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Characteristics of antiemetic drugs

Characteristics of antiemetic drugs
Authors:
George F Longstreth, MD
Paul J Hesketh, MD
Section Editor:
Nicholas J Talley, MD, PhD
Deputy Editor:
Shilpa Grover, MD, MPH, AGAF
Literature review current through: Dec 2022. | This topic last updated: Jul 19, 2021.

INTRODUCTION — Several classes of antiemetic drugs are available that antagonize the neurotransmitter receptors known to be involved in the physiology of nausea and vomiting. The antiemetic drugs are classified according to their primary action; some agents affect multiple receptors.

Five neurotransmitter receptor sites are of primary importance in the vomiting reflex:

●M1 – muscarinic

●D2 – dopamine

●H1 – histamine

●5-hydroxytryptamine (HT)-3 – serotonin

●Neurokinin 1 (NK1) receptor – substance P

The area postrema is an important site for M1, D2, 5-HT3, and NK1 receptors, although other central and peripheral sites play a role, including H1 receptors in the vestibular nucleus and 5-HT3 receptors on vagal afferent neurons [1,2]. A review of the pathogenesis of vomiting is discussed elsewhere. (See "Approach to the adult with nausea and vomiting".)

Despite the frequent occurrence of nausea and vomiting, there are relatively few published studies that compare some of the common antiemetic drugs in specific disorders. Thus, drug selection in many clinical situations is based upon empiricism, the preferred route of administration, and safety. Therapy has been most extensively evaluated in chemotherapy-induced emesis. (See "Prevention of chemotherapy-induced nausea and vomiting in adults" and "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting".)

The available antiemetic drugs will be reviewed here, using a classification system based upon their site of action. A general approach to the patient with nausea and vomiting and the treatment of nausea and vomiting caused by gastric dysmotility are discussed separately. (See "Approach to the adult with nausea and vomiting" and "Treatment of gastroparesis".)

ANTICHOLINERGIC AGENTS — The M1-muscarinic receptor antagonist, scopolamine is the major anticholinergic drug that is an effective antiemetic. It is predominantly used as prophylaxis against motion sickness.

Scopolamine is delivered transdermally, 1 mg every 72 hours. Side effects include dry mouth, drowsiness, and vision disturbance [3].

ANTIHISTAMINES — The antihistamines are primarily used for motion sickness. (See "Motion sickness", section on 'Approach to management'.)

Available agents include: diphenhydramine, 25 to 50 mg PO every six hours or 10 to 50 mg IV or IM; dimenhydrinate, 50 mg PO every four hours; and meclizine, 25 to 50 mg PO every 24 hours.

Sedation is a common side effect with any of these drugs.

DOPAMINE RECEPTOR ANTAGONISTS — Three classes of dopamine receptor antagonists may be used in patients with nausea or vomiting:

●Phenothiazines

●Butyrophenones

●Benzamides

Phenothiazines — The phenothiazines were the first group of drugs to demonstrate substantial activity in the prevention of chemotherapy-induced emesis (CIE) [4]. They act predominantly by antagonizing D2-dopamine receptors in the area postrema of the midbrain, but also have M1-muscarinic and H1-histamine blocking effects.

Prochlorperazine is the most commonly used antiemetic in this class; it is moderately effective for nausea caused by various gastrointestinal disorders and mild to moderate but not highly emetogenic chemotherapy [4-6]. However, careful clinical studies of the efficacy of this agent are not available, and a placebo effect may occur in nearly 80 percent of patients [5]. Typical dose regimens are 5 to 10 mg PO every six to eight hours, 5 to 10 mg IM or 2.5 to 10 mg IV every three to four hours, or 25 mg by rectal suppository every 12 hours.

