eravacycline (Rx)

1-10%

Infusion site reactions (7.7%)

Nausea (6.5%)

Vomiting (3.7%)

Diarrhea (2.3%)

Hypotension (1.3%)

Wound dehiscence (1.3%)

<1%

Cardiac disorders: Palpitations

Gastrointestinal system: Acute pancreatitis, pancreatic necrosis

General disorders and administrative site conditions: Chest pain

Immune system disorders: Hypersensitivity

Laboratory investigations: Increased amylase, lipase, ALT, GGT; prolonged aPTT; decreased creatinine clearance, WBC count; neutropenia

Metabolism and nutrition disorders: Hypocalcemia

Nervous system: Dizziness, dysgeusia

Psychiatric disorders: Anxiety, insomnia, depression

Respiratory, thoracic, and mediastinal system: Pleural effusion, dyspnea

Skin and subcutaneous tissue disorders: Rash, hyperhidrosis

Contraindications

Hypersensitivity to eravacycline, tetracycline antibacterials, or any of the excipients

Cautions

Life-threatening hypersensitivity (anaphylaxis) reported; avoid with history of tetracycline allergy; discontinue if allergic reaction occurs

Clostridium difficile-associated diarrhea (CDAD) reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis; if CDAD is suspected or confirmed, consider discontinuing ongoing antibacterial drug use not directed against C difficile and initiating treatment-appropriate measures

Structurally similar to tetracyclines and may have similar adverse reactions, including photosensitivity; pseudotumor cerebri; and antianabolic action, which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests

May cause overgrowth of nonsusceptible organisms, including fungi

Prescribing without proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria

Use during tooth and bone development

• Use during tooth development (last half of pregnancy, infancy, and childhood to age 8 years) may cause permanent discoloration of the teeth (yellow-grey-brown); enamel hypoplasia reported with tetracyclines; advise patient of potential risk
• May cause reversible inhibition of bone growth during pregnancy, infancy, and early childhood
• All tetracyclines form a stable calcium complex in any bone-forming tissue
• Decreased fibula growth rate observed in premature infants given PO tetracycline in doses of 25 mg/kg q6hr; reversible when drug discontinued
• Also see Pregnancy

Drug interaction overview

• Coadministration with strong CYP3A inducers decreases eravacycline exposure, which may reduce efficacy; increased eravacycline dose is recommended (see Dosage Modifications)
• Tetracyclines may depress plasma prothrombin activity; patients taking an anticoagulant therapy may require a lower anticoagulant dose

Pregnancy

Like other tetracycline-class antibacterial drugs, may cause discoloration of deciduous teeth and reversible inhibition of bone growth when administered during second and third trimesters of pregnancy

Animal data

• Animal studies indicate that eravacycline crosses the placenta and is found in fetal plasma; doses above ~3 and 2.8 times the clinical exposure, based on AUC in rats and rabbits, respectively, administered during the period of organogenesis, were associated with decreased ossification, decreased fetal body weight, and/or increased postimplantation loss

Infertility

• Based on animal studies, can lead to impaired spermiation and sperm maturation, resulting in abnormal sperm morphology and poor motility

Lactation

Unknown if excreted in human breast milk

Eravacycline (and its metabolites) is excreted in the milk of lactating rats

Tetracyclines are excreted in human milk; however, extent of absorption of tetracyclines, including eravacycline, by the breastfed infant is not known

Since other antibacterial drug options are available to treat cIAI in lactating women and because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during treatment and for 4 days (based on half-life) after the last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Fluorocycline antibacterial within the tetracycline class; disrupts bacterial protein synthesis by binding the 30S ribosomal subunit, thus preventing incorporation of amino acid residues into elongating peptide chains

Absorption

Peak plasma concentration: 2125 ng/mL (Day 1); 1825 ng/mL (Day 10)

AUC: 4305 ng·h/mL (Day 1); 6809 ng·h/mL (Day 10)

Distribution

Protein bound: 79-90%

Vd: 321 L

Metabolism

Metabolized primarily by CYP3A4- and FMO-mediated oxidation

Elimination

Half-life: 20 hr

Excretion: 34% urine (20% unchanged); 47% feces (17% unchanged)

IV Compatibilities

0.9% NaCl

IV Preparation

Reconstitution

• Reconstitute 50-mg vial with 5 mL sterile water for injection, to result in 10-mg/mL solution
• Gently swirl vial until powder completely dissolved; avoid shaking or rapid movement to avoid foaming
• Reconstituted solution should appear clear, pale yellow to orange
• Do not use if particles are noticed or solution is cloudy
• Reconstituted solution is not for direct injection

Further dilute reconstituted solution

• Dilute further in 0.9% NaCl infusion bag to a target concentration of 0.3 mg/mL (range of 0.2-0.6 mg/mL)
• Do not shake diluted bag
• Must be infused within 6 hr of preparation if stored at room temperature or within 24 hr if refrigerated (see Storage); do not freeze

IV Administration

Infuse over ~60 minutes

May be administered IV through dedicated line or Y-site

If same IV line is used for sequential infusion of several drugs, flush before and after eravacycline infusion with 0.9% NaCl

Storage

Unopened vial

• Refrigerate at 2-8°C (36-46°F)
• Keep vial in carton until use

Reconstituted vial or diluted solution

• Must be infused within 6 hr if stored at room temperature (not to exceed 25°C/77°F) or within 24 hr if refrigerated at 2-8°C (36-46°F)
• Do not freeze