Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Xerava: 50 mg (1 ea)
Pharmacology
Mechanism of Action
Eravacycline is a fluorocycline antibiotic within the tetracycline class that binds to the 30S ribosomal subunit and prevents the incorporation of amino acid residues into elongating peptide chains, thereby, inhibiting bacterial protein synthesis.
Pharmacokinetics/Pharmacodynamics
Distribution
Vdss: ~321 L (~4 L/kg) (Newman 2018)
Metabolism
Primarily by CYP3A4- and FMO-mediated oxidation
Excretion
Urine: ~34% (20% as unchanged drug); Feces: 47% (17% as unchanged drug)
Half-Life Elimination
20 hours
Protein Binding
79% to 90% (increases with increasing plasma concentrations)
Use in Specific Populations
Special Populations: Hepatic Function Impairment
Cmax was 13.9%, 16.3%, and 19.7% higher and AUC was 22.9%, 37.9%, and 110.3% higher in patients with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment compared to healthy subjects, respectively.
Use: Labeled Indications
Intra-abdominal infections, complicated: Treatment of complicated intra-abdominal infections 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.
Limitations of use: Not indicated for the treatment of complicated urinary tract infections.
Contraindications
Hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or any component of the formulation.
Dosage and Administration
Dosing: Adult
Intra-abdominal infections, complicated: IV: 1 mg/kg every 12 hours for 4 to 14 days
Dosage adjustment with concomitant strong CYP3A inducers (eg, rifampin): Increase to 1.5 mg/kg every 12 hours.
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Reconstitute each vial with 5 mL NS or SWFI to a concentration of 10 mg/mL. Swirl gently; avoid shaking, which may cause foaming. Do not use if solution is cloudy or has visible particles. Reconstituted solution must be further diluted to allow for IV administration. Transfer full or partial vial contents to an IV bag of NS to a final concentration of 0.3 mg/mL (within a range of 0.2 to 0.6 mg/mL). Do not shake the bag. Reconstituted solution should be clear, yellow to orange color.
Administration
IV: Infuse diluted solution IV over ~60 minutes through dedicated line or via Y-site. If the same IV line is used for sequential infusion of several drugs, flush line with NS before and after eravacycline administration. Do not mix with other drugs or add to solutions containing other drugs.
Storage
Store intact vials in original carton at 2°C to 8°C (36°F to 46°F). Reconstituted vial may be stored at room temperature (≤25°C [77°F]) but must be further diluted within 1 hour. Diluted solutions for infusion may be stored at room temperature (≤25°C [77°F]) for up to 24 hours or refrigerated (2°C to 8°C [36°F to 46°F]) for up to 7 days. Do not freeze. Note: Prior to October 2019, the manufacturer's labeling stated diluted solutions for infusion could be stored at room temperature (≤25°C [77°F]) for ≤6 hours or refrigerated (2°C to 8°C [36°F to 46°F]) for ≤24 hours.
Drug Interactions
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Eravacycline. Management: Increase the eravacycline dose to 1.5 mg/kg every 12 hours when combined with strong CYP3A4 inducers. Consider therapy modification
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy
Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination
Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination
Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Monitor therapy
Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Exceptions: Adapalene; Bexarotene (Topical); Tretinoin (Topical). Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy
Adverse Reactions
1% to 10%:
Cardiovascular: Hypotension (1%)
Gastrointestinal: Nausea (7%), vomiting (4%), diarrhea (2%)
Local: Infusion site reaction (8%)
Miscellaneous: Wound dehiscence (1%)
<1%, postmarketing, and/or case reports: Acute pancreatitis, anaphylaxis, anxiety, chest pain, decreased creatinine clearance, decreased white blood cell count, depression, dizziness, dysgeusia, dyspnea, hyperhidrosis, hypersensitivity reaction, hypocalcemia, increased amylase, increased gamma-glutamyl transferase, increased serum alanine aminotransferase, increased serum lipase, insomnia, neutropenia, palpitations, pancreatic necrosis, pleural effusion, prolonged partial thromboplastin time, skin rash
Warnings/Precautions
Concerns related to adverse effects:
- Anaphylactic/Hypersensitivity reactions: Life-threatening (anaphylactic) reactions have been reported; discontinue if an allergic reaction occurs. Avoid use in patients with known hypersensitivity to tetracyclines.
- Antianabolic effects: May be associated with antianabolic effects observed with the tetracycline class (including increased BUN, azotemia, acidosis, and hyperphosphatemia).
- Hepatotoxicity: May be associated with abnormal liver function tests due to structural similarities with tetracyclines; discontinue use when suspected.
- Pancreatitis: May be associated with pancreatitis due to structural similarities with tetracyclines.
- Photosensitivity: May be associated with photosensitivity due to structural similarities with tetracyclines.
- Pseudotumor cerebri: May be associated with pseudotumor cerebri due to structural similarities with tetracyclines.
- Superinfection: Use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile infection (CDI) and colitis; CDI has been observed >2 months postantibiotic treatment.
Disease-related concerns:
- Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in severe hepatic impairment.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: May cause permanent tooth discoloration, enamel hypoplasia, or reversible inhibition of bone growth; use should be avoided during tooth and bone development (children <8 years of age).
Other warnings/precautions:
- Limitations of use: Not indicated for the treatment of complicated urinary tract infection in adults; eravacycline failed to demonstrate efficacy in 2 randomized, double-blind, active-controlled clinical trials.
Monitoring Parameters
Monitor hepatic function periodically. Observe for signs and symptoms of anaphylaxis during administration.
Pregnancy
Pregnancy Considerations
Tetracyclines cross the placenta.
As a class, tetracyclines accumulate in developing teeth and long tubular bones (Mylonas 2011). Exposure during the second and third trimesters of pregnancy may cause reversible inhibition of bone growth. Permanent discoloration of teeth (yellow, gray, brown) can occur following in utero exposure and is more likely to occur following long-term or repeated exposure.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience nausea, vomiting, injection site irritation, or diarrhea. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of acidosis (confusion, fast breathing, fast heartbeat, abnormal heartbeat, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or loss of strength and energy), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), headache, vision changes, change in amount of urine passed, unable to pass urine, or signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