Chlorpromazine is used less often than prochlorperazine; the dose of this drug is 10 to 25 mg PO every four to six hours, 25 mg IV every three to four hours. Thiethylperazine is another alternative; it is given at a dose of 10 mg PO or 2 mg IM every 8 to 24 hours. Promethazine (an antihistamine and phenothiazine) is used in motion sickness if transdermal scopolamine and antihistamines are not effective; it is given at a dose of 12.5 to 25 mg PO or IM every four hours or 12.5 to 25 mg rectally every four to six hours. Due to tolerability concerns, UpToDate authors avoid administering more than 50 mg/day of promethazine for its various uses. (See "Motion sickness", section on 'Patients who have failed transdermal scopolamine and antihistamines'.)

The main adverse effects of the phenothiazines are extrapyramidal reactions such as dystonia and, with prolonged use, tardive dyskinesia. Acute dystonia can be treated with diphenhydramine 25 to 50 mg IV or IM. Hypotension can also occur, particularly in older adults or with intravenous infusion. (See "First-generation (typical) antipsychotic medication poisoning", section on 'Acute extrapyramidal syndromes'.)

Butyrophenones — Butyrophenones are major tranquilizers that potentiate the actions of opioids and have an antiemetic effect when used alone. They are primarily used as a preanesthetic agent or for procedural sedation, but are also effective for postoperative nausea and vomiting [7].

Butyrophenones have also been used for the treatment of nausea and vomiting in other settings. Droperidol, a short-acting drug, is usually given in a dose of 0.625-2.5 mg IM; haloperidol has a considerably longer half-life of about 18 hours which limits its use.

The side effect profile and antiemetic efficacy of the butyrophenones appear to be similar to those of the phenothiazines. Intravenous administration of haloperidol and droperidol carries a dose-dependent risk of QT prolongation and torsades de pointes and patients who are medically ill, older adults, or receiving other agents that prolong QT interval should be monitored before and for two to three hours after drug administration [8,9]. Additional side effects include hypotension, alpha blockade, and acute dystonia.

Prior to the advent of the 5-HT3 receptor antagonists, these agents at higher doses were a reasonable alternative to high-dose metoclopramide [10]. However, in recent years, the need for this class of agents and their utilization has declined.

Benzamides — Metoclopramide causes central and peripheral dopamine D2 antagonism at low doses, and weak 5-HT3 blockade at the higher doses used for emesis caused by cytotoxic drug therapy [6]. It also stimulates cholinergic receptors on gastric smooth muscle cells and enhances acetylcholine release at the neuromuscular junction.

The side effects associated with metoclopramide include central side effects of anxiety, restlessness, and depression, hyperprolactinemia, and QT interval prolongation [11,12]. Metoclopramide has a black box warning from the US Food and Drug Administration related to risks of irreversible tardive dyskinesia with higher dosing and long-term use. (See "Tardive dyskinesia: Etiology, risk factors, clinical features, and diagnosis", section on 'Metoclopramide'.)

At standard doses, metoclopramide has a modest antiemetic effect [13]. It also speeds gastric emptying in patients with gastroparesis and increases tone in the lower esophageal sphincter.

High-dose intravenous metoclopramide combined with dexamethasone and diphenhydramine (to counteract the dopaminergic toxicity of metoclopramide) was formerly the antiemetic regimen of choice with highly emetogenic chemotherapy [6,14,15]. However, it has largely been replaced by the 5-HT3 receptor antagonists due to their superior efficacy and safety. Metoclopramide crosses the blood-brain barrier. Thus, it commonly causes neurologic side effects such as akathisia, dystonia, and tardive dyskinesia, especially in the elderly and at high doses [16]. Metoclopramide is primarily used at present as an adjunctive agent for the prevention of cisplatin-induced delayed emesis and with emesis failing first-line treatment.

Two other benzamides are trimethobenzamide and domperidone. Trimethobenzamide can be given at doses of 250 mg PO every six to eight hours or 200 mg IM. However, this agent was no better than placebo in one study of patients with a variety of illnesses [5], and was only mildly effective in patients receiving chemotherapy in other reports [4,17]. Prochlorperazine was more effective [4,5].

