In preclinical trials of intravenous eravacycline, serum aminotransferase elevations were mild and no more frequent than with placebo or comparator treatment arms. There were no instances of clinically apparent liver injury that could be attributed to eravacycline. Nevertheless, other tetracycline antibiotics are well known causes of drug induced liver injury. In particular, high doses of intravenous tetracycline are known to be able to cause severe hepatic microvesicular steatosis with lactic acidosis and severe hepatic dysfunction (LASH syndrome). For this reason, intravenous tetracycline was withdrawn from use. This complication has not been reported with intravenous eravacycline, omadacycline or tigecycline. The tetracyclines have also been linked to idiosyncratic liver injury with autoimmune features that generally arise with long term use and has most commonly been associated with minocycline. This complication also has not been reported with eravacycline, omadacycline or tigecycline.
The most common adverse reactions (incidence ≥ 3%) are infusion site reactions, nausea, and vomiting [FDA label]. Less common (incidence ≥ 1%) adverse effects are palpitations, chest pain, acute pancreatitis, pancreatic necrosis, hypocalcemia, dizziness, dysgeusia, anxiety, insomnia, depression, pleural effusion, dyspnea, rash and hyperhidrosis [FDA label]. The following are various side effects that may occur due to eravacycline use [FDA label]: **Hypersensitivity:** Life-threatening anaphylaxis has been reported with the administration of eravacycline. Antibacterial drugs and should be avoided in patients with known hypersensitivity to tetracycline-class antibacterial drugs [FDA label]. **Tooth Discoloration/enamel hypoplasia**: The use of this drug during tooth development (last half of pregnancy, infancy and childhood to the age of 8 years) may lead to the permanent discoloration of teeth (yellow-grey-brown) [FDA label]. **Inhibition of bone growth:** The use of eravacycline during the second and third trimester of pregnancy, infancy and childhood until the age of 8 years old may cause reversible inhibition of bone growth. All tetracyclines form a stable calcium complex in bone-forming tissue [FDA label]. **Clostridium difficile-Associated diarrhea:** Clostridium difficile associated diarrhea (CDAD) has been reported with use of the majority of antibacterial agents, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents changes the normal flora of the colon, leading to an overgrowth of C. difficile. **Tetracycline class adverse reactions:** This drug is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse reactions. Adverse reactions including photosensitivity, pseudotumor cerebri, and anti-anabolic action which has led to increased BUN, azotemia, acidosis, hyperphosphatemia, pancreatitis, and abnormal liver function tests, have been reported for other tetracycline-class antibacterial agents, and may occur with eravacycline. Discontinue eravacycline if any of these adverse reactions are suspected or observed [FDA label]. **Potential for microbial overgrowth:** The use of eravacycline may result in overgrowth of non-susceptible organisms, including fungi. If such infections occur, discontinue eravacycline and manage with appropriate therapy [FDA label]. **Development of drug-resistant bacteria:** Prescribing eravacycline in the absence of a 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 [FDA label].
Protein binding of eravacycline to human plasma proteins increases with increasing plasma concentrations, with 79% to 90% (bound) at plasma concentrations ranging from 100 to 10,000 ng/mL [FDA label].
Following single-dose intravenous administration, eravacycline AUC (area under the curve) and Cmax (maximum concentration) increase dose-proportionally for doses from 1 mg/kg - 3 mg/kg (3 times the approved dose). There is approximately 45% accumulation following intravenous dosing of 1 mg/kg every 12 hours [FDA label].
Following a single intravenous dose of radiolabeled eravacycline 60 mg, approximately 34% of the dose is excreted in urine and 47% in feces as unchanged eravacycline (20% in urine and 17% in feces) and metabolites [FDA label].
来源:DrugBank
吸收、分配和排泄
分布容积
稳态下分布容积大约为321升（美国食品药品监督管理局标签）。
The volume of distribution at steady-state is approximately 321 L [FDA label].
