Prescription Drug Information: Abacavir (Page 2 of 7)
6 ADVERSE REACTIONS
The following adverse reactions are discussed in other sections of the labeling:
- Serious and sometimes fatal hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.1)].
- Lactic acidosis and severe hepatomegaly with steatosis [see Warnings and Precautions (5.2)].
- Immune reconstitution syndrome [see Warnings and Precautions (5.3)].
- Myocardial infarction [see Warnings and Precautions (5.4)].
6.1 Clinical Trials Experience in Adult Subjects
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Serious and Fatal Abacavir-Associated Hypersensitivity Reactions
In clinical trials, serious and sometimes fatal hypersensitivity reactions have occurred with abacavir [see Boxed Warning, Warnings and Precautions (5.1)]. These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome.
Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with these hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and others did not have a rash). There were reports of erythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevated creatine phosphokinase, elevated creatinine, and lymphopenia, and abnormal chest x-ray findings (predominantly infiltrates, which were localized).
Additional Adverse Reactions with Use of Abacavir sulfate
Therapy-Naive Adults: Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a greater than or equal to 5% frequency during therapy with abacavir sulfate 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with zidovudine 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily from CNA30024 are listed in Table 2.
| ||
| Adverse Reaction | Abacavir sulfate plus Lamivudine plus Efavirenz (n = 324) | Zidovudine plus Lamivudine plus Efavirenz (n = 325) |
| Dreams/sleep disorders | 10% | 10% |
| Drug hypersensitivity | 9% | <1%† |
| Headaches/migraine | 7% | 11% |
| Nausea | 7% | 11% |
| Fatigue/malaise | 7% | 10% |
| Diarrhea | 7% | 6% |
| Rashes | 6% | 12% |
| Abdominal pain/gastritis/ gastrointestinal signs and symptoms | 6% | 8% |
| Depressive disorders | 6% | 6% |
| Dizziness | 6% | 6% |
| Musculoskeletal pain | 6% | 5% |
| Bronchitis | 4% | 5% |
| Vomiting | 2% | 9% |
Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with a greater than or equal to 5% frequency during therapy with abacavir sulfate 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 3.
| Adverse Reaction | Abacavir sulfate 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 subjects receiving abacavir sulfate in CNA3005 experienced worsening of pre-existing depression compared with none in the indinavir arm. The background rates of pre-existing depression were similar in the 2 treatment arms.
Abacavir sulfate Once Daily versus Abacavir sulfate Twice Daily (CNA30021): Treatment-emergent clinical adverse reactions (rated by the investigator as at least moderate) with a greater than or equal to 5% frequency during therapy with abacavir sulfate 600 mg once daily or abacavir sulfate 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily from CNA30021, were similar. For hypersensitivity reactions, subjects receiving abacavir sulfate once daily showed a rate of 9% in comparison with a rate of 7% for subjects receiving abacavir sulfate twice daily. However, subjects receiving abacavir sulfate 600 mg once daily experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received abacavir sulfate 300 mg twice daily. Five percent (5%) of subjects receiving abacavir sulfate 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving abacavir sulfate 300 mg twice daily. Two percent (2%) of subjects receiving abacavir sulfate 600 mg once daily had severe diarrhea while none of the subjects receiving abacavir sulfate 300 mg twice daily had this event.
Laboratory Abnormalities: Laboratory abnormalities (Grades 3-4) in therapy-naive adults during therapy with abacavir sulfate 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily compared with zidovudine 300 mg twice daily, lamivudine 150 mg twice daily, and efavirenz 600 mg daily from CNA30024 are listed in Table 4.
| ULN = Upper limit of normal | ||
| n = Number of subjects assessed. | ||
| Grade 3/4 Laboratory Abnormalities | Abacavir sulfate plus Lamivudine plus Efavirenz (n = 324) | Zidovudine plus Lamivudine plus Efavirenz (n = 325) |
| Elevated CPK (>4 X ULN) | 8% | 8% |
| Elevated ALT (>5 X ULN) | 6% | 6% |
| Elevated AST (>5 X ULN) | 6% | 5% |
| Hypertriglyceridemia (>750 mg/dL) | 6% | 5% |
| Hyperamylasemia (>2 X ULN) | 4% | 5% |
| Neutropenia (ANC <750/ mm3) | 2% | 4% |
| Anemia (Hgb ≤6.9 gm/dL) | <1% | 2% |
| Thrombocytopenia (Platelets <50,000/ mm3) | 1% | <1% |
| Leukopenia (WBC ≤1,500/ mm3) | <1% | 2% |
Laboratory abnormalities in CNA3005 are listed in Table 5.
| ULN = Upper limit of normal | ||
| n = Number of subjects assessed. | ||
| Grade 3/4 Laboratory Abnormalities | Abacavir sulfate 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%) |
The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in CNA30021.
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