For six years, the physicians at San Antonio Ambulatory Surgery Center in Upland, Calif., were devoted users of Diprivan, the popular brand of propofol. They knew that generic propofol was available, but they were worried that the generic could cause a potentially harmful allergic reaction in some patients because of its sodium bisulfite additive. From their point of view, there was no reason to consider the non-name-brand drug.

But the facility's director of nursing, Susan Liptak, RN, saw things differently. She found out that a 20ml bottle of Diprivan cost $5.65 while the same amount of generic propofol cost $3.34. Now, $2.21 may not seem like much, but Ms. Liptak figured it adds up: An average of 30ml is used on each patient in a surgery center that does about 430 cases per month. The difference is even greater for the 50ml bottles, where the brand name cost her $11.29 and the generic cost her $6.69. "There's a big savings there," she says.

To get the physicians' buy-in on the idea of using generic anesthetics, she designed an experiment: For one month, the surgery center kept a supply of both Diprivan and generic propofol to let anyone who was reluctant about using the generic continue to use the name brand. The physicians agreed because they thought that this was a reasonable way to be sure the treatment was safe before accepting it, and at the end of the month they would revisit the issue and talk about any problems they experienced. As you'll see, the doctors accepted the off-patent drug.

This may seem like a novel approach, but with several commonly used anesthetic and anti-emetic drugs recently going off-patent, you might want to consider a similar method to introduce less expensive therapies into your facilities. But keep in mind that your anesthesia providers and surgeons may have reservations about changing the way they work, so it's important to address their concerns when suggesting a switch to generics. In this article, we'll review the latest generics and tell you what you need to know about them.

When patents expire
Surgical administrators looking for ways to cut costs got an early Christmas present last year: On Dec. 24, the patent expired for ondansetron (Zofran), a popular antiemetic. In January, the utility patent expired on desflurane (Suprane), an inhaled anesthetic. Later this year, on Dec. 29, we'll see another anti-emetic available in generic form when Roche's granisetron (Kytril) - which, like ondansetron, is a serotonin 5-HT3 receptor antagonist - goes off patent. Many of the most common anesthetics are already available in generic forms. Now this will also be true of the anti-emetics used as adjunctive treatments.

This is not to say that the story of generic therapies used in anesthesia has been uneventful. Take, for example, an incident involving the anti-emetic droperidol. In 2001, the generic version of this treatment received a "black box" warning from the FDA, indicating that there was a risk of serious proarrhythmogenic effects and even death from small doses of droperidol. Opponents of this warning note that in the preceding 30 years this drug had been used, there hadn't been a single documented case of arrhythmias occurring in treated patients during the post-op period. Rather, the complications seemed to occur when droperidol was administered to psychiatric patients at far larger doses than anesthesia providers use.1

In November 2003, Tong J. Gan, MD, FRCA, represented the Society of Ambulatory Anesthesia at an FDA open public hearing session and presented evidence that this drug is safe and effective as an anti-emetic, but left with the impression that the agency had no intentions of removing the warning anytime soon.2

Regardless of the FDA's opinion, droperidol evidently holds its own when compared to the other treatments for this condition. In a study of six PONV therapies and 5,199 patients, droperidol proved as effective as ondansetron and dexamethasone. The study's authors concluded that since the anti-emetic interventions are similarly effective and work independently, the best first-line choice is usually the safest and least expensive agent.3 This makes droperidol look like a good option, even though the "black box" warning may make some physicians wary about using it and prevents some groups from purchasing it.

"My experience, and that of the vast majority of anesthesiologists using droperidol in anesthetic doses, primarily as an anti-emetic, has been uniformly successful and uneventful," says Adam F. Dorin, MD, MBA, the medical director of the Sharp Grossmont Plaza Surgery Center in San Diego, Calif.

Similar studies were done to evaluate the safety and efficacy of the injected anesthetic propofol (Diprivan) when it went off patent in 1999. One head-to-head comparison study of the name brand and a bisulfite-containing generic conducted in 2000 found that fewer patients who received the generic version recalled pain on injection after surgery.4 Another study that compared the same two agents also found they had similar efficacy at a specified, bispectral index-defined depth of anesthesia.5 However, concerns that the sulfa would cause harmful or fatal anaphylactic reactions among patients has prompted some to suggest that outpatient surgery centers should steer clear of using propofol with sodium bisulfite.6

Ms. Liptak says the physicians at San Antonio Ambulatory Surgery Center were concerned about sulfa allergy reactions, but during the one-month trial they didn't see a single incident. They agreed to use generic propofol over the name brand, and six months later they still have yet to report a problem. "Right now, it seems like the generic propofol is OK," says Ms. Liptak.

For now, this is the only generic anesthetic her facility uses, but Ms. Liptak says this successful experience has made her doctors willing to consider other generic treatments such as sevoflurane and desflurane.

