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The following adverse reactions are discussed in greater detail in other sections of the labeling:

Serious and sometimes fatal hypersensitivity reaction. In one study, once-daily dosing of abacavir was associated with more severe hypersensitivity reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS].

• Lactic acidosis and severe hepatomegaly [see BOXED WARNING, WARNINGS AND PRECAUTIONS].
• Immune reconstitution syndrome [see WARNINGS AND PRECAUTIONS].
• Fat redistribution [see WARNINGS AND PRECAUTIONS].
• Myocardial infarction [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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adults

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 ZIAGEN 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.

Table 2: Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, > 5% Frequency) in Therapy-Naive Adults (CNA30024^a) Through 48 Weeks of Treatment

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 ZIAGEN 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.

Table 3: 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

Five patients receiving ZIAGEN 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.

ZIAGEN Once Daily Versus ZIAGEN 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 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 from CNA30021 were similar. For hypersensitivity reactions, patients receiving ZIAGEN once daily showed a rate of 9% in comparison with a rate of 7% for patients receiving ZIAGEN twice daily. However, 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.

Laboratory Abnormalities

Laboratory abnormalities (Grades 3-4) in therapy-naive adults during therapy with ZIAGEN 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.

Table 4: Laboratory Abnormalities (Grades 3-4) in Therapy-Naive Adults (CNA30024) Through 48 Weeks of Treatment

Laboratory abnormalities in CNA3005 are listed in Table 5.

Table 5: Treatment-Emergent Laboratory Abnormalities (Grades 3-4) in CNA3005

The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups in CNA30021.

Pediatric Patients

Therapy-Experienced Pediatric Patients: 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 ZIAGEN 8 mg/kg twice daily, lamivudine 4 mg/kg twice daily, and zidovudine 180 mg/m twice daily compared with lamivudine 4 mg/kg twice daily and zidovudine 180 mg/m² twice daily from CNA3006 are listed in Table 6.

Table 6: Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2-4, > 5% Frequency) in Therapy-Experienced Pediatric Patients (CNA3006) Through 16 Weeks of Treatment

Laboratory Abnormalities: In Study CNA3006, laboratory abnormalities (anemia, neutropenia, liver function test abnormalities, and CPK elevations) were observed with similar frequencies as in a study of therapy-naive adults (CNA30024). Mild elevations of blood glucose were more frequent in pediatric patients receiving ZIAGEN (CNA3006) as compared with adult patients (CNA30024).

Other Adverse Events

In addition to adverse reactions and laboratory abnormalities reported in Tables 2, 3, 4, 5, and 6, other adverse reactions observed in the expanded access program were pancreatitis and increased GGT.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following reactions have been identified during postmarketing use of ZIAGEN. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to ZIAGEN.

Body as a Whole: Redistribution/accumulation of body fat.

Cardiovascular: Myocardial infarction.

Hepatic: Lactic acidosis and hepatic steatosis.

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.

Ethanol

Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure [see CLINICAL PHARMACOLOGY].

Methadone

The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir. In a study of 11 HIV-1-infected patients receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see CLINICAL PHARMACOLOGY]. This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients.

Last reviewed on RxList: 3/26/2012
This monograph has been modified to include the generic and brand name in many instances.