Domperidone is a D2-blocker with selective peripheral activity in the upper gastrointestinal tract. The major advantage of this drug is that it does not cross the blood-brain barrier and therefore lacks the neurologic side effects of metoclopramide. It is available in the United States only through an investigational new drug program. The US Food and Drug Administration domperidone investigational new drug section can be contacted at DomperidoneIND@fda.hhs.gov.

SEROTONIN RECEPTOR ANTAGONISTS

5-HT3 receptor antagonists — The 5-HT3 receptor antagonists has a high therapeutic index for prevention of chemotherapy-induced emesis (CIE) [18]. Chemotherapy drugs are classified according to the associated risk of emesis and antiemetic therapy is individualized according to that risk. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)

The serotonin antagonists form the cornerstone of therapy for the control of acute emesis with chemotherapy agents with moderate to high emetogenic potential. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".). Some data suggest potential value of these drugs for treatment of chemotherapy-induced delayed emesis associated with moderately emetogenic chemotherapy as well [19,20].

Four 5-HT3 receptor antagonists are currently approved in the United States: ondansetron, granisetron, dolasetron, and palonosetron. Several well-conducted, randomized, comparative trials have failed to demonstrate any convincing difference in efficacy or tolerability between the three first-generation agents (ondansetron, granisetron, dolasetron) when used at effective doses [21-23]. Palonosetron differs from the other three in having both a higher receptor binding affinity and much longer half-life. Phase III trials of single agent palonosetron [24,25] and palonosetron combined with dexamethasone [26] demonstrated superiority to first-generation 5-HT3 receptor antagonists in the prevention of delayed as well as acute emesis. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)

The oral formulation of these drugs have comparable efficacy to intravenous dosing for both moderate and highly emetogenic chemotherapy [27,28]. Furthermore, repetitive dosing is not superior to a single dose given immediately before chemotherapy [29,30]. The recommended prophylactic regimen for the most emetogenic chemotherapy consists of a 5-HT3 receptor antagonist combined with dexamethasone, olanzapine, and a neurokinin-1 receptor antagonist. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)

5-HT3 receptor antagonists are generally well tolerated, with mild headache the most frequent adverse event, occurring in approximately 15 to 20 percent of patients. Asthenia and constipation occur in 5 to 10 percent, and dizziness occurs in approximately 10 percent of patients treated intravenously and in 5 percent of those receiving the oral formulation [28]. Electrocardiogram (ECG) interval changes are a class effect of the first-generation 5-HT3 antagonists, including ondansetron, granisetron, and dolasetron. They appear to be most prominent one to two hours after a dose of these agents, are mostly small and clinically insignificant, and return to baseline within 24 hours [31-33]. However, potentially fatal cardiac arrhythmias, including torsade de pointes, have been reported in association with QTc prolongation [31,33-35]. 5-HT3 receptor antagonists have not been associated with cognitive, psychomotor, or affective disturbances [36]. The US Food and Drug Administration recommends ECG monitoring in patients with electrolyte abnormalities such as hypokalemia or hypomagnesemia, heart failure, bradyarrhythmias, or patients taking concomitant medications that prolong the QT interval [35].

Olanzapine — Olanzapine is a second-generation antipsychotic that blocks serotonin 5-hydroxytryptamine (5-HT2) receptors and dopamine D2 receptors, may be a particularly useful agent for the prevention of both acute and delayed nausea and vomiting following highly emetogenic chemotherapy, and is discussed in detail, separately. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Olanzapine'.)

NEUROKININ RECEPTOR ANTAGONISTS — Substance P is a mammalian neuropeptide found in neurons that innervate the brainstem nucleus tractus solitarius and the area postrema, two areas intimately involved in the induction of vomiting. The emetogenic effects of substance P are mediated through the neurokinin-1 (NK1) receptor, a member of the G protein receptor superfamily [37,38].

