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The efficacy of postoperative ondansetron (Zofran) orally disintegrating tablets for preventing nausea and vomiting after acoustic neuroma surgery.

Postoperative nausea and vomiting is a frequent complication of craniotomy. We evaluated the ability of intraoperative IV ondansetron followed by postoperative ondansetron in an orally disintegrating tablet formulation to reduce the frequency and severity of postoperative nausea and vomiting in a prospective, randomized, placebo-controlled double-blind trial of 60 patients undergoing acoustic neuroma resection. Each patient received intraoperative ondansetron (4 mg IV) or placebo 30 min before case end. Postoperatively, patients received ondansetron in an orally disintegrating tablet formulation (8 mg BID) or placebo twice a day for up to 72 h. Metoclopramide was available as rescue therapy for both groups. Severity of nausea (as measured on a 10-cm visual scale), number of emetic episodes, and requirement for rescue therapy were recorded. In the immediate postoperative period, nausea severity was less in patients treated with ondansetron than placebo (3.3 +/- 4.1 versus 7.3 +/- 4.2; P < 0.001) and fewer patients experienced vomiting (3 of 28 versus 11 of 32; chi2 P < 0.01). More patients required some form of rescue treatment in the placebo group on the first postoperative day (26 of 32 versus 16 of 28; chi2 P < 0.01). We conclude that after acoustic neuroma surgery IV ondansetron treatment prevents immediate postoperative nausea and vomiting. Postoperative treatment with ondansetron in an orally disintegrating tablet formulation was associated with less frequent rescue therapy as compared with placebo on the first postoperative day.

Administration, Oral↗

Recent smoking behavior and postoperative nausea and vomiting.

The risk of postoperative nausea and vomiting (PONV) is reduced in cigarette smokers by unknown mechanisms. If protection is related to an acute effect of smoke constituents, smokers with the most recent exposure to cigarette smoke would be most protected. We tested the hypothesis that in cigarette smokers, postoperative nausea is correlated with recent exposure to cigarette smoke as quantified by exhaled carbon monoxide (CO) concentrations. In this observational study, exhaled CO levels were measured in 140 female smokers preoperatively. PONV was assessed over the first 24 h after surgery. There was no correlation (assessed with Spearman rank correlation) between preoperative CO and nausea scores at recovery room discharge. Significant correlations were found between nausea assessed over the first 24 h postoperatively and a history of PONV or motion sickness, the use of intraoperative antiemetic prophylaxis, duration of anesthesia, and use of opioids in the postanesthesia care unit. However, there was no correlation between preoperative CO and nausea over the first 24 h. These preliminary data suggest that the effect of smoking in reduced PONV is not directly related to preoperative exhaled CO levels.

Adolescent↗

[The effect of oral ondansetron in the prevention of postoperative nausea and vomiting].

OBJECTIVES: Not so many years ago, the incidence of postoperative nausea and vomiting used to reach 40% to 50%. More recent publications indicate that this complication still reaches considerable frequency: 20 to 30%. The present study had the objective of evaluating the impact of oral administration of ondansetron on the incidence of postoperative nausea and vomiting among patients submitted to general anesthesia. METHODS: This was a prospective, randomized, controlled, double-blind study. It included 178 patients divided into two groups: Ondansetron (n = 89) and Placebo (n = 89). Fast-dissolving oral tablets specially prepared for this study were utilized. The medication was administered between 60 and 30 minutes before anesthesia was induced. Factors with possible influence on the event were noted down, such as gender, age, history of dyskinesia or postoperative nausea and vomiting, smoking, type of surgery, body mass index, reversal of neuromuscular blockade using neostigmine, and the severity of postoperative pain. RESULTS: There was no significant difference between the characteristics of the groups regarding the factors annotated, except in relation to smoking and body mass index, which were greater in the Placebo group. These factors did not interfere in the analysis of the results. Postoperative nausea and vomiting were observed in 23 patients (26%) of the Ondansetron group and 38 patients (43%) of the Placebo group (p < 0.05). CONCLUSION: Ondansetron, 16 mg orally, administered before the operation significantly reduced the incidence of postoperative nausea and vomiting. The simplicity of administration and low cost of this presentation justify the choice of this administration route.

Adolescent↗

Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma.

