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8/10/2001

Manufacturing Change Has Unexpected Effects

Kate Traynor

Michael J. Reeves, a pharmacy technician at the Tri-City Regional Surgery Center in Richland, Wash., has been dealing with an unusual drug-product safety issue this summer.

Reeves said that ampuls of Anzemet injection, containing dolasetron mesylate, have been shattering when people snap the neck of the glass container to open it. At least two nurses at Tri-City have been cut when they opened ampuls of the antinausea product, which Reeves said is in daily use at the outpatient surgery center.

One nurse’s hand injuries were more than an inconvenience. "She wasn’t able do the typical nursing things for a couple of days," Reeves said.

The problem apparently results from a change to the ampul. Instead of a full score that runs around the circumference of the ampul's neck, recently manufactured versions of dolasetron have a small "one-point-cut" score.

"A lot of the nurses aren’t getting it completely lined up. And when they go to snap it, they’re getting cut," Reeves said.

Reeves spoke with people at Aventis Pharmaceuticals Inc., which manufactures the ampuls, and Abbott Laboratories, which copromotes the product, about his colleagues’ problems with the ampuls. And he even tested the ampul-opening instructions that Aventis provided him. He said he cleanly opened two of three ampuls, but the third shattered in his hands.

Health care workers elsewhere have also been injured when opening dolasetron ampuls.

"We have had several people complain that the ampul has actually shattered in their hand," said Kelly M. Smith, Pharm.D., interim director of the drug information center at the University of Kentucky College of Pharmacy.

"There have been numerous cuts, and some folks have had to get stitches as well," she added.

Ampul breakage is not the only problem associated with the new packaging. Aventis also changed the text on the ampul's label—from black on a mostly white background to green text on white.

Compared with the old product label, Reeves described the green text as "very difficult to read."

He said the nursing, anesthesia, and surgical staffs at Tri-City have become disillusioned with the product. "The...nurses just got tired of not being able to read the label and [the ampul] not snapping as easily as it had in the past," he said.

The end result at Tri-City is that Reeves was asked to remove dolasetron from the formulary and replace it with GlaxoSmithKline’s ondansetron hydrochloride product, Zofran. When the change was discussed, Reeves reminded staff members that Zofran costs more than Anzemet.

"They said they would still rather have Zofran just because of the problems," he said.

Smith said the medical staff at Kentucky decided to stick with dolasetron despite their frustrations with the product—frustrations they have voiced to Aventis.

"[Dolasetron] fits in nicely with our system," Smith said. "We have some guidelines for postoperative nausea and vomiting that rely on dolasetron as a very important component."

And, Smith noted, reports of ampul-related injuries at her organization have declined as the staff has learned to live with the product’s hazards.

"What a lot of people have resorted to doing is to either wrap a piece of gauze or an alcohol swab around their hands before they try to open the amp," she says. "[They] try to put a barrier there to protect themselves."

Both Reeves and Smith said they submitted their concerns about Anzemet to the Food and Drug Administration’s MedWatch medication-safety reporting program. Problems with the ampuls have also been reviewed by the Institute for Safe Medication Practices (ISMP). A May 30 ISMP Medication Safety Alert! featured color photographs showing the new and old ampuls and ampuls that did not break cleanly at the neck.

Marisol Peron, associate manager for product communications at Aventis, said that changes to the ampul’s scoring were an unexpected byproduct of a switch in manufacturing plants.

"We had an external manufacturer that was doing the ampuls, and we switched to an Aventis internal manufacturing plant," Peron said. "The machines changed—everything changed."

"We were getting a lot of complaints," she added.

In response to these complaints, Peron said, Aventis plans to change its dolasetron ampuls back to the more familiar, fully scored format. She expects that fully scored ampuls will be available during the fourth quarter of 2001.

And the text on the ampul's label is now red, which, Peron said, should make the text easier to read. She said ampuls with the new label are already on the market.