(1%).
b Fatigue: includes fatigue, asthenia, and malaise.
Less Common Adverse Reactions
The following adverse reactions occurred in <2% of subjects receiving dolutegravir pluslamivudine or are from studies described in the prescribing information of the individualcomponents, TIVICAY (dolutegravir) and EPIVIR (lamivudine). Some events have beenincluded because of their seriousness and assessment of potential causal relationship.
Blood and Lymphatic Systems Disorders: Anemia, neutropenia, thrombocytopenia.
Gastrointestinal Disorders: Abdominal discomfort, abdominal pain, flatulence, upper abdominalpain, vomiting.
General: Fever.
Hepatobiliary Disorders: Hepatitis.
Immune System Disorders: Hypersensitivity, immune reconstitution syndrome.
Musculoskeletal Disorders: Myositis.
Nervous System Disorders: Somnolence.
Psychiatric Disorders: Anxiety, abnormal dreams, depression. Suicidal ideation, attempt,behavior, or completion; these events were observed primarily in subjects with a pre-existinghistory of depression or other psychiatric illness.
Renal and Urinary Disorders: Renal impairment.
Skin and Subcutaneous Tissue Disorders: Pruritus, rash.
Laboratory Abnormalities
Selected laboratory abnormalities with a worsening grade from baseline and representing theworst-grade toxicity in ≥2% of subjects are presented in Table 3. The mean change from baselineobserved for selected lipid values is presented in Table 4.
Table 3. Selected Laboratory Abnormalities (Grades 2 to 4; Week 48 Pooled Analyses)
in GEMINI-1 and GEMINI-2 Trials
Laboratory Parameter
Preferred Term
TIVICAY plus EPIVIR
(n = 716)
TIVICAY plus
TRUVADA
(n = 717)
ALT
Grade 2 (>2.5-5.0 x ULN) 2% 3%
Grade 3 to 4 (>5.0 x ULN) 3% 3%
AST
Grade 2 (>2.5-5.0 x ULN) 3% 3%
Grade 3 to 4 (>5.0 x ULN) 2% 3%
Total Bilirubin
Grade 2 (1.6-2.5 x ULN) 1% 2%
Grade 3 to 4 (>2.5 x ULN) <1% <1%
Creatine kinase
Grade 2 (6.0-9.9 x ULN) 4% 3%
Grade 3 to 4 (≥10.0 x ULN) 4% 5%
Hyperglycemia
Grade 2 (126-250 mg/dL) 7% 4%
Grade 3 to 4 (>250 mg/dL) <1% <1%
Hypophosphatemia (Phosphate)
Grade 2 (1.4 to <2.0 mg/dL) 7% 8%
Grade 3 to 4 (<1.4 mg/dL) <1% <1%
Lipase
Grade 2 (>1.5-3.0 x ULN) 5% 5%
Grade 3 to 4 (>3.0 x ULN) <1% 3%
ULN = Upper limit of normal.
Table 4. Mean Change from Baseline in Fasted Lipid Values (Week 48 Pooled
Analysesa
) in GEMINI-1 and GEMINI-2 Trials
Laboratory Parameter
Preferred Term
TIVICAY plus
EPIVIR
(n = 716)
TIVICAY plus
TRUVADA
(n = 717)
Cholesterol (mg/dL) 13.3 -6.9
HDL cholesterol (mg/dL) 5.6 0.8
LDL cholesterol (mg/dL) 7.5 -6.3
Triglycerides (mg/dL) 3.7 -6.9
Total cholesterol/HDL cholesterol ratio -0.1 -0.3
a Subjects on lipid-lowering agents at baseline are excluded (TIVICAY plus EPIVIR, n = 29;
TIVICAY plus TRUVADA, n = 23). Lipid last observation carried forward data were used
such that the last available fasted, on-treatment lipid value prior to the initiation of a lipidloweringagent is used in place of future observed values. A total of 23 and 13 subjectsreceiving TIVICAY plus EPIVIR and TIVICAY plus TRUVADA, respectively, initiated lipidloweringagents post-baseline.
Changes in Serum Creatinine: Dolutegravir has been shown to increase serum creatinine due toinhibition of tubular secretion of creatinine without aff |
