IMPORTANT SAFETY INFORMATION

Hypersensitivity Reaction (HSR)

TRIZIVIR contains abacavir sulfate, which has been associated with serious and sometimes fatal hypersensitivity reactions. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups:

	Symptom(s)
Group 1	Fever
Group 2	Rash
Group 3	Nausea, vomiting, diarrhea, or abdominal (stomach area) pain
Group 4	Generally ill feeling, extreme tiredness, or achiness
Group 5	Shortness of breath, cough, or sore throat

• Discontinue TRIZIVIR as soon as a hypersensitivity reaction is suspected. Permanently discontinue TRIZIVIR if hypersensitivity cannot be ruled out, even when other diagnoses are possible
• Following a hypersensitivity reaction to abacavir, NEVER restart TRIZIVIR or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death
• Re-introduction of TRIZIVIR or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours

Management

• When HSR is suspected, discontinue therapy with TRIZIVIR
• DO NOT RE-CHALLENGE IF HYPERSENSITIVITY CANNOT BE RULED OUT
  • Abacavir should not be restarted following a hypersensitivity reaction because more severe symptoms can recur within hours and may include life-threatening hypotension and death
• To avoid a delay in diagnosis and minimize the risk of a life-threatening hypersensitivity reaction, TRIZIVIR should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible (eg, acute onset respiratory diseases, gastroenteritis, or reactions to other medications)

Other Important Safety Information

Zidovudine has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced HIV disease. Prolonged use of zidovudine has been associated with symptomatic myopathy.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, lamivudine, zidovudine, and other antiretrovirals.

TRIZIVIR Tablets are contraindicated in patients with hepatic impairment.

Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV and have discontinued lamivudine, which is one 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 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon with or without ribavirin. Patients receiving interferon with or without ribavirin and TRIZIVIR should be closely monitored for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia. Discontinuation of TRIZIVIR should be considered as medically appropriate.

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including TRIZIVIR. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.

The most common adverse events (≥5% Grades 2-4) were nausea (19%), headache (13%), malaise and fatigue (12%), nausea and vomiting (10%), hypersensitivity reaction (8%), diarrhea (7%), fever and/or chills (6%), depressive disorders (6%), musculoskeletal pain (5%), skin rashes (5%), ear/nose/throat infections (5%), viral respiratory infections (5%), and anxiety (5%).