Eravacycline

Indications

Eravacycline is used for: Intra-abdominal Infections

Adult Dose

Intra-abdominal Infections Indicated for treatment of complicated intra-abdominal infections (cIAIs) 1 mg/kg IV q12hr x 4-14 days; infuse IV over ~60 minutes

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Administration

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

Contra Indications

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

Precautions

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

Pregnancy-Lactation

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

Interactions

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

Adverse Effects

Side effects of Eravacycline : 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

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