Abacavir

Dosages

Interactions

Contraindicated

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

Serious

• ganciclovir
• ribavirin
• valganciclovir

Monitor Closely

• atazanavir
• cabozantinib
• didanosine
• efavirenz
• emtricitabine
• enfuvirtide
• fosamprenavir
• indinavir
• lamivudine
• methadone
• nelfinavir
• nevirapine
• orlistat
• ritonavir
• saquinavir
• stavudine
• tenofovir DF
• tipranavir
• zidovudine

Minor

• ethanol

Adverse 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

Black Box Warnings

• Prior hypersensitivity reaction to abacavir
• Presence of HLA-B*5701 allele
• Moderate or severe hepatic impairment

Safety Advice

Pharmacology

Mechanism of Action: Guanosine analogue that inhibits HIV-1 reverse transcriptase by competing with dGTP as substrate, which in turn inhibits viral replication

General Considerations

• Hypersensitivity reaction to Abacavir usually occur within 9 days of starting abacavir; ~ 90% occur within 6 weeks, although these reactions may occur at any time during therapy.
• These hypersensitivity reactions to Abacavir usually include signs or symptoms from two or more of the following: Fever, skin rash, constitutional symptoms (malaise, fatigue, aches), respiratory symptoms (e.g. pharyngitis, dyspnea, cough), and GI symptoms (e.g. abdominal pain, diarrhoea, nausea, vomiting). Other signs and symptoms include lethargy, headache, myalgia, oedema, abnormal chest x-ray findings, arthralgia and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis and death have occurred in association with hypersensitivity reactions.
• Physical findings (lymphadenopathy, erythema multiforme, mucous membrane lesions and rash [maculopapular, urticarial or variable]) and laboratory abnormalities (e.g. elevated liver function tests, elevated creatine phosphokinase, elevated creatinine and lymphopenia) may occur.
• Abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible and regardless of HLA-B*5701 status.
• Abacavir should not be restarted because more severe symptoms may occur within hours, including life-threatening hypotension and death.

General Monitoring Parameters

• CBC with differential, serum creatine kinase, CD4 count, HIV RNA plasma levels, serum transaminases, triglycerides, serum amylase 
• HLA-B*5701 genotype status prior to initiation of therapy and prior to reinitiation of therapy in patients of unknown HLA-B*5701 status 
• Signs and symptoms of hypersensitivity 

Practice Insights

• Do not re-challenge patients who have experienced hypersensitivity to Abacavir regardless of HLA-B*5701 status.
• Abacavir is always used as a combination drug.
• Abacavir is contraindicated in infants less than 90 days.
• Meta-analysis has failed to show a causal association between Abacavir and myocardial infarction so far.
• Meta-analysis has shown that Abacavir related toxicity is manageable and can be safely used as first or second-line antiretroviral therapy especially in the population where HLA B5701 is rare (as in sub-Saharan Africa)