CONTEXT AND OBJECTIVE: Chemotherapy-induced emesis is a limiting factor in treating children with malignancies. Intensive chemotherapy regimens along with emetogenic drug administration have increased the frequency and severity of emesis and nausea. Our study was designed to consider the importance of this problem and the need for improvement in emesis treatment for patients receiving chemotherapy. Our objective was to compare the efficacy and safety of the antiemetic drug granisetron and a regimen of metoclopramide plus dimenhydrinate. DESIGN AND SETTING: Open, prospective and randomized study at Instituto de Oncologia Pediátrica, Department of Pediatrics, Universidade Federal de São Paulo. METHODS: From February to August 1994, 26 patients (mean age: 14 years) with osteosarcoma received 80 chemotherapy cycles of iphosphamide (2,500 mg/m2) plus epirubicin (75 mg/m2) or carboplatin (600 mg/m2), or epirubicin (75 mg/m2) plus carboplatin (600 mg/m2). Eighty chemotherapy treatments were analyzed regarding nausea and vomiting control. Patients were randomized to receive either a single dose of granisetron (50 microg/kg) or metoclopramide (2 mg/kg) plus dimenhydrinate (5 mg/kg infused over eight hours). Emesis and nausea were monitored for 24 hours by means of the modified Morrow Assessment of Nausea and Emesis. Statistical analysis utilized the chi-squared, Student t and Mann-Whitney tests, plus data exploration techniques. RESULTS: 62.5% of the patients undergoing chemotherapy responded completely to granisetron, whereas 10% responded to metoclopramide plus dimenhydrinate (p < 0.0001). No severe adverse reactions were found in either of the treatments given. CONCLUSION: In children and adolescents with osteosarcoma, granisetron was safe and more efficient than metoclopramide plus dimenhydrinate for controlling chemotherapy-induced emesis and nausea.

Adolescent↗

5-HT3 receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting. A comparison of their pharmacology and clinical efficacy.

In the mid-1980s it was discovered that serotonin (5-hydroxytryptamine; 5-HT) was at least partially responsible for producing chemotherapy-induced nausea and vomiting. It was therefore realised that serotonin receptor blockade with serotonin 5-HT3 receptor antagonists could inhibit chemotherapy-induced nausea and vomiting. 5-HT3 antagonists have different chemical structures and receptor binding affinity. Granisetron, dolasetron and its major metabolite are pure 5-HT3 antagonists, while ondansetron and tropisetron are weak antagonists at the 5-HT4 receptor. Ondansetron has also been demonstrated to bind at other serotonin receptors and to the opioid mu receptor. The half-lives of granisetron, tropisetron and the active metabolite of dolasetron are 2 to 3 times longer than that of ondansetron. These observations initially suggested that more frequent ondansetron administration would be required; however, it has now been shown that receptor blockade does not correlate with elimination half-life and all 5-HT3 antagonists can be effectively administered once daily. Clinical trials have been conducted that directly compare the 5-HT3 antagonists. To compare these studies, it is necessary to assess trial design, including known risk factors for the development of chemotherapy-induced nausea and vomiting, and response criteria. Stratification for risk factors, use of strict efficacy criteria and randomisation to a blinded trial using an appropriate comparative regimen are essential for a well designed antiemetic trial. Comparative clinical trials using various doses, routes and regimens of administration have been conducted with 5-HT3 antagonists. Despite some trial design shortcomings, most of the studies show equal efficacy between the agents, especially in moderately emetogenic chemotherapy and mild, infrequently occurring adverse effects. The addition of steroids also appears to improve outcome. However, since many doses and regimens of ondansetron were used, further study is needed to determine the optimal regimen. The efficacy of 5-HT3 antagonists in controlling delayed nausea and vomiting from chemotherapy is less well studied. Further, there is no good scientific rationale for the use of 5-HT3 antagonists in controlling delayed nausea and vomiting since serotonin has not been shown to be released during the delayed phase. In fact, most studies show no benefit or modest benefit of 5-HT3 antagonists over placebo. Because the 5-HT3 antagonists perform similarly in the clinical setting, pharmacological differences do not seem to translate into therapeutic differences. There is also no appreciable difference in the incidence or severity of adverse effects among the 5-HT3 antagonists. Determination of clinical use may then be driven by cost.

Antiemetics↗

Does position and size of corpus luteum have any effect on nausea of pregnancy?