NK1 receptor antagonists include the oral agent aprepitant and its parenteral version fosaprepitant, netupitant (which is available in a fixed-dose combination with palonosetron [NEPA]), and rolapitant. Unlike the first-generation serotonin receptor antagonists, they prevent not only acute but also delayed emesis in patients treated with highly emetogenic chemotherapy drugs (ie, cisplatin) [39-41]. However, they appear to work best when used in conjunction with serotonin receptor antagonists and dexamethasone [42]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Neurokinin-1 receptor antagonists'.)

A potential clinical issue with aprepitant, fosaprepitant, and netupitant is that they are moderate inhibitors of the CYP3A4 metabolic pathway, and dose reduction may be needed for concurrently administered drugs that are primarily metabolized through CYP3A4. To date, the only class of agents that have been routinely dose reduced when administered with these NK1 receptor antagonists are the glucocorticoids (table 1). (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Inhibition of CYP3A4 and implications for concurrently used drugs'.)

Rolapitant does not inhibit CYP3A4 but inhibits CYP2D6, which is responsible for metabolizing certain drugs such as thioridazine; the use of both drugs together is not recommended. Anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have also been reported in patients receiving intravenous rolapitant emulsion, some requiring hospitalization [43,44]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on 'Rolapitant'.)

GLUCOCORTICOIDS — Glucocorticoids are effective and well-tolerated antiemetics for chemotherapy-induced emesis (CIE). Their mechanism of action remains to be elucidated. Insomnia, increased energy, and mood changes are common side effects.

As single agents, glucocorticoids are used prophylactically with mildly emetogenic chemotherapy and are the current drug of choice in this category [45,46]. Although a variety of glucocorticoids have been employed in clinical trials, dexamethasone has been the most extensively evaluated and is used to the greatest extent.

In the setting of acute CIE, glucocorticoids combined with a 5-HT3 receptor antagonist form the cornerstone of antiemetic therapy with moderately emetogenic chemotherapy. With highly emetogenic chemotherapy and in patients receiving a combination of an anthracycline and cyclophosphamide, glucocorticoids are also an essential component of therapy when used in combination with a 5-HT3 receptor antagonist, olanzapine, and an NK1 receptor antagonist. For delayed emesis, glucocorticoids are effective with both cisplatin and non-cisplatin-based chemotherapy [19]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults".)

CANNABINOIDS — The potential antiemetic utility of cannabinoids was first observed in scattered reports of improved emetic control in patients using marijuana during chemotherapy [47]. Subsequent clinical trials using nabilone and dronabinol (a purified synthetic delta-9-tetrahydrocannabinol) confirmed antiemetic activity that was superior to placebo, and in some studies, superior to prochlorperazine [48,49]. In contrast, dronabinol was inferior to metoclopramide in a trial with highly emetogenic chemotherapy [50].

The modest antiemetic activity of this class of agents combined with their relatively unfavorable side effect profile (vertigo, xerostomia, hypotension, dysphoria), especially in older patients, has limited their clinical utility. However, some side effects (eg, sedation and euphoria) could be beneficial. Dronabinol is available by prescription, 5 to 10 mg orally every six to eight hours. Nabilone is usually given in a dose of 1 to 2 mg every 12 hours [51]. These preparations might be useful as adjunctive therapy in selected patients [51]. Nabilone was discontinued in the United States in 2019 but remains available in other countries.

Rigorous comparisons of marijuana with the most effective antiemetic therapies are lacking. The use of medical marijuana is controversial and is discussed in detail, separately. (See "Cancer pain management: Role of adjuvant analgesics (coanalgesics)", section on 'Cannabis and cannabinoids'.)

BENZODIAZEPINES — As single agents, the benzodiazepines are relatively weak antiemetic agents. The most commonly used drugs in this class include lorazepam and alprazolam. They are given primarily as adjunctive agents to reduce anxiety and akathisia associated with dexamethasone and metoclopramide, respectively [52]. They may also be useful in reducing anticipatory emesis [53]. (See "Pathophysiology and prediction of chemotherapy-induced nausea and vomiting".) Sedation is the main side effect.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Nausea and vomiting with cancer treatment (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Several classes of antiemetic drugs are available that antagonize the neurotransmitter receptors known to be involved in the physiology of nausea and vomiting. The antiemetic drugs are classified according to their primary action; some agents affect multiple receptors. (See 'Introduction' above.)

