With the approval of eravacycline in mid-2018 many people are wondering how this new tetracycline class antibiotic is different than tigecycline. In this article an infectious diseases pharmacists provides a general comparison of eravacycline (Xerava) versus tigecycline (Tygacil).
Authored By: Timothy P. Gauthier, Pharm.D., BCPS-AQ ID
[Last updated: 27 September 2018 ]
Eravacycline (Xerava) is the latest antibiotic to hit the U.S. market, gaining FDA approval in August of 2018 for complicated intra-abdominal infection (note, studies for urinary tract infection have not been favorable). Inevitably as people learn about this new drug, questions will arise about it’s role in therapy and how it compares to other drugs.
Tigecycline (Tygacil) is the last tetracycline drug to come to market prior to eravacycline. Tigecycline and eravacycline share a number of commonalities, so in turn, many people are likely wondering how the two drugs compare.
In this article I provide a general comparison of eravacycline versus tigecycline. It should be noted that this is not a comprehensive review of the literature and readers are referred to the below references for more detailed information. This is not meant to support clinical decision making, but rather provide a superficial overview of how the drugs compare.
To start off, here is a table comparing eravacycline versus tigecycline. Much of the data below provided on eravacycline was derived from the manufacturer’s package insert, as published data with this antibiotic is currently limited…
Table 1. Comparison of Eravacycline (Xerava) versus Tigecycline (Tygacil)
|
Eravacycline |
Tigecycline |
|
| Brand name: |
Xerava |
Tygacil |
| Generic available: |
No |
Yes |
| Manufacturer: |
Tetraphase |
Pfizer |
| Drug class: |
Flurocycline type tetracycline |
Glycylcycline tetracycline |
| FDA approval: |
August 2018 |
June 2005 |
|
FDA-indications: |
cIAI |
cIAI, cSSSI, CABP |
| Mechanism of action: |
Inhibition of bacterial synthesis via the 30S ribosomal subunit |
Inhibition of bacterial synthesis via the 30S ribosomal subunit |
| Type of killing: |
Mostly bacteriostatic |
Mostly bacteriostatic |
| Mechanism(s) of resistance: |
Efflux pumps, target site modifications |
Efflux pumps |
| Effected by beta-lactamases: |
No |
No |
| MRSA activity: |
Yes |
Yes |
| VRE activity: |
Yes |
Yes |
| E. coli activity: |
Yes |
Yes |
| Klebsiella activity: |
Yes |
Yes |
| Acinetobacter activity: |
Yes |
Yes |
| Pseudomonas activity: |
No |
No |
| Bacteroides activity: |
Yes |
Yes |
| Mycobacterium activity: |
Unable to find data |
Yes |
| Adult dosing: |
1mg/kg BID |
100mg x1, then 50mg BID |
| Renal adjust: |
No |
No |
| Hepatic adjust: |
Child Pugh C |
Child Pugh C |
| Primary elimination route: |
Fecal |
Biliary/ fecal |
| Urine excretion: |
20% unchanged drug |
22% unchanged drug |
| Available oral: |
No |
No |
| Available IV: |
Yes |
Yes |
| Infusion time: |
60 minutes |
30-60 minutes |
| FDA boxed warning: |
None |
Higher all-cause mortality than comparators |
| Avoid in age <8 years: |
Yes |
Yes |
| Other side effects: |
Infusion site reactions, nausea / vomiting (less than tigecycline) |
Hepatic effects, pancreatitis, nausea / vomiting |
| Can cause fetal harm: |
Yes |
Yes |
| Safe during lactation: |
No |
Unknown |
| Major drug-drug interactions: |
Strong CYP3A inducers & inhibitors; warfarin |
Warfarin, oral contraceptives |
| Cost: |
Not yet available |
$157-$188 per 50mg |
Abbreviations: cIAI = complicated intra-abdominal infection, cSSSI = complicated skin and skin structure infection, CABP = community acquired bacterial pneumonia, MRSA = methicillin-resistant Staphylococcus aureus, VRE = vancomycin-resistant Enterococci
What are the important differences?
Reflecting on the above table, package insert data, and literature below, eravacycline and tigecycline appear to share much common ground. As for the more notable differences between the two, the clinical relevance of these points are not entirely clear yet, but includes:
- Less nausea and vomiting with eravacycline as compared to tigecycline
- More potent activity against carbapenem-resistant Enterobacteriaceae with eravacycline as compared to tigecycline
- Better serum levels with eravacycline as compared to tigecycline
- Less drug-drug interactions with tigecycline as compared to eravacycline
- More clinical experience with tigecycline as compared to eravacycline
- Tigecycline carries an FDA boxed warning that eravacycline does not
There may be other important differences not listed.
When might eravacycline be used?
Looking to when eravacycline may be employed in clinical practice, it seems the most obvious scenario will be as a substitute for tigecycline when a patient with significant nausea/ vomiting issues requires therapy for an intra-abdominal infection due to a multi-drug resistant organism (and/or if multiple allergies are present).
In a recent blog post, Dr. Paul Sax suggested several instances when eravacycline may be considered in practice, which is available here.
Questions I am still pondering…
- What is the chance that a tigecycline-resistant isolate will also be eravacycline-resistant?
- How difficult will it be for clinicians to procure eravacycline sensitivity testing?
- If a patient has a tigecycline allergy, what is the chance that they also will have an eravacycline allergy?
- What role does eravacycline have for the treatment of Mycobacterium spp.?
- What consequences may arise from long-term eravacycline use?
- What is the role of eravacycline for infections beyond intra-abdominal infections?
Closing comments
An expanding antimicrobial armamentarium is a good thing for patients with complicated infectious diseases, but new antibiotics bring many questions. Hopefully in the coming years additional data will be made available to address some of the questions posed here and also to further clarify what we have learned about eravacycline thus far.
Recommended Readings & Resources
- Eravacycline (Xerava) package insert
- Tigecycline (Tygacil) package insert
- Eravacycline Approved by FDA – How Might It Be Used Today, And In The Future [HIV & ID Observations 2018]
- Eravacycline for the treatment of intra-abdominal infections [EOID 2014]
- Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent [Drugs 2016]
- Antibacterial Efficacy of Eravacycline In Vivo against Gram-Positive and Gram-Negative Organisms [AAC 2016]
- Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial: A Randomized Clinical Trial [JAMA SURG 2017]
- Tigeycline Boxed Warning
- Tigecycline: a critical safety review [EODS 2015]
- Efficacy and safety of tigecycline for the treatment of severe infectious diseases: an updated meta-analysis of RCTs [IJID 2015]
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