Long-term Medicaid excess payments from alleged price manipulation of generic lorazepam.

BACKGROUND: Cost savings from the use of generic drugs versus brand-name drugs are well known. Both private and public prescription drug plans encourage the use of generic drugs through a variety of mechanisms. The magnitude of cost savings for a given generic drug is dependent on the degree to which the generic market is competitive. Should the competitive structure become compromised, higher prices and reduced cost savings may result. An alleged conspiracy between Mylan Laboratories and its active-ingredient suppliers in 1997 was associated with an increase in seller concentration in the generic lorazepam market. The Federal Trade Commission (FTC) alleged that Mylan raised costs to consumers by $120 million because of price increases for generic lorazepam from March through December 1998 and for generic clorazepate from January through December 1998. In November 2002, a settlement with Mylan was approved by the FTC, and a federal district court required Mylan to pay $147 million, including $28.2 million to state agencies including Medicaid. OBJECTIVES: To (a) describe the seller concentration in the national Medicaid generic lorazepam market over a 19-year period from January 1991 through December 2009, (b) estimate the excess payments for generic lorazepam by Medicaid between 1998 and 2009, and (c) investigate potentially increased utilization and prices of 2 substitute pharmaceuticals: branded lorazepam (Ativan) and generic alprazolam (another widely used intermediate-acting benzodiazepine). METHODS: Using Medicaid State Drug Utilization Data from the Centers for Medicare Medicaid Services, we calculated the 4-firm concentration ratio (CR4) and the Herfindahl-Hirschman Index (HHI) for the Medicaid generic lorazepam market, along with pre-rebate reimbursement for pharmacy claims, number of claims (utilization), and average pre-rebate reimbursement per claim (average "price") for generic lorazepam, from 1991 through 2009. Medicaid's excess payments were estimated under 2 different assumptions regarding what the average generic lorazepam price would have been in the absence of the alleged conspiracy. To find counterfactual prices, the average per-claim reimbursement for lorazepam for the 4 quarters prior to the alleged conspiracy, $6.80, was inflated using (a) the quarterly change in the average per-claim reimbursement for generic alprazolam and (b) the Consumer Price Index (CPI) for all urban consumers, all goods. Potential impact of the alleged conspiracy on the branded lorazepam and generic alprazolam markets was investigated. RESULTS: The average pre-rebate reimbursements per claim for generic lorazepam were $10.25, $23.12, and $8.48 in 1991, 1998, and 2009, respectively. For the same 3 years, CR4 = 52.80, 76.02, and 86.74, while HHI = 905.71, 2,166.25, and 2,233.36. Medicaid's excess payments from 1998-2009 were estimated at approximately $625-$657 million. The data also suggest the possibility of small impacts on the utilization of branded lorazepam and the price of generic alprazolam. CONCLUSIONS: Prior to the alleged conspiracy in 1997, average pre-rebate reimbursement per claim for generic lorazepam was declining, while seller concentration was rising. After a jump in average payment per claim in the years immediately following the alleged conspiracy, prices have gradually returned to their pre-1998 levels. However, the generic lorazepam market was more concentrated in 2009 than prior to the alleged conspiracy.

Economic evaluation of propofol and lorazepam for critically ill patients undergoing mechanical ventilation.

OBJECTIVE: The economic implications of sedative choice in the management of patients receiving mechanical ventilation are unclear because of differences in costs and clinical outcomes associated with specific sedatives. Therefore, we aimed to determine the cost-effectiveness of the most commonly used sedatives prescribed for mechanically ventilated critically ill patients. DESIGN, SETTING, AND PATIENTS: Adopting the perspective of a hospital, we developed a probabilistic decision model to determine whether continuous propofol or intermittent lorazepam was associated with greater value when combined with daily awakenings. We also evaluated the comparative value of continuous midazolam in secondary analyses. We assumed that patients were managed in a medical intensive care unit and expected to require ventilation for > or = 48 hrs. Model inputs were derived from primary analysis of randomized controlled trial data, medical literature, Medicare reimbursement rates, pharmacy databases, and institutional data. MAIN RESULTS: We measured cost-effectiveness as costs per mechanical ventilator-free day within the first 28 days after intubation. Our base-case probabilistic analysis demonstrated that propofol dominated lorazepam in 91% of simulations and, on average, was both $6,378 less costly per patient and associated with more than three additional mechanical ventilator-free days. The model did not reveal clinically meaningful differences between propofol and midazolam on costs or measures of effectiveness. CONCLUSION: Propofol has superior value compared with lorazepam when used for sedation among the critically ill who require mechanical ventilation when used in the setting of daily sedative interruption.