●Five neurotransmitter receptor sites are of primary importance in the vomiting reflex:

•M1 – muscarinic

•D2 – dopamine

•H1 – histamine

•5-hydroxytryptamine (HT)-3 – serotonin

•Neurokinin-1 (NK1) receptor – substance P

●The M1-muscarinic receptor antagonist, scopolamine is the major anticholinergic drug that is an effective antiemetic. It is predominantly used as prophylaxis against motion sickness. (See 'Anticholinergic agents' above.)

●The antihistamines are primarily used for motion sickness. Available agents include diphenhydramine, dimenhydrinate, meclizine, and promethazine. Sedation is a common side effect with any of these drugs. (See 'Antihistamines' above.)

●The phenothiazines were the first group of drugs to demonstrate substantial activity in the prevention of chemotherapy-induced emesis. Prochlorperazine is the most commonly used antiemetic in this class. The main adverse effects of the phenothiazines are extrapyramidal reactions such as dystonia, and with prolonged use, tardive dyskinesia. (See 'Phenothiazines' above.)

●Butyrophenones are major tranquilizers that potentiate the actions of opioids and have an antiemetic effect when used alone. Droperidol is a short-acting drug, whereas haloperidol has a considerably longer half-life (about 18 hours), which limits its use. The side effect profile and antiemetic efficacy of the butyrophenones appear to be similar to those of the phenothiazines. (See 'Butyrophenones' above.)

●Metoclopramide is a benzamide that causes central and peripheral dopamine D2 antagonism at low doses, and weak 5-HT3 blockade at the higher doses used for emesis caused by cytotoxic drug therapy. It also stimulates cholinergic receptors on gastric smooth muscle cells and enhances acetylcholine release at the neuromuscular junction. At standard doses, metoclopramide has a modest antiemetic effect. However, it has been associated with irreversible tardive dyskinesia.

Two other benzamides are trimethobenzamide and domperidone. The major advantage of domperidone is that it does not cross the blood-brain barrier and therefore lacks the neurologic side effects of metoclopramide. It is available in the United States only through an investigational new drug program. (See 'Benzamides' above.)

●The serotonin antagonists form the cornerstone of therapy for the control of acute emesis with chemotherapy agents with moderate to high emetogenic potential. Four 5-HT3 receptor antagonists are currently approved in the United States: ondansetron, granisetron, dolasetron, and palonosetron. (See 'Serotonin receptor antagonists' above.)

●NK1 receptor antagonists (eg, the oral agent aprepitant and its parenteral version fosaprepitant; netupitant, which is available as a fixed-dose combination containing palonosetron [NEPA]; and rolapitant) are used in the prevention of both acute and delayed chemotherapy-induced emesis (see 'Neurokinin receptor antagonists' above). They are used in combination with a 5-HT3 receptor antagonist and a glucocorticoid, typically for patients receiving highly emetic chemotherapy.

●Glucocorticoids are effective and well-tolerated antiemetics for chemotherapy-induced emesis. Their mechanism of action remains to be elucidated. Insomnia, increased energy, and mood changes are common side effects. (See 'Glucocorticoids' above.)

●Cannabinoids (eg, nabilone and dronabinol) have been used for nausea related to chemotherapy. However, the modest antiemetic activity of this class of agents combined with their relatively unfavorable side effect profile (vertigo, xerostomia, hypotension, dysphoria), especially in older patients, has limited their clinical utility. (See 'Cannabinoids' above.)

●As single agents, the benzodiazepines are relatively weak antiemetic agents. The most commonly used drugs in this class include lorazepam and alprazolam. (See 'Benzodiazepines' above.)

