Showing papers on "Granisetron published in 2005"

A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study

Abstract: In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naive cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naive patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin ≥70 mg/m2). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin ≥50 mg/m2). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.

Prevention and treatment of postoperative nausea and vomiting.

Abstract: Purpose. The physiology, risk factors, and prevention and treatment of postoperative nausea and vomiting (PONV) are discussed. Summary. Factors to consider when determining a patient’s risk for PONV include sex, history of PONV, history of motion sickness, smoking status, duration of anesthesia, use of opioids, and type of surgery. Receptors that, when activated, can cause nausea or vomiting or both include dopamine type 2, serotonin type 3, histamine type 1, and muscarinic cholinergic type 1 receptors. Patients at moderate to high risk for PONV benefit from the administration of a prophylactic antiemetic agent that blocks one or more of these receptors. Effective agents include transdermal scopolamine, prochlorperazine, promethazine, droperidol, ondansetron, dolasetron, granisetron, and dexamethasone. In high-risk patients, combining two or more antiemetics with different mechanisms of action has been shown to be more effective than using a single agent. In addition to administering a prophylactic antiemetic, it is important to reduce the patient’s risk by considering regional anesthesia, considering inducing and maintaining general anesthesia with propofol, ensuring good intravenous hydration, avoiding hypotension, and providing effective analgesia. If PONV occurs in the immediate postoperative period, it is best treated with an antiemetic agent from a pharmacologic class different from that of the prophylactic agent. Conclusion. Prophylactic antiemetic therapy for PONV is effective, but combinations of agents may be necessary for high-risk patients. Nonpharmacologic strategies are also important.

Selective serotonin 5-HT3 receptor antagonists for postoperative nausea and vomiting: Are they all the same?

Abstract: Selective serotonin 5-HT3 receptor antagonists have proven safe and effective for the management of postoperative nausea and vomiting. Dolasetron, granisetron, ondansetron and tropisetron selectively and competitively bind to 5-HT3 receptors, blocking serotonin binding at vagal afferents in the gut and in the regions of the CNS involved in emesis, including the chemoreceptor trigger zone and the nucleus tractus solitarii. Despite their shared mechanism of action, 5-HT3 receptor antagonists have different chemical structures and exhibit differences in receptor binding affinity, dose response and duration of effect. Furthermore, although dolasetron, granisetron, ondansetron and tropisetron are all extensively metabolised by the cytochrome P450 (CYP) system, different components of this system predominate in the metabolism of each of these agents. Hence, although these agents are considered equally effective in the overall population, their pharmacokinetic and pharmacodynamic differences may explain the variability in individual responses to these drugs. This review discusses the pharmacological profiles of dolasetron, granisetron, ondansetron and tropisetron, and the clinical implications of differences in their profiles.

Association of the ABCB1 3435C>T polymorphism with antiemetic efficacy of 5-hydroxytryptamine type 3 antagonists.

Abstract: Background Resistance to antiemetic treatment with 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists is still a major problem resulting in patient discomfort and poor compliance to chemotherapy. We hypothesized that clinical resistance to 5-HT3 antagonists is associated with the single-nucleotide polymorphism (3435C > T) in the gene that codes for the drug efflux transporter adenosine triphosphate–binding cassette subfamily B member 1 (ABCB1). Methods Patients with cancer (N = 216) treated with chemotherapeutic regimens composed of highly or moderately emetogenic agents were examined for their antiemetic responses to tropisetron, ondansetron, or granisetron. The efficacy of antiemetic treatment was documented by self-report charts for 5 days after chemotherapy. ABCB1 3435C > T genotype was determined to analyze its association with the antiemetic efficacy of 5-HT3 antagonists. Results Within the first 24 hours of chemotherapy, the complete control rate of nausea and vomiting was higher in subjects with the ABCB1 TT genotype (n = 49) as compared with those with the CC (n = 60) or CT (n = 107) genotype (P = .044). The type of 5-HT3 antagonists influenced the effect of genotype on antiemetic responses. The complete control rates were 92.9% in TT subjects (n = 14) in comparison to homozygote (47.6%, n = 21, P = .009) or heterozygote (56.1%, n = 41, P = .02) carriers of the 3435 C allele in granisetron-treated patients. However, during the delayed phase of chemotherapy, the complete control rates did not differ across genotypes. Conclusion These results suggest that ABCB1 3435C > T polymorphism is associated with antiemetic treatment efficacy in patients with cancer treated with 5-HT3 antagonists, particularly in granisetron-treated patients, during the short-term phase of chemotherapy. Clinical Pharmacology & Therapeutics (2005) 78, 619–626; doi: 10.1016/j.clpt.2005.08.015

5-HT(3)-receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment.