Effect of sedation with dexmedetomidine vs lorazepam on acute brain dysfunction in mechanically ventilated patients: the MENDS randomized controlled trial.

CONTEXT: Lorazepam is currently recommended for sustained sedation of mechanically ventilated intensive care unit (ICU) patients, but this and other benzodiazepine drugs may contribute to acute brain dysfunction, ie, delirium and coma, associated with prolonged hospital stays, costs, and increased mortality. Dexmedetomidine induces sedation via different central nervous system receptors than the benzodiazepine drugs and may lower the risk of acute brain dysfunction. OBJECTIVE: To determine whether dexmedetomidine reduces the duration of delirium and coma in mechanically ventilated ICU patients while providing adequate sedation as compared with lorazepam. DESIGN, SETTING, PATIENTS, AND INTERVENTION: Double-blind, randomized controlled trial of 106 adult mechanically ventilated medical and surgical ICU patients at 2 tertiary care centers between August 2004 and April 2006. Patients were sedated with dexmedetomidine or lorazepam for as many as 120 hours. Study drugs were titrated to achieve the desired level of sedation, measured using the Richmond Agitation-Sedation Scale (RASS). Patients were monitored twice daily for delirium using the Confusion Assessment Method for the ICU (CAM-ICU). MAIN OUTCOME MEASURES: Days alive without delirium or coma and percentage of days spent within 1 RASS point of the sedation goal. RESULTS: Sedation with dexmedetomidine resulted in more days alive without delirium or coma (median days, 7.0 vs 3.0; P = .01) and a lower prevalence of coma (63% vs 92%; P < .001) than sedation with lorazepam. Patients sedated with dexmedetomidine spent more time within 1 RASS point of their sedation goal compared with patients sedated with lorazepam (median percentage of days, 80% vs 67%; P = .04). The 28-day mortality in the dexmedetomidine group was 17% vs 27% in the lorazepam group (P = .18) and cost of care was similar between groups. More patients in the dexmedetomidine group (42% vs 31%; P = .61) were able to complete post-ICU neuropsychological testing, with similar scores in the tests evaluating global cognitive, motor speed, and attention functions. The 12-month time to death was 363 days in the dexmedetomidine group vs 188 days in the lorazepam group (P = .48). CONCLUSION: In mechanically ventilated ICU patients managed with individualized targeted sedation, use of a dexmedetomidine infusion resulted in more days alive without delirium or coma and more time at the targeted level of sedation than with a lorazepam infusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00095251.

Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis.

STUDY OBJECTIVE: To characterize inpatient use of intravenous sedatives in the real-world setting, and to evaluate clinical and economic outcomes when dexmedetomidine was used with midazolam and propofol for select cardiovascular procedures. DESIGN: 12-month retrospective analysis. DATA SOURCE: An administrative claims database of operational data from a nationally representative sample of 250 medical and surgical hospitals. PATIENTS: Patients who received midazolam plus propofol (9996 patients) or dexmedetomidine, midazolam, plus propofol (356 patients) after cardiac valve or vessel surgery. MEASUREMENTS AND MAIN RESULTS: The source of patient demographics (e.g., age, sex, Charlson Comorbidity Index) and outcomes (e.g., charges, length of stay, mortality rate) was the hospital billing claim form. Patients in the dexmedetomidine-midazolam-propofol cohort tended to be younger and male and to have fewer comorbidities than those midazolam-propofol cohort. The primary outcomes for the three-drug cohort showed significant reductions in total charges/patient (approximately $18,000, p<0.05), total hospital length of stay (0.6 days, p<0.0001), days in the intensive care unit or cardiac care unit (3.87 days, p<0.0001), and mortality (2%, p=0.0142). Although pharmacy charges were higher (approximately $4000/patient), lower charges for the intensive care or cardiac care unit, operating room, room and board, and respiratory services were observed in the dexmedetomidinemidazolam-propofol cohort compared with the two-drug cohort. Also, mechanical ventilation was shorter by approximately 0.5 day in the three-drug cohort (p<0.01). CONCLUSION: These initial findings of a real-world assessment of dexmedetomidine use with other agents suggest favorable clinical and economic outcomes. Further research through randomized clinical trials of dexmedetomidine is warranted to better understand its optimum patient population, dosage, and the causality of the results, and to confirm the potential clinical and economic benefits observed in our patients.

