ADVERSE REACTIONS
Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir sulfate, a component of EPZICOM.
In one study, once-daily dosing of ZIAGEN was associated with more severe hypersensitivity reactions (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 ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily are listed in Table 4.
Table 4. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, ≥5% Frequency) in Therapy-Naive Adults (CNA30021) Through 48 Weeks of Treatment
| Adverse Event |
ZIAGEN 600 mg q.d.
plus EPIVIR plus Efavirenz
(n = 384) |
ZIAGEN 300 mg b.i.d.
plus EPIVIR plus Efavirenz
(n = 386) |
|
Drug hypersensitivity*
†
|
9% |
7% |
| Insomnia |
7% |
9% |
| Depression/Depressed mood |
7% |
7% |
| Headache/Migraine |
7% |
6% |
| Fatigue/Malaise |
6% |
8% |
| Dizziness/Vertigo |
6% |
6% |
| Nausea |
5% |
6% |
| Diarrhea* |
5% |
6% |
| Rash |
5% |
5% |
| Pyrexia |
5% |
3% |
| Abdominal pain/gastritis |
4% |
5% |
| Abnormal dreams |
4% |
5% |
| Anxiety |
3% |
5% |
| * Patients receiving ZIAGEN 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with patients who received ZIAGEN 300 mg twice daily. Five percent (5%) of patients receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of patients receiving ZIAGEN 300 mg twice daily. Two percent (2%) of patients receiving ZIAGEN 600 mg once daily had severe diarrhea while none of the patients receiving ZIAGEN 300 mg twice daily had this event. |
| † Study CNA30024 was a multi-center, double-blind, controlled study in which 649 HIV-1-infected, therapy-naive adults were randomized and received either ZIAGEN (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily) or zidovudine (300 mg twice daily), EPIVIR (150 mg twice daily), and efavirenz (600 mg once daily). CNA30024 used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the study, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 patients in the abacavir group and 3% of 325 patients in the zidovudine group. |
Laboratory abnormalities observed in clinical studies of ZIAGEN were anemia, neutropenia, liver function test abnormalities, and elevations of CPK, blood glucose, and triglycerides. Additional laboratory abnormalities observed in clinical studies of EPIVIR were thrombocytopenia and elevated levels of bilirubin, amylase, and lipase.
The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in Study CNA30021.
In addition to adverse reactions listed above, other adverse events observed in the expanded access program for abacavir were pancreatitis and increased GGT.
The following reactions have been identified during post-approval use of abacavir and lamivudine. 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 abacavir and/or lamivudine.
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.
Body as a Whole:
Redistribution/accumulation of body fat (see PRECAUTIONS: Fat Redistribution).
Digestive:
Stomatitis.
Endocrine and Metabolic:
Hyperglycemia.
General:
Weakness.
Hemic and Lymphatic:
Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic:
Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbation of hepatitis B (see WARNINGS).
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.
|
