The FDA has issued a drug safety communication regarding the risk of intoxication with the intravenous ethanol-containing chemotherapy docetaxel. The drug is marketed as generic docetaxel and under the brand names Taxotere, Docefrez, and Docetaxel Injection.
The warning was issued based on a review of the FDA Adverse Event Reporting System database and medical literature that revealed three cases of alcohol intoxication associated with docetaxel. In the review, intoxication occurred during docetaxel infusion for two patients and within 24 hours for the third. The review contained data from a 2011 paper published by the Royal College of Radiologists on the risk of intoxication with docetaxel.
"The alcohol content in a dose of docetaxel may affect the central nervous system and should be taken into account for patients in whom alcohol intake should be avoided or minimized, including patients with hepatic impairment," the FDA cautioned in a Drug Safety Communication. "Slowing the infusion rate during administration may help resolve symptoms of alcohol intoxication."
In the case samples used to sculpt the new warning, various methods were utilized to avoid intoxication. In one situation, a slower infusion rate successfully allowed for the completion of therapy, whereas in the other two, a different formulation of docetaxel was selected that contained lower alcohol content.
Altogether, eight formulations of docetaxel were identified by the FDA and ranked in order of their ethanol content. The highest concentration of ethanol within a 200 mg dose of docetaxel was found in a version of the injection manufactured by Pfizer. This formulation contained 6.4 grams of ethanol per dose. Additionally, a version of docetaxel manufactured by Sandoz contained 5.5 grams per dose.
The FDA advised that physicians should "consider a docetaxel formulation with the lowest possible alcohol content for patients who experience adverse reactions."
The lowest concentration was found in a two-vial formulation of the drug manufactured by Sanofi, with 2 grams per 200 mg dose. The next lowest ethanol level was found in Docefrez, manufactured by Sun Pharma, at 2.9 grams per dose. Various other formulations of the drug contained doses ranging from 3.7 grams to 4.0 grams per 200 mg dose.
The FDA advised that patients should be counseled on the possible risk of intoxication with docetaxel prior to the administration of the drug. Additionally, they noted that certain medications, such as pain relievers and sleep aids, could adversely interact with the alcohol within docetaxel during infusion worsening the effects.