Always cheaper and sometimes better
Generics cost, on average, 30 to 50 percent less than name brands, say experts. But don't think less expensive means inferior quality when it comes to generics.

"I am not aware of any significant quality issues relating to generic medications, whether in anesthesiology or the general practice of medicine," says Dr. Dorin. "In fact, generics are well accepted by physicians and a welcome relief in costs for offices, facilities and patients."

Dr. Dorin says he has used a generic version of ondansetron at his surgery center and hospital and found it to be highly comparable to the name brand. He says he has also not experienced any problems when using the generic formulations of many other common anesthetic drugs, such as propofol or muscle relaxants.

Another anesthesiologist who's been using the generic form of ondansetron gave the generic high marks. "So far, so good," says Howard Leibowitz, MD, the medical director of the Memorial Same Day Surgery Center-West in Pembroke Pines, Fla. "[In the few weeks I've been using it], it seems to be just as effective and it costs close to one-third less than the name brand."

Dr. Leibowitz says he has also used midazolam, the generic form of Versed, for a long time and has always found it to be effective. "Sometimes I hear people say it doesn't work as well, but I don't believe it," says Dr. Leibowitz. "I'm a firm believer that generic drugs are equally effective as the name brand."

Dr. Dorin seconds the sentiment. "I know that the major pharmaceutical companies make a huge marketing investment trying to convince consumers that their original brand drug is superior, but there is no evidence to support this," he says.

According to Dr. Dorin, the FDA must approve every individual generic medicine; the treatments must contain the exact quantities in the same dosage of the brand name; and the treatments must be within 80 to 125 percent bioequivalent. This may seem like a wide range, but Dr. Dorin says the FDA certifies the activity of the active ingredient and that this is a reasonable variance. These drugs must also have the same formulation of the drug product and the same therapeutic effect and the same labeling as the original brand in addition to meeting the FDA standards for purity, quality, stability and strength.

Interestingly, the subtle changes made to the generics may sometimes yield favorable results. For example, Jay Horowitz, CRNA, of the Quality Anesthesia Care Corporation in Sarasota, Fla., says he witnessed cases where patients who received an intubating dose of the non-depolarizing muscle relaxant Pavulon had a very rapid heart rate, but he never saw this happen when the generic form of pancuronium was used. "Here, the generic was actually better," he says.

So many choices for one drug
As of this writing, 16 companies are listed in the FDA's electronic "Orange Book" as having approval to bring their own versions of ondansetron to the market: 13 offering injectable versions; one offering orally dissolving tablets; one offering swallowed tablets; and one offering an oral solution. "This drug met an unmet patient need, and this is a recognition of that," says Mary Anne Ryhne, spokeswoman for Zofran's manufacturer, GlaxoSmithKline.

The question here may be not whether to buy a generic drug, but from whom to buy it. Although most companies are on the level, Dr. Dorin says the widespread availability of counterfeit pharmaceuticals means you should evaluate generic manufacturers to be sure they are making a quality product.

Dr. Leibowitz says he makes it a point to buy generic treatments from reputable suppliers. Even then, he says he sometimes does a little checking up on them. "I like it when you do a little research and see the generic is made by the same company and in the same manufacturing plant as the name brand," he says.

Ms. Liptak says she uses the same supplier for her generic propofol as she used for the name brand Diprivan, which gives her an option if the physicians at her facility change their minds. "We can change back anytime we want to," she says.

References:
1. White, PF. Droperidol: A Cost-Effective Antiemetic for Over Thirty Years. Anesth & Analg 2002;95:789-790.
2. Gan, TJ. "Black Box" Warning on Droperidol: Report of the FDA Convened Expert Panel. Anesth & Analg 2004; 98:16479.A0.
3. Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, Zernak C, Danner K, Jokela R, Pocock SJ, Trenkler S, Kredel M, Biedler A, Sessler DI, and Roewer N. A Factorial Trial of Six Interventions for the Prevention of Postoperative Nausea and Vomiting. NEJM 2004;350:2441-2451.
4. Shao X, Li H, White PF, Kline KW, Kulstad C, and Owens A. Bisulfite-Containing Propofol: Is it a Cost-Effective Alternative to Diprivan for Induction of Anesthesia? Anesth & Analg 2000;91:871-875.
5. Olufolabi AJ, Gan TJ, Lacassie HJ, White WD, and Habib AS. A randomized, prospective double-blind comparison of the Efficacy of Generic Propofol (Sulphite Additive) With Diprivan. European Journal of Anaesthesiology 2006;23(4):341-5.
6. Shiffman MA. Dangers of Propofol in Cosmetic Surgery. International Journal of Cosmetic Surgery and Aesthetic Dermatology 2003;5:83-85.