6 ADVERSE REACTIONS The most common adverse reactions (≥2%) are nausea, headache, diarrhea, vomiting, and dizziness. (6) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Adverse Reactions in Clinical Trials Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be compared directly to rates from clinical trials of another drug and may not reflect rates observed in practice. Adverse reactions were evaluated for 1050 patients treated with SIVEXTRO and 662 patients treated with the comparator antibacterial drug in two Phase 2 and two Phase 3 clinical trials. The median age of patients treated with SIVEXTRO in the Phase 2 and Phase 3 trials was 42 years, ranging between 17 and 86 years old. Patients treated with SIVEXTRO were predominantly male (65%) and White (82%). Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 12/662 (1.8%) of patients treated with SIVEXTRO and in 13/662 (2.0%) of patients treated with the comparator. SIVEXTRO was discontinued due to an adverse reaction in 3/662 (0.5%) of patients and the comparator was discontinued due to an adverse reaction in 6/662 (0.9%) of patients. Most Common Adverse Reactions The most common adverse reactions in patients treated with SIVEXTRO were nausea (8%), headache (6%), diarrhea (4%), vomiting (3%), and dizziness (2%). The median time of onset of adverse reactions was 5 days for both SIVEXTRO and linezolid with 12% occurring on the second day of treatment in both treatment groups. Table 2 lists selected adverse reactions occurring in at least 2% of patients treated with SIVEXTRO in clinical trials. Table 2: Selected Adverse Reactions Occurring in ≥2% of Patients Receiving SIVEXTRO in the Pooled Phase 3 ABSSSI Clinical Trials Adverse Reactions Pooled Phase 3 ABSSSI Clinical Trials SIVEXTRO (200 mg oral/intravenous once daily for 6 days) (N=662) Linezolid (600 mg oral/intravenous twice daily for 10 days) (N=662) Gastrointestinal Disorders Nausea 8% 12% Diarrhea 4% 5% Vomiting 3% 6% Nervous System Disorder Headache 6% 6% Dizziness 2% 2% Safety was additionally evaluated in a randomized, double-blind, multicenter study conducted in China, the Philippines, Taiwan, and the US, which included a total of 292 adult patients treated with tedizolid 200 mg administered IV and/or oral once daily for 6 days for the treatment of ABSSSI. The safety profile in this study was similar to the Phase 3 clinical trials; however, infusion site reactions (phlebitis) were reported in 3.1% of tedizolid-treated subjects, particularly among Asian patients. The following selected adverse reactions were reported in SIVEXTRO-treated patients at a rate of less than 2% in these clinical trials: Blood and Lymphatic System Disorders: anemia Cardiovascular: palpitations, tachycardia Eye Disorders: asthenopia, vision blurred, visual impairment, vitreous floaters General Disorders and Administration Site Conditions: infusion-related reactions Immune System Disorders: drug hypersensitivity Infections and Infestations: Clostridium difficile colitis, oral candidiasis, vulvovaginal mycotic infection Investigations: hepatic transaminases increased, white blood cell count decreased Nervous System Disorders: hypoesthesia, paresthesia, VIIth nerve paralysis Psychiatric Disorders: insomnia Skin and Subcutaneous Tissue Disorders: pruritus, urticaria, dermatitis Vascular Disorders: flushing, hypertension Laboratory Parameters Hematology laboratory abnormalities that were determined to be potentially clinically significant in the pooled Phase 3 ABSSSI clinical trials are provided in Table 3. Table 3: Potentially Clinically Significant Lowest Laboratory Values in the Pooled Phase 3 ABSSSI Clinical Trials Laboratory Assay Potentially Clinically Significant Values<75% (<50% for absolute neutrophil count) of lower limit of normal (LLN) for values normal at baseline Represents lowest abnormal post-baseline value through the last dose of active drug SIVEXTRO (200 mg oral/intravenous once daily for 6 days) (N=618)Number of patients with non-missing laboratory values Linezolid (600 mg oral/intravenous twice daily for 10 days) (N=617) M = male; F = female Hemoglobin (<10.1 g/dL [M]) (<9 g/dL [F]) 3.1% 3.7% Platelet count (<112 × 103/mm3) 2.3% 4.9% Absolute neutrophil count (<0.8 × 103/mm3) 0.5% 0.6% Myelosuppression Phase 1 studies conducted in healthy adults exposed to SIVEXTRO for 21 days showed a possible dose and duration effect on hematologic parameters beyond 6 days of treatment. In the Phase 3 trials, clinically significant changes in these parameters were generally similar for both treatment arms (see Table 3). Peripheral and Optic Neuropathy Peripheral and optic neuropathy have been described in patients treated with another member of the oxazolidinone class for longer than 28 days. In Phase 3 trials, reported adverse reactions for peripheral neuropathy and optic nerve disorders were similar between both treatment arms (peripheral neuropathy 1.2% vs. 0.6% for tedizolid phosphate and linezolid, respectively; optic nerve disorders 0.3% vs. 0.2%, respectively). No data are available for patients exposed to SIVEXTRO for longer than 6 days.