This is the first alcohol-free formulation to be approved in the United States.
According to a statement from the manufacturer Teikoku Pharma, the formulation does not require prior dilution and is available in a 20 mg/ml single-dose vial or in a multiple dose vial of 80 mg/4 ml or 160 mg/8 ml. In the United States, the new formulation will be distributed and marketed by Eagle Pharmaceuticals, following a licensing agreement with Teikoku in October 2015.
"As the first alcohol-free formulation approved in the US, we believe the benefits of this novel formulation will provide an option for patients with alcohol sensitivity or a preference for an alcohol-free treatment," Scott Tarriff, president and chief executive officer of Eagle Pharmaceuticals, said in a statement.
The need for an alcohol-free formulation followed a drug safety communication issued by the FDA in June 2014 regarding the risk of intoxication with the intravenous ethanol-containing formulation of docetaxel, which 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.
"Docetaxel Injection addresses a compelling need in the docetaxel market," said Tarriff. "We are excited to add alcohol-free docetaxel to our growing portfolio of differentiated injectable products and believe it has the potential to improve the lives of patients, resolve concerns among healthcare professionals at hospitals and infusion centers, and ultimately drive value for Eagle stakeholders."
Each milliliter of the alcohol-free formulation contains 20 mg of docetaxel along with 27.5 mg of soybean oil, 585.0 mg of polysorbate 80, 10.0 mg of citric acid, and 442.2 mg polyethylene glycol 300. For the new formulation, the FDA noted that prior dilution was not necessary and that the medication could be added directly to infusion solution, which could consist of a 250 mL infusion bag or bottle of either 0.9% Sodium Chloride solution or 5% Dextrose solution. The final concentration should be between 0.3 mg/mL and 0.74 mg/mL.
The clinical efficacy across indications was not reassessed, since the active ingredient of the alcohol-free formulation is docetaxel. As with other formulations, the most common adverse events with docetaxel are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia. Similar warnings and contraindications apply to the new formulation of docetaxel.
"The approval of Docetaxel Injection, our first oncology product, is a significant milestone in Teikoku's history," Paul Mori, president and CEO of Teikoku, said in a statement. "Eagle Pharmaceuticals' strong presence in the oncology space makes Eagle an excellent partner for our product."
Following the expiration of the patent for Taxotere in 2011, several formulations of docetaxel that contain alcohol have gained approval. The approval of the alcohol-free formulation marks the first for this type of docetaxel.
According to the FDA, when it issued its safety communication in 2014, 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 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.