Abstract: The 5-HT3-receptor antagonists, considered as ‘gold standard’ therapy for cancer patients, are generally perceived to have similar efficacy and safety profiles, andmost antiemetic guideline

A randomized, double-blind study of granisetron plus dexamethasone versus ondansetron plus dexamethasone to prevent postoperative nausea and vomiting in patients undergoing abdominal hysterectomy.

Abstract: In this randomized, double-blind study, we evaluated whether small-dose granisetron (0.1 mg) plus dexamethasone 8 mg (G+D) was as effective as ondansetron 4 mg plus dexamethasone 8 mg (O+D) for preventing vomiting during the 0 to 2 h after tracheal extubation in patients undergoing abdominal hysterectomy requiring general anesthesia. Dexamethasone (D) was administered at induction of anesthesia, and granisetron (G) or ondansetron (O) was given approximately 15 min before tracheal extubation. Data on postoperative nausea and vomiting were collected at 0, 2, 6, and 24 h. For the primary efficacy endpoint, most patients in each group had no vomiting in the 0- to 2-h interval (82/87 [94%] for G+D versus 86/89 [97%] for O+D). Effectiveness of G+D was demonstrated versus O+D. Treatment groups were similar with regard to moderate or severe nausea, complete response, rescue medication use, and total control over 24 h. A descriptive assessment of adverse events showed that both combinations were well tolerated with infrequent and similar incidences of adverse events. The combination of small-dose G administered just before tracheal extubation plus D given at induction of anesthesia is an effective alternative to O+D in preventing vomiting during the 0- to 2-h interval after tracheal extubation.

The effects of ondansetron and granisetron on electrocardiography in children receiving chemotherapy for acute leukemia.

Abstract: :5-HT3 receptor antagonists, including granisetron and ondansetron, are widely used in the prophylactic treatment of chemotherapy-induced nausea and vomiting. Although the cardiac safety of granisetron and ondansetron has been investigated in several adult studies, there is no report investi

The Utility of Antiemetics in the Prevention and Treatment of Postoperative Nausea and Vomiting in Patients Scheduled for Laparoscopic Cholecystectomy

Abstract: Postoperative nausea and vomiting (PONV) are distressing and frequent adverse events of anesthesia and surgery, with a relatively high incidence after laparoscopic cholecystectomy. Numerous antiemetics have been studied for the prevention and treatment of PONV in patients scheduled for laparoscopic cholecystectomy. Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV. The available nontraditional antiemetics for the prophylaxis against PONV are dexamethasone and propofol. Serotonin receptor antagonists (ondansetron, granisetron, tropisetron, dolasetron, and ramosetron), compared with traditional antiemetics, are highly efficacious for PONV. The prophylactic ondansetron, granisetron, tropisetron, and dolasetron in antiemetic efficacy are comparable. Ramosetron is effective for the long-term prevention of PONV. None of the available antiemetics is entirely effective, perhaps because most of them act through the blockade on one type of receptor. There is a possibility that combined antiemetics with different sites of activity would be more effective than one drug alone for the prophylaxis against PONV. Combination antiemetic therapy is often effective for the prevention of PONV following laparoscopic cholecystectomy. The efficacy of a combination of serotonin receptor antagonists (ondansetron and granisetron) and droperidol is superior to monotherapy with a serotonin receptor antagonist or droperidol. Similarly, adding dexamethasone to ondansetron or granisetron improves antiemetic efficacy in PONV. Knowledge regarding antiemetics is necessary to completely prevent and treatment of PONV in patients scheduled for laparoscopic cholecystectomy.

Cytochrome P450 2D6 metabolism and 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting.

