavir sulfate is a synthetic carbocyclic nucleoside analogue with inhibitory activity against HIV-1. The chemical name of abacavir sulfate is ( 1 S,cis)- 4-[2-amino-6-(cyclopropylamino)-9 H -purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S , 4R absolute configuration on the cyclopentene ring.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Abacavir is an antiretroviral agent [see Microbiology (12.4) ]. 12.3 Pharmacokinetics Pharmacokinetics in Adults The pharmacokinetic properties of abacavir were independent of dose over the range of 300 to 1,200 mg per day. Absorption: Following oral administration, abacavir is rapidly absorbed and extensively distributed. The geometric mean absolute bioavailability of the tablet was 83%. Plasma abacavir AUC was similar following administration of the oral solution or tablets. After oral administration of 300 mg twice daily in 20 subjects, the steady-state peak serum abacavir concentration (C max ) was 3 ± 0.89 mcg per mL (mean ± SD) and AUC (0-12 h) was 6.02 ± 1.73 mcg•hour per mL.

Indications

  • 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)

Common Doses

  • 600 mg
  • 300 mg
  • 200 mg
  • 150 mg

Dosage

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.

Black Box Warning

WARNING: HYPERSENSITIVITY REACTIONS Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir. Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele [see Warnings and Precautions (5.1) ]. Abacavir is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients [see Contraindications (4) , Warnings and Precautions (5.1) ].

Contraindications

  • 4 CONTRAINDICATIONS Abacavir tablets are contraindicated in patients: who have the HLA-B*5701 allele [see Warnings and Precautions (5.1) ]. with prior hypersensitivity reaction to abacavir [see Warnings and Precautions (5.1) ]. with moderate or severe hepatic impairment [see Use in Specific Populations (8.6) ]. Presence of HLA-B*5701 allele. (4) Prior hypersensitivity reaction to abacavir. (4) Moderate or severe hepatic impairment. (4)

Side Effects

  • 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Serious and sometimes fatal hypersensitivity reactions [see Boxed Warning , Warnings and Precautions (5.1) ]. Lactic acidosis and severe hepatomegaly with steatosis [see Warnings and Precautions (5.2) ]. Immune reconstitution syndrome [see Warnings and Precautions (5.3) ]. Myocardial infarction [see Warnings and Precautions (5.4) ].

Interactions

  • 7 DRUG INTERACTIONS Methadone: An increased methadone dose may be required in a small number of patients. (7.1) Riociguat: The riociguat dose may need to be reduced. (7.2) 7.1 Methadone In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of abacavir twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology (12.3) ]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients. 7.