Terra Sigillata

This sad story harkens back to my days as a pharmacy prof when students would argue for points on an incorrect pharmaceutical calculations exam by saying, “well, only the decimal point was off.”

A pharmacy erroneously made a drug 10 times more potent than intended, which killed three people who received it at an Oregon clinic, the state medical examiner said Friday.

ApotheCure Inc., a drug compounding pharmacy company in Texas, said an employee made a weighing error in the creation of the drug colchicine.

Drug compounding pharmacies have often attracted controversy. While they fulfill the classical Rockwellian pharmacist’s role of making drug formulations to order, particularly ointments or suppositories, they have often come under FDA scrutiny for making unapproved drug formulations, especially hormones and obsolete drugs. Regular readers will recall that a Canadian compounding pharmacist was recently asked to stop selling his formulation of an investigational cancer drug, dichloroacetate (DCA).

There are quite a few odd issues in this story, not the least of which is that three people died over the course of weeks from an unconventional use of the natural product drug, colchicine. Dervied from the Colchicum species of meadow saffron, this alkaloid inhibits microtubule polymerization and neutrophil motility. Although it acts in a manner similar to some anticancer drugs, its most prevalent use has been to treat gout.

The drug was only sent to the Center for Integrative Medicine in Portland, where three people received injections of the defective batch to treat back pain, ApotheCure said.

As pointed out by PharmGirl, MD, who tipped me on this story, injectable colchicine is not a standard practice for back pain. So much for integrative medicine being more “natural” and less invasive than conventional medical practice.

Even more appalling was the response from one of the ApotheCure pharmacists:

“We are kind of the leaders in the industry,” Osborn said. “But you know what people say, stuff happens.”

Leaders in the industry? Three deaths from an unconventional use of a drug due to a ten-fold dosing error and the defense is “stuff happens?” I cannot imagine a context in the course of a reporter’s interview where this quote would’ve been appropriate. And surely the mistake might have been caught after the first, and certainly the second, death.

So, yes, pharmacy students…the decimal point matters.

Addendum (2 May 2007): The US FDA MedWatch program has issued a manufacturer recall for the injectable colchicine product produced by this compounding pharmacy.

Comments

#1 Roy
April 30, 2007

Part of the problem is the stubborn refusal of the medical industry to adopt SI without cheating.

Decades ago, solutions were prepared in terms of “milligram per cent” — a sloppy shorthand expression for “milligrams per hundred cubic centimeters”. After being browbeaten by real scientists over this, the industry’s response was to denominate in “mg/mL” — which deliberately persists in using double scaling, a practice known to encourage mistakes, and the mistakes are order-of-magnitude errors — misplacing the decimal point.

Real chemists use single scaling, as in mg/L or ug/L. The medical industry should start practicing real chemistry, for, after all, those are real chemicals they are compounding, and every single chemical species is toxic at some concentration.
#2 Rick @ shrimp and grits
April 30, 2007

This is getting forwarded to my introductory students, who complain rather loudly when I don’t give credit for incorrect drug calculations.

But … “Stuff happens”? Wow. Just, … wow.
#3 ukcommunitypharmacist
May 2, 2007

Similar things have happened in the UK – for example http://www.pjonline.com/Editorial/20000311/news/babymanslaughter.html

Many pharmacys in the UK do not dispense extemporaneously, but order the product from specialist manufacturing companies – far safer and far more profitable.

Roy – mg/ml makes life straightforward and is safer than parts (i.e. 1 in 1000, 1 in 10,000). Far easier to prescribe amoxicillin 125mg/5ml 5ml three times a day, than amoxicillin 25,000mg/L, 5ml three times a day, which makes everyone have to think a lot more.
#4 fusilier
May 3, 2007

About six months ago, Methodist Hospital, here in Indianapolis, suffered three deaths in the pediatric ICU. The cause was traced to an incorrect dosage of heparin in the IVs.

Instead of loading an automatic dispenser with the pediatric vials, adult vials were loaded into the machine. A pharmacy tech and at least three RN’s failed to read the labels correctly.

I pointed this out to my ANP students. Believe it or not, I got responses like “My sister knows one of those nurses, and she didn’t mean to do that!”
#5 Abel Pharmboy
May 3, 2007

Rick, glad you hold your students to such high standards. It really does matter!

Roy and ukcommunitypharmacist, I also prefer to use mg/mL in the lab when not working in molarity. I think I may have spotted another reason why this ten-fold error occurred as detailed in this post.

fusilier, I guess we’ve got to do a better job of convincing our students that they really are the last check between the pharmacy and the patient. Checking and doublechecking are the responsibilities of a profession.
#6 Colst
May 3, 2007

“Real chemists use single scaling, as in mg/L or ug/L”

I’d like to meet these real chemists. Just today I’ve read papers with both ug/ml and mg/l (as well as an assortment of other concentration units).
#7 Joe
May 4, 2007

@UKComPharm, unless I misunderstand, this [i]was[/i] a “specialist manufacturer.” This well-illustrates a big problem with “compounding” pharmacies- no quality control analysis.