Abstract: Postoperative nausea and vomiting (PONV) affects approximately one third of patients and may lead to aspiration, dehiscence, esophageal rupture, and increased treatment costs if inadequately controlled An important therapeutic option for prevention of PONV is 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists Nonetheless, therapeutic failure sometimes occurs Metabolism by the cytochrome P450 (CYP) system differs among the 5-HT3 receptor antagonists, and provides a rational explanation for decreased therapeutic efficacy in some patients Four of the 5-HT3 receptor antagonist agents (dolasetron, ondansetron, palonosetron, and tropisetron) are metabolized in various degrees via CYP2D6, an isoform subject to marked genetic polymorphism In patients with duplicate CYP2D6 alleles, degradation into inactive metabolites occurs rapidly with these four 5-HT3 receptor antagonists, resulting in decreased efficacy for preventing PONV Granisetron is the only agent in this class that is not metabolized via CYP2D6 Instead, granisetron is metabolized via the CYP3A4 isoform, which is not subject to significant genetic polymorphism CYP2D6 genotype screening prior to PONV treatment may allow for modification of antiemetic dosing An alternative is to use a 5-HT3 agent that is metabolized independently of the CYP2D6 isoform, such as granisetron, that would obviate the need for genotyping and may lead to improved prophylaxis of PONV

CYP1A1 is a major enzyme responsible for the metabolism of granisetron in human liver microsomes.

Abstract: Granisetron, a potent 5-HT3 receptor antagonist, has been reported to be mainly metabolized to 7- hydroxygranisetron and a lesser extent to 9-desmethylgranisetron in humans. A previous study indicated that cytochrome P450 (CYP)3A4 is a major catalyst of 9-demethylation, although the major CYP isoform(s) responsible for 7- hydroxylation are unknown. To clarify granisetron 7-hydroxylase, the in vitro metabolism of granisetron using expressed human CYPs and human liver microsomes was investigated. 7-Hydroxygranisetron was produced almost exclusively by CYP1A1, while, apparently, 9-desmethylgranisetron was preferentially produced by CYP3A4. Marked inter-individual differences in the ratio of the formation of 7-hydroxygranisetron and 9-desmethylgranisetron in human liver microsomes was observed. Granisetron 7-hydroxylase activity was strongly correlated with benzo[a]pyrene 3-hydroxylase activity (p < 0.0001), but not with testosterone 6b-hydroxylase activity in human liver microsomes. Furthermore, an anti-human CYP1A1 antibody completely inhibited 7-hydroxylation in human liver microsomes, however, the reaction was not inhibited at all by an anti-CYP3A4 antibody. On the other hand, granisetron 9-demethylase activity correlated significantly not only with testosterone 6b-hydroxylase activity (p < 0.0001) but also with benzo[a]pyrene 3-hydroxylase activity (p < 0.01). Consistent with this, both the anti-CYP1A1 and anti-human CYP3A4 antibodies inhibited the 9-demethylase activity. These data indicate that CYP1A1 is a major enzyme responsible for the metabolism of granisetron via a main 7- hydroxylation pathway and an alternative 9-demethylation route. This is the first report demonstrating the substantial contribution of CYP1A1 to the metabolism of a drug, although its role in the metabolism of environmental compounds is well established.

Pharmacokinetics of palonosetron in combination with aprepitant in healthy volunteers

Abstract: Background: Palonosetron is a second-generation 5-HT3 receptor antagonist with a prolonged duration of action and higher receptor binding affinity than first-generation agents (ondansetron, granisetron, and dolasetron). Aprepitant is a selective antagonist of substance P/neurokinin 1 that augments the benefit of 5-HT3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting.Methods: This randomized, open-label, two-way, crossover trial was designed to evaluate the effect of oral aprepitant on the pharmacokinetics and safety of a single intravenous (IV) dose of palonosetron in 12 healthy subjects. Treatment A consisted of a single IV bolus dose of palonosetron 0.25 mg on day 1. Treatment B added oral aprepitant 125 mg on day 1 (30 minutes prior to palonosetron) and 80 mg on days 2 and 3. Blood for pharmacokinetic evaluations was collected through 168 hours after palonosetron administration on days 1 and 15; safety was monitored through day 22.Results: Mean plasma concentra...

A randomized, double-blind, close-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients abdominal hysterectomy.

