The following adverse reactions are discussed in greater detail in other sections of the labeling:
Hematologic toxicity, including neutropenia and anemia [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
Symptomatic myopathy [see BOXED WARNING, WARNINGS AND PRECAUTIONS]. Lactic acidosis and hepatomegaly with steatosis [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
Acute exacerbations of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS]. Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C [see WARNINGS AND PRECAUTIONS].
Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine [see WARNINGS AND PRECAUTIONS]. Pancreatitis [see WARNINGS AND PRECAUTIONS].
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Lamivudine Plus Zidovudine Administered As Separate Formulations
In 4 randomized, controlled trials of EPIVIR 300 mg per day plus RETROVIR 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (see Tables 1 and 2).
Table 1: Selected Clinical Adverse Reactions ( ≥ 5% Frequency) in 4 Controlled Clinical Trials With EPIVIR 300 mg/day and RETROVIR 600 mg/day
|Adverse Reaction||EPIVIR plus RETROVIR
(n = 251)
|Body as a whole|
|Malaise & fatigue||27%|
|Fever or chills||10%|
|Nausea & vomiting||13%|
|Anorexia and/or decreased appetite||10%|
|Insomnia & other sleep disorders||11%|
|Nasal signs & symptoms||20%|
Pancreatitis was observed in 9 of the 2,613 adult patients (0.3%) who received EPIVIR in controlled clinical trials [see WARNINGS AND PRECAUTIONS].
Selected laboratory abnormalities observed during therapy are listed in Table 2.
Table 2: Frequencies of Selected Laboratory Abnormalities Among Adults in 4 Controlled Clinical Trials of EPIVIR 300 mg/day plus RETROVIR 600 mg/daya
|Test (Abnormal Level)||EPIVIR plus RETROVIR %
|Neutropenia (ANC < 750/mm³)||7.2% (237)|
|Anemia (Hgb < 8.0 g/dL)||2.9% (241)|
|Thrombocytopenia (platelets < 50,000/mm³)||0.4% (240)|
|ALT ( > 5.0 x ULN)||3.7% (241)|
|AST ( > 5.0 x ULN)||1.7% (241)|
|Bilirubin ( > 2.5 x ULN)||0.8% (241)|
|Amylase ( > 2.0 x ULN)||4.2% (72)|
|ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
n = Number of patients assessed.
a Frequencies of these laboratory abnormalities were higher in patients with mild laboratory abnormalities at baseline.
In addition to adverse reactions reported from clinical trials, the following reactions have been identified during post-approval use of EPIVIR, RETROVIR, and/or COMBIVIR. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to EPIVIR, RETROVIR, and/or COMBIVIR.
Body as a Whole: Redistribution/accumulation of body fat [see WARNINGS AND PRECAUTIONS].
Endocrine and Metabolic: Gynecomastia, hyperglycemia.
Gastrointestinal: Oral mucosal pigmentation, stomatitis.
General: Vasculitis, weakness.
Hemic and Lymphatic: Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbation of hepatitis B [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Paresthesia, peripheral neuropathy, seizures.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.