Delafloxacin Meglumine

FDA Drug Information • Also known as: Baxdela

Brand Names: Baxdela
Dosage Form: POWDER, FOR SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS and EXACERBATION OF MYASTHENIA GRAVIS Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together (5.1), including: Tendinitis and tendon rupture (5.2) Peripheral neuropathy (5.3) Central nervous system effects (5.4) Discontinue BAXDELA immediately and avoid the use of fluoroquinolones, including BAXDELA, in patients who experience any of these serious adverse reactions (5.1) Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid BAXDELA in patients with known history of myasthenia gravis. (5.5) WARNING: SERIOUS ADVERSE REACTIONS INCLUDING TENDINITIS, TENDON RUPTURE, PERIPHERAL NEUROPATHY, CENTRAL NERVOUS SYSTEM EFFECTS, and EXACERBATION OF MYASTHENIA GRAVIS See full prescribing information for complete boxed warning. Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together ( 5.1 ), including: Tendinitis and tendon rupture ( 5.2 ) Peripheral neuropathy ( 5.3 ) Central nervous system effects ( 5.4 ) Discontinue BAXDELA immediately and avoid the use of fluoroquinolones, including BAXDELA, in patients who experience any of these serious adverse reactions. ( 5.1 ) Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid BAXDELA in patients with known history of myasthenia gravis. ( 5.5 )

Description

11 DESCRIPTION BAXDELA (delafloxacin) for Injection and BAXDELA (delafloxacin) Tablets contain meglumine salt of delafloxacin, a fluoroquinolone antibacterial. Delafloxacin meglumine is identified chemically as 1-Deoxy-1-(methylamino)-D-glucitol, 1-(6-amino-3,5-difluoropyridin-2-yl)-8-chloro-6-fluoro-7-(3-hydroxyazetidin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate (salt), the chemical structure of which is shown below. The meglumine salt has a molecular weight of 635.97 g/mol, whereas the molecular weight of the delafloxacin free acid is 440.76 g/mol. Figure 1 Chemical Structure C 18 H 12 ClF 3 N 4 O 4 ∙ C 7 H 17 NO 5 M.W. 635.97 BAXDELA is intended for intravenous infusion or oral administration. BAXDELA is supplied as a sterile, lyophilized powder for injection and oral tablets as follows: BAXDELA for Injection Each vial of BAXDELA for Injection, 300 mg, is a sterile lyophilized powder that contains 300 mg delafloxacin (equivalent to 433 mg delafloxacin meglumine) and the following inactive ingredients: Edetate disodium (EDTA), (3.4 mg); meglumine (59 mg); sulfobutylether-β-cyclodextrin (2400 mg). Sodium hydroxide and/or hydrochloric acid may have been used to adjust the pH. BAXDELA Tablets Each BAXDELA tablet for oral use contains 450 mg delafloxacin (equivalent to 649 mg delafloxacin meglumine) and the following inactive ingredients: Citric acid anhydrous (5.5 mg); crospovidone (109 mg); magnesium stearate (10 mg); microcrystalline cellulose (417 mg); povidone (34 mg); sodium bicarbonate (140 mg); sodium phosphate monobasic monohydrate (5.5 mg). Chemical Structure

What Is Delafloxacin Meglumine Used For?

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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For ABSSSI and CABP: Administer BAXDELA for injection 300 mg by intravenous infusion over 60 minutes, every 12 hours, or a 450 mg BAXDELA tablet orally every 12 hours. ( 2.1 , 2.2 ) Recommended duration of treatment: ( 2.2 ) ABSSSI: 5 to 14 days CABP: 5 to 10 days Dosage for patients with renal impairment is based on the estimated glomerular filtration rate (eGFR) ( 2.3 ) Estimated Glomerular Filtration Rate (eGFR)(mL/min/1.73m 2 ) Estimate of GFR based on a Modification of Diet in Renal Disease (MDRD) equation. Recommended Dosage Regimen for BAXDELA For a total treatment duration of 5 to 14 days for the treatment of ABSSSI and 5 to 10 days for the treatment of CABP. Oral Intravenous All intravenous doses of BAXDELA are administered over 60 minutes. 30-89 No dosage adjustment No dosage adjustment 15-29 No dosage adjustment 200 mg every 12 hours End Stage Renal Disease (ESRD) (< 15 including hemodialysis) Not Recommended Not recommended due to insufficient information to provide dosing recommendations. 2.1 Important Administration Instructions BAXDELA Tablets Administer BAXDELA at least 2 hours before or 6 hours after antacids containing magnesium, or aluminum, with sucralfate, with metal cations such as iron, or with multivitamin preparations containing zinc or iron, or with didanosine buffered tablets for oral suspension or the pediatric powder for oral solution [see Drug Interactions (7.1) ] . BAXDELA Tablets can be taken with or without food [see Clinical Pharmacology (12.3) ] . If patients miss a dose, they should take it as soon as possible anytime up to 8 hours prior to their next scheduled dose. If less than 8 hours remain before the next dose, wait until their next scheduled dose. BAXDELA for Injection Do NOT administer BAXDELA for Injection with any solution containing multivalent cations, e.g., calcium and magnesium, through the same intravenous line [see Drug Interactions (7.1) ]. Do NOT co-infuse BAXDELA for Injection with other medications [see Dosage and Administration (2.4) ] . 2.2 Recommended Dosage Regimen For treatment of adults with ABSSSI or CABP, the recommended dosage regimen of BAXDELA is described in Table 1 below. Table 1 Dosage of BAXDELA in Adult ABSSSI or CABP Patients Infection Dosage and Route of Administration Total Duration (days) ABSSSI 300 mg of BAXDELA for Injection every 12 hours over 60 minutes by intravenous infusion Or 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 Or 450 mg BAXDELA tablet orally every 12 hours. 5 to 14 CABP 5 to 10 2.3 Dosage in Patients with Renal Impairment Table 2 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/1.73m 2 ). In patients...