Abstract: BACKGROUND AND OBJECTIVE Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs For surgical procedures with a high risk of PONV, prevention is preferable to treatment In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy METHODS This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 01, 02 or 03 mg or placebo administered approximately 15 min prior to the end of surgery The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration No inferential statistics were planned RESULTS The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%) Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals Similar proportions of patients in each treatment group reported at least one adverse event CONCLUSIONS Granisetron at doses of 01, 02 and 03 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy This pilot study did not identify a dose-response relationship

The effect on mechanical pain threshold over human muscles by oral administration of granisetron and diclofenac-sodium.

Abstract: Previous studies indicate that plasma levels of serotonin (5-HT) and intramuscular prostaglandin E2 (PGE2) participate in determining the mechanical pain threshold and tolerance level to pressure applied on the skin over healthy muscles. Other studies reported gender differences regarding responses to noxious stimuli. The present study aimed to determine whether the mechanical pain threshold of healthy muscles is influenced by oral administration of 5-HT3 or PGE2-inhibitors and if there are any gender differences in this respect. Ten healthy female subjects and 10 age-matched healthy male subjects participated in the study, which was randomized and double blind with crossover design. Granisetron (5-HT3-antagonist), diclofenac-sodium (PGE2-antagonist) and placebo were administered for 3 days. The pressure pain threshold (PPT) was recorded bilaterally with an algometer over certain orofacial, trunk, and limb muscles before and after administration of the antagonists. The PPT over all muscles combined increased after administration of granisetron. There was no change after administration of placebo. The difference between granisetron and placebo was significant for the trapezius and tibialis anterior muscles. Diclofenac-sodium did not influence the PPT and there was no difference compared to placebo. Although the basal PPT values were lower in females, the PPT response to granisetron differed significantly between genders only in the tibialis anterior muscle. In conclusion, the results of this study showed that oral administration of the 5-HT3-antagonist granisetron increased the PPT over healthy trunk and limb muscles but not over orofacial muscles, and that the response in the limb muscles was greater in males.

5-hydroxytryptamine type-3 receptor antagonists for chemotherapy-induced and radiotherapy-induced nausea and emesis: can we safely reduce the dose of administered agents?

Abstract: BACKGROUND Nausea and emesis as a consequence of chemotherapy or radiotherapy can have an adverse effect on patients' quality of life during cancer treatment and may last for > 5 days after administration. Guidelines suggest that, used at appropriate doses, the 5-hydroxytryptamine type-3 (5-HT3) receptor antagonists—which are considered the antiemetic “gold standard” when they are administered in combination with corticosteroids—demonstrate equivalent efficacy and safety. However, due to financial considerations, these agents often are used at lower doses than recommended. METHODS A literature review of relevant publications pertaining to the control of chemotherapy-induced nausea and emesis and dosing issues of the 5-HT3 receptor antagonists was undertaken to provide a comprehensive review of dosing issues relevant to the 5-HT3 receptor antagonists. RESULTS The issue of “down dosing” was particularly pertinent because of the nature of the 5-HT3 receptor antagonist dose-response curve: A steep dose-response profile within a narrow dose range suggests that antiemetic control will be lost suddenly after dose deescalation. However, the array of predisposing and confounding patient factors indicates that it is unlikely that a loss of antiemetic control will be apparent across a population; rather, individuals will experience loss of control as the dose is reduced below threshold. Of the 4 5-HT3 receptor antagonists currently licensed in the United States (granisetron, ondansetron, dolasetron, and palonosetron), ondansetron is used sometimes at lower than optimal doses, and there is evidence to suggest that even the approved oral dose of dolasetron may be suboptimal. CONCLUSIONS Suboptimal dosing not only will be detrimental to patients' quality of life but, ultimately, will prove counterproductive in terms of hospital resources, and it will add to the already significant socioeconomic burden associated with cancer therapy. Therefore, the dose of antiemetic agent administered should be sufficiently high to ensure good emesis control across the whole patient population. Cancer 2005. © 2005 American Cancer Society.

Chemotherapy-induced emesis in elderly cancer patients: the role of 5-HT3-receptor antagonists in the first 24 hours.