It is a puzzling fact that emesis might occur in one pregnancy, whereas other pregnancies in the same woman could be either free or again associated with nausea. Pregnancy-associated hormones are believed to cause nausea, possibly through effects mediated via the liver. In 43 women who applied for a legal abortion in early pregnancy the occurrence of nausea was recorded and the position and size of the corpus luteums were measured by means of ultrasound. It was found that emesis was associated with corpus luteum located predominantly on the right side, while the non-emetic pregnancy often had a left-sided corpus luteum. It is suggested that the venous drainage, which differs between the right and the left side, may be responsible for the fact that the same woman can either suffer from or be free from nausea during pregnancy. Ovarian vein insufficiency, being more common in multigravidity, may also explain why nausea is more common in multigravidae.

Corpus Luteum↗

A randomized controlled trial of oxygen for reducing nausea and vomiting during emergency transport of patients older than 60 years with minor trauma.

OBJECTIVE: To test the hypothesis that oxygen administration reduces nausea and vomiting in patients with minor trauma during ambulance transport. PATIENTS AND METHODS: This study, conducted from January to April 2000, consisted of 100 patients older than 60 years with minor trauma, who were randomly assigned to breathe air or 100% oxygen at 10 L/min through a facemask during ambulance transport. A paramedic, blinded to treatment, recorded vomiting episodes during transport. Patients, also blinded to treatment, rated their levels of pain, nausea, vomiting, anxiety, and overall satisfaction with their care on 100-mm visual analog scales, with greater values indicating more intense sensation. Results from the 2 groups were compared with chi2 or unpaired 2-tailed t tests and presented as means +/- SDs. RESULTS: Before randomization, patients subsequently assigned to receive oxygen had significantly greater pain and nausea. On arrival at the hospital, oxygen saturation was higher in the 50 patients given oxygen (99% +/- 1 % vs 96% +/- 2%; P<.001) than in the 50 patients who breathed air. Reported pain remained greater in the oxygen group. However, those given oxygen had less nausea (22 +/- 29 vs 54 +/- 38 mm; P<.001) and vomiting (4 vs 19 episodes; P<.001), lower heart rates (86 +/- 12 vs 94 +/- 13 beats/min; P<.001), and higher overall satisfaction scores (54 +/- 33 vs 33 +/- 23 mm; P<.001). CONCLUSION: Our results indicate that supplemental oxygen during ambulance transport reduced nausea scores by 50% and decreased vomiting 4-fold. Consequently, patients reported greater satisfaction with their care. Thus, we recommend that patients be given supplemental oxygen during ambulance transport.

Aged↗

An open multicentre study of tropisetron for cisplatin-induced nausea and vomiting.

OBJECTIVES: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To investigate whether dexamethasone added to tropisetron improves the control of emesis for patients who do not achieve a complete response to tropisetron alone. (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting. DESIGN: A prospective open label phase II trial over one or two cycles of chemotherapy. Data collection was based on observed response and patients' self-reporting. SETTING: Twenty Australian tertiary care hospitals in 1994. PATIENTS: 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing > or = 50 mg/m2 cisplatin. INTERVENTION: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamethasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 could be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1. MAIN OUTCOME MEASURES: Number of vomiting episodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oestradiol levels in women; and past alcohol consumption in men and women. RESULTS: (i) The complete response rate (CR) for acute emesis in Cycle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% CI, 76%-90%) having < or = 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI, 47%-66%), with 97% (95% CI, 91%-99%) having < or = 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30%). Seventy-one patients received Cycle 2. The main side effects were headache (20 patients) and constipation (16 patients). The control of acute emesis was rated as "good" or "very good" by 68% of investigators; 85% rated the tolerability of treatment as "good" or "very good". Treatment was rated as "very satisfactory" or "satisfactory" by 52% of patients. (ii) The CR for acute emesis with dexamethasone added was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol levels had better control of emesis, although this difference was not statistically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response. CONCLUSIONS: Tropisetron was effective for acute cisplatin-induced emesis; adding dexamethasone enhanced this response. Both single and combined therapy had less effect on delayed emesis. The impact of alcohol on control of emesis is a chronic rather than acute phenomenon which requires prospective testing.

Adolescent↗

Ondansetron compared with high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting. A multicenter, randomized, double-blind, crossover study.

