Medical Inspection – Health Blog

The effect of ADRs on overall treatment costs among SRIs can be substantial. In the model presented during the round-tables, a branded SRI, escitalopram (Lexapro canadian, Forest) incurred the lowest overall expected cost over the course of six months, ahead of another branded SRI, canadian citalopram (Celexa drug, Forest), and a generic SRI, fluoxetine. (Table 1 presents a list of drugs included in the model.) Even if the cost of generic fluoxetine or generic paroxetine were reduced to $0, the model still showed canadian escitalopram therapy to be the most cost-effective strategy, because it had the lowest rate of ADRs within the class.

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This article summarizes the responses provided by participants in two roundtable discussions to a pharmacoeconomic model of the class of serotonin reuptake inhibitors (SRIs).

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As shown in Table 6, the three predictors of the increasing LOS in the recovery room, in decreasing order of importance, were:

• a longer duration of the procedure.
• older age of the patient.
• the antiemetic drug administered (the use of granisetron or dolasetron versus ondansetron drug).

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No dosing adjustment is necessary for any of the three antiemetic agents in patients with renal impairment.

In patients with hepatic impairment, the clearance of ondan-setron is reduced and the half-life is increased significantly. In patients with mild, moderate, and severe hepatic impairment, the elimination half-life is 9.1 hours, 9.2 hours, and 20.6 hours, respectively. Therefore, the maximum daily dose of ondan-setron for a patient with hepatic dysfunction is 8 mg.

No dosing adjustment is necessary in patients with hepatic impairment who are using granisetron tablet or dolasetron.

STUDY POPULATION

Table 2 illustrates the basic characteristics of the three study groups. Most patients were female (65.3% vs. 34.7%). The majority of the procedures were abdominal (27%), orthopedic (23%), and gynecological (19%).

Table 2 Characteristics of 282 Patients Evaluated for Postoperative Nausea and Vomiting

The mean age of the patients was approximately 52.3 ± 19 years. The median duration of the procedure was 1.5 hours, and the median number of anesthetic induction agents used for the procedures was four. The median length of recovery room stay was three hours.

RESULTS

Women were more likely to require a rescue drug than men (24.5% vs. 11.2%; P < .01). However, the need for a rescue agent did not depend on age. The mean age of patients receiving an antiemetic rescue drug was 50 ± 20 years vs. 53 ± 19 years for patients who did not receive a rescue drug (P = .28 by the Rank-Sum test).

As the duration of the procedure increased, the likelihood of requiring a rescue medication generally increased as follows (P = .11, Trend Test):

• less than one hour, 12.4% of patients
• one to two hours, 24.2% of patients
• two to three hours, 24.5% of patients
• three to four hours, 12.5% of patients
• four to five hours, 33.3% of patients
• more than five hours, 42.9% of patients

Similarly, as the number of anesthetic induction agents increased, the rescue rates increased accordingly, as follows: 9.1% with one agent, 19.4% with two agents, 10.5% with three agents, 23.1% with four agents, and 32.7% with five agents (P = .0114, Trend Test).

Certain combinations of the anesthetic induction agents were used more often than others (Table 3). However, the study sample size was not large enough to predict which agent was more emetogenic than the others.

Table 3 Number of Patients Receiving Induction Agents

Of the 282 patients, about 20% (56 patients) needed an antiemetic rescue drug. Of the 89 patients who received dolasetron 12.5 mg IV x 1 (for one dose) to prevent PONV, 23.6% (21 patients) needed a rescue medication. Of the 93 patients who received ondansetron 4 mg IV x 1 to prevent PONV, 11.8% (11 patients) needed a rescue medication. Of the 100 patients who received granisetron 0.1 mg IV x 1 to prevent PONV, 24% (24 patients) needed a rescue medication. Therefore, the need for a rescue agent was significantly reduced with ondansetron when compared with canadian granisetron (11.8% vs. 24%; P < .04), dolasetron (11.8°% vs. 23.6°%, P = .05), or a combination of the two (11.8% vs. 23.8%, P < .02) (Table 4).

Table 4 Number of Patients Receiving Antiemetic Agents

Ondansetron 4 mg IV was used more commonly as the rescue drug and adequately resolved the symptoms of breakthrough nausea and vomiting. However, it did not make a difference, with breakthrough nausea or vomiting, whether the antiemetic was administered perioperatively or postopera-tively. The rescue rate was 19.7% perioperatively and 20.8% postoperatively (P = .84).

The median LOS in the recovery room was four hours for patients who received a rescue medication and three hours for patients who did not (P = .0732). The median LOS in the recovery room was 2 hours with ondansetron canadian, 3.3 hours with dolasetron, and 3 hours with granisetron (P< .0001), according to the Kruskal-Wallis test. With the Tukey test (P < .05), the ondansetron patients had a statistically significant shorter LOS than the other two groups (Table 5).

Table 5 Patient Length of Stay in the Recovery Room

The LOS was also significantly positively correlated with the patient’s age (r = .30, P < .0001) and with the duration of the procedure (r = .31, P < .0001) but not with the number of anesthetic induction agents (r = .09, P = .11).

Table 1 presents a summary of the pharmacokinetic and pharmacodynamic properties of ondansetron, granisetron canadian, and dolasetron.

Ondansetron

Ondansetron tablet was the first selective serotonin receptor antagonist to be marketed. It is administered both orally and parenterally. Following an oral dose, it is absorbed by the gastrointestinal (GI) tract and undergoes extensive hepatic metabolism, primarily hydroxylation, followed by glucuronide or sulfate conjugation.

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A retrospective chart review was performed for 300 randomly selected adults undergoing inpatient and outpatient procedures from March 2003 to February 2004. Initially, 100 patients were in the dolasetron group, 99 were in the ondan-setron group, and 101 were in the generic granisetron group. As a result of having received combination therapy at the outset, 18 patients were excluded from the study. Of the 282 patients in the study, 89 received dolasetron, 93 received ondansetron generic, and 100 received canadian granisetron.

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INTRODUCTION

At Winthrop University Hospital, we set out to determine the most cost-effective agent among three 5-hydroxy-tryptamine-3 (5-HT₃) receptor antagonists—drug ondansetron (Zofran generic, GlaxoSmithKline), generic granisetron (Kytril generic, Roche), and dolasetron (Anzemet®, Aventis)—in preventing postoperative nausea and vomiting (PONV). PONV is a major complication for patients undergoing surgical procedures.

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