Pharmacoeconomic modeling of lorazepam, midazolam, and propofol for continuous sedation in critically ill patients.

STUDY OBJECTIVE: To compare the expected costs of short-, intermediate-, and long-term sedation (< 24, 24-72, and > 72 hrs, respectively) with propofol, lorazepam, and midazolam in an intensive care unit. METHODS: Decision-analysis models were constructed for each sedative and each duration by using institutional costs associated with drug administration and adverse events (including personnel time). Costs were expressed in 2002 U.S. dollars. Adverse events were agitation, hypertriglyceridemia and/or pancreatitis, hypotension, nutritional changes, ventilator-associated pneumonia, and prolonged awakening and/or extubation. MEDLINE and EMBASE databases were searched to obtain durations of sedation, the incidence of outcomes, and cost estimates of outcomes. The ability to maintain specific levels of sedation was assumed equivalent among the sedatives. Univariate sensitivity analyses were conducted to determine the cost-driving variables, and probabilistic sensitivity analyses were conducted by using second-order Monte Carlo simulations. RESULTS: Weighted mean durations of sedation from 50 studies were 13.46 (short term), 45.27 (intermediate term), and 119.78 (long term) hours. Expected costs for sedation with lorazepam, midazolam, and propofol, respectively, were 497 dollars, 294 dollars, and 272 dollars short term; 932 dollars, 587 dollars, and 674 dollars intermediate term; and 1604 dollars, 1737 dollars, and 2033 dollars long term. Propofol was least costly in 86% of the short-term simulations, midazolam was least costly in 97.5% of the intermediate-term simulations, and lorazepam was least costly in 84% of the long-term simulations. The most important cost-driver for all sedatives was drug cost. Prolonged extubation after sedation was an important cost-driver for lorazepam and midazolam, especially as sedation was lengthened. CONCLUSION: Propofol, midazolam, and lorazepam had the lowest expected costs for short-, intermediate-, and long-term sedation, respectively. Many factors aside from drug costs influenced the cost of sedation.

A comparison of lorazepam and diazepam as initial therapy in convulsive status epilepticus.

BACKGROUND: Previous trials have suggested lorazepam may be superior to diazepam as first-line treatment of convulsive status epilepticus (CSE), with improved seizure outcome, and a lower incidence of side-effects. Many published guidelines however still recommend diazepam. AIM: To compare the efficacy, safety and cost of lorazepam compared to diazepam, in adults with CSE. DESIGN: Retrospective case note audit. METHODS: Cases of CSE were retrospectively identified over two 18-month periods either side of the introduction of a new management protocol in May 1997, in which lorazepam 4 mg i.v. was substituted for diazepam 10 mg i.v. as first-line treatment for CSE. Diagnostic codes for all admissions and casualty presentations of patients over 16 years of age were examined for primary or secondary codes including 'epilepsy', 'fits' or 'status epilepticus'. Medical records and casualty notes were reviewed to identify CSE cases. Treatment groups were compared using ANOVA and a Tukey post hoc analysis. Treatment success was defined as cessation of seizures without recurrence in the subsequent 12 h. RESULTS: In both premonitory and established CSE, both drugs were equally effective at terminating seizures, but significantly fewer seizure recurrences followed lorazepam, and fewer repeat doses were needed. There were no differences in reported adverse events or in drug costs. DISCUSSION: We recommend that lorazepam be the first-line therapy in preference to diazepam in adults with CSE.

Sedation in the intensive care unit.

OBJECTIVE: To describe the goals of sedative use in the intensive care unit and review the pharmacology of commonly used sedative drugs as well as to review pertinent publications in the literature concerning the comparative pharmacology of these drugs, with emphasis on outcomes related to sedation and comparative pharmacoeconomics. DATA SOURCES: Publications in the scientific literature. DATA EXTRACTION: Computer search of the literature with selection of representative articles. SYNTHESIS: Proper choice and use of sedative drugs is based on knowledge of the pharmacology of commonly used agents and is an essential component of caring for patients in the intensive care unit. The large variability in pharmacokinetics and pharmacodynamics in the critically ill make it difficult to directly compare agents. Midazolam provides rapid and reliable amnesia, even when administered for low levels of sedation. Propofol may be useful when deeper levels of sedation and more rapid awakening are required. Lorazepam can be used for long-term sedation in more stable patients if rapidity of effect is not required. Further investigation in assessment of depth of sedation in the critically ill is needed. Continued study of costs, side effects, and appropriate dosing strategies of all sedative agents is needed to answer questions not sufficiently addressed in the current literature. CONCLUSION: An individualized approach to sedation based on knowledge of drug pharmacology is needed because of confounding variables including concurrent patient illness, depth of sedation, and concomitant use of analgesic agents. (Crit Care Med 2000; 28:854-866)

