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 || |
|Headache ||35% |
|Malaise & fatigue ||27% |
|Fever or chills ||10% |
| Digestive || |
|Nausea ||33% |
|Diarrhea ||18% |
|Nausea & vomiting ||13% |
|Anorexia and/or decreased appetite ||10% |
|Abdominal pain ||9% |
|Abdominal cramps ||6% |
|Dyspepsia ||5% |
| Nervous system || |
|Neuropathy ||12% |
|Insomnia & other sleep disorders ||11% |
|Dizziness ||10% |
|Depressive disorders ||9% |
| Respiratory || |
|Nasal signs & symptoms ||20% |
|Cough ||18% |
| Skin || |
|Skin rashes ||9% |
| Musculoskeletal || |
|Musculoskeletal pain ||12% |
|Myalgia ||8% |
|Arthralgia ||5% |
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/day*
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. |
| * 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 (5.4),].
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.