|Systematic (IUPAC) name|
|Trade names||Zofran, Ondisolv, others|
|Oral, rectal, IV, IM|
|Metabolism||Liver (CYP3A4, CYP1A2, CYP2D6)|
|Biological half-life||5.7 hours|
|CAS Number||99614-02-5 Y|
|ATC code||A04AA01 (WHO)|
|Molar mass||293.4 g/mol|
|3D model (Jmol)||Interactive image|
Ondansetron, marketed under the brand name Zofran, is a medication used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery. It is also useful in gastroenteritis. It has little effect on vomiting caused by motion sickness. It can be given by mouth, by injection into a muscle or into a vein.
Common side effects include diarrhea, constipation, headache, sleepiness, and itchiness. Serious side effects include QT prolongation and severe allergic reaction. It appears to be safe during pregnancy but has not been well studied in this group. It is a serotonin 5-HT3 receptor antagonist. It does not have any effect on dopamine receptors or muscarinic receptors.
Ondansetron was first used medically in 1990. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system. It is available as a generic medication. The wholesale cost of the injectable form in the developing world is about 0.10 to 0.76 USD per dose. In the United States it costs about 1.37 USD per tablet.
- 1 Medical uses
- 1.1 Cancer treatment
- 1.2 Postoperative
- 1.3 Pregnancy
- 1.4 Cyclic vomiting syndrome
- 1.5 Gastroenteritis
- 2 Special populations
- 2.1 Children
- 2.2 Elderly
- 2.3 Poor liver function
- 3 Adverse effects
- 3.1 QT prolongation
- 3.2 Overdose
- 4 Pharmacodynamics
- 5 History
- 6 Society and culture
- 6.1 Publication bias
- 6.2 Availability
- 7 Research
- 7.1 Psychiatric disorders
- 7.2 Substance use
- 7.3 Postanesthetic shivering
- 8 References
- 9 External links
Although an effective antiemetic agent, the high cost of brand-name ondansetron initially limited its use to controlling postoperative nausea and vomiting and chemotherapy-induced nausea and vomiting.
The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting and radiotherapy-induced nausea and vomiting.
A number of medications including ondansetron appear to be effective in controlling postoperative nausea and vomiting. It is more effective than metoclopramide, and less sedating than cyclizine or droperidol.
Ondansetron is used off-label to treat morning sickness and hyperemesis gravidarum of pregnancy. It is typically used after trials of other drugs have failed.
Animal reproduction studies have not shown evidence of harm to the baby or impairment of fertility with use of high daily doses of ondansetron. A study of over 600,000 pregnancies in Denmark found that ondansetron during pregnancy was not associated with a significantly increased risk of spontaneous abortion, stillbirth, major birth defect, preterm birth, low birth weight, or small for gestational age. Other studies concluded that there is an increase in major congenital malformations due to an increase in heart problems among the babies.
Ondansetron is in pregnancy category B in the US. It is not known if ondansetron is excreted in breast milk.
Cyclic vomiting syndrome
Ondansetron is one of several antiemetic agents used during the vomiting phase of cyclic vomiting syndrome.
Trials in emergency department settings support the use of ondansetron to reduce vomiting associated with gastroenteritis and dehydration. A retrospective review found it was used commonly for this purpose, being administered in over 58% of cases. Its use reduced hospital admissions, but was also associated with higher rates of return visits to the ED. Furthermore, patients who had initially received ondansetron were more likely to be admitted on the return visit than patients who had not received the drug. However, this effect may simply be due to the agent being used more frequently in patients who present with more severe illness. Its use was not found to mask serious diagnoses.
Ondansetron has rarely been studied in patients under 4 years of age. As such, little data are available to guide dosage recommendations.
It is not necessary to adjust the dosage for elderly patients under 75 years of age. The use of Zofran has not been studied in patients older than 75 years of age, and it is not known if dosage should be adjusted for these patients.
Poor liver function
The maximum recommended dose for patients with severe liver function impairment is 8 mg/day. In these patients, Zofran is cleared from the body at half to one-third the rate as in healthy patients. The concentration of Zofran in body tissues as opposed to plasma is also higher than in healthy patients.
Ondansetron is a well-tolerated drug. Constipation, diarrhea, dizziness, and headache are the most commonly reported side effects. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system. Anecdotally, ototoxicity has also been reported if injected too quickly.
Use of ondansetron has been associated with prolongation of the QT interval, which can lead to the potentially fatal heart rhythm known as torsades de pointes. Although this may happen in any patient with any formulation, the risk is most salient with the injectable (intravenous) form of the drug, and increases with dose. The risk is also higher in patients taking other medicines that prolong the QT interval, as well as in patients with congenital long QT syndrome, congestive heart failure, and/or bradyarrhythmias. As such, single doses of injectable ondansetron should not exceed 16 mg at one time. (Oral dosing recommendations remain intact, including the recommendation of a single 24-mg oral dose when indicated.) Electrolyte imbalances should be corrected before the use of injectable ondansetron. Patients are cautioned to seek immediate medical care if symptoms such as irregular heartbeat/palpitations, shortness of breath, dizziness, or fainting occur while taking ondansetron.
