Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

Abstract

PURPOSE: Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. MATERIALS AND METHODS: We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. RESULTS: Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. CONCLUSION: Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

A Multicenter, Prospective, Observational Study to Evaluate Ethanol-Induced Symptoms in Patients Receiving Docetaxel Chemotherapy

“…Ethanol is a commonly used solvent to increase solubility when manufacturing anticancer drugs for injection. According to a recent study conducted by Hiver et al [ 11 ] on ethanol contained in anticancer drugs available in France, the content of ethanol contained in each anticancer drug was 91 to 400 mg/mL for docetaxel, 395 to 440 mg/mL for gemcitabine, 385 to 402 mg/mL for paclitaxel, and 241 to 248 mg/mL for etoposide, respectively. In addition, the analysis showed that 3,172 of the 63,613 chemotherapy preparations (4.99%) contained more than 3 g of ethanol [ 11 ].…”

“…According to a recent study conducted by Hiver et al [ 11 ] on ethanol contained in anticancer drugs available in France, the content of ethanol contained in each anticancer drug was 91 to 400 mg/mL for docetaxel, 395 to 440 mg/mL for gemcitabine, 385 to 402 mg/mL for paclitaxel, and 241 to 248 mg/mL for etoposide, respectively. In addition, the analysis showed that 3,172 of the 63,613 chemotherapy preparations (4.99%) contained more than 3 g of ethanol [ 11 ]. Several previous studies have reported that the concentration of ethanol in the blood may increase, and ethanol-induced symptoms may occur after administering anticancer drug-containing ethanol to a patient.…”

“…This study included patients who (1) were aged 19 years or older, (2) were diagnosed with cancer, (3) received chemotherapy including docetaxel (above 50 mg/m 2 ) that contained ethanol, (4) had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, (5) could read and understand documents written in Korean, and (6) signed the informed consent form. The exclusion criteria were as follows: (1) could not read and write the survey documents, (2) with significant neurological or psychiatric disorder, (3) metastasis to the central nervous system, (4) active hepatitis, (5) significant anemia (hemoglobin < 9 g/dL), ( 6) abnormal liver function test results (aspartate aminotransferase, alanine aminotransferase, or total bilirubin ≥ two times or more than the upper limits of the normal range), (7) received chemotherapeutic drug(s) containing ethanol except docetaxel, (8) consumed alcohol within 24 h before docetaxel administration, (9) intake of hypnotics or sedatives within 24 h before docetaxel administration, (10) pregnant or breastfeeding, (11) participated in another clinical trial or had a plan to participate during the study period, (12) and deemed not suitable to participate in the study as judged by the investigator.…”