ADVERSE REACTIONS
Clinical Trials
TRUVADA
Four hundred and forty-seven HIV-1 infected patients have received combination therapy with EMTRIVA and VIREAD with either a non-nucleoside reverse transcriptase inhibitor or protease inhibitor for 48 weeks in clinical studies.
Study 934 - Treatment Emergent Adverse Events
Adverse events observed in this study were generally consistent with those seen in other studies in treatment-experienced or treatment-naïve patients receiving VIREAD and/or EMTRIVA (Table 8).
Table 8 Selected Treatment-Emergent Adverse Events (Grades 2–4) Reported in ≥3% in Any Treatment Group in Study 934 (0–48 Weeks) | | EMTRIVA+VIREAD+EFV | AZT/3TC+EFV |
|---|
| | N=257 | N=254 |
|---|
| Gastrointestinal Disorder | | |
| Diarrhea | 7% | 4% |
| Nausea | 8% | 6% |
| Vomiting | 1% | 4% |
| General Disorders and Administration Site Condition | | |
| Fatigue | 7% | 6% |
| Infections and Infestations | | |
| Sinusitis | 4% | 2% |
| Upper respiratory tract infections | 3% | 3% |
| Nasopharyngitis | 3% | 1% |
| Nervous System Disorders | | |
| Somnolence | 3% | 2% |
| Headache | 5% | 4% |
| Dizziness | 8% | 7% |
| Psychiatric Disorders | | |
| Depression | 4% | 7% |
| Insomnia | 4% | 5% |
| Abnormal dreams | 4% | 3% |
| Skin and Subcutaneous Tissue Disorders | | |
| Rash | 5% | 4% |
Laboratory Abnormalities
Laboratory abnormalities observed in this study were generally consistent with those seen in other studies of VIREAD and/or EMTRIVA (Table 9).
Table 9 Significant Laboratory Abnormalities Reported in ≥1% of Patients in Any Treatment Group in Study 934 (0–48 Weeks) | | EMTRIVA + VIREAD+EFV | AZT/3TC + EFV |
|---|
| | N=257 | N=254 |
|---|
Any ≥ Grade 3 Laboratory
Abnormality | 25% | 22% |
Fasting Cholesterol
(>240 mg/dL) | 15% | 17% |
Creatine Kinase
(M: >990 U/L)
(F: >845 U/L) | 7% | 6% |
| Serum Amylase (>175 U/L) | 7% | 3% |
| Alkaline Phosphatase (>550 U/L) | 1% | 0% |
AST
(M: >180 U/L)
(F: >170 U/L) | 3% | 2% |
ALT
(M: >215 U/L)
(F: >170 U/L) | 2% | 2% |
| Hemoglobin (<8.0 mg/dL) | 0% | 3% |
| Hyperglycemia (>250 mg/dL) | 1% | 1% |
| Hematuria (>75 RBC/HPF) | 2% | 2% |
| Neutrophils (<750/mm3) | 3% | 4% |
Fasting Triglycerides
(>750 mg/dL) | 4% | 2% |
In addition to the events described above for Study 934, other adverse events that occurred in at least 5% of patients receiving EMTRIVA or VIREAD with other antiretroviral agents in clinical trials include anxiety, arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, rhinitis and rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction).
Skin discoloration has been reported with higher frequency among EMTRIVA treated patients. Skin discoloration, manifested by hyperpigmentation on the palms and/or soles was generally mild and asymptomatic. The mechanism and clinical significance are unknown.
In addition to the laboratory abnormalities described above for Study 934, Grade 3/4 elevations of bilirubin (>2.5 × ULN), pancreatic amylase (>2.0 × ULN), serum glucose (<40 or >250 mg/dL), serum lipase (>2.0 × ULN), and urine glucose (≥3+) occurred in up to 3% of patients treated with EMTRIVA or VIREAD with other antiretroviral agents in clinical trials.
For more information, please consult the EMTRIVA and VIREAD package inserts.
Post Marketing Experience
EMTRIVA
No additional events have been identified for inclusion in this section.
VIREAD
The following events have been identified during post-approval use of VIREAD. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion because of a combination of their seriousness, frequency of reporting or potential causal connection to VIREAD.
IMMUNE SYSTEM DISORDERS
Allergic reaction
METABOLISM AND NUTRITION DISORDERS
Hypophosphatemia, Lactic acidosis
RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS
Dyspnea
GASTROINTESTINAL DISORDERS
Abdominal pain, Increased amylase, Pancreatitis
HEPATOBILIARY DISORDERS
Increased liver enzymes, Hepatitis
SKIN AND SUBCUTANEOUS TISSUE DISORDERS
Rash
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Myopathy, Osteomalacia (both associated with proximal renal tubulopathy)
RENAL AND URINARY DISORDERS
Renal insufficiency, Renal failure, Acute renal failure, Fanconi syndrome, Proximal tubulopathy, Proteinuria, Increased creatinine, Acute tubular necrosis, Nephrogenic diabetes insipidus, Polyuria, Interstitial nephritis (including acute cases)
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS
Asthenia
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