Eravacycline (Xerava) - Uses, Dose, MOA, Side effects

Eravacycline (Xerava) is an injectable antibiotic of the tetracycline class that acts by inhibiting bacterial protein synthesis. It is used in the treatment of complicated intraabdominal infections.

Eravacycline (Xerava) Uses:

  • Complicated intra-abdominal infections:

    • It is indicated for the treatment of complicated intra-abdominal infections in adults 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
  • Limitations of use:
    • It should not be used in patients younger than 18 years of age and for the treatment of complicated urinary tract infections.

Eravacycline (Xerava) Dose in Adults

Eravacycline (Xerava) Dose in the treatment of complicated Intra-abdominal infections:

  • 1 mg/kg administered intravenously twice a day for 4 to 14 days.
  • Dosage adjustment with concomitant strong CYP3A inducers (eg, rifampin):

    • Increase the dose to 1.5 mg/kg IV twice daily.

Use in Children:

Not indicated.

Pregnancy Category: N (Not assigned)

  • Tetracyclines may cross the placental boundary. 
  • Tetracyclines can also accumulate in the developing teeth or long bones, especially if administered during the third trimester.
  • It can cause irreversible inhibition of bone development. 
  • Exposure to it in utero for long periods or repeatedly can cause permanent discoloration of teeth (yellow or gray).

Use during breastfeeding:

  • It is unknown whether the drug can be excreted into breastmilk. Breastmilk may also contain other tetracyclines.
  • Due to the possibility of serious and permanent adverse drug reactions in infants, the manufacturer suggests that you avoid the drug during breastfeeding and for at least four days following the last dose. 
  • These adverse drug reactions can include the inability to grow bone and discoloration of teeth.

Dose in Kidney disease:

Dosage adjustment is not required. 

Dose in Liver disease:

  • Mild to moderate impairment (Child-Pugh class A or B):

    • Dosage adjustment is not required. 
  • Severe impairment (Child-Pugh class C):

    • 1 mg/kg twice daily on day 1, then 1 mg/kg once daily.

Side Effects of Eravacycline (Xerava):

  • Cardiovascular:

    • Hypotension
  • Gastrointestinal:

    • Nausea
    • Vomiting
    • Diarrhea
  • Local:

    • Infusion site reaction
  • Miscellaneous:

    • Wound dehiscence

Contraindications to Eravacycline (Xerava):

Hypersensitivity to any ingredient of the tetracycline antibacterial medication family.

Warnings and precautions

  • Anaphylactic and hypersensitivity reactions:

    • It is possible for anaphylactic reactions to occur, which could be life-threatening. 
    • It is important to stop using the drug immediately. Patients who have had anaphylactic reactions in the past should not be given tetracyclines or structurally similar drugs.
  • Antianabolic effects

    • Tetracyclines have shown antianabolic effects, manifesting in raised BUN, azotemia and hyperphosphatemia.
  • Hepatotoxicity:

    • Hepatotoxicity can manifest as anorexia, jaundice and abdominal pain. If hepatotoxicity is detected, treatment must be stopped immediately.
  • Pancreatitis

    • Pancreatitis may be caused by structurally similar drugs and tetracyclines. 
    • Patients should be closely monitored for symptoms such as nausea, vomiting, or new-onset abdominal pain.
  • Photosensitivity

    • Photosensitivity can be caused by photosensitivity-causing antibiotics such as tetracyclines or structurally similar ones.
  • Pseudotumor cerebri:

    • Given that tetracyclines have been linked to the onset of benign intracranial hypertension, patients should be constantly watched for the signs and symptoms of the condition.
  • Superinfection

    • Superinfection can occur from prolonged antibiotic use. Superinfections can be fungal or bacterial, including colitis and Clostridium difficile (formerly Clostridium) infection (CDI).
    • CDI can occur up to 2 months after the last anti-biotic dose.
  • Hepatic impairment

    • Patients with severe liver impairment should be cautious when taking the drug. Dosage adjustment is recommended for severe hepatic impairment.

Eravacycline: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)

Aminolevulinic Acid (Topical) Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
BCG Vaccine (Immunization) Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization).
Lactobacillus and Estriol Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol.
Mipomersen Tetracyclines may enhance the hepatotoxic effect of Mipomersen.
Neuromuscular-Blocking Agents Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents.
Porfimer Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
Verteporfin Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
Vitamin K Antagonists (eg, warfarin) Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists.

Risk Factor D (Consider therapy modification)

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.
Penicillins Tetracyclines may diminish the therapeutic effect of Penicillins.
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.
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.

Risk Factor X (Avoid combination)

Aminolevulinic Acid (Systemic) Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Systemic).
BCG (Intravesical) Antibiotics may lessen BCG's therapeutic effects (Intravesical).
Cholera Vaccine The therapeutic benefit of the cholera vaccine may be reduced by antibiotic use. Management: Cholera vaccine should not be administered to individuals taking systemic antibiotics or within 14 days after taking oral or parenteral antibiotics.
Mecamylamine Tetracyclines might strengthen Mecamylamine's ability to suppress neuromuscular activity.
Methoxyflurane Tetracyclines might make Methoxyflurane's nephrotoxic effects worse.
Retinoic Acid Derivatives Tetracyclines might make retinoic acid derivatives more harmful or poisonous. It is especially concerning when pseudotumor cerebri develops. Adapalene, Bexarotene (Topical), and Tretinoin are exceptions (Topical).

Monitoring parameters:

  • Liver function tests should be monitored at periodic intervals.
  • Patients should be monitored for features of hepatic dysfunction and signs of anaphylactic reactions (when the drug is administered).

How to administer Eravacycline (Xerava)?

  • It is administered as an intravenous infusion over an hour or more via a Y-site or a dedicated IV line.
  • The IV line should be flushed with an NS before and after the infusion if concurrent drugs are to be infused through the same line. Do not combine the medicine with other prescription drugs.

Mechanism of action of Eravacycline (Xerava):

  • Fluorocycline antibiotic of the tetracycline family.
  • By interacting with the ribosomal 30S subunit, it stops amino acids from being added to lengthy peptide chains.
  • It prevents the synthesis of bacterial proteins.

Protein binding:

  • 79% to 90% (increases with increasing plasma concentrations) (increases with increasing plasma concentrations)

Metabolism:

  • Primarily by CYP3A4- and FMO-mediated oxidation

Half-life elimination:

  • 20 hours

Excretion:

  • Urine: ~34% (20% as unchanged drug);
  • Feces: 47% (17% as unchanged drug)

International Brand Names of Eravacycline:

  • Xerava

Eravacycline Brand Names in Pakistan:

No Brands Available in Pakistan.