Continuous infusions of lorazepam, midazolam, and propofol for sedation of the critically ill surgery trauma patient: a prospective, randomized comparison.

OBJECTIVE: To compare the efficacy, safety, and cost of continuous infusions of lorazepam, midazolam, and propofol in a critically ill trauma/surgery patient population. DESIGN: A prospective, randomized, nonblinded, single center. SETTING: A 16-bed intensive care unit. PATIENTS: A total of 30 ventilated patients who were 18-70 yrs of age and required pharmacologic sedation. Patients with renal and/or liver failure, a history of alcohol abuse, a head injury, or in a coma were excluded. INTERVENTIONS: Patients were randomized by block design to receive lorazepam, midazolam, or propofol. Initial boluses and infusion rates were as follows: lorazepam 0.05 mg/kg, then 0.007 mg/kg/hr; midazolam 0.05 mg/kg, then 0.003 mg/kg/hr; and propofol 0.25 mg/kg, then 0.06 mg/kg/hr. Sedation was assessed and agents titrated every 5-10 mins to achieve > or =2 and <5 on the modified Ramsay scale. Once adequate response was achieved, agents were titrated to maintain the desired level of sedation. MEASUREMENTS AND MAIN RESULTS: Maintenance doses of lorazepam 0.02+/-0.01 mg/kg/hr, midazolam 0.04+/-0.03 mg/kg/hr, and propofol 2.0+/-1.5 mg/kg/hr achieved the desired level of sedation 68%, 79%, and 62% of the time, respectively. Oversedation occurred most often with lorazepam, compared with midazolam and propofol, at 14%, 6%, and 7% of the assessment times, respectively. Undersedation occurred most frequently with propofol compared with lorazepam and midazolam, at 31%, 18%, and 16% of the assessment times, respectively. The mean number of dosage changes per day was 7.8+/-4.3 for lorazepam, 4.4+/-2.9 for midazolam, and 5.6+/-6.0 for propofol (p = .91). Sedation costs per patient day (mean +/- SD) were $48+/-$76 (lorazepam), $182+/-$98 (midazolam), and $273+/-$200 (propofol) (p = .005). The potential savings, if all study patients had received lorazepam, is $14,208 compared with $8,808 if all received midazolam. CONCLUSIONS: The data suggest that lorazepam appears to be a cost-effective choice for sedation; however, oversedation may be problematic. Midazolam is the most titratable drug in our population, avoiding excessive oversedation or undersedation. Trauma patients may respond inadequately to propofol even at higher doses. Lorazepam may be the sedative of choice in critically ill trauma/surgery patients.

Continuous infusion of lorazepam versus medazolam in patients in the intensive care unit: sedation with lorazepam is easier to manage and is more cost-effective.

OBJECTIVE: To evaluate the effectiveness of lorazepam and midazolam for long-term sedation of critically ill, mechanically ventilated patients. DESIGN: Double-blind, randomized, controlled study. SETTING: Medical intensive care unit in a university teaching hospital. PATIENTS: Sixty-four evaluable adult patients admitted to the intensive care department requiring mechanical ventilation for >3 days. INTERVENTIONS: Patients were randomized to receive blinded solutions of either lorazepam or midazolam by continuous infusion. The lowest dose that achieved an adequate sedation was infused. The maximum dose allowed for each drug was 60 mg/hr for midazolam and 4 mg/hr for lorazepam. Sedation was assessed initially and at least every 8 hrs thereafter on a seven-point scale if the sedation was adequate and every 2 hrs if it was not. MEASUREMENTS AND MAIN RESULTS: Measurements included the score on the sedation scale, the time between determination of the desired level of sedation and the achievement of that level, and plasma concentrations. It is significantly easier to reach a desired level of sedation with lorazepam than with midazolam. No difference in recovery was found in the 24 hrs after discontinuation of therapy. The fact that there are many factors influencing midazolam pharmacokinetics may explain the more difficult management of desired sedation levels. The equipotent dose of 10 mg of midazolam proved to be 0.7 mg of lorazepam in long-term sedation. The average cost for therapy with midazolam was approximately ten times more than that with lorazepam. CONCLUSIONS: Lorazepam is a useful alternative to midazolam for the long-term sedation of patients in the medical intensive care unit and provides easier management of the sedation level. Sedation with lorazepam offers a significant cost-savings.