OBJECTIVE: To compare the efficacy and side effects of ondansetron with those of high-dose metoclopramide in treating acute and delayed cisplatin-induced nausea and vomiting. DESIGN: Randomized, double-blind, crossover trial. SETTING: Conducted at two university hospitals, a cancer institute, and six community hospitals. PATIENTS: Of 125 patients, 95 were evaluable for the acute phase and 79 for the delayed phase. Major reasons for not being evaluable were no second course (14 patients), protocol violation (5 patients), and change in cisplatin dose (3 patients) for the acute phase, and rescue medication on day 1 (7 patients), protocol violation (3 patients), and inadequate data (4 patients) for the delayed phase. INTERVENTIONS: All patients received cisplatin, 50 to 100 mg/m2 body surface area (median, 75 mg/m2); none had previously received chemotherapy. Thirty minutes before the cisplatin administration, ondansetron was given intravenously over 15 minutes, at a loading dose of 8 mg followed by a continuous infusion of 1 mg/h for 24 hours. Metoclopramide was given at a loading dose of 3 mg/kg body weight, followed by a continuous infusion for 8 hours (4 mg/kg). For the delayed phase (days 2 through 6), the first oral dose was given as soon as the infusion was completed; the oral dose consisted of either metoclopramide, 20 mg three times daily, or ondansetron, 8 mg three times daily for another 5 days. MEASUREMENTS AND MAIN RESULTS: In the acute phase, a major or complete response was seen in 72% of the ondansetron-treated and 41% of the metoclopramide-treated patients (P less than 0.001). Nausea was significantly better controlled among the ondansetron-treated patients (P = 0.04). In the delayed phase, no statistically significant difference was seen between ondansetron- and metoclopramide-treated patients. Nausea was significantly better controlled with metoclopramide (P = 0.016). CONCLUSIONS: Ondansetron is significantly more effective than metoclopramide in preventing acute nausea and vomiting. In the delayed phase, the results of both drugs were disappointing, although metoclopramide's effect on delayed nausea was superior. Patients preferred ondansetron.

Adult↗

Comparison of ondansetron and placebo for preventing postoperative nausea and emesis in gastrointestinal tract surgery: a multicenter randomized controlled trial.

BACKGROUND: Nausea and emesis are undesirable events that may cause discomfort and suffering in the postoperative period. This study was carried out to evaluate the efficacy and safety of ondansetron for preventing postoperative nausea and vomiting in patients undergoing gastrointestinal tract surgery. METHODS: Using a randomized double-blind study design, 408 surgical patients (163 male and 245 female) receiving general endotracheal anesthesia were studied at five medical centers in Bangkok. Ondansetron (4 mg) or placebo was administered prior to induction of anesthesia. Episodes of nausea and vomiting, adverse events and laboratory tests (complete blood count and liver function test) were evaluated during 24 hours after study drug administration. RESULTS: The incidence of postoperative nausea and vomiting in the placebo group (42.7 and 35.2%) were significantly higher than the ondansetron group (23.9 and 15.4%). However, no significant differences occurred in the incidence of adverse events or changes in laboratory tests in the ondansetron group compared to the placebo group. CONCLUSIONS: Ondansetron 4 mg given intravenously before surgery is safe and effective for preventing postoperative nausea and emesis following gastrointestinal tract surgery.

Adolescent↗

[Postoperative nausea and vomiting. Controversies, evidence and new drugs].

In spite of the availability of drugs to control postoperative nausea and vomiting, emesis remains an unresolved problem for the anesthesiologist. The etiology of postoperative nausea and vomiting is multifactorial: some causes are well-defined whereas others continue to be the object of debate. Statistical methods applying logistical regression have proven valuable for assessing the risk of emesis in individual patients. Taking a preanesthetic case history to investigate the presence of factors that might lead to emesis allows the anesthesiologist to establish with a certain degree of credibility that a patient, a priori, is likely to experience nausea or vomiting. Various strategies for preventing or treating emesis can then be established in function of risk. Meta-analysis has been applied to the large body of literature that evaluates and/or compares a variety of drugs and anesthetic techniques, thus facilitating evidence-based decision-making. The therapeutic options available for postoperative nausea and vomiting are moderately effective and are distinguishable by their side effects and prices. Clinical trials with a new group of drugs (neurokinin receptor antagonists) are currently underway. With their wider spectrum of action and absence of side effects, these drugs may represent a qualitative advance in the treatment of postoperative nausea and vomiting.

Antiemetics↗

Vagal changes following cancer chemotherapy: implications for the development of nausea.

