Dosing and uses of Ziagen (abacavir)
Adult dosage forms and strengths
oral solution
- 20mg/mL
tablet
- 300mg
HIV Infection
300 mg PO q12hr, Or
600 mg PO qDay in combination with other antiretroviral agents
Dosage modifications
Renal impairment: No dosage adjustment required
Hepatic impairment
- Mild (Child-Pugh 5-6): Reduce dose to 200 mg q12hr (use oral solution)
- Moderate-to severe: Contraindicated
Pediatric dosage forms and strengths
oral solution
- 20mg/mL
tablet
- 300mg
HIV Infection
Neonates/Infants: Safety and efficacy not established
3 months-16 years: 8 mg/kg PO q12hr or 16 mg/kg/day; not to exceed 600 mg/day in combination with other antiretroviral agents
≥14 kg: Available as a scored tablet; if unable to reliably swallow tablets, prescribe the oral solution
>16 years: 300 mg PO q12hr, OR 600 mg PO qDay in combination with other antiretroviral agents
Ziagen (abacavir) adverse (side) effects
>10%
Nausea (17-19%)
Headache (9-13%)
Malaise/Fatigue (12%)
Nausea & vomiting (10%)
1-10%
Hypersensitivity reaction (2-8%)
Diarrhea (5-7%)
Musculoskelatal pain (5-7%)
Hypertriglyceridemia (6%)
Hepatic: AST Increased (6%)
Depression (4-6%)
Fever/chills (3-6%)
Viral respiratory infections (5%)
Ear/nose /throat infections (4-5%)
Rash (4-5%)
Anxiety (3-5%)
Thrombocytopenia (1%)
<1%
Anaphylactoid reaction
Pulmonary hypertension
Erythema multiforme
Redistribution/accumulation of body fat
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Pancreatitis
GGT increased
Hepatic steatosis
Heptaomegaly
Hepatotoxicity
Lactic acidosis
MI
Warnings
Black box warnings
Hypersensitivity Reactions
- Severe and sometimes fatal hypersensitivity reactions (discontinue immediately if hypersensitivity reaction suspected); Never restart after suspected hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death
- Reintroduction of abacavir or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result (within hours) in serious or fatal hypersensitivity reactions
- Hypersensitivity reaction to this drug is a multiorgan clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: (1) fever, (2) rash, (3) gastrointestinal (including nausea, vomiting, diarrhea, or abdominal pain, (4) constitutional (eg, generalized malaise, fatigue, achiness), and (5) respiratory (eg, pharyngitis, dyspnea, cough)
- Hypersensitivity reactions & HLA-B*5701 allele (section 2) HLA-B*5701 allele carriers at high risk for hypersensitivity reaction, Prior to initiating therapy, screen for the HLA-B*5701 allele; this approach decreases risk of hypersensitivity reaction
- Screening also recommended prior to reinitiation in patients of unknown HLA-B*5701 status who have previously tolerated abacavir therapy
- HLA-B*5701 allele-negative patients may develop hypersensitivity reaction, although frequency significantly less than in HLA-B*5701-positive patients
- Regardless of HLA-B*5701 status, permanently discontinue if hypersensitivity cannot be ruled out, even when other diagnoses are possible
Lactic Acidosis and Hepatomegaly
- Lactic acidosis and hepatomegaly with steatosis (including fatal cases) reported with use of nucleoside analogues alone or in combination
Contraindications
Hypersensitivity;
Presence of HLA-B*5701 allele
do not restart abacavir following hypersensitive reaction without regard of HLA-B-5701, may cause hypotension, death
Moderate or severe hepatic impairment
Cautions
(All NRTIs): Risk of potentially fatal lactic acidosis & severe hepatomegaly with steatosis when used alone or in combination with other antiretrovirals
Risk of immune reconstitution syndrome if used in combination w/ other antiretroviral drugs
Increased risk of serious or fatal hypersensitivity reactions in patients w/ human leukocyte antigen allele, HLA-B*5701; do not restart abacavir following hypersensitive reaction without regard of HLA-B-5701, may cause hypotension, death
May cause redistribution of fat that may result in cushingoid appearance
Pregnancy and lactation
Pregnancy category: C; If pregnant woman exposed to abacavir, report to the Antiretroviral Pregnancy Registry 1-800-258-4263
Lactation: Nor recommended; HIV+ women are advised not to breastfeed
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ziagen (abacavir)
Mechanism of action
Guanosine analog that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which in turn inhibits viral replication
Pharmacokinetics
Absorption: Rapid & extensive absorption
Vd: 0.86 L/kg
Protein Bound: 50%
Metabolism: hepatic via alcohol dehydrogenase & glucuronyl transferase to inactive carboxylate & glucuronide metabolites
Bioavailability: 83%
Half-life elimination: 1.5 hr
Peak Plasma Time: 0.7-1.7 hr
Excretion: Urine (80%); feces (16%)
Pharmacogenomics
Patients who carry the HLA-B*5701 allele are at high risk for experiencing a hypersensitivity reaction
Prior to initiating therapy with abacavir, screening for the HLA-B*5701 allele is recommended
For HLA-B*5701-positive patients, treatment with an abacavir-containing regimen is not recommended
Genetic testing laboratories
- The following companies provide genetic testing for HLA variants
- Kashi Clinical Laboratories (www.kashilab.com)
- LabCorp (https://www.labcorp.com/)
- Specialty Laboratories (https://www.specialtylabs.com)
- Quest (https://www.questdialgnotics.com)
