Characteristics of Antiemetic Drugs

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Characteristics of antiemetic drugs

AUTHORS: George F Longstreth, MD, Paul J Hesketh, MD
SECTION EDITOR: Nicholas J Talley, MD, PhD
DEPUTY EDITOR: Sara Swenson, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Sep 2024.

This topic last updated: Jul 12, 2023.
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
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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 older
adults 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]. IV dolasetron mesylate is no longer FDA approved to prevent
nausea and vomiting associated with cancer chemotherapy in adult and pediatric patients
due to an associated dose-dependent increase in QTc prolongation. 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]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on

'Dolasetron'.)
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'). Fosaprepitant has also been associated with a
low frequency of infusion site reactions and occasional systemic hypersensitivity reactions
[45,46].
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 [47,48]. 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 [49]. 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 [50,51]. In contrast, dronabinol was inferior to
metoclopramide in a trial with highly emetogenic chemotherapy [52].
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 [53]. These
preparations might be useful as adjunctive therapy in selected patients [53]. 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 [54]. They may also be useful in reducing
anticipatory emesis [55]. (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
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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.)
Use of UpToDate is subject to the Terms of Use.
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Risk of Abnormal Heart Rhythms. www.fda.gov/Safety/MedWatch/SafetyInformation/Saf
etyAlertsforHumanMedicalProducts/ucm272041.htm (Accessed on September 20, 2011).
36. Benline TA, French J. Anti-emetic drug effects on cognitive and psychomotor
performance: granisetron vs. ondansetron. Aviat Space Environ Med 1997; 68:504.
37. Saito R, Takano Y, Kamiya HO. Roles of substance P and NK(1) receptor in the brainstem
in the development of emesis. J Pharmacol Sci 2003; 91:87.
38. Tattersall FD, Rycroft W, Francis B, et al. Tachykinin NK1 receptor antagonists act
centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets.
Neuropharmacology 1996; 35:1121.
39. Gralla RJ, Bosnjak SM, Hontsa A, et al. 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.
Ann Oncol 2014; 25:1333.
40. dos Santos LV, Souza FH, Brunetto AT, et al. Neurokinin-1 receptor antagonists for
chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst
2012; 104:1280.
41. Rapoport BL, Chasen MR, Gridelli C, et al. 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. Lancet Oncol 2015; 16:1079.
42. Campos D, Pereira JR, Reinhardt RR, et al. Prevention of cisplatin-induced emesis by the
oral neurokinin-1 antagonist, MK-869, in combination with granisetron and
dexamethasone or with dexamethasone alone. J Clin Oncol 2001; 19:1759.
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ty+Alert (Accessed on January 17, 2018).
45. Boccia R, Geller RB, Clendeninn N, Ottoboni T. Hypersensitivity and infusion-site adverse
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46. Laird CM, Glode AE, Schwarz K, et al. Evaluation of fosaprepitant-associated
hypersensitivity reactions at a National Cancer Center. J Oncol Pharm Pract 2020;
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47. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical
Oncology clinical practice guideline update. J Clin Oncol 2011; 29:4189.
48. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the
prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of
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50. Sallan SE, Zinberg NE, Frei E 3rd. Antiemetic effect of delta-9-tetrahydrocannabinol in
patients receiving cancer chemotherapy. N Engl J Med 1975; 293:795.
51. Sallan SE, Cronin C, Zelen M, Zinberg NE. Antiemetics in patients receiving
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Topic 2538 Version 37.0
GRAPHICS
Cytochrome P450 3A (including 3A4) inhibitors and inducers
Strong inhibitors Moderate Strong inducers Moderate inducers