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  49. Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. N Engl J Med 1980; 302:135.
  50. Gralla RJ, Tyson LB, Bordin LA, et al. Antiemetic therapy: a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treat Rep 1984; 68:163.
  51. Jordan K, Schmoll HJ, Aapro MS. Comparative activity of antiemetic drugs. Crit Rev Oncol Hematol 2007; 61:162.
  52. Bowcock SJ, Stockdale AD, Bolton JA, et al. Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy. Br Med J (Clin Res Ed) 1984; 288:1879.
  53. Kris MG, Gralla RJ, Clark RA, et al. Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial. Cancer 1987; 60:2816.
Topic 2538 Version 33.0

References

1 : Central mechanisms of vomiting.

2 : Central neurocircuitry associated with emesis.

3 : Transdermal hyoscine (Scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy.

4 : A CONTROLLED CLINICAL EVALUATION OF ANTIEMETIC DRUGS.

5 : A controlled double-blind study of trimethobenzamide, prochlorperazine, and placebo

6 : Antiemetic efficacy of high-dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy-induced nausea and vomiting.

7 : A quantitative systematic review of ondansetron in treatment of established postoperative nausea and vomiting.

8 : Conduction disturbances associated with administration of butyrophenone antipsychotics in the critically ill: a review of the literature.

9 : Physical health monitoring of patients with schizophrenia.

10 : Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study.

11 : Extrapyramidal reactions with metoclopramide.

12 : Review article: metoclopramide and tardive dyskinesia.

13 : Metoclopramide. A review of antiemetic trials.

14 : Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine. Results of consecutive trials in 255 patients.

15 : Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

16 : The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders.

17 : Trimethobenzamide HCl in the treatment of nausea and vomiting associated with antineoplastic chemotherapy.

18 : Are all 5-HT3 receptor antagonists the same?

19 : Drug treatment of chemotherapy-induced delayed emesis.

20 : Effect of schedule and maintenance on the antiemetic efficacy of ondansetron combined with dexamethasone in acute and delayed nausea and emesis in patients receiving moderately emetogenic chemotherapy: a phase III trial by the National Cancer Institute of Canada Clinical Trials Group.

21 : Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer. Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group.

22 : Comparative clinical trial of granisetron and ondansetron in the prophylaxis of cisplatin-induced emesis. The Granisetron Study Group.

23 : Is Navoban (tropisetron) as effective as Zofran (ondansetron) in cisplatin-induced emesis? The French Navoban Study Group.

24 : Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron.

25 : Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron.

26 : Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial.

27 : Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy.

28 : Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study.

29 : A double-blind comparison of the efficacy of two dose regimens of oral granisetron in preventing acute emesis in patients receiving moderately emetogenic chemotherapy.

30 : A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis.

31 : Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine3 receptor antagonists.

32 : Electrocardiographic findings after 5-HT3 receptor antagonists and chemotherapy in children with cancer.

33 : Other drugs acting on nervous system associated with QT-interval prolongation.

34 : Dolasetron-induced torsades de pointes.

35 : Dolasetron-induced torsades de pointes.

36 : Anti-emetic drug effects on cognitive and psychomotor performance: granisetron vs. ondansetron.

37 : Roles of substance P and NK(1) receptor in the brainstem in the development of emesis.

38 : Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets.

39 : A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy.

40 : Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review.

41 : Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials.

42 : Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone.

43 : Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone.

44 : Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone.

45 : Antiemetics: American Society of Clinical Oncology clinical practice guideline update.

46 : Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference.

47 : Medicinal cannabis in oncology practice: still a bridge too far?

48 : Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy.

49 : Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine.

50 : Antiemetic therapy: a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol.

51 : Comparative activity of antiemetic drugs.

52 : Antiemetic prophylaxis with high dose metoclopramide or lorazepam in vomiting induced by chemotherapy.

53 : Antiemetic control and prevention of side effects of anti-cancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone. A double-blind, randomized trial.