Emtricitabine adverse reactions

# Adverse Reactions
The following adverse reactions are discussed in other sections of the labeling:
- Lactic acidosis/severe hepatomegaly with steatosis.
- Severe acute exacerbations of Hepatitis B.
- Immune reconstitution syndrome.

## Adverse Reactions from Clinical Trials Experience

### Clinical Trials in Adult Subjects
More than 2,000 adult subjects with HIV-1 infection have been treated with EMTRIVA alone or in combination with other antiretroviral agents for periods of 10 days to 200 weeks in clinical trials.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The most common adverse reactions (incidence greater than or equal to 10%, any severity) identified from any of the 3 large controlled clinical trials include headache, diarrhea nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough, and rhinitis.
Treatment Emergent Adverse Reactions: The most common adverse reactions that occurred in subjects receiving EMTRIVA with other antiretroviral agents in clinical trials 301A and 303 were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of subjects discontinued participation in the clinical trials due to these events. All adverse reactions were reported with similar frequency in EMTRIVA and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the EMTRIVA treated group.
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.
Laboratory Abnormalities: Laboratory abnormalities in these trials occurred with similar frequency in the EMTRIVA and comparator groups. A summary of Grades 34 laboratory abnormalities is provided in Table 3 below
Treatment Emergent Adverse Reactions: In Study 934, 511 antiretroviral-naive 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-naive subjects (Table 4).
Study 934  Laboratory Abnormalities: Significant laboratory abnormalities observed in this trial are shown in Table 5.

## Clinical Trials in Pediatric Subjects
Assessment of adverse reactions is based on data from Study 203, an open label, uncontrolled trial of 116 HIV-1-infected pediatric subjects who received emtricitabine through 48 weeks. The adverse reaction profile in pediatric subjects was generally comparable to that observed in clinical trials of EMTRIVA in adult subjects. Hyperpigmentation was more frequent in children. Additional adverse reactions identified from this trial include anemia.
Selected treatment-emergent adverse events, regardless of causality, reported in subjects during 48 weeks of treatment were the following: infection (44%), hyperpigmentation (32%), increased cough (28%), vomiting (23%), otitis media (23%), rash (21%), rhinitis (20%), diarrhea (20%), fever (18%), pneumonia (15%), gastroenteritis (11%), abdominal pain (10%), and anemia (7%). Treatment-emergent grades 34 laboratory abnormalities were experienced by 9% of pediatric subjects, including elevated amylase (>2.0  ULN) (n=4), decreased neutrophils (5  ULN) (n=2), elevated CPK (>4  ULN) (n=2) and one subject each with elevated bilirubin (>3.0  ULN), elevated GGT (>10  ULN), elevated lipase (>2.5  ULN), decreased hemoglobin (<7 g/dL), and decreased glucose (<40 mg/dL).