ADVERSE REACTIONS
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* |
Test
(Abnormal Level) |
EPIVIR plus RETROVIR
% (n) |
| 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. |
Postmarketing Experience
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].
Cardiovascular: Cardiomyopathy.
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 (5.3), (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.
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