Abacavir Sulfate (Page 3 of 9)

5.5 Myocardial Infarction

In a published prospective, observational, epidemiological study designed to investigate the rate of myocardial infarction in patients on combination antiretroviral therapy, the use of abacavir within the previous 6 months was correlated with an increased risk of myocardial infarction (MI).¹ In a sponsor-conducted pooled analysis of clinical trials, no excess risk of myocardial infarction was observed in abacavir-treated subjects as compared with control subjects. In totality, the available data from the observational cohort and from clinical trials are inconclusive.

As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, hyperlipidemia, diabetes mellitus, smoking).

6 ADVERSE REACTIONS

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

• Serious and sometimes fatal hypersensitivity reaction. In one trial, once daily dosing of abacavir was associated with more severe hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.1)].
• Lactic acidosis and severe hepatomegaly [see Boxed Warning, Warnings and Precautions (5.2)].
• Immune reconstitution syndrome [see Warnings and Precautions (5.3)].
• Fat redistribution [see Warnings and Precautions (5.4)].
• Myocardial infarction [see Warnings and Precautions (5.5)].

6.1 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 abacavir 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 to 4, ≥ 5% Frequency) in Therapy-naive Adults (CNA30024*) Through 48 Weeks of Treatment

* This trial used double-blind ascertainment of suspected hypersensitivity reactions. During the blinded portion of the trial, suspected hypersensitivity to abacavir was reported by investigators in 9% of 324 subjects in the abacavir group and 3% of 325 subjects in the zidovudine group. † Ten (3%) cases of suspected drug hypersensitivity were reclassified as not being due to abacavir following unblinding.
Adverse Reaction	Abacavir plusLamivudine plus Efavirenz(n = 324)	Zidovudine plus Lamivudineplus 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 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 to 4, ≥ 5% Frequency) in Therapy-naive Adults (CNA3005) Through 48 Weeks of Treatment

Adverse Reaction	Abacavir plusLamivudine/Zidovudine(n = 262)	Indinavir plusLamivudine/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 in CNA3005 experienced worsening of preexisting depression compared with none in the indinavir arm. The background rates of preexisting depression were similar in the two treatment arms.