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 susceptible isolates of the following:

Gram-positive organisms: 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, and Enterococcus faecalis.

Gram-negative organisms: Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.

1.2 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 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.

2.1 Important Administration Instructions

2.2 Recommended Dosage Regimen

For treatment of adults with ABSSSI, the recommended dosage regimen of BAXDELA is as follows:

• Administer 300 mg of BAXDELA for Injection every 12 hours over 60 minutes by intravenous infusion for 5 to 14 days or,
• Administer 300 mg of BAXDELA for Injection every 12 hours over 60 minutes by intravenous infusion, then switch to a 450 mg BAXDELA tablet orally every 12 hours at the discretion of the physician for a total duration of 5 to 14 days or,
• Administer a 450 mg BAXDELA tablet orally every 12 hours for a total duration of 5 to 14 days.

2.3 Dosage in Patients with Renal Impairment

Table 1 below describes the dosage modification based on the estimated glomerular filtration rate (eGFR) that is recommended in patients with renal impairment. Dosage adjustment is required for patients with severe renal impairment (eGFR 15-29 mL/min/1.73m2).

In patients with severe renal impairment receiving BAXDELA intravenously, closely monitor serum creatinine levels and eGFR [see Use in Specific Populations (8.7)]. If serum creatinine level increases, consider switching to BAXDELA Tablets. Discontinue BAXDELA if eGFR decreases to <15 mL/min/1.73 m2.

1.BAXDELA must be reconstituted and then further diluted under aseptic conditions. Reconstitute the powder in the BAXDELA vial using 10.5 mL of 5% Dextrose Injection (D5W) or 0.9% Sodium Chloride Injection for each 300 mg vial. Shake the vial vigorously until contents are completely dissolved. The reconstituted vial contains 300 mg per 12 mL (25 mg/mL) of BAXDELA as a clear yellow to amber colored solution.

2.The reconstituted solution must then be diluted to a total volume of 250 mL using either 0.9% Sodium Chloride or D5W to achieve a concentration of 1.2 mg/mL, prior to administration. Prepare the required dose for intravenous infusion by withdrawing the appropriate volume from the reconstituted vial per Table 2 below:

Storage of the Reconstituted and Diluted Solutions

Reconstituted vials, as described above, may be stored either refrigerated at 2°C to 8°C (36°F to 46°F), or at controlled room temperature 20°C to 25°C (68°F to 77°F) for up to 24 hours. Do not freeze.

Once diluted into the intravenous bag, as described above, BAXDELA may be stored either refrigerated at 2°C to 8°C (36°F to 46°F) or at a controlled room temperature of 20°C to 25°C (68°F to 77°F) for up to 24 hours. Do not freeze.

Administration

After reconstitution and dilution, administer BAXDELA by intravenous infusion, using a total infusion time of 60 minutes [see Dosage and Administration (2.1)].

The compatibility of reconstituted BAXDELA with intravenous medications, additives, or substances other than D5W or 0.9% Sodium Chloride Injection has not been established. If a common intravenous line is being used to administer other drugs in addition to BAXDELA the line should be flushed before and after each BAXDELA infusion with 0.9% Sodium Chloride Injection or D5W.

BAXDELA for Injection: A sterile, lyophilized powder containing 300 mg delafloxacin (equivalent to 433 mg delafloxacin meglumine) in a single-dose vial which must be reconstituted and further diluted prior to intravenous infusion. The lyophilized powder is a light yellow to tan cake, which may exhibit cracking and shrinkage and slight variation in texture and color.

BAXDELA Tablets: Modified capsule shaped tablets in beige to mottled beige color with RX3341 debossed on one side containing 450 mg delafloxacin (equivalent to 649 mg delafloxacin meglumine).

