Overview
11 DESCRIPTION XERAVA contains eravacycline, a synthetic tetracycline-class antibacterial agent for intravenous administration. Chemically, eravacycline is a C7-, C9-substituted sancycline derivative. The chemical name of eravacycline dihydrochloride is [(4S,4aS,5aR,12aS)-4-(dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9-[2‑(pyrrolidin-1-yl)...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Eravacycline is an antibacterial drug [see Microbiology ( 12.4 )]. 12.2 Pharmacodynamics The AUC divided by the MIC of eravacycline has been shown to be the best predictor of activity. Based on the flat exposure-response relationship observed in clinical studies, eravacycline exposure achieved with the recommended dosage regimen appears to be on the plateau of the exposure-response curve. Cardiac Electrophysiology The effect of XERAVA on the QTc interval was evaluated in a Phase 1 randomized, placebo and positive controlled, double-blind, single-dose, crossover thorough QTc study in 60 healthy adult subjects. At the 1.5 mg/kg single dose (1.
Indications
- 1 INDICATIONS AND USAGE XERAVA is a tetracycline class antibacterial indicated for the treatment of complicated intra‑abdominal infections in patients 18 years of age and older. ( 1.1 ) Limitations of Use XERAVA is not indicated for the treatment of complicated urinary tract infections (cUTI). ( 1.1 ) To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. ( 1.2 ) 1.
Common Doses
- 1 mg
- 1.5 mg
- 5 mL
- 50 mg
Dosage
2 DOSAGE AND ADMINISTRATION Administer XERAVA for injection 1 mg/kg by intravenous infusion over approximately 60 minutes every 12 hours for a total duration of 4 to 14 days. ( 2.1 ) Severe Hepatic Impairment (Child Pugh C): 1 mg/kg XERAVA every 12 hours on Day 1, then 1 mg/kg every 24 hours starting on Day 2 for a total duration of 4 to 14 days. ( 2.2 ) Concomitant Use of a Strong Cytochrome P450 (CYP) Isoenzyme 3A Inducer: 1.5 mg/kg XERAVA every 12 hours for a total duration of 4 to 14 days. ( 2.3 ) See full prescribing information for the preparation of XERAVA. ( 2.4 ) 2.
Contraindications
- 4 CONTRAINDICATIONS XERAVA is contraindicated for use in patients with known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or to any of the excipients [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]. Known hypersensitivity to eravacycline, tetracycline-class antibacterial drugs, or any of the excipients in XERAVA. ( 4 , 5 , 6 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in the Warnings and Precautions section: Hypersensitivity Reactions [Warning and Precautions ( 5.1 )] Tooth Discoloration [ Warning and Precautions ( 5.2 )] Inhibition of Bone Growth [Warning and Precautions ( 5.3 )] Clostridioides difficile -Associated Diarrhea [Warning and Precautions ( 5.4 )] Tetracycline Class Adverse Reactions [Warning and Precautions ( 5.5 )] Most common adverse reactions (incidence ≥ 3%) are infusion site reactions, nausea, and vomiting. ( 6.
Interactions
- 7 DRUG INTERACTIONS Strong CYP 3A Inducers: Co-administration decreases the exposure of eravacycline; increase XERAVA dose with concomitant use. ( 2.3 , 7.1 , 12.3 ) Anticoagulant Drugs: Downward adjustment of anticoagulant dosage may be required. ( 7.2 ) 7.1 Effect of Other Drugs on XERAVA Strong CYP3A Inducers Concomitant use of strong CYP3A inducers decreases the exposure of eravacycline, which may reduce the efficacy of XERAVA [see Clinical Pharmacology ( 12.3 )] . Increase XERAVA dose in patients with concomitant use of a strong CYP3A inducer [see Dosage and Administration ( 2.3 )] . 7.