XERAVA- Eravacycline

XERAVA™ - Eravacycline

Usual Diluents

Standard Dilutions   [Amt of drug] [Infusion vol] [Infusion rate]

70 kg x 1 mg/kg = 70mg. 
Target volume:  70/0.3= 233 mL.  70mg/257 mL = 0.27 (desired range: 0.2 to  0.6 mg/mL)
Reconstitute 2 vials - each with 5 mL  sterile Water for Injection. Concentration: 10mg/mL

Add 7 ml (70 mg) to 250 mL NS and infuse over 60 minutes every 12 hours (patient is not receiving a strong CYP3A inducer and does not have severe hepatic impairment)
Total volume of solution: 257 mL after using a standard 250mL IV bag.

Preparation:

XERAVA is supplied as a sterile yellow to orange dry powder in a single-dose vial that must be reconstituted and further diluted prior to intravenous infusion as outlined below. XERAVA does not contain preservatives. Aseptic technique must be used for reconstitution and dilution as follows:

1. Calculate the dose of XERAVA based on the patient weight; 1 mg/kg actual body weight. Prepare the required dose for intravenous infusion, by reconstituting the appropriate number of vials needed. Reconstitute each vial of XERAVA with 5 mL of Sterile Water for Injection, USP. When the XERAVA vial content is reconstituted with 5 mL sterile Water for Injection, USP it will deliver 50 mg (10 mg/mL) of eravacycline (free base equivalents).
2. Swirl the vial gently until the powder has dissolved entirely. Avoid shaking or rapid movement as it may cause foaming. The reconstituted XERAVA solution should be a clear, pale yellow to orange solution. Do not use the solution if you notice any particles or the solution is cloudy. Reconstituted solution is not for direct injection.
3. The reconstituted XERAVA solution is further diluted for intravenous infusion to a target concentration of 0.3 mg/mL, in a 0.9% Sodium Chloride Injection, USP infusion bag before intravenous infusion. To dilute the reconstituted solution, withdraw the full or partial reconstituted vial content from each vial and add it into the infusion bag to generate an infusion solution with a target concentration of 0.3 mg/mL (within a range of 0.2 to 0.6 mg/mL). Do not shake the bag.
4. The reconstituted and diluted solutions must be infused within 6 hours if stored at room temperature (not to exceed 25°C/77°F) or within 24 hours if stored refrigerated at 2 °C to 8 °C (36 °F to 46 °F). Reconstituted XERAVA solutions and diluted XERAVA infusion solutions should not be frozen.

WARNINGS 

DESCRIPTION 

XERAVA contains eravacycline, a synthetic tetracycline-class antibacterial agent for intravenous administration. Chemically, eravacycline is a C7-, C9-substituted sancycline derivative. The chemical name of eravacycline dihydrochloride is [(4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9-[2‑(pyrrolidin-1-yl) acetamido]-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide] dihydrochloride. The molecular formula for eravacycline dihydrochloride is C27H31FN4O8•2HCl, and its molecular weight is 631.5.

XERAVA is a sterile, preservative-free, yellow to orange, lyophilized powder in a glass single-dose vial for intravenous infusion after reconstitution and dilution. Each vial of XERAVA contains 50 mg of eravacycline (equivalent to 63.5 mg of eravacycline dihydrochloride) and the excipient, mannitol (150 mg). Sodium hydroxide and hydrochloric acid are used as needed for pH adjustment to 5.5 to 7.0.

CLINICAL PHARMACOLOGY:

Eravacycline is a fluorocycline antibacterial within the tetracycline class of antibacterial drugs. Eravacycline disrupts bacterial protein synthesis by binding to the 30S ribosomal subunit thus preventing the incorporation of amino acid residues into elongating peptide chains.

In general, eravacycline is bacteriostatic against gram-positive bacteria (e.g., Staphylococcus aureus and Enterococcus faecalis); however, in vitro bactericidal activity has been demonstrated against certain strains of Escherichia coli, Klebsiella pneumoniae.

INDICATIONS AND USAGE 

Limitations of Use
XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI) [see Clinical Studies (14.2)].

1.2 Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA 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.

CONTRAINDICATIONS

XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients [see Warnings and Precautions (5.1) and Adverse Reactions (6)].

PRECAUTIONS

WARNINGS AND PRECAUTIONS:

• Hypersensitivity Reactions: Life-threatening hypersensitivity (anaphylactic) reactions have been reported with tetracycline antibacterial drugs, including XERAVA. Avoid use in patients with known hypersensitivity to tetracyclines. ( 5.1)
• Tooth Discoloration and Enamel Hypoplasia: The use of XERAVA during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and enamel hypoplasia. ( 5.2, 8.1, 8.4)
• Inhibition of Bone Growth: The use of XERAVA during the second and third trimester of pregnancy, infancy and childhood up to the age of 8 years may cause reversible inhibition of bone growth ( 5.3, 8.1, 8.4).
• Clostridium difficile-associated diarrhea: Evaluate if diarrhea occurs. ( 5.4)

ADVERSE REACTIONS

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information (pdf)

DOSAGE AND ADMINISTRATION 

2.1 Recommended Adult Dosage

The recommended dose regimen of XERAVA is 1 mg/kg every 12 hours. Administer intravenous infusions of XERAVA over approximately 60 minutes every 12 hours.

