Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

A summary of Emtriva treatment-emergent clinical adverse reactions in Studies 301A and 303 is provided in Table 2.

Table 2 Selected Treatment-Emergent Adverse Reactions (All Grades, Regardless of Causality) Reported in ≥3% of Emtriva-Treated Subjects in Either Study 301A or 303 (0–48 Weeks)  303 301A
Emtriva
+ ZDV/d4T
+ NNRTI/PI
(N=294) Lamivudine
+ ZDV/d4T
+ NNRTI/PI
(N=146) Emtriva
+ didanosine + efavirenz
(N=286) Stavudine
+ didanosine
+ efavirenz
(N=285)
Body as a Whole    
  Abdominal pain 8% 11% 14% 17%
  Asthenia 16% 10% 12% 17%
  Headache 13% 6% 22% 25%
Digestive System    
  Diarrhea 23% 18% 23% 32%
  Dyspepsia 4% 5% 8% 12%
  Nausea 18% 12% 13% 23%
  Vomiting 9% 7% 9% 12%
Musculoskeletal    
  Arthralgia 3% 4% 5% 6%
  Myalgia 4% 4% 6% 3%
Nervous System    
  Abnormal dreams 2% <1% 11% 19%
  Depressive disorders 6% 10% 9% 13%
  Dizziness 4% 5% 25% 26%
  Insomnia 7% 3% 16% 21%
  Neuropathy/peripheral neuritis 4% 3% 4% 13%
  Paresthesia 5% 7% 6% 12%
Respiratory    
  Increased cough 14% 11% 14% 8%
  Rhinitis 18% 12% 12% 10%
Skin    
  Rash event* 17% 14% 30% 33%
Studies 301A and 303 - Laboratory Abnormalities: Laboratory abnormalities in these trials occurred with similar frequency in the Emtriva and comparator groups. A summary of Grades 3–4 laboratory abnormalities is provided in Table 3 below.

Table 3 Treatment-Emergent Grades 3–4 Laboratory Abnormalities Reported in ≥1% of Emtriva-Treated Subjects in Either Study 301A or 303  303 301A
Emtriva
+ ZDV/d4T
+ NNRTI/PI
(N=294) Lamivudine
+ ZDV/d4T
+ NNRTI/PI
(N=146) Emtriva
+ Didanosine
+ Efavirenz
(N=286) Stavudine
+ Didanosine
+ Efavirenz
(N=285)
*
ULN = Upper limit of normal
Percentage with grade 3 or grade 4 laboratory abnormality 31% 28% 34% 38%
ALT (>5.0 × ULN*) 2% 1% 5% 6%
AST (>5.0 × ULN) 3% <1% 6% 9%
Bilirubin (>2.5 × ULN) 1% 2% <1% <1%
Creatine kinase
(>4.0 × ULN) 11% 14% 12% 11%
Neutrophils (<750 mm3) 5% 3% 5% 7%
Pancreatic amylase
(>2.0 × ULN) 2% 2% <1% 1%
Serum amylase
(>2.0 × ULN) 2% 2% 5% 10%
Serum glucose
<40 or >250 mg/dL) 3% 3% 2% 3%
Serum lipase
(>2.0 × ULN) <1% <1% 1% 2%
Triglycerides
(>750 mg/dL) 10% 8% 9% 6%
Study 934 - Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naïve subjects received either VIREAD® + Emtriva administered in combination with efavirenz (N=257) or zidovudine/lamivudine administered in combination with efavirenz (N=254). Adverse reactions observed in this trial were generally consistent with those seen in previous trials in treatment-experienced or treatment-naïve subjects (Table 4).

Table 4 Selected Treatment-Emergent Adverse Reactions* (Grades 2–4) Reported in ≥5% in Any Treatment Group in Study 934 (0&nda