ADVERSE REACTIONS
Hypersensitivity Reaction:
Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate, a component of TRIZIVIR (see WARNINGS and PRECAUTIONS: Information for Patients).
Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a ≥5% frequency during therapy with abacavir 300 mg twice daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily compared with indinavir 800 mg 3 times daily, lamivudine 150 mg twice daily, and zidovudine 300 mg twice daily from CNA3005 are listed in Table 5.
Table 5. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4,≥5% Frequency) in Therapy-Naive Adults (CNA3005) Through 48 Weeks of Treatment | Adverse Reaction |
ZIAGEN plus
Lamivudine/Zidovudine
(n = 262)
|
Indinavir plus
Lamivudine/Zidovudine
(n = 264)
|
| Nausea | 19% | 17% |
| Headache | 13% | 9% |
| Malaise and fatigue | 12% | 12% |
| Nausea and vomiting | 10% | 10% |
| Hypersensitivity reaction | 8% | 2% |
| Diarrhea | 7% | 5% |
| Fever and/or chills | 6% | 3% |
| Depressive disorders | 6% | 4% |
| Musculoskeletal pain | 5% | 7% |
| Skin rashes | 5% | 4% |
| Ear/nose/throat infections | 5% | 4% |
| Viral respiratory infections | 5% | 5% |
| Anxiety | 5% | 3% |
| Renal signs/symptoms | <1% | 5% |
| Pain (non-site-specific) | <1% | 5% |
Five patients receiving abacavir in study CNA3005 experienced worsening of pre-existing depression compared to none in the indinavir arm. The background rates of pre-existing depression were similar in the 2 treatment arms.
Laboratory Abnormalities:
Laboratory abnormalities in study CNA3005 are listed in Table 6.
Table 6. Treatment-Emergent Laboratory Abnormalities (Grades 3-4) in Study CNA3005 | Grade 3/4 Laboratory Abnormalities | Number of Subjects by Treatment Group |
|
ZIAGEN plus
Lamivudine/Zidovudine
(n = 262)
|
Indinavir plus
Lamivudine/Zidovudine
(n = 264)
|
| Elevated CPK (>4 x ULN) | 18 (7%) | 18 (7%) |
| ALT (>5.0 x ULN) | 16 (6%) | 16 (6%) |
| Neutropenia (<750/mm3) | 13 (5%) | 13 (5%) |
| Hypertriglyceridemia (>750 mg/dL) | 5 (2%) | 3 (1%) |
| Hyperamylasemia (>2.0 x ULN) | 5 (2%) | 1 (<1%) |
| Hyperglycemia (>13.9 mmol/L) | 2 (<1%) | 2 (<1%) |
| Anemia (Hgb ≤6.9 g/dL) | 0 (0%) | 3 (1%) |
| ULN = Upper limit of normal. |
| n = Number of patients assessed. |
Other Adverse Events:
In addition to adverse reactions in Tables 5 and 6, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT .
Observed During Clinical Practice:
The following events have been identified during post-approval use of abacavir, lamivudine, and/or zidovudine. 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 lamivudine and/or zidovudine.
Abacavir:
Cardiovascular: Myocardial infarction.
Skin: Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving abacavir primarily in combination with medications known to be associated with SJS and TEN, respectively. Because of the overlap of clinical signs and symptoms between hypersensitivity to abacavir and SJS and TEN, and the possibility of multiple drug sensitivities in some patients, abacavir should be discontinued and not restarted in such cases.
There have also been reports of erythema multiforme with abacavir use.
Abacavir, Lamivudine, and/or Zidovudine:
Body as a Whole: Redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).
Cardiovascular: Cardiomyopathy.
Digestive: Stomatitis.
Endocrine and Metabolic: Gynecomastia, hyperglycemia.
Gastrointestinal: Anorexia and/or decreased appetite, abdominal pain, dyspepsia, oral mucosal pigmentation.
General: Vasculitis, weakness.
Hemic and Lymphatic: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly, thrombocytopenia.
Hepatic and Pancreatic: Lactic acidosis and hepatic steatosis, elevated bilirubin, elevated transaminases, pancreatitis, posttreatment exacerbation of hepatitis B (see WARNINGS).
Hypersensitivity: Sensitization reactions (including anaphylaxis), urticaria.
Musculoskeletal: Arthralgia, myalgia, muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Dizziness, paresthesia, peripheral neuropathy, seizures.
Psychiatric: Insomnia and other sleep disorders.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, erythema multiforme, Stevens-Johnson syndrome.
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