A cost analysis of enterally administered lorazepam in the pediatric intensive care unit.

OBJECTIVE: To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation. DESIGN: Retrospective review of patients treated according to a preestablished pediatric intensive care unit (ICU) sedation protocol. SETTING: Twenty-six-bed pediatric ICU in a tertiary care children's hospital. PATIENTS: The records of 30 mechanically ventilated children were analyzed. The median age was 1.5 yrs and the median weight was 8.0 kg. Patients required continuous sedation for a total of 16 days (median). INTERVENTIONS: According to our pediatric ICU sedation protocol, midazolam infusion was continued until the hourly midazolam requirement was stable for at least 24 hrs. Thereafter, patients with a nasojejunal tube who were likely to require a minimum of three additional days of continuous sedation were transitioned from intravenous midazolam to enterally administered lorazepam. The goal in transitioning therapy was to titrate the lorazepam dose and reduce midazolam administration while maintaining an unchanged level of sedation. MEASUREMENTS AND MAIN RESULTS: The rate of midazolam administration was significantly (p<.05) reduced beginning on day 1 of lorazepam treatment. Midazolam was successfully discontinued in 24 (80%) patients in 3 days (median), and adequate and appropriate sedation was maintained with lorazepam monotherapy. Six patients in whom midazolam could not be discontinued experienced a 52% reduction in the rate of midazolam administration as a result of adding lorazepam. Total projected midazolam utilization was defined as the sum of midazolam administration before initiating lorazepam and the projected midazolam requirement after initiating lorazepam. Projected midazolam cost was calculated as the product of total projected midazolam utilization and midazolam acquisition cost. Actual expenditures for both midazolam and lorazepam were subtracted from the projected midazolam cost to calculate the estimated cost savings. Overall, midazolam utilization (in milligrams) was reduced by 46.7+/-27.6% (median 52). Total projected midazolam cost for the 30 patients was $90,771. The actual cost of midazolam and lorazepam combined was $47,867, resulting in a cost savings of $42,904. CONCLUSIONS: Transitioning from intravenous midazolam to enterally administered lorazepam in critically ill children who require long-term sedation results in significant cost savings. The oral formulation of lorazepam was convenient to use, inexpensive, and effective in maintaining a continuous and appropriate level of sedation once midazolam was discontinued.

Lorazepam and midazolam in the intensive care unit: a randomized, prospective, multicenter study of hemodynamics, oxygen transport, efficacy, and cost.

OBJECTIVES: To evaluate and compare the clinical efficacy, impact on hemodynamic and oxygen transport variables, safety profiles, and cost efficiency of sedation and anxiolysis with lorazepam vs. continuous infusion of midazolam in critically ill, intensive care unit patients. DESIGN: Multicenter, prospective, randomized, open-label study. SETTING: Teaching hospitals. PATIENTS: Ninety-five critically ill, mechanically ventilated patients with fiberoptic pulmonary artery catheters in place were randomly assigned to receive short-term (8 hrs) sedation with either intermittent intravenous injection lorazepam (group A, n = 50) or continuous intravenous infusion midazolam (group B, n = 45) titrated to clinical response. MEASUREMENTS AND MAIN RESULTS: The severity of illness, demographic characteristics, levels of anxiety and agitation, hemodynamic parameters, oxygen transport variables, quality of sedation, nursing acceptance, and laboratory chemistries reflecting drug safety were recorded. There were no significant differences with regard to demographic data, hemodynamic and oxygen transport variables, or levels of anxiety/agitation between the two groups at baseline, 5 mins, 30 mins, and 4 and 8 hrs after administration of sedation. There were no significant differences in the quality of sedation or anxiolysis. Midazolam-treated patients used significantly larger amounts of drug for similar levels of sedation and anxiolysis (14.4 +/- 1.2 mg/8 hrs vs. 1.6 +/- 0.1 mg/8 hrs, p = .001). Both drugs were safely administered and patient and nurse satisfaction was similar. CONCLUSIONS: Sedation and anxiolysis with lorazepam and midazolam in critically ill patients is safe and clinically effective. Hemodynamic and oxygen transport variables are similarly affected by both drugs. The dose of midazolam required for sedation is much larger than the dose of lorazepam required for sedation, and midazolam is therefore less cost-efficient.

