Intellipharmaceutics International Inc. (IPCI)

[WeeZuhl]

Rexista users could turn blue and die.

Has there ever been an explanation for the delay in the rexista nda? First it was Q2/Q3 in their January biotech presentation, then it was June/July (in March at the Roth presentation) then it was August (in the PR updating rexista progress) and now we believe sometime in the next 2 months (based on their Rodman presentation).

The delay in Rexista filing is most likely due to a safety concern. My best guess is that it has something to do with the "stigmatizing blue dye" that is touted as an ADF feature. If the drug is chewed, the abuser's teeth, lips, and oral mucosa are colored with a deep blue dye. This presents several dilemmas. First, every person who uses the drug as intended is going to be exposed to a biochemical (blue dye) which is meant only for the abuser. Blue dye will release from the tablet matrix and enter the G.I. tract of every user- not just the abusers. This practice was specifically identified as an ethical concern and disallowed by the FDA in previous ADF formulations which contained niacin as an aversive nasal irritant.


The second dilemma about the blue dye is related to specific toxicities of synthetic dyes. All currently-approved dyes for food & drugs are derived from petroleum or coal tar. Since the FDA began regulating dyes in the 1960's, all but 8 have been banned for human use due to specific, proven carcinogenic or teratogenic effects. Of the 8 dyes which remain legal, Blue #1 and Blue #2 are both banned in multiple European countries because they cause tumors in animal models.


Which blue dye is used for this purpose and what concentration of blue dye is required for the ADF effect? The company clearly describes the "stigmatizing blue dye" as an active part of their ADF and not just an additive colorant. Has a regimen of two daily doses of blue dye at this concentration been tested and proven to be safe? Risk of cancer and birth defects in proper users would prevent me from prescribing this drug for my patients, but the most acute risk of daily G.I. tract exposure from blue dye is the subject of an FDA Public Health Advisory.





http://www.fda.gov/ForIndustry/ColorAdditives/ColorAdditivesinSpecificProducts/InMedicalDevices/ucm142395.htm

FDA Public Health Advisory: Subject: Reports of Blue Discoloration and Death in Patients Receiving Enteral Feedings Tinted With The Dye, FD&C Blue No. 1

September 29, 2003


Dear Health Care Professional:

The Food and Drug Administration (FDA) would like you to be aware of several reports of toxicity, including death, temporally associated with the use of FD&C Blue No. 1 (Blue 1) in enteral feeding solutions. In these reports, Blue 1 was intended to help in the detection and/or monitoring of pulmonary aspiration in patients being fed by an enteral feeding tube. Reported episodes were manifested by blue discoloration of the skin, urine, feces, or serum and some were associated with serious complications such as refractory hypotension, metabolic acidosis and death.

As of September, 2003, the FDA is aware of 20 cases from the scientific literature or in FDA post-marketing adverse event reports associating the use of blue dye in tube feedings with blue discoloration of body fluids and skin, as well as more serious complications. There have been 12 reported deaths and one case with an unknown outcome.

Other blue dyes, such as methylene blue and FD&C Blue No. 2, may have similar if not greater toxicity potential than Blue 1 and would not be appropriate replacements.