Ondansetron

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Ondansetron

Systematic (IUPAC) name

(RS)-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-2,3-dihydro-1H-

carbazol-4(9H)-one

Identifiers

CAS number 99614-02-5

ATC code A04AA01

PubChem CID 4595

DrugBank APRD00481

ChemSpider 4434 

UNII 4AF302ESOS 
 KEGG D00456 

ChEMBL CHEMBL46 

Chemical data

Formula C18H19N3O 

Mol. mass 293.4 g/mol

SMILES eMolecules & PubChem

InChI[show]

Pharmacokinetic data

Bioavailability ~60%

Protein binding 70%-76%

Metabolism Hepatic (CYP3A4, CYP1A2,CYP2D6)

Half-life 5.7 hours

Excretion Renal

Therapeutic considerations

Pregnancy cat. B1(AU) B(US)

Legal status Prescription Only (S4) (AU) POM(UK) ℞-only (US)

Routes Oral, rectal, IV, IM

  (what is this?)  (verify)
Ondansetron HCl (INN) (pronounced /ɒnˈdænsɛtrɒn/) (developed and first marketed
by GlaxoSmithKline as Zofran) is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to
treat nausea and vomiting, often following chemotherapy. Its effects are thought to be on both peripheral and
central nerves. Ondansetron reduces the activity of the vagus nerve, which deactivates the vomiting center in
the medulla oblongata, and also blocks serotonin receptors in the chemoreceptor trigger zone. It has little effect
on vomiting caused by motion sickness, and does not have any effect on dopaminereceptors or muscarinic
receptors.

Contents
 [hide]

1 History

2 Brand names

3 Clinical uses

o 3.1 Investigational and off-label

 3.1.1 Schizophrenia

 3.1.2 Sleep apnea

 3.1.3 Parkinson's disease

 3.1.4 Obsessive Compulsive

Disorder

 3.1.5 Alcoholism

 3.1.6 Opioid addiction

 3.1.7 Irritable bowel

syndrome

o 3.2 Postanesthetic shivering

4 Adverse effects

5 See also

6 References

7 External links

[edit]History

Ondansetron was developed around 1984 by scientists working at Glaxo's laboratories in London. It is in both
the imidazole and carbazole families of heterocyclic compounds. After several attempts the company
successfully filed for U.S. patent protection for the drug in 1986. U.S. Patent 4,695,578 was granted in
September 1987 while U.S. Patent 4,753,789 was granted in June 1988. U.S. Patent 5,578,628, a divisional
patent of U.S. Patent 4,753,789, was granted on November 26, 1996. Ondansetron was granted FDA approval
as Zofran in January 1991. Glaxo did pediatric research on Zofran's uses, and gained a patent extension as a
result, extending U.S. exclusivity until December 24, 2006. The FDA subsequently approved the first generic
versions in December 2006, with marketing approval granted to Teva Pharmaceuticals USA and SICOR
Pharmaceuticals.

[edit]Brand names

Ondansetron is currently marketed by GlaxoSmithKline (GSK) under the trade name Zofran. Other

manufacturers include Strativa Pharmaceuticals (Zuplenz), Cipla Ltd. (Emeset), Gedeon Richter
Ltd. (Emetron), Korea United Pharmaceuticals (Emodan), Zentiva a.s. (Ondemet), Strides Arcolab
(Setronax), Glenmark Generics Ltd. (India) (Ondansetron) and Novell Pharmaceutical Laboratories
(Ondavell). On May 29, 2006, Baxter Healthcarereceived tentative approval[1] to market its own label of
Ondansetron Injection, USP, 8 mg/50 mL and 32 mg/50 mL iso-osmotic sodium chloride solution, beginning
upon expiration of GSK's patent later that year.

[edit]Clinical uses

See also:  5-HT3 antagonist

The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea
and vomiting (CINV). A common use case is to give them intravenously about 30 minutes before
commencement of a chemotherapy treatment. Ondansetron is also effective in controlling post-operative
nausea and vomiting (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea
and vomiting due to acute or chronic medical illness or acute gastroenteritis.

Although it is highly effective, the high cost of the brand-name version had limited its use to controlling PONV
and CINV. It is also used off-label to treathyperemesis gravidarum in pregnant women, but there is no
conclusive data available on its safety in pregnancy, especially during the first trimester. It is also used to
treat cyclic vomiting syndrome; although there have been no formal trials to confirm efficacy, case reports
suggests it can be helpful in some cases. The drug is administered 1–3 times daily, depending on the severity
of nausea and/or vomiting. The normal oral dose for adults and children over the age of 12 is 8 mg initially,
followed by a second dose of 8 mg eight hours later. The drug is then administered once every 12 hours,
usually for not more than 2–3 days. Following oral administration, it takes about 1.5 to 2 hours to reach
maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.

The clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it
with dexamethasone.

[edit]Investigational and off-label

[edit]Schizophrenia
A 2006 double-blind, randomized controlled trial indicated that ondansetron may have value in the treatment of
schizophrenia, as an adjunct to haloperidol. The study found the combination
tosignificantly improve negative schizophrenia symptoms, and people taking both drugs experienced fewer of
the adverse effects commonly associated with haloperidol. [2] 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. [3][4]

[edit]Sleep apnea

A patent for the use of ondansetron in the treatment of sleep apnea has been filed.[5]

[edit]Parkinson's disease

Early studies have also examined ondansetron as a possible treatment for psychosis resulting from
advanced Parkinson's disease.[6] 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.

[edit]Obsessive Compulsive Disorder

Hewlett and others found that the treatment of obsessive compulsive disorder with Ondansetron 1 mg three
times daily was associated with a significant decrease in the Yale Brown Obsessive Compulsive scores in a
small (n=8), 8-week, open-label study.[7]

[edit]Alcoholism

Ondansetron lowers the cravings for alcohol, especially in early-onset alcoholics. In one cognitive-behavioral
therapy study, ondansetron patients with early-onset alcoholism had fewer drinks per day and reported more
days without drinking at all, as compared to the other groups in the study. Also of note, individuals with the LL
genotype show significant improvements in alcohol misuse when treated with ondansetron, compared with
individuals with the other genotypes of the 5HTTLPR polymorphism, who showed no improvement over
placebo.[8][9][10]

[edit]Opioid addiction

Researchers at the Stanford University School of Medicine have demonstrated that ondansetron might be

useful and effective for treating withdrawal symptoms of opioid addictions. [11] Unlike the existing
treatments methadone and buprenorphine, it is not itself an opioid.[11] Additionally, it does not require continued
supervision like treatment with clonidine.[11]

The original experiment used mice who were injected with increasing doses of morphine, assayed
with naloxone and then underwent haplotypic analysis to isolate a gene candidate.[12] HTR3A which codes for
the 5-HT3 receptor emerged as the primary candidate, which suggested 5-HT 3 antagonist ondansetron as a
possible treatment.[12] The researchers were then able to show using an acute morphine administration model
the efficacy in withdrawal symptom control in humans.[12]

[edit]Irritable bowel syndrome

Ondansetron blocks the 5-HT3 receptor in the enteric nervous system, and thereby reduces colonic
contractions, sensory perception, and motility. A large number of drugs in this category, 5-HT3 antagonist, have
been shown to have this effect, which positively impacts irritable bowel syndrome with diarrhea (IBS-D). Thus,
ondansetron has been effective in treating diarrhea-predominant IBS in initial studies, and is being used off
label for this exact effect.[13]

[edit]Postanesthetic shivering
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 IV dose before anesthesia. [14]

[edit]Adverse effects

Ondansetron is a well-tolerated drug with few side effects. Constipation, dