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Ethanol diluent in injectables an intoxication risk says US FDA

By Gareth MacDonald+

24-Jun-2014
Last updated on 25-Jun-2014 at 16:30 GMT2014-06-25T16:30:54Z

"Alcohol! The cause of... and solution to... all of life's problems": US FDA warns about ethanol in docetaxel

The use of ethanol as a diluent in injectables is under the spotlight following a new US FDA warning that its presence in the cancer medicine docetaxel poses an intoxication risk.

The Agency issued the warning last Friday , citing several instances of patients becoming intoxicated after receiving docetaxel and explaining that in two cases doctors decided to use different formulations of the drug with lower alcohol content for subsequent treatments.

The Food and Drug Administration (FDA) has asked docetaxel manufacturers – such as Pfizer, Sandoz, Accord, Actavis, Hospira and Sun Pharma - to revise warning labels to warn about the potential risks.

The US regulator also advised cancer patients treated with docetaxel to “avoid driving, operating machinery, or performing other activities that are dangerous for one to two hours after the infusion” and said doctors should consider the risk posed by ethanol.

The move is in step with advice already given by the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

A spokesman for the UK Agency told in-Pharmatechnologist.com that: “The product information for docetaxel-containing medicines already states that they contain alcohol and includes relevant warnings about the possible risks associated with this.”

It also fits with advice given to UK doctors. Jean Slocombe, Cancer Research UK’s senior cancer information nurse, told us that: “In the UK we know there is alcohol in  the chemotherapy drug docetaxel. So the Medicines and Healthcare Products Regulation agency (MHRA) advises patients they should probably avoid driving home or operating heavy machinery after taking it.”

Pfizer told us that its "docetaxel Injection already includes a precaution relating to the ethanol content of the product" and added that it has no plans to find a replacement diluent.

Ethanol applications

The docetaxel active pharmaceutical ingredient (API) is derived from a yew tree extract – or in a few cases from a plant cell-based fermentation process - and is usually sold as a white powder accompanied by a diluent solution containing polysorbate 80 and ethanol in saline.

Ethanol’s role is as a co-solvent to help the API to dissolve, specifically by increasing its solubility in combination with water.

Docetaxel is just one of many drugs in which ethanol is used according to Mark Iacobucci, managing director of API supplier Phyton Biotech LLC , who told us that "Ethanol is commonly used to help solubilize API’s.  Changes to drug formula would require new clinical studies to ensure no change to PK, or the effect, of the drug." 

This echoes the view of the American Coalition for Ethanol (ACE), which states on its website that “as a solvent for the pharmaceutical industry, ethanol is useful for processing antibiotics, vaccines, tablets, pills, and vitamins.

The characteristics of ethyl alcohol make it a prime carrier for a whole spectrum of medicines including cough treatments, decongestants, iodine solution, and many others.”

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