Replies to post #18217 on Intellipharmaceutics International Inc. (IPCI)

[WeeZuhl]

Rexista's Blue Dye Problem

The dye is batch certified by the FDA and is widely used in food products (candies, confections, beverages, etc.) in amounts consistent with good manufacturing practices (generally at parts per million). There have been no reports of toxicity associated with this general use.

A "stigmatizing blue dye" is a novel use of blue dye. That's why many are surprised there was no Safety & Efficacy Phase 3 requirement. The "general use" referred to in the docuent you cite is a concentration required to make a blue tablet. Rexista contains a concentration of blue dye sufficient to humiliate an abuser with blue lips, blue gums, and blue teeth. But to the normal user, this is twice daily concentrated doses of a possible carcinogen-- twice daily indefinitely-- without any benefit at all to the normal user. Again, even if prescribed by another practitioner, I would feel ethically-obligated to advise my patients to refuse to take it for this reason.


But the turning blue & pissing blue & shitting blue & bleeding blue & then croaking blue is a real damn thing. If the blue dye is going down the same hole, then it makes no difference if the dye came from a tablet or a tube feed. They are both going into the stomach and processing through the G.I. tract. And the tube feeds were short-term, but Rexista will deliver blue dye forever.


Look at the FDA advisory. The effect was independent of time & dose, but it was associated with sepsis from infections. Chronic pain is proven immunosuppressive, and studies suggest use of chronic opioids is immunosuppressive. For sure chronic pain patients are more likely to have medical comorbidities, such as diabetes and peripheral vascular disease, that increase their risk of infections. Someone taking 100mg+ of oxycodone every day is at higher risk for sepsis associated with skin infections, aspiration pneumonia, or opioid-induced ileus/bowel obstruction. Sepsis is a generalized whole-body inflammatory response to a focal infection, such as UTI or pneumonia. Once the sepsis syndrome begins, the G.I. tract permeability becomes altered, and the presence of the blue dye seems to hasten onset of severe sepsis and death from multi-system organ failure, despite full life-support measures.


Are you on gluten-free diet because of celiac sprue? Do you have kidney problems? Do you take pain medicine because of Crohn's or ulcerative colitis? Trauma? Surgery? The FDA Advisory specifically warns that you are at increased risk from the blue dye that will be in Rexista-- without any benefit to you at all. Hard to believe these guys are going to get away without doing a Safety & Efficacy Phase 3 Study. BWAHAHAHA if you like, but mark this post, the blue dye will cause problems for Rexista, maybe already has. I can't wait for the Rexista AdComm. I'm going to take that day off work.


Doesn't matter how the blue dye got there-- people with blue dye in their gut when they become septic can turn blue & die before they ever have a chance to seek help. Not my patients. Any responsible physician should refuse to prescribe this drug until safety is well-established.




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

SUMMARY OF REPORTS

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.

In more than 75% of all reported cases, patients had a reported history of sepsis (and therefore likely altered gut permeability) before or during systemic absorption of Blue 1.

Time of onset of toxicity from first use of Blue 1 varied from several hours to 20 days of continuous use in enteral feedings.

At this time, the FDA believes practitioners should be aware of the following points:

Use of Blue 1-tinted enteral feedings for detecting aspiration has been associated with several serious adverse events, including death, although a direct causal relationship has not been definitely established.

The safety of Blue 1-tinted enteral feedings for detecting aspiration has not been documented.

Based on the reports received to date, patients at risk for increased intestinal permeability, which includes those with sepsis, burns, trauma, shock, surgical interventions, renal failure, celiac sprue, or inflammatory bowel disease, appear to be at increased risk of absorbing Blue 1 from tinted enteral feedings.

In addition to the possibility of systemic toxicity, Blue 1-tinted enteral feedings may interfere with diagnostic stool examinations, such as the hemoccult test.

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.