Many physiological changes that occur contemporaneously with nausea are mediated by the autonomic nervous system, but the specific autonomic changes associated with nausea have not been characterized. Cardiac parasympathetic (vagal) activity as indicated by heart rate variability, measured as the standard deviation of successive differences (SDSD) in beat-to-beat intervals, was assessed in 24 women with ovarian cancer immediately prior to and accompanying nausea that occurred following anticancer chemotherapy. A progressive increase in SDSD followed infusion of the chemotherapy agent, indicating a rise in cardiac parasympathetic (vagal) activity, with onset of nausea consistently occurring after the peak activity had been reached, at a time when SDSD was decreasing. An increase in parasympathetic activity seems to set the stage for the expression of nausea but an additional stimulus is apparently needed to finally trigger the event.

Aged↗

Prevention of acute and delayed cisplatin-induced nausea and vomiting with intravenous ondansetron plus intravenous dexamethasone.

BACKGROUND: We conducted a prospective study to evaluate the anti-emetic effect of cisplatin-induced nausea and vomiting with intravenous (i.v.) ondansetron plus i.v. dexamethasone. METHODS: One hundred forty-six chemotherapy (CT)-naive patients were enrolled in the study. They were scheduled to receive cisplatin 50 to 100 mg/m2 (mean, 53 mg/m2) on day 1 followed immediately by continuous infusion of 5-fluorouracil with or without other CT agents on the subsequent days. Three 8 mg doses of ondansetron i.v. were given at 4-hour intervals plus 20 mg dexamethasone i.v. infusions from the start of CT, followed by 5 mg dexamethasone i.v. every 12 hours, and the administration of dexamethasone was discontinued after the completion of CT. RESULTS: The rates of complete protection from acute and delayed vomiting/nausea obtained in these patients were 97.3%/93.2% and 71.2%/60.3%, respectively. The rates of complete protection from both acute and delayed nausea were 70.5% and 58.9%, respectively. By comparison, the total control rate of vomiting was less in female patients than in male patients (p = 0.017), and the total control rate of nausea was lower in the age group less than 50 years (p = 0.045). The time from the start of CT to the onset of nausea appeared to be earlier than that for vomiting (log-rank test, p = 0.045). Adverse events tended to be minor, with constipation and hiccups as the most common. CONCLUSION: These results indicate that i.v. ondansetron plus i.v. dexamethasone is a feasible anti-emetic therapy in an inpatient setting. I.v. ondansetron plus i.v. dexamethasone is highly effective in preventing acute cisplatin-induced nausea and vomiting.

Acute Disease↗

Parameters that influence the outcome of nausea and emesis in cisplatin based chemotherapy.

Some factors have demonstrated an influence on emesis and antiemetic response. In order to study these factors, 306 patients (pts) entered this study receiving cisplatin based combination chemotherapy (CT) (100 mg/m3, with ondansetron (8 mg, 3 times daily for 4 days) as the only antiemetic treatment. Known factors that influence the result of antiemetic therapy such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss, anxiety, depression, psychological problems related to CT (psychological PRC) etc, were included in the evaluation. We evaluated the number of vomits, retches and nausea. The existence of psychological PRC was found to be a prominent factor for the development of nausea and emesis, being at the same time strongly associated with scaling variables (Gralla, retching and nausea grading) used to measure the severity of nausea and emesis (p = 0.001). Stress was also a significant predictor; patients with stress had an almost two times higher probability to develop nausea or retching compared to patients without stress indications (p = 0.001), while the occurrence of retching was marginal. Younger patients (less than 40 years old) were found to be almost three times more susceptible to retching compared to older patients (more than 40 years old) (P 0.006). With all possible evaluations, we concluded that significant factors are psychological PRC, stress and age. In conclusion, three factors, age, stress and psychological PRC, should be taken seriously into consideration in the design of future trials evaluating antiemetic treatment, as well as in the every-day clinical practice, in order to provide patients with a better quality of life during emetogenic CT.

Adult↗

[Effects of dexamethasone on epidural morphine-related nausea and vomiting].