Trends in the management of alcohol withdrawal syndrome.

Alcohol use among head and neck cancer patients is common. Alcohol withdrawal (especially delirium tremens) poses significant potential morbidity to postsurgical patients. Treatment with newer benzodiazepines (BZDs) such as lorazepam and midazolam has become more widespread, and mortality rates from severe alcohol withdrawal have decreased in recent years. The authors retrospectively studied 102 patients with a diagnosis of alcohol withdrawal, including 20 patients undergoing surgery for cancer of the head and neck. There were 81 men and 21 women, with a mean (+/- standard deviation [SD]) age of 52.3 (+/- 16.1) years. Many of these patients (46%) were treated with more than one BZD or other neuroleptic, while 49% received single agent therapy of either chlordiazepoxide (26%) or lorazepam (23%). Delirium tremens occurred in 12% of all patients undergoing withdrawal and in 10% of head and neck cancer patients, with a mortality rate of 9% and 0%, respectively. Single agent use was successful in greater than 95% when either lorazepam or chlordiazepoxide was used. Instances of combination treatment where older BZDs were used yielded a 69% success rate. The higher complication rate and lower treatment success with combination treatment was multifactorial. Optimal management of the alcohol withdrawal syndrome requires an understanding of its pathophysiology and the principles of its prevention along with a familiarity of BZD pharmacokinetic drug profiles. The authors present a treatment plan which is cost-effective, keeps morbidity low, and should allow a continued decreasing trend in mortality rates from delirium tremens.

A retrospective review and assessment of benzodiazepines in the treatment of alcohol withdrawal in hospitalized patients.

Little information has been published concerning differences among the benzodiazepines in treating hospitalized patients with severe symptoms of alcohol withdrawal. We attempted to determine the length and type of hospital stay, and the pattern and appropriateness of administration, dosage requirements, and costs associated with benzodiazepines in patients undergoing alcohol withdrawal. A 1-year retrospective analysis was performed for 57 hospitalized patients. Appropriate therapy was defined as lorazepam for patients 60 years and older or those with hepatic dysfunction, and chlordiazepoxide or diazepam for all other patients. Drug costs were calculated based on acquisition costs. The mean number of days of benzodiazepine treatment and length of stay in the intensive care unit (ICU) were 6.2 days (range 1-30 days) and 3.9 days (range 0-12 day), respectively. Fifty-six patients were admitted to the ICU for management or for monitoring continuous-infusion lorazepam; one patient received chlordiazepoxide on a general ward. Total mean lorazepam infusion required per patient was 324 mg (range 2-5956 mg). The total benzodiazepine acquisition cost was $56,489 (mean $1009, range $0.06-7157/patient). The total costs of benzodiazepine acquisition and ICU charge were $404,346 (mean $7462/patient). Based on our criteria, 41 of 57 patients could have been treated appropriately with chlordiazepoxide, which would have resulted in an estimated drug-acquisition cost savings of at least $37,000. Mean benzodiazepine dosage requirements in patients hospitalized for alcohol withdrawal appear higher than previously reported. Approximately 70% of our patients were not of advanced age and had no evidence of organ dysfunction, and therefore, could have been treated with an oxidized benzodiazepine (i.e., chlordiazepoxide).(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-effectiveness analysis of antiemetic treatment.

To address the economic issues posed by the introduction of 5-hydroxytryptamine3 receptor antagonist (5-HT3 RA), we performed a cost-effectiveness analysis based on clinical trial data published in the recent literature. Cost calculations include initial treatment and a second-line salvage treatment. The average cost and incremental cost were established. Incremental cost corresponds to the extra cost involved in achieving total control of emesis in 1% extra patients. If 5-HT3 RA is not part of the initial treatment, salvage treatment with ondansetron is not cost-effective. Moreover, starting with the combination of ondansetron plus dexamethasone saves more money than starting with ondansetron alone. However, if the difference in emesis control is only minimal, treatment with the 5-HT3 RA remains more expensive.