Baxdela™ (delafloxacin) For Injection

BAXDELA™ (delafloxacin) for injection, for intravenous use

Usual Diluents

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

Renal dosing:
[200mg]  [250 ml]  [60 minutes]

Reconstitution and Dilution

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:

Table 2 Preparation of BAXDELA Doses
[Dose]        [Volume of Reconstituted Solution to Withdraw]
[ 300 mg ]   [ 12 mL]
[ 200 mg ]   [ 8 mL ]

3. Aseptically transfer the required volume of BAXDELA reconstituted solution from the vial to an intravenous bag to achieve a 250 mL volume of infusion solution. Discard any unused portion of the reconstituted solution.

WARNINGS 

DESCRIPTION 

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-ß-cyclodextrin (2400 mg).

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).

CLINICAL PHARMACOLOGY:

INDICATIONS AND USAGE 

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.

CONTRAINDICATIONS

PRECAUTIONS

1. Hypersensitivity Reactions: May occur after first or subsequent doses of BAXDELA. Discontinue BAXDELA at the first sign of a skin rash or any other sign of hypersensitivity. (5.7)
2. Clostridium difficile-associated diarrhea: Evaluate if diarrhea occurs. (5.8)

ADVERSE REACTIONS

• 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 (844) 635-4682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION 

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, 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.

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Table 1 Dosage Adjustment of BAXDELA in Patients with Renal Impairment

Estimated Glomerular Filtration Rate (eGFR)
(mL/min/1.73 m2)*

BAXDELA for Injection‡
[ 30-89 ] No dosage adjustment

[ 15-29 ] 200 mg every 12 hours Or 200 mg every 12 hours, then switch to a 450 mg BAXDELA tablet orally every 12 hours at the discretion of the physician

[ End Stage Renal Disease (ESRD) (<15), including patients on hemodialysis (HD)]  Not Recommended§

* As calculated using the MDRD eGFR equation as follows: eGFR (mL/min/1.73m 2)= 175 × (serum creatinine) ^-1.154 × (age) ^-0.203× (0.742 if female) × (1.212 if African American)

† For a total treatment duration of 5 to 14 days.

‡ All doses of BAXDELA are administered by intravenous infusion over 60 minutes.

§ Not recommended due to insufficient information to provide dosing recommendations
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2.4 Preparation and Administration of BAXDELA for Injection Intravenous Solution
Reconstitution and Dilution

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:

Table 2 Preparation of BAXDELA Doses
[Dose]        [Volume of Reconstituted Solution to Withdraw]
[ 300 mg ]   [ 12 mL]
[ 200 mg ]   [ 8 mL ]

3. Aseptically transfer the required volume of BAXDELA reconstituted solution from the vial to an intravenous bag to achieve a 250 mL volume of infusion solution. Discard any unused portion of the reconstituted solution.

4. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
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.

HOW SUPPLIED 

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 70842-102-03), packaged in cartons of 10.

Storage and Stability

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. Do not freeze.