OBJECTIVE: To observe the effect of intravenous dexamethasone injections in preventing nausea and vomiting resulted from epidural morphine for post-operation pain relief. METHODS: Eighty-four adult patients (ASA class I to II ) requiring epidural anesthesia for low abdominal surgical procedures were randomly divided into 2 groups, of which Group 1 (n=42) received intravenous dexamethasone injections at 10 mg and Group 2 (n=42) intravenous injection of 2 ml normal saline before administration of 2 mg epidural morphine for post-operation pain relief. The incidence of nausea and vomiting were recorded within 24 h after surgery. RESULTS: The incidence of nausea and vomiting were 12% and 7% in Group 1, while 31% and 21% in Group 2 respectively, showing significant difference between the 2 groups (P<0.05). The total incidence of nausea and vomiting were also significantly different (19% vs 52%, P<0.01). CONCLUSION: Intravenous dexamethasone injections at 10 mg can significantly decrease the incidence of epidural morphine-related nausea and vomiting.

Adult↗

Postoperative pain and nausea after laparoscopic cholecystectomy.

Postoperative discomfort following cholecystectomy has diminished considerably since laparoscopic surgery was introduced. This study assessed the degree of postoperative pain and nausea when, during the operation, the trocar sites had been infiltrated with bupivacaine and antiemetics (ondansetron) had been administered. Postoperative pain intensity was moderate as 20% of the patients were managed without any opiates postoperatively and 88% did not require any opiates after discharge from the recovery room. Postoperative nausea and vomiting is known to be a problem that occasionally has been reported to delay discharge from the hospital. A single dose of ondansetron at the end of the operation seems to reduce postoperative nausea effectively. Two-thirds of the patients had no complaints of nausea, and the majority of the remainder experienced only mild and transitory nausea. We recommend that stab-wound sites be infiltrated with local anesthetics and that antiemetics be administered at the end of the operation.

Adult↗

Nausea and vomiting and cancer patients' quality of life: a discussion of Professor Selby's paper.

It is evident from the data presented above that nausea and vomiting are frequent side effects which are often persistent and distressing to patients. Evidence suggests, and intuitively it appears that avoidance of nausea and vomiting is important to the patients' ability to maintain their quality of life during the treatment period. It is of particular interest to note that in the literature reviewed in this paper standard antiemetic prescribing and practice were followed. It would, therefore, appear that available antiemetic agents are not always effective or may not be adequately employed. The toxicities associated with dopamine receptor antagonists, the current standard of antiemetic regimens, limit their usefulness in the clinical setting. In fact, the contribution of antiemetic therapy toxicities to the incidence of anxiety, fatigue, and restlessness which were commonly reported by patients in the studies reviewed should be considered. Additional effort to characterise the impact of nausea and vomiting on cancer patients' quality of life is needed. Clearly, the data available suggest that these symptoms should be included as part of the physical domain component of quality of life instruments used in cancer patients. Ideally, the instrument used should contain separate items for nausea and vomiting. Major side effects of antiemetic therapy should also be assessed since these may be as debilitating as the effects of nausea and vomiting. Increased awareness of total patient impact of emesis and antiemetic therapy will serve as an impetus for improvements in antiemetic therapy strategies and practices.

Antineoplastic Agents↗

Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea.

Newer antidepressants are generally as efficacious as but often have fewer side effects than their predecessors such as the tricyclic antidepressants and monoamine oxidase inhibitors. These newer antidepressants include the selective serotonin reuptake inhibitors (SSRIs) citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; venlafaxine, a serotonin-norepinephrine reuptake inhibitor; and bupropion, a selective norepinephrine and dopamine reuptake inhibitor. Most of these antidepressants have half-lives that enable them to be administered as infrequently as 1 to 3 times per day. To further improve upon the ease of use, controlled-release formulations of bupropion, fluoxetine, paroxetine, and venlafaxine have been manufactured. Potential pharmacokinetic advantages of these formulations include lower peak plasma drug concentrations and smaller fluctuations between peak and trough plasma drug concentrations, which might influence the tolerability of these medications. Tolerability advantages seen with some of these medications include diminished nausea. The 3 controlled-release agents that are designed to be taken daily--bupropion, paroxetine, and venlafaxine--are associated with lower incidences of nausea overall and nausea leading to treatment discontinuation than are their immediate-release formulations. However, the rates of nausea are similar with both formulations of fluoxetine, despite higher peak plasma drug concentrations and greater fluctuation between peak and trough plasma drug concentrations with fluoxetine weekly than with fluoxetine daily. Although the connection has not been proven, more stable pharmacokinetic profiles might be the cause for the low occurrence of nausea with some controlled-release newer antidepressants.

Antidepressive Agents↗