inhibitors
Adagrasib Amiodarone ¶ Apalutamide Bexarotene

Atazanavir Aprepitant Carbamazepine Bosentan
Ceritinib Avacopan Encorafenib Cenobamate
Clarithromycin Berotralstat Enzalutamide Dabrafenib
¶
Cobicistat and Cimetidine Fosphenytoin Dexamethasone Δ
cobicistat- Conivaptan Lumacaftor Dipyrone
containing Crizotinib Lumacaftor- Efavirenz
coformulations ivacaftor
Cyclosporine ¶ Elagolix, estradiol,
Darunavir Mitotane and norethindrone
Diltiazem
Idelalisib Phenobarbital therapy pack ◊
Duvelisib
Indinavir Phenytoin Eslicarbazepine
Dronedarone
Itraconazole Primidone Etravirine
Erythromycin
Ketoconazole Rifampin Lorlatinib
Fedratinib
Levoketoconazole (rifampicin) Mitapivat
Fluconazole
Lonafarnib Modafinil
Fosamprenavir
Lopinavir Nafcillin
Fosaprepitant ¶
Mifepristone * Pexidartinib
Fosnetupitant-
Nefazodone palonosetron Repotrectinib
Nelfinavir Grapefruit juice Rifabutin
Nirmatrelvir- Imatinib Rifapentine
ritonavir Sotorasib
Isavuconazole
Ombitasvir- (isavuconazonium St. John's wort
paritaprevir- sulfate)
ritonavir
Lefamulin
Ombitasvir-
Letermovir
paritaprevir-
Netupitant
ritonavir plus
dasabuvir Nilotinib
Nirogecestat
Posaconazole
Ribociclib
Ritonavir and
ritonavir-containing Schisandra
coformulations Verapamil
Saquinavir
Tucatinib
Voriconazole
For drug interaction purposes, the inhibitors and inducers of CYP3A metabolism listed above can
alter serum concentrations of drugs that are dependent upon the CYP3A subfamily of liver
enzymes, including CYP3A4, for elimination or activation.

These classifications are based upon US Food and Drug Administration (FDA) guidance. [1,2] Other
sources may use a different classification system, resulting in some agents being classified
differently.
Data are for systemic drug forms. Degree of inhibition or induction may be altered by dose,
method, and timing of administration.
Weak inhibitors and inducers are not listed in this table with exception of a few examples. Clinically
significant interactions can occasionally occur due to weak inhibitors and inducers (eg, target drug
is highly dependent on CYP3A4 metabolism and has a narrow therapeutic index). Accordingly,
specific interactions should be checked using a drug interaction program such as the drug
interactions program included within UpToDate.
Refer to UpToDate topics on specific agents and indications for further details.
CYP: cytochrome P450.
* Mifepristone is a strong inhibitor of CYP3A4 when used chronically (eg, for hyperglycemia in
patients with Cushing syndrome). The CYP3A4 inhibitory effect of a single 200 mg mifepristone dose
is likely to be weaker and transient; however, specific data are lacking.
¶ Classified as a weak inhibitor of CYP3A4, according to FDA system. [1]
Δ Classified as a weak inducer of CYP3A4, according to FDA system. [1]
◊ The fixed-dose combination therapy pack taken in the approved regimen has moderate CYP3A4
induction effects. When elagolix is used as a single agent, it is a weak CYP3A4 inducer. Norethindrone
and estradiol are not CYP3A4 inducers.
Data from: UpToDate Lexidrug. More information available at https://online.lexi.com/.
References:
1. Clinical Drug Interaction Studies — Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance
for Industry (January 2020) available at: https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions.
2. US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers.
Available at: FDA.gov website.
Graphic 76992 Version 103.0
Contributor Disclosures
George F Longstreth, MD No relevant financial relationship(s) with ineligible companies to
disclose. Paul J Hesketh, MD No relevant financial relationship(s) with ineligible companies to
disclose. Nicholas J Talley, MD, PhD Patent Holder: Australian Provisional Patent [Diagnostic marker
for functional gastrointestinal disorders]; Biomarkers of irritable bowel syndrome [Irritable bowel
syndrome]; Mayo Clinic [Dysphagia questionnaire]; Mayo Clinic [Bowel Disease questionnaire]; Nepean
Dyspepsia Index [Dyspepsia]; Nestec [Irritable bowel syndrome]; Singapore Provisional Patent [BDNF
Tissue Repair Pathway]; US patent application [Age-related neurodegenerative disease associated with
dysbiosis]. Grant/Research/Clinical Trial Support: Alimetry [Gastric mapping device research
collaboration]; Allakos [Gastric eosinophilic disease]; AstraZeneca [Eosinophilic gastritis, eosinophilic
gastroenteritis]; Intrinsic Medicine [Bowel syndrome with constipation]; NHMRC Centre for Research
Excellence in Digestive Health [NHMRC Investigator grant]. Consultant/Advisory Boards: AusEE
[Eosinophilic gut diseases]; Bayer [Inflammatory bowel syndrome]; BluMaiden [Microbiome Ad Board];
Comvita Mānuka Honey [Digestive health]; International Foundation for Functional Gastrointestinal
Disorders [Advisory board, functional GI disorders]; Intrinsic Medicine [Human milk oligosaccharide].
Other Financial Interest: Elsevier textbook royalties [Medical education]. All of the relevant financial
relationships listed have been mitigated. Sara Swenson, MD No relevant financial relationship(s) with
ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these
are addressed by vetting through a multi-level review process, and through requirements for
references to be provided to support the content. Appropriately referenced content is required of all
authors and must conform to UpToDate standards of evidence.
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11/10/2024, 15:48 Characteristics of antiemetic drugs - UpToDate

