1 INDICATIONS AND USAGE BAXDELA is a fluoroquinolone antibacterial indicated for the treatment of adults with the following infections caused by designated susceptible bacteria: Acute Bacterial Skin and Skin Structure Infections (ABSSSI) ( 1.1 ) Community-Acquired Bacterial Pneumonia (CABP) ( 1.2 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

( 1.3 ) 1.1 Acute Bacterial Skin and Skin Structure Infections BAXDELA is indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by the following susceptible microorganisms: Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Staphylococcus haemolyticus, Staphylococcus lugdunensis, Streptococcus agalactiae , Streptococcus anginosus Group (including Streptococcus anginosus , Streptococcus intermedius , and Streptococcus constellatus ), Streptococcus pyogenes , Enterococcus faecalis , Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

1.2 Community-Acquired Bacterial Pneumonia BAXDELA is indicated in adults for the treatment of community-acquired bacterial pneumonia (CABP) caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible [MSSA] isolates only), Klebsiella pneumoniae , Escherichia coli, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae , Chlamydia pneumoniae , Legionella pneumophila, and Mycoplasma pneumoniae.

1.3 Usage To reduce the development of drug-resistant bacteria and maintain the effectiveness of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy.

In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

6 ADVERSE REACTIONS The following serious and otherwise important adverse reactions are discussed in greater detail in other sections of labeling: Disabling and Potentially Irreversible Serious Adverse Reactions [see Warnings and Precautions (5.1) ] Tendinitis and Tendon Rupture [see Warnings and Precautions (5.2) ] Peripheral Neuropathy [see Warnings and Precautions (5.3) ] Central Nervous System Effects [see Warnings and Precautions (5.4) ] Hypersensitivity Reactions [see Warnings and Precautions (5.6) ] Clostridium difficile -Associated Diarrhea [see Warnings and Precautions (5.7) ] Blood Glucose Disturbances [see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence ≥ 2%) are nausea, diarrhea, headache, transaminase elevations, and vomiting.

( 6.1 ) 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 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of BAXDELA cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.

Overview of the Safety Evaluation of BAXDELA BAXDELA was evaluated in three Phase 3 multicenter, multinational, randomized, double-blind clinical trials.

These trials included two trials in ABSSSI patients (Trial 1 and Trial 2) and one trial in CABP (Trial 3).

A total of 1170 patients were treated with BAXDELA across all Phase 3 trials (741 patients in the two ABSSSI trials and 429 patients in the CABP trial).

Acute Bacterial Skin and Skin Structure Infections (ABSSSI) BAXDELA was evaluated in two multicenter, multinational, randomized, double-blind, double-dummy, non-inferiority trials (Trial 1 and Trial 2) in adults with ABSSSI.

In Trial 1 patients received BAXDELA 300 mg by intravenous infusion every 12 hours and in Trial 2 the patients received BAXDELA 300 mg by intravenous infusion every 12 hours for 6 doses then were switched to BAXDELA 450 mg tablets every 12 hours.

The total treatment duration was 5 to 14 days.

Adverse reactions were evaluated for 741 patients treated with BAXDELA and 751 patients treated with comparator antibacterial drugs.

The median age of patients treated with BAXDELA was 49 years, ranging between 18 and 94 years old; 15% were age 65 years and older.

Patients treated with BAXDELA were predominantly male (62%) and Caucasian (86%).

The BAXDELA treated population included 44% obese patients (BMI ≥ 30 kg/m 2 ), 11% with diabetes, and 16% with baseline renal impairment (calculated creatinine clearance less than 90 mL/min).

Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 3/741 (0.4%) of patients treated with BAXDELA and in 6/751 (0.8%) of patients treated with the comparator.

BAXDELA was discontinued due to an adverse reaction in 7/741 (0.9%) patients and the comparator was discontinued due to an adverse reaction in 21/751 (2.8%) patients.

The most commonly reported adverse reactions leading to study discontinuation in the BAXDELA arm included urticaria (2/741; 0.3%) and hypersensitivity (2/741; 0.3%); whereas, the most commonly reported adverse reactions leading to study discontinuation in the comparator arm included urticaria (5/751; 0.7%), rash (4/751; 0.5%), hypersensitivity and infusion site extravasation (2/751; 0.3%).

Most Common Adverse Reactions The most common adverse reactions in patients treated with BAXDELA were nausea (8%), diarrhea (8%), headache (3%), transaminase elevations (3%), and vomiting (2%).

Table 4 lists selected adverse reactions occurring in ≥ 2% of patients receiving BAXDELA in the pooled adult Phase 3 clinical trials.