Side Effects (Adverse Reactions)

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...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Chelation Agents: Antacids, Sucralfate, Metal Cations, Multivitamins Fluoroquinolones form chelates with alkaline earth and transition metal cations. Oral administration of BAXDELA with antacids containing aluminum or magnesium, with sucralfate, with metal cations such as iron, or with multivitamins containing iron or zinc, or with formulations containing divalent and trivalent cations such as didanosine buffered tablets for oral suspension or the pediatric powder for oral solution, may substantially interfere with the absorption of BAXDELA, resulting in systemic concentrations considerably lower than desired. Therefore, BAXDELA should be taken at least 2 hours before or 6 hours after these agents [see Dosage and Administration (2.1) ] . There are no data concerning an interaction of intravenous BAXDELA with oral antacids, sucralfate, multivitamins, didanosine, or metal cations. However, BAXDELA should not be co-administered with any solution containing multivalent cations, e.g., magnesium, through the same intravenous line [see Dosage and Administration (2.1) ] .

Contraindications

4 CONTRAINDICATIONS BAXDELA is contraindicated in patients with known hypersensitivity to delafloxacin or any of the fluoroquinolone class of antibacterial drugs, or any of the components of BAXDELA [see Warnings and Precautions (5.6) ] . Known hypersensitivity to BAXDELA or other fluoroquinolones. ( 4 , 5.6 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary The limited available data with BAXDELA use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriages. When delafloxacin (as the N-methyl glucamine salt) was administered orally to rats during the period of organogenesis, no malformations or fetal death were observed at up to 7 times the estimated clinical exposure based on AUC. When rats were dosed intravenously in late pregnancy and through lactation, there were no adverse effects on offspring at exposures approximating the clinical intravenous (IV) exposure based on AUC [see Data ]. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Animal Data In embryo-fetal studies, oral administration of delafloxacin to pregnant rats during the period of major organogenesis resulted in maternal toxicity and reduced fetal body weights at the highest dose (1600 mg/kg/day) and fetal ossification delays at all doses. No malformations were reported up to the highest dose tested (approximately 7 times the estimated human plasma exposure based on AUC). The lowest dose, 200 mg/kg/day (approximately 2.5 times the estimated human plasma exposure based on AUC), was still toxic to the fetus, based on ossification delays. In rabbits, a species known to be extremely sensitive to maternal toxicity of antibacterial drugs, no embryo-fetal developmental toxicity was observed up to the highest dose which induced maternal toxicity (1.6 mg/kg/day, or approximately 0.01 times the estimated human plasma exposure based on AUC). In a pre-postnatal study in rats of IV administered delafloxacin, dams at the highest dose tested (120 mg/kg/day) exhibited slightly lower body weights and slightly longer gestation length than control animals. Exposure at that...

Overdosage

10 OVERDOSAGE Treatment of overdose with BAXDELA should consist of observation and general supportive measures. Hemodialysis removed about 19% of delafloxacin and 56% of SBECD (Sulfobutylether β cyclodextrin) after intravenous administration of BAXDELA [see Clinical Pharmacology (12.3) ].

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 BAXDELA for Injection BAXDELA is supplied as a sterile, lyophilized powder in single-dose clear glass vials of 300 mg delafloxacin (equivalent to 433 mg delafloxacin meglumine). The lyophilized powder is a light yellow to tan cake, which may exhibit cracking and shrinkage and slight variation in texture and color. They are supplied as follows: 300 mg single-dose vials (NDC 70842-102-01), packaged in cartons of 10 vials (NDC 70842-102-03). 16.2 BAXDELA Tablets BAXDELA Tablets contain 450 mg delafloxacin (equivalent to 649 mg delafloxacin meglumine); each modified capsule-shaped tablet in beige to mottled beige color is debossed with RX3341 on one side. They are supplied as follows: Bottles of 20 tablets with child-resistant closure (NDC 70842-101-01) Unit dose blister packs which contain 20 tablets (2 blister cards of 10 tablets each) (20 tablet blister pack: NDC 70842-101-02, 10 tablet blister card: NDC 70842-101-03) 16.3 Storage and Handling BAXDELA Tablets and BAXDELA for Injection should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . The reconstituted powder may be stored for up to 24 hours under refrigerated or controlled room temperature and then further diluted for intravenous infusion. The reconstituted solution in the infusion bag may be stored under refrigerated or controlled room temperature conditions for up to 24 hours [see Dosage and Administration (2.4) ] . Do not freeze.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.