Official reprint from UpToDate®

Literature review current through: Sep 2024.

Available agents include: diphenhydramine, 25 to 50 mg PO every six hours or 10 to 50 mg IV

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

DOPAMINE RECEPTOR ANTAGONISTS

Phenothiazines — The phenothiazines were the first group of drugs to demonstrate

Prochlorperazine is the most commonly used antiemetic in this class; it is moderately

Butyrophenones — Butyrophenones are major tranquilizers that potentiate the actions of

Benzamides — Metoclopramide causes central and peripheral dopamine D2 antagonism at

High-dose intravenous metoclopramide combined with dexamethasone and

Two other benzamides are trimethobenzamide and domperidone. Trimethobenzamide can

Domperidone is a D2-blocker with selective peripheral activity in the upper gastrointestinal

SEROTONIN RECEPTOR ANTAGONISTS

[35]. (See "Prevention of chemotherapy-induced nausea and vomiting in adults", section on

Olanzapine — Olanzapine is a second-generation antipsychotic that blocks serotonin 5-

NEUROKININ RECEPTOR ANTAGONISTS

Substance P is a mammalian neuropeptide found in neurons that innervate the brainstem

Glucocorticoids are effective and well-tolerated antiemetics for chemotherapy-induced

As single agents, glucocorticoids are used prophylactically with mildly emetogenic

INFORMATION FOR PATIENTS

SUMMARY AND RECOMMENDATIONS

• Neurokinin-1 (NK1) receptor – substance P

● The M1-muscarinic receptor antagonist, scopolamine is the major anticholinergic drug

● Metoclopramide is a benzamide that causes central and peripheral dopamine D2

Two other benzamides are trimethobenzamide and domperidone. The major

● Glucocorticoids are effective and well-tolerated antiemetics for chemotherapy-induced

Use of UpToDate is subject to the Terms of Use.

4. MOERTEL CG, REITEMEIER RJ, GAGE RP. A CONTROLLED CLINICAL EVALUATION OF

5. Bardfield PA. A controlled double-blind study of trimethobenzamide, prochlorperazine,

Pharmacotherapy 1997; 17:531.

21. Hesketh P, Navari R, Grote T, et al. Double-blind, randomized comparison of the

24. Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. Improved prevention of moderately

Cytochrome P450 3A (including 3A4) inhibitors and inducers

Strong inhibitors Moderate Strong inducers Moderate inducers

Adagrasib Amiodarone ¶ Apalutamide Bexarotene

enzymes, including CYP3A4, for elimination or activation.

CYP: cytochrome P450.

¶ Classified as a weak inhibitor of CYP3A4, according to FDA system. [1]

Δ Classified as a weak inducer of CYP3A4, according to FDA system. [1]

Data from: UpToDate Lexidrug. More information available at https://online.lexi.com/.

Graphic 76992 Version 103.0

Conflict of interest policy

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