Table 4 Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving BAXDELA in the Pooled Adult Phase 3 ABSSSI Clinical Trials Adverse Reactions BAXDELA N = 741 (%) Vancomycin/aztreonam N = 751 (%) Nausea 8% 6% Diarrhea 8% 3% Headache The data are not an adequate basis for comparison of rates between the study drug and the active control.

3% 6% Transaminase Elevations Pooled reports include hypertransaminasaemia, increased transaminases, and increased ALT and AST.

3% 4% Vomiting 2% 2% Community-Acquired Bacterial Pneumonia BAXDELA was evaluated in one multicenter, multinational, randomized, double-blind trial in adults with CABP (Trial 3).

Patients received BAXDELA 300 mg over 60 minutes every 12 hours for a minimum of 6 doses with an option to switch to oral BAXDELA tablet 450 mg every 12 hours for the remaining doses (total of 10 to 20 doses of intravenous infusion and oral combined).

Adverse reactions were evaluated for 429 patients treated with BAXDELA and 427 patients treated with moxifloxacin.

The median age of patients treated with BAXDELA was 63 years, ranging between 18 and 89 years; 47.1% were 65 years of age and older and 19.6% were 75 years of age and older.

Patients treated with BAXDELA were predominantly male (58.3%) and white (92.3%).

The BAXDELA-treated population included patients with obesity (BMI greater than or equal to 30) (24.0%), COPD/asthma (14.2%), cardiac disease (24.2%), diabetes (16.3%), and baseline renal impairment including 36.4% with moderate renal impairment (CrCl less than 30-59 mL/min), and 4.0% with severe renal impairment (CrCl less than 29 mL/min).

Overall, approximately 12.4% of patients were in PORT Risk Class II, 60.1% were in PORT Risk Class III, 26.6% were in PORT Risk Class IV, and 0.9% were in PORT Risk Class V.

Serious Adverse Reactions and Adverse Reactions Leading to Discontinuation Serious adverse reactions occurred in 2/429 (0.5%) of patients treated with BAXDELA and in 1/427 (0.2%) of patients treated with moxifloxacin.

Discontinuation due to an adverse reaction occurred in 9/429 (2.1%) patients treated with BAXDELA and in 4/427 (0.9%) treated with moxifloxacin.

The most commonly reported adverse reactions leading to study drug discontinuation in the BAXDELA arm were transaminase elevations (2/429; 0.5%).

The most commonly reported adverse reactions leading to study drug discontinuation in the comparator arm were infusion site reactions (1/427; 0.2%).

Most Common Adverse Reactions The most common adverse reactions in patients treated with BAXDELA were diarrhea (5%) and transaminase elevations (5%).

Table 5 lists selected adverse reactions occurring in ≥ 2% of patients receiving BAXDELA in the adult Phase 3 CABP clinical trial.

Table 5 Selected Adverse Reactions Occurring in ≥ 2% of Patients Receiving BAXDELA in the Adult Phase 3 CABP Clinical Trial Adverse Reactions BAXDELA N = 429 Moxifloxacin N = 427 Diarrhea 5% 3% Transaminase elevations Includes hepatic enzyme increased, transaminases increased and alanine aminotransferase (ALT) increased.

5% 3% Adverse Reactions Occurring in Less Than 2% of Patients Receiving BAXDELA in the ABSSSI (Trials 1 and 2) and CABP (Trial 3) Clinical Trials The following selected adverse reactions were reported in BAXDELA-treated patients at a rate of less than 2% in the ABSSSI (Trials 1 and 2) and CABP (Trial 3) clinical trials: Blood and Lymphatic System Disorders: agranulocytosis , anemia, leukopenia, neutropenia, pancytopenia Cardiac Disorders : sinus tachycardia, palpitations, bradycardia, ventricular extrasystoles Ear and Labyrinth Disorders: tinnitus, vertigo, vestibular disorder Eye Disorders : vision blurred General disorders and administration site conditions: infusion related reactions Gastrointestinal Disorders : abdominal pain, dyspepsia Immune System Disorders : hypersensitivity Infections and Infestations : Clostridium difficile infection, fungal infection, oral candidiasis, vulvovaginal candidiasis Laboratory Investigations : blood alkaline phosphatase increased, blood creatinine increased, blood creatine phosphokinase increased Metabolism and Nutrition Disorders: hyperglycemia, hypoglycemia Musculoskeletal and Connective Tissue Disorders: myalgia Nervous System Disorders : dizziness, hypoesthesia, paraesthesia, dysgeusia, presyncope, syncope Psychiatric Disorders : agitation, anxiety, confusional state, insomnia, abnormal dreams Renal and Urinary: renal impairment, renal failure Skin and Subcutaneous Tissue Disorders : pruritus, urticaria, dermatitis, rash Vascular Disorders: flushing, hypotension, hypertension