HYPERSENSITIVITY REACTIONS, HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY, AND EXACERBATIONS OF HEPATITIS B

Hypersensitivity Reactions

• Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of TRIZIVIR® (abacavir, lamivudine, and zidovudine). 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)].
• TRIZIVIR 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)]. All patients should be screened for the HLA?B*5701 allele prior to initiating therapy with TRIZIVIR or reinitiation of therapy with TRIZIVIR, unless patients have a previously documented HLA?B*5701 allele assessment. Discontinue TRIZIVIR immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see Contraindications (4), Warnings and Precautions (5.1)].
• Following a hypersensitivity reaction to TRIZIVIR, NEVER restart TRIZIVIR or any other abacavir?containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see Warnings and Precautions (5.1)].

Hematologic Toxicity

• Zidovudine, a component of TRIZIVIR, has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV?1) disease [see Warnings and Precautions (5.2)].

Myopathy

• Prolonged use of zidovudine has been associated with symptomatic myopathy [see Warnings and Precautions (5.3)].

Lactic Acidosis and Severe Hepatomegaly with Steatosis

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Discontinue TRIZIVIR if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see Warnings and Precautions (5.4)].

Exacerbations of Hepatitis B

• Severe acute exacerbations of hepatitis B have been reported in patients who are co?infected with hepatitis B virus (HBV) and HIV?1 and have discontinued lamivudine, a component of TRIZIVIR. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue TRIZIVIR and are co-infected with HIV?1 and HBV. If appropriate, initiation of anti?hepatitis B therapy may be warranted [see Warnings and Precautions (5.5)].

Pregnancy Risks

• Hyperlactatemia, which may be due to mitochondrial dysfunction, has been reported in infants with in utero exposure to zidovudine-containing products. These events were transient and asymptomatic in most cases. There have been few reports of developmental delay, seizures, and other neurological disease. However, a causal relationship between these events and exposure to zidovudine-containing products in utero or peri-partum has not been established.