Sivextro Adverse Reactions

Clinical Trials Experience: SIVEXTRO was evaluated in two comparator-controlled clinical trials of ABSSSI, which included a total of 662 patients treated with SIVEXTRO [200 mg administered oral and/or IV once daily (331/662 patients)] for 6 days and 662 patients treated with linezolid (600 mg administered oral and/or IV every 12 hours) for 10 days.
Safety was additionally evaluated in two post-marketing studies of ABSSSI: 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, and 297 patients treated with linezolid 600 mg administered IV and/or oral every 12 hours for 10 days, and also in a randomized, open-label, active-controlled study in Japan, which included 83 adult patients treated with tedizolid 200 mg administered IV and/or oral once daily for 7-21 days. The safety profile in these studies was similar to the Phase 3 clinical trials; however, infusion site reactions (phlebitis) were reported more frequently (2.1%) in tedizolid-treated subjects than in the linezolid control group (0%), particularly among Asian patients. These findings suggest a higher frequency of infusion related reactions (phlebitis) than was observed in previous clinical studies with tedizolid phosphate.
The most common adverse reactions occurring in patients receiving SIVEXTRO in the pooled Phase 3 clinical trials were nausea, headache, diarrhea and vomiting. Treatment discontinuations due to adverse events occurred in 12/1037 (1.2%) of patients receiving SIVEXTRO and 13/1000 (1.3%) receiving linezolid, with the most common adverse events leading to discontinuations for both treatments being gastrointestinal disorders at a rate of 0.2% in the SIVEXTRO group and 0.3% in the linezolid group. A total of 30 (2.9%) of patients receiving SIVEXTRO in controlled trials experienced a serious adverse event.
During clinical trials of SIVEXTRO, the following adverse drug reactions were reported during therapy and during follow-up. The adverse drug reactions are organized by system organ class, and the frequency categories for these adverse drug reactions are reported in Table 9 as follows: Very common: ≥1/10 (≥10%), Common: ≥1/100 and <1/10 (≥1% and <10%), Uncommon: ≥1/1000 and <1/100 (≥0.1% and <1%), Rare: ≥1/10,000 and <1/1000 (≥0.01% and <0.1%), Very rare: <1/10,000 (<0.01%). (See Table 9.)

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In hematologic monitoring of the comparator controlled studies, the frequency of values below the lower limit of normal in patients treated with tedizolid phosphate and linezolid, respectively, were: hemoglobin (40.2% vs 44.5%); platelet count (6.4% vs 12.6%); and absolute neutrophil count (ANC) (1.9% vs 4.7%). The frequency of values determined to be potentially clinically significant for these parameters (< 75% (< 50% for absolute neutrophil count) of lower limit of normal (LLN) for values normal at baseline) are summarized in Table 10. (See Table 10.)

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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 neutrophil and hemoglobin were generally similar for both treatment arms, but fewer patients had substantially abnormal platelet values in the tedizolid arm than in the linezolid arm (see Table 10). Thrombocytopenia has been reported in patients treated with tedizolid phosphate in post-marketing experience. Most cases of thrombocytopenia occurred with treatment lasting longer than the recommended duration.
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. 0.7% for tedizolid phosphate and linezolid, respectively; optic nerve disorders 0.3% vs. 0.1%, respectively). No data are available for patients exposed to SIVEXTRO for longer than 6 days. A 9-month rat neurotoxicity study did not show evidence of optic or peripheral nerve toxicity at exposures approximately 8-fold greater than anticipated human clinical oral exposure at the recommended dose of tedizolid [see Pharmacology: Nonclinical Toxicology under Actions].
Post-marketing Experience: The following adverse drug reaction, not listed previously, has been reported during worldwide post-marketing experience: Blood and Lymphatic System Disorders: Thrombocytopenia.