The Institute for Safe Medication Practices has a very good piece on IV promethazine safety posted on their website. It was orginally published in their newsletter as a result of responses to a survey on IV promethazine safety.
http://www.ismp.org/newsletters/acutecare/articles/20061102.asp

While i do not know if Wyeth funds the Institute for Safe Medication Practices, they may want to a donation to cover increased PR and dissemination of this important safety information. A donation might also help out Wyeth’s reputation. In addition to the write off, the company can probably use some favorable press.

The dissemination of new insert information also troubles me. T

he New York Attorney General’s Office drug wholesaler subpeonaes pretty much forced the big three drug wholesalers to shut down their secondary drug wholesale subsidiaries by the end of 2005. Basically, the big three would buy large quantities of drugs before price increases, stockpile them, and distribute and/or trade the drugs at the higher prices (drug arbitrage) to increase profit. This led to large numbers of aged drugs - potentially including drugs with outdated package inserts -being distributed and dispensed to patients. These type of profit strategies also increase the risk of exposure to adulterating elements and/or product tampering and can lead to higher rates of drug adulteration and additional or amplified mechanism of actions.

If Baxter changed their Phenergan package insert in 2005, it may have taken until well into 2006 before the new package insert was on or included in the dispense, and it could have taken months longer for the pharmacist, doctor or nurse to read it and incorporate it into their practice. Note that I am not mentioning medical practice risk management consultants, accountants and attorneys, all of whom have more and more influence of what gets dispensed and how it gets dispensed.

Also, just b/c a drug company updates the package insert, it does not mean that the old package inserts are destroyed and replaced with new package inserts containing updated drug or device safety information. The old package inserts that are already on packaging in warehouses or pharmacy shelves are still in circulation. It can take awhile before the new warnings are disseminated and become generally acknowledged.

We had one instance where one treating doctor received a Dear Doctor letter. A second treating doctor had not, and the drug rep dropped off drug samples that had the outdated package insert on them. On learning about the Dear Doctor letter, the second physician (older and a computer novice) checked the old sample inserts, but because these were outdated he/she continued to prescribe based on outdated information for over 7 months until receiving and REVIEWING the following year’s PDR.

The FDA can require a pharmaceutical company or device company to update drug or device safety information, but to the best of my knowledge, they cannot regulate or force the company or other companies involved in distribution or dispense to disseminate the new drug safety information to pharmacists, doctors and other medical professionals who are directly involved (and LIABLE FOR) dispense and adminstration.

Below is a section copied from Levine’s brief:

“In 1973, Wyeth submitted a supplemental application
for Phenergan that included revised labeling.
JA270. FDA “recommend[ed]” a series of changes to
Wyeth’s proposed package insert. JA271. One was
to change the “Warnings” section to note that the
“intravenous use of” Phenergan “is not without
hazard.” Id. That suggestion duplicated the statement
in the “Dosage and Administration” section
that “proper intravenous administration of promethazine
hydrochloride is well tolerated, but use of
this route is not without some hazard.” JA277.
In 1975, Wyeth submitted another supplemental
application containing revised labeling for Phenergan.
JA280. FDA again wrote Wyeth with revisions
that “should” be made to the proposed label. Id.
Most did not pertain to the risk of arterial exposure.
JA280-86. FDA suggested that a warning, in capital
letters, about arterial exposure be included in the
“Cardiovascular Effects” section. JA283. FDA also
recommended an addition to the Warnings section to
clarify that medical practitioners cannot rely on the
color of the blood drawn back into an intravenous
setup to determine whether it is venous (dark red)
or arterial (bright red) blood, because Phenergan
discolors arterial blood. JA282. Consistent with
FDA’s lack of authority to require label changes for
previously authorized drugs, see supra p. 8, Wyeth
declined to implement many of FDA’s recommendations.
Compare JA281 (FDA recommending a
warning to reduce dosages for elderly patients) with
JA290 (noting that Wyeth “disagree[d]” with that
recommendation).”

Some drug companies pushed off submitting new drug safety information to the FDA, and then decided not to submit documents for enhanced K-H drug approval once their drug was off patent. There was a big push at the FDA around 2003- 2004 to try to get pharmaceutical companies to submit new FDA approval documents for their pre 1962 drugs.

Does anyone know if and when Wyeth sumitted post 1962 Phenergan documents to the FDA? Does anyone know how K-H works when it comes to the drug safety lableing of generics that may be manufactured by more than one company?

Did new documents include enhanced safety information about IV administration and does the information include the increased risk specifically associated with IV Push adminstration and not just IV administration?

The Phenegran package insert should include the year of the last insert label revision. Baxter revised their Phenergan IV label insert in 2005. Baxter’s Phenergan package insert is available online here:
http://www.baxter.com/products/anesthesia/anesthetic_pharmaceuticals/downloads/phenergan.pdf

Do you have a link for the transcipts?

Thanks

Jim

For expectable reasons, my tea leaves are suggesting that Wyeth will prevail, but it will be considerably more narrow than it might have been, more linked to the specific (and not that widely applicable) circumstances of the Levine case. Parallel claims violations, fraud and negligence, and the various kinds of mischief most of us are concerned about seem less likely to preempted by this ruling.

But wudda I know.

Also in the last pharmalot preemption post there was a link to an article which described how Dan Troy, and other FDA chief counsels, have deliberately promoted preemption, as part of a broad white house plan to create corporate immunity in all areas, depriving Americans of their rights, and making this much more than just a drug-niche issue.

That said, the current administration has been carefully crafting the Supremes to be in their image, and are probably looking at this as their moment to *shine*.

Sigh.

Thanks for the update.