XERAVA: THE FIRST FULLY SYNTHETIC FLUOROCYCLINE ANTIBACTERIAL1,2

Key structural modifications to the tetracycline core differentiate XERAVA from other tetracyclines2

  • The C7 and C9 substitutions are not present in any naturally occurring or semisynthetic tetracyclines and the substitution pattern imparts microbiologic activities, including in vitro activity against Gram-positive and Gram-negative strains expressing certain tetracycline-specific resistance mechanisms1
  • Retains activity against certain tetracycline resistance mechanisms1
    • Efflux mediated by tet(A), tet(B), and tet(K)
    • Ribosomal protection as encoded by tet(M) and tet(Q)
  • XERAVA was 2- to 4-fold more potent than tigecycline in vitro against Gram-positive and Gram-negative bacteria, and 2- to 8-fold more potent against most anaerobes2
  • Low rates of infusion site reactions (7.7%), nausea (6.5%), and vomiting (3.7%)1

Comparison of tetracycline structures1,3

MIC, minimum inhibitory concentration.

References: 1. XERAVA [prescribing information]. Watertown, MA: Tetraphase Pharmaceuticals, Inc.; 2018. 2. Zhanel GG, Cheung D, Adam H, et al. Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs. 2016;76(5):567-588. 3. Tygacil [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals, Inc.; 2018. 4. Grossman TH, Starosta AL, Fyfe C, et al. Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012;56(5):2559-2564. 5. US National Institutes of Health. US National Library of Medicine. Efficacy and safety study of eravacycline compared with ertapenem in complicated intra-abdominal infections (IGNITE1). Clinicaltrials.gov website. Updated March 21, 2016. https://clinicaltrials.gov/ct2/show/NCT01844856?term=IGNITE+eravacycline&rank=1. Accessed July 26, 2018. 6. US National Institutes of Health. US National Library of Medicine. Efficacy and safety study of eravacycline compared with meropenem in complicated intra-abdominal infections (IGNITE4). Clinicaltrials.gov website. Updated April 11, 2018. https://clinicaltrials.gov/ct2/show/NCT02784704?term=IGNITE4&rank=1. Accessed July 26, 2018. 7. Data on file. Watertown, MA: Tetraphase Pharmaceuticals, Inc.; 2018.

Indications and Usage; Important Safety Information

EXPAND COLLAPSE

Indications and Usage

XERAVA is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus anginosus group, Clostridium perfringens, Bacteroides species, and Parabacteroides distasonis in patients 18 years or older.

Limitations of Use

XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI).

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.

Important Safety Information

XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with XERAVA.

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.

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.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis.

The most common adverse reactions observed in clinical trials (incidence ≥3%) were infusion site reactions (7.7%), nausea (6.5%), and vomiting (3.7%).

XERAVA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial drugs, and may occur with XERAVA. Discontinue XERAVA if any of these adverse reactions are suspected.

To report SUSPECTED ADVERSE REACTIONS, contact Tetraphase Pharmaceuticals Inc., at 1-833-7-XERAVA (1-833-793-7282) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for XERAVA.

Indications and Usage

XERAVA is indicated for the treatment of complicated intra-abdominal infections (cIAI) caused by susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Klebsiella oxytoca, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus anginosus group, Clostridium perfringens, Bacteroides species, and Parabacteroides distasonis in patients 18 years or older.

Limitations of Use

XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI).

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.

Important Safety Information

XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients. Life-threatening hypersensitivity (anaphylactic) reactions have been reported with XERAVA.

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.

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.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis.

The most common adverse reactions observed in clinical trials (incidence ≥3%) were infusion site reactions (7.7%), nausea (6.5%), and vomiting (3.7%).

XERAVA is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial drugs, and may occur with XERAVA. Discontinue XERAVA if any of these adverse reactions are suspected.

To report SUSPECTED ADVERSE REACTIONS, contact Tetraphase Pharmaceuticals Inc., at 1-833-7-XERAVA (1-833-793-7282) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for XERAVA.