The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions, including Anaphylaxis [see Warnings and Precautions ( 5.1 )] Infusion-related Reactions [see Warnings and Precautions ( 5.2 )] Hepatic Adverse Reactions [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (incidence ≥ 5%) are hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Melinta Therapeutics at 1-844-633-6568 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of REZZAYO cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of REZZAYO was assessed in 76 subjects in phase 1 studies and 232 patients with candidemia and invasive candidiasis in Trials 1 and 2, who received a 400 mg loading dose followed by a 200 mg dose once weekly or higher (please note that after the loading dose of 400 mg, weekly doses higher than 200 mg are not approved).
A total of 151 patients received an initial 400 mg loading dose followed by a 200 mg dose once weekly thereafter (400 mg/200 mg dose); the maximum duration of dosing was 4 weekly doses (including the loading dose). In the pooled Trial 1 and 2 safety database of REZZAYO patients treated with the 400 mg/200 mg dose, the age range was 19-91 years, the gender distribution was 64.9% male and 35.1% females, and the race distribution was 66.2% White, 7.9% Black, 17.9% Asian, 2.7% other, and 5.3% not reported.
Adverse Reactions Leading to Discontinuation in Patients with Candidemia and Invasive Candidiasis The number of patients with an adverse reaction leading to discontinuation of study medication was 9.3% in the REZZAYO arm and 9.0% in the caspofungin arm. In Trial 2, patients with a history (or presenting with significant symptoms) of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's Disease or Huntington's Disease) or currently taking a known neurotoxic medication were excluded from the trial.
Most Common Adverse Reactions in Patients with Candidemia and Invasive Candidiasis Selected adverse reactions occurring in 5% or more of the patients, who received a 400 mg loading dose followed by a 200 mg dose of REZZAYO once weekly are shown in Table 2 . Table 2: Adverse Reactions Reported in ≥5% of Adult Patients Receiving REZZAYO Therapy for Candidemia/Invasive Candidiasis Adverse Reaction REZZAYO N = 151 n (%) Caspofungin N = 166 n (%) Gastrointestinal disorders Diarrhea 17 (11%) 17 (10%) Vomiting 14 (9%) 7 (4%) Nausea 13 (9%) 8 (5%) Abdominal pain 11 (7%) 9 (5%) Constipation 8 (5%) 8 (5%) Metabolism and nutrition disorders Hypokalemia 22 (15%) 17 (10%) Hypomagnesemia 12 (8%) 5 (3%) Hypophosphatemia 8 (5%) 5 (3%) General disorders Pyrexia 18 (12%) 11 (7%) Blood and lymphatic system disorders Anemia 15 (10%) 13 (8%) Less Common Adverse Reactions in Patients with Candidemia and Invasive Candidiasis The following selected adverse reactions occurred in <5% of patients receiving REZZAYO: infusion-related reactions, tremor, disseminated intravascular coagulation, dysphagia, gastrointestinal hemorrhage, fluid overload, insomnia, erythema, headache, dizziness, acute kidney injury, abnormal liver tests (including hypertransaminasemia and increased gamma-glutamyltransferase), peripheral neuropathy (includes neuropathy peripheral, polyneuropathy, and peroneal nerve palsy).
Tremors Tremors were reported in 4/151 (2.6%) of REZZAYO-treated patients and none of the caspofungin-treated patients in Trials 1 and 2. All tremors developed in the second or third week after initiation of REZZAYO treatment and resolved within a month of onset.
6.2Postmarketing Experience
The following adverse reactions have been identified during post approval use of REZZAYO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Immune system disorders : drug hypersensitivity, anaphylactic reaction