No specific treatment is available for ondansetron overdose; patients are managed with supportive measures. An antidote to ondansetron is not known.
Ondansetron is a highly specific and selective serotonin 5-HT3 receptor antagonist, with low affinity for dopamine receptors. The 5-HT3 receptors are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. Serotonin is released by the enterochromaffin cells of the small intestine in response to chemotherapeutic agents and may stimulate vagal afferents (via 5-HT3 receptors) to initiate the vomiting reflex. It is not certain whether ondansetron's antiemetic action is mediated centrally, peripherally, or in both sites.
Ondansetron (marketed under the brand name Zofran) was developed in the mid-1980s by GlaxoSmithKline in London. It was granted US patent protection in September 1987, received a use patent June 1988, and was approved by the US FDA in January 1991. It was granted another divisional patent in November 1996. Finally, owing to GlaxoSmithKline's research on pediatric use, ondansetron's patent protection was extended until December 2006. By this final year of its patent (2006), Zofran had become the 20th highest-selling brand-name drug in the United States, with sales of US$1.3 billion in the first 9 months of 2006 (80% from the US). The first generic versions were approved by the US FDA in December 2006, with marketing approval granted to Teva Pharmaceuticals USA and SICOR Pharmaceuticals.
Society and culture
In 1997, ondansetron was the subject of a meta-analysis case study published in the British Medical Journal. Researchers examined 84 trials, with 11,980 patients receiving ondansetron, published between 1991 and September 1996. Intravenous ondansetron 4 mg versus placebo was investigated in 16 reports and three further reports which had been duplicated a total of six times. The number needed to treat (NNT) to prevent vomiting within 24 hours was 9.5, with 95% confidence interval 6.9 to 15, in the 16 nonduplicated reports. In the three duplicated reports, the NNT was significantly lower at 3.9 (3.3 to 4.8). When all 25 reports were combined, the apparent NNT improved to 4.9 (4.4 to 5.6). Inclusion of duplicate reports led to a 23% overestimation of ondansetron's antiemetic efficacy.
In addition, the authors found the covert duplication of reports on ondansetron was not easy to detect, because of lack of cross-referencing between papers, and reports containing duplicate findings were cited in eight reviews of the drug. Their analysis was a subject of an editorial in the Journal of the American Medical Association in 1999.
Ondansetron is a generic drug and is available in many countries under many brand names.
A 2006 double-blind, randomized controlled trial indicated ondansetron may have value in the treatment of schizophrenia, as an adjunct to haloperidol. The study found the combination to significantly improve negative schizophrenia symptoms, and people taking both drugs experienced fewer of the adverse effects commonly associated with haloperidol. An earlier, smaller, open-label trial had found ondansetron to be useful in treating antipsychotic-induced tardive dyskinesia in people with schizophrenia, and the study patients also showed significant improvement in the disease's symptoms.
Early studies have also examined ondansetron as a possible treatment for psychosis resulting from advanced Parkinson's disease. Its apparent benefits despite a lack of any significant antagonistic properties at dopamine receptors or the 5-HT2A receptor raises interesting questions about the etiology of psychosis.
There is tentative evidence that it may be useful in decreasing the desired effects of alcohol. There is also some tentative evidence in those who are addicted to stimulants.
Two small, placebo-controlled trials have been conducted to assess the efficacy of ondansetron for postanesthetic shivering, a common occurrence after surgery. Ondansetron was found to be as effective as pethidine (meperidine, Demerol) when given as a single intravenous dose before anesthesia.
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|5-HT3 serotonin ion
|5-HT serotonin G-protein
Serotonin receptor modulators
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- … In addition, the effects of ondansetron, a serotonin (5-HT)3 receptor antagonist, on the inhibition of solid gastric emptying induced by salmon calcitonin, copper sulfate, cisplatin and doxorubicin were also assessed. … We also found that the inhibition of solid gastric emptying induced by cisplatin and doxorubicin was dose-dependently antagonized by ondansetron. … However, ondansetron failed to antagonize the salmon calcitonin-induced delay, but exerted only very weak effects with copper sulfate. …
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- Ondansetronとは？goo Wikipedia (ウィキペディア) 。出典：Wikipedia（ウィキペディア）フリー百科事典。 Ondansetronとは - goo Wikipedia (ウィキペディア) gooトップ サイトマップ スタートページに設定 RSS ...
- Ondansetron may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away: headache constipation weakness tiredness chills drowsiness Some side effects can be serious. If you ...
- 5-HT3受容体はリガンドの結合により開閉してNa+, K+の等価に関わる。ニコチン性受容体に似ている。(GOO.299)
- somatodendritic 5-HT1A autoreceptors descrease raphe cell fireing when activated by 5-HT released from axon collaterals of the same or adjacent neurons. (GOO.301)