The recommended duration of treatment with XERAVA for cIAI is 4 to 14 days. The duration of therapy should be guided by the severity and location of infection and the patient’s clinical response.

2.2 Dosage Modifications in Patients with Hepatic Impairment

In patients with severe hepatic impairment (Child Pugh C), administer XERAVA 1 mg/kg every 12 hours on Day 1 followed by XERAVA 1 mg/kg every 24 hours starting on Day 2 for a total duration of 4 to 14 days. No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

2.3 Dosage Modifications in Patients with Concomitant Use of a Strong Cytochrome P450 Isoenzymes (CYP) 3A Inducer

With concomitant use of a strong CYP3A inducer, administer XERAVA 1.5 mg/kg every 12 hours for a total duration of 4 to 14 days. No dosage adjustment is warranted in patients with concomitant use of a weak or moderate CYP3A inducer [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)]. Drug information (pdf)

2.4 Preparation and Administration

XERAVA is for intravenous infusion only. Each vial is for a single dose only.

Preparation:

XERAVA is supplied as a sterile yellow to orange dry powder in a single-dose vial that must be reconstituted and further diluted prior to intravenous infusion as outlined below. XERAVA does not contain preservatives. Aseptic technique must be used for reconstitution and dilution as follows:

1. Calculate the dose of XERAVA based on the patient weight; 1 mg/kg actual body weight. Prepare the required dose for intravenous infusion, by reconstituting the appropriate number of vials needed. Reconstitute each vial of XERAVA with 5 mL of Sterile Water for Injection, USP. When the XERAVA vial content is reconstituted with 5 mL sterile Water for Injection, USP it will deliver 50 mg (10 mg/mL) of eravacycline (free base equivalents).
2. Swirl the vial gently until the powder has dissolved entirely. Avoid shaking or rapid movement as it may cause foaming. The reconstituted XERAVA solution should be a clear, pale yellow to orange solution. Do not use the solution if you notice any particles or the solution is cloudy. Reconstituted solution is not for direct injection.
3. The reconstituted XERAVA solution is further diluted for intravenous infusion to a target concentration of 0.3 mg/mL, in a 0.9% Sodium Chloride Injection, USP infusion bag before intravenous infusion. To dilute the reconstituted solution, withdraw the full or partial reconstituted vial content from each vial and add it into the infusion bag to generate an infusion solution with a target concentration of 0.3 mg/mL (within a range of 0.2 to 0.6 mg/mL). Do not shake the bag.
4. The reconstituted and diluted solutions must be infused within 6 hours if stored at room temperature (not to exceed 25°C/77°F) or within 24 hours if stored refrigerated at 2 °C to 8 °C (36 °F to 46 °F). Reconstituted XERAVA solutions and diluted XERAVA infusion solutions should not be frozen.
5. Visually inspect the diluted XERAVA solution for particulate matter and discoloration prior to administration (the XERAVA infusion solution for administration is clear and ranges from light yellow to orange). Discard unused portions of the reconstituted and diluted solution.

Administration of the Intravenous Infusion

The diluted XERAVA solution is administered as an intravenous infusion over approximately 60 minutes.

XERAVA may be administered intravenously through a dedicated line or through a Y-site. If the same intravenous line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of XERAVA with 0.9% Sodium Chloride Injection, USP.

2.5 Drug Compatibilities

XERAVA is compatible with 0.9% Sodium Chloride Injection, USP. The compatibility of XERAVA with other drugs and infusion solutions has not been established. XERAVA should not be mixed with other drugs or added to solutions containing other drugs.

HOW SUPPLIED 

XERAVA for injection is a yellow to orange, sterile, preservative-free, lyophilized powder in single-dose vials containing 50 mg of eravacycline (equivalent to 63.5 mg eravacycline dihydrochloride) for reconstitution and further dilution.

Storage and Stability

XERAVA for injection, 50 mg/vial, is a yellow to orange, sterile, preservative-free powder for reconstitution in single-dose 10-mL clear glass vials with a rubber stopper and an aluminum overseal. Each vial contains 50 mg of eravacycline (equivalent to 63.5 mg of eravacycline dihydrochloride). XERAVA is supplied in two packaging configurations:

Single-vial carton containing one 50 mg single-dose vial: NDC 71773-050-05.

Twelve-vial carton containing twelve 50 mg single-dose vial cartons: NDC 71773-050-12.

16.2 Storage and Handling
Prior to reconstitution, XERAVA should be stored at 2°C to 8°C (36°F to 46°F) [see Dosage and Administration 2.4]. Keep vial in carton until use.

Distributed by:
Tetraphase Pharmaceuticals, Inc.
480 Arsenal Way, Ste 110
Watertown, MA 02472

XERAVA™ is a trademark of Tetraphase Pharmaceuticals, Inc.
©2018, Tetraphase Pharmaceuticals, Inc. All rights reserved.