5.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon Rupture, Peripheral Neuropathy and Central Nervous System Effects

Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions from different body systems that can occur together in the same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia, myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety, depression, insomnia, severe headaches, and confusion). These reactions could occur within hours to weeks after starting a fluoroquinolone. Patients of any age or without pre-existing risk factors have experienced these adverse reactions [see Warnings and Precautions (5.2, 5.3 and 5.4)].

Discontinue BAXDELA immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including BAXDELA, in patients who have experienced any of these serious adverse reactions associated with fluoroquinolones.

5.2 Tendinitis and Tendon Rupture

Fluoroquinolones have been associated with an increased risk of tendinitis and tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and other tendons. Tendinitis or tendon rupture can occur, within hours or days of starting a fluoroquinolone, or as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon rupture can occur bilaterally.

This risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in patients over age 60 years of age, in patients taking corticosteroid drugs, and, in patients with kidney, heart, and lung transplant. Other factors that may independently increase the risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who do not have the above risk factors.

Discontinue BAXDELA immediately if the patient experiences pain, swelling, inflammation or rupture of a tendon. Advise patients, at the first sign of tendon pain, swelling, or inflammation, to stop taking BAXDELA, to avoid exercise and use of the affected area, and to promptly contact their healthcare provider about changing to a non-quinolone antimicrobial drug. Avoid BAXDELA in patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture.

5.3 Peripheral Neuropathy

Fluoroquinolones have been associated with an increased risk of peripheral neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported in patients receiving fluoroquinolones, including BAXDELA. Symptoms may occur soon after initiation of fluoroquinolones and may be irreversible in some patients [see Warnings and Precautions (5.1) and Adverse Reactions (6.1)].

Discontinue BAXDELA immediately if the patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness, and/or weakness or other alterations of sensation including light touch, pain, temperature, position sense, and vibratory sensation and/or motor strength in order to minimize the development of an irreversible condition. Avoid fluoroquinolones, including BAXDELA in patients who have previously experienced peripheral neuropathy [see Adverse Reactions (6.1)].

5.4 Central Nervous System Effects

Fluoroquinolones have been associated with an increased risk of central nervous system (CNS) reactions, including: convulsions and increased intracranial pressure (including pseudotumor cerebri) and toxic psychosis. Fluoroquinolones, including BAXDELA, may also cause CNS reactions of nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or acts. These adverse reactions may occur following the first dose. If these reactions occur in patients receiving BAXDELA, discontinue BAXDELA immediately and institute appropriate measures. As with all fluoroquinolones, use BAXDELA when the benefits of treatment exceed the risks in patients with known or suspected CNS disorders (e.g., severe cerebral arteriosclerosis, epilepsy) or in the presence of other risk factors that may predispose to seizures or lower the seizure threshold.

5.5 Exacerbation of Myasthenia Gravis

Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Post-marketing serious adverse reactions, including death and requirement for ventilator support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid BAXDELA in patients with known history of myasthenia gravis [see Patient Counseling Information (17)].

5.6 Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving fluoroquinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and itching. Hypersensitivity reactions have been reported in patients receiving BAXDELA. These reactions may occur after first or subsequent doses of BAXDELA [see Adverse Reactions (6.1)]. Discontinue BAXDELA at the first appearance of a skin rash or any other sign of hypersensitivity.

5.7 Clostridium difficile-Associated Diarrhea

Clostridium difficile-associated diarrhea (CDAD) has been reported in users of nearly all systemic antibacterial drugs, including BAXDELA, with severity ranging from mild diarrhea to fatal colitis. Treatment with antibacterial agents can alter the normal flora of the colon, and may permit overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antibacterial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibacterial use not directed against C. difficile should be discontinued, if possible. Appropriate measures such as fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical eva luation should be instituted as clinically indicated

5.8 Development of Drug-Resistant Bacteria

Prescribing BAXDELA in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

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.

BAXDELA was eva luated 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 eva luated 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/m2), 11% with diabetes, and 16% with baseline renal impairment (calculated creatinine clearance less than 90 mL/min).