Abstract: Objective: This review highlights the need to optimize 5-HT3-receptor-antagonist-based antiemetic therapy for elderly cancer patients, particularly during the first 24 h

Granisetron versus tropisetron for prophylaxis of acute chemotherapy-induced emesis: a pooled analysis

Abstract: This analysis compares the antiemetic efficacy of the 5-HT3-receptor antagonists granisetron and tropisetron in acute chemotherapy-induced nausea and vomiting (CINV). All published randomized studies comparing granisetron with tropisetron in conventionally-dosed, emetogenic chemotherapy are included in this pooled analysis. The target criterion for antiemetic success was ‘acute complete response’ (complete absence of vomiting in the 24 h after the start of chemotherapy) and the rate of successful treatment reported as ‘response rate’ (acute complete response rate per patient). Twelve studies were used comprising 810 patients. Comparison between granisetron and tropisetron in patients receiving cisplatin-based therapy showed superiority of granisetron (odds ratio above 1.0) in six out of seven studies. However, this difference did not reach statistical significance. In patients receiving noncisplatin-based therapies, four out of five studies showed an advantage of granisetron over tropisetron with one study showing a significant advantage. Pooled analysis of all studies demonstrated a significant overall advantage for granisetron over tropisetron (p=0.042). This is supported by the individual studies: overall, ten out of the 12 studies analyzed showed an advantage for granisetron, with a 6.4% difference in response rate. This advantage was more pronounced in noncisplatin-based therapy (7.3%), whereas in cisplatin-based therapy, the difference was 5.4%. The overall results of this pooled analysis of cisplatin and noncisplatin-based studies suggest that granisetron has a marginal but clinically potentially relevant statistically significant advantage in efficacy over tropisetron for the control of acute CINV.

Isolated urticaria to ondansetron and successful treatment with granisetron.

Abstract: Blood pressure was 120/60 mmHg, while the pulse was arrhythmic as well as the heart beat.Electrocardiogram(ECG) showed atrial fibrillation (average ventricular frequency 120 beats/min). He was treated with 1 g of hydrocortisone i.v. and 10 mg clorpheniramine maleate i.m.; after 10 min, as he did not improve, 250 ml of saline solution with 1 g of methylprednisolone and 50 mg ranitidine i.v. were administered. The patient after 5 min improved and presented only a mild erythema of the face and chest. Another ECG was carried out and showed sinus rhythm (78 beats/ min.) so that no antiarrhytmogenic drugs had to be administered. Echocardiographyshowednoventricular kinetic disorder, normal cardiac size, normal valvular flow, ejection fraction 60%. Blood tests were normal except for eritrosedimentation rate ( 1 ESR) (25 mm), C reactive protein (CRP) (19.50 mg/l), gammaglobulins (22.5%), glycemia (171 mg/dl), uric acid (9.40 mg/dl), alkaline phosphatase (353 U/l), neutrophilia (76%), monocytes (3%). The patient reported that he had been under treatment for over 25 years with histamine antagonists (H1 and H2) associated, more recently, with anti-leucotrienes because of a systemic mastocytosis diagnosed elsewhere after skin, bone and bone marrow biopsy. He reported frequent episodes of flushing with intense pruritus, dyspnoea, diarrhoea and severe hypotension; during the last two attacks, about 1 year and 6 months before, treated elsewhere, atrial fibrillation had been registered. In literature, it has been reported that cardiac involvement may occur during systemic anaphylaxis (3); in fact it has been shown that mastocytes are present in human heart (4), that during anaphylaxis there is a release ofmediators from cardiac mastocytes (5) and that histamine causes an increased frequency and ejection fraction (6). This may explain the cardiac involvement in the case of systemic mastocytosis above reported as the patient had a negative history of cardiac disease and there were no predisposing factors for arrhythmia (alcohol, coffee, cocaine, hyperthyroidism, drugs). We considered it of interest to report this case as it suggests that cardiac anaphylaxis may occur during a systemic mastocytosis attack even if further studies on the cardiac involvement in systemic mastocytosis are needed.

Effects of granisetron with droperidol or dexamethasone on prevention of postoperative nausea and vomiting after general anesthesia for cesarean section.

