One of the prescriptions that I write for the most is not a chemotherapy drug. It’s for Vitamin Z. Zofran (ondansetron). It’s a staple of our trade. It is for oncologists what Lasix (furosemide) is for cardiologists, and what Flonase (fluticasone) is for allergists. We give it out like Pez. Very, very expensive Pez. Pez that requires ‘prior approvals’ from insurance companies. Why so expensive? Because until recently, it was still covered by its patent.
Now, believe me, there’s no doubt that it works. Ondansetron and its other “setron” cousins have revolutionized what we can do in terms of chemotherapy. The older anti-nausea/vomiting drugs (Phernegan (promethazine), Compazine (prochlorperazine), Reglan (metoclopramide)) never worked particularly well and were not-infrequently accompanied by side effects including drowsiness, dry mouth, and a horrible type of muscle spasm called a dystonic reaction. These older drugs worked by tweaking multiple receptors in the brain, notably acetylcholine, histamine and dopamine receptors. Compazine is related to the 50’s antipsychotic drug Thorazine (chlorpromazine). As you can imagine, taking an antipsychotic drug to control your nausea from chemotherapy could make for a really bad week.
Enter ondansetron, a drug developed in the early 1980s and approved by the FDA in 1991. This drug targets and blocks the 5-HT3 serotonin receptor. It is thought to work by reducing activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, as well as by blocking serotonin receptors in the chemoreceptor trigger zone (CTZ). Because it works well, it became popular very quickly, and its price remained high. In 2005, Zofran was the 20th most expensive brand-name drug used in hospitals in the US, with total costs of $839 million.
As you can imagine, people also looked at Zofran for other indications besides chemotherapy-induced nausea and vomiting (CINV). After this paper was published in Pediatrics in 2002, I’ve seen a tremendous increase in the use of Zofran for vomiting associated with acute gastroenteritis in children. Given that the incidence of gastroenteritis (3 million cases/year seen by physicians) is so much higher than chemotherapy use, it is not hard to imagine that widespread use of Zofran in this population could dramatically increase the cost of acute gastroenteritis.
Fortunately, December 24th marked a banner day in oncologic economics. Zofran went “off-patent”. Just as quickly, the FDA approved the first generic versions, recognizing that this should substantially decrease costs.
In the past few years, there we’ve seen several “second generation” drugs of the ’setron’ class, including Kytril (granisetron), Anzamet (dolasetron), and Navoban (tropisetron). I’m curious to see how much harder these are pushed, and whether or not they’ll creep into the non-chemotherapy market. For now, though, I’ll feel a little better about writing for generic ondansetron.