Abstract: This prospective, placebo-controlled, double-blinded, and randomized study was undertaken to compare the efficacy of granisetron, droperidol, and combinations of granisetron with droperidol or dexamethasone on postoperative nausea and vomiting in patients undergoing general anesthesia for cesarean section. Patients (n = 150) who were scheduled for cesarean section under general anesthesia were randomly assigned to one of the five groups: physiological saline 5 ml in Group A, granisetron 40 microg/kg + dexamethasone 8 mg in Group B, granisetron 40 microg/kg + droperidol 1.25 mg in Group C, droperidol 1.25 mg in Group D, and granisetron 40 microg/kg in Group E were administered intravenously after clamping of the fetal umbilical cord. Postoperative nausea and vomiting was observed for 024 h after the anesthesia. Cesarean sections were all performed under general anesthesia. Postoperative nausea and vomiting was more common in placebo group (56.7%) than the others during the 0-24 h after the anesthesia (p < 0.05). All granisetron groups were more effective than placebo and droperidol groups during the postoperative 3-24 h (p < 0.01). Although this trial lacks statistical power, granisetron alone and combinations with droperidol or dexamethasone were effective similarly. All treatment groups, except droperidol during the postoperative 3-24 h, were effective for prevention of postoperative nausea and vomiting during the postoperative 0-24 h.

Midazolam for acute emesis refractory to dexamethasone and granisetron after highly emetogenic chemotherapy: a phase II study

Abstract: Goals of the work To assess whether the addition of midazolam to dexamethasone and granisetron could ameliorate the refractory acute nausea and/or vomiting caused by a highly emetogenic platinum-based chemotherapy.

An evaluation of potential signals for ventricular arrhythmia and cardiac arrest with dolasetron, ondansetron, and granisetron in the fda combined spontaneous reporting system/adverse event reporting system.

Abstract: Background: Of the US Food and Drug Administration (FDA)-approved5-hydroxytryptamine type 3 (5-HT3)-receptor antagonists, dolasetron, ondan-setron, granisetron, and palonosetron, only dolasetron and palonosetron have a precaution in their FDA labeling concerning corrected QT interval (QTc) prolongation. At FDA approved doses, QTc prolongation has been observed in clinical trials with some 5-HT3 receptor antagonists (however, palonosetron has been only recently approved, with few published clinical data available). However, due to patient exclusion criteria, such trials with 5-HT3 receptor antagonists may have failed to examine the risk of these agents in “real world” patients with cancer.

Granisetron in the control of radiotherapy-induced nausea and vomiting: a comparison with other antiemetic therapies.

Abstract: Radiotherapy-induced nausea and vomiting (RINV) can be one of the most distressing symptoms of radiotherapy treatment, which if incompletely controlled may last for several weeks with fractionated radiotherapy and prevent completion of the planned treatment course. Current treatment guidelines recommend the use of 5-HT3 receptor antagonists with or without corticosteroids for highly and moderately emetogenic radiotherapy, though only granisetron and ondansetron are currently indicated for RINV in most countries. Granisetron is a potent and highly selective 5-HT3 receptor antagonist, with demonstrated efficacy in RINV in both placebo-controlled and comparative studies. In this paper the clinical experience with granisetron in RINV is reviewed, and its efficacy and safety compared with other antiemetic therapies.

Comparison of Ramosetron and Granisetron for the Prevention of Acute and Delayed Emesis in Cisplatin-Based Chemotherapy: a Randomized Controlled Trial

Abstract: Methods: Cisplatin at a dose of >70 mg/m 2 was administered as a single intravenous (i.v.) infusion over 4 h. Patients were randomly assigned to receive either ramosetron (0.3 mg i.v. bolus 30 min before cisplatin on Day 1 and a 0.1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 36) or granisetron (3 mg i.v. infusion 30 min before cisplatin on Day 1 and a 1 mg tablet in the morning for Days 2 to 5 after completion of chemotherapy; n = 37). The observation period started with the initiation of chemotherapy (0 h) and continued for 24 h after completion of the chemotherapy for acute emesis, and on Days 2 to 5 for delayed nausea and vomiting. Results: A total of 73 patients were eligible for evaluation, with 36 patients in the ramosetron group and 37 in the granisetron group. The efficacy of both drugs was analyzed in terms of the degree of achievement in each day of treatment. Ramosetron was as effective as granisetron in preventing nausea and vomiting (both acute and delayed emesis). The two drugs had a similar safety profile and adverse events were generally mild and transient. Conclusions: Ramosetron is effective and safe for the control of acute and delayed emesis induced by cisplatin.

Antiemetic efficacy of an oral suspension of granisetron plus dexamethasone and influence of quality of life on risk for nausea and vomiting.

Abstract: Objectives: To assess the antiemetic efficacy of an oral suspension of granisetron/dexamethasone in patients receiving chemotherapy and to determine whether quality-of-life parameters influence the

Alprazolam significantly improves the efficacy of granisetron in the prophylaxis of emesis secondary to moderately emetogenic chemotherapy in patients with breast cancer.

Abstract: Background: Alprazolam, a newer benzodiazepine, may be useful in the control of nausea and vomiting in breast cancer patients. Methods: Nineteen operable breast cancer patients were included in this randomized prospective crossover open-label trial. Patients received either granisetron (G) alone, or in combination with alprazolam (A). Group A patients received G+A first and then crossed over to G-alone after the 2nd or 3rd cycle. Group B patients received the reverse order. Eighty-four cycles were evaluated. Results: In group A, complete remission (CR) plus major response (MR) was higher (93.9%) with G+A than with G-alone (83.3%; p = 0.0001) in the first 24-hour period. In group B, CR plus MR was higher in G+A cycles (100%) than in G-alone cycles (85.7%; p = 0.035) in the 24-hour period and in the 25- to 129-hour period (92 vs. 90.5%, respectively; p = 0.022). Conclusion: Alprazolam increases the efficacy of granisetron in patients with breast cancer treated with an anthracycline-containing regimen.

Low-dose granisetron for prophylaxis of acute chemotherapy-induced nausea and vomiting: a pilot study.

Abstract: Objectives Chemotherapy-induced nausea and vomiting (QTNV) are very uncomfortable symptoms for patients with cancer, which can be circumvented in most of them with drug combinations containing serotonin receptor antagonists (5-HT3 receptor antagonists) such as granisetron. In an attempt to decrease costs of QTNV prophylaxis, we studied a lower dose regimen of granisetron.

Ramosetron Compared with Granisetron for the Prevention of Postoperative Nausea and Vomiting following General Anesthesia for Breast Mass Excision

Abstract: Ramosetron Compared with Granisetron for the Prevention of Postoperative Nausea and Vomiting following General Anesthesia for Breast Mass Excision Ji Eun Kim, M.D., Chang Bong Lee, M.D., Sun Chong Kim, M.D., Soon Im Kim, M.D., and Si Young Ok, M.D. Department of Anesthesiology and Pain Medicine, Soonchunhyang University Hospital, Seoul, Korea Background: Women undergoing general anesthesia for breast mass excision have a high risk for postoperative nausea and vomiting (PONV). We therefore evaluated the efficacy of ramosetron versus granisetron for preventing PONV. Methods: One hundred twenty women scheduled for breast mass excision received, in a randomized allocated, double-blind manner, an intravenous placebo (P group), granisetron 40/kg (G group) or ramosetron 6 /kg (R group) at the end of surgery. Emetic episode and side effects were assessed. Results: The incidence and severity of nausea in G and R group was less than P group (P ＜ 0.05) during the first 24 hrs. The incidence of vomiting in R group was less than P group (P ＜ 0.05) during the first 6 hrs. However there was no significant difference in the incidence of PONV between G and R group. Conclusions: Our results showed that both granisetron and ramosetron significantly decreased the occurrence of PONV compared to placebo. However, any different efficacy for preventing PONV was not revealed between granisetron and ramosetron.

Clinical usefulness of oral granisetron hydrochloride for alleviation of delayed nausea and vomiting induced by CPT-11.

Abstract: This open label pilot study evaluated the safety and efficacy of the oral 5-HT3 receptor antagonist granisetron for prophylaxis of delayed chemotherapy-induced nausea and vomiting (CINV) in 30 patients with advanced or recurrent colorectal cancer. Patients were studied during two cycles of a 5-week regimen with irinotecan (CPT-11) and UFT. Patients received prophylactic anti-emetic therapy that included intravenous granisetron. If Grade 1 or higher severity gastrointestinal symptoms occurred during 6 days after CPT-11 administration in Cycle 1, then oral granisetron was administered daily for the following 5 days of CPT-11 in Cycle 2. Sixteen patients (53.3%) experienced delayed CINV in Cycle 1. The incidence of Grade 2 or higher vomiting was 32.1% and 27.7% in Cycles 1 and 2 in males (P = 0.554) respectively, and 54.6% and 32.4% in females (P = 0.001) respectively. Granisetron is effective against delayed Grade 2 or higher vomiting induced by CPT-11/UFT in female patients, although granisetron alone may not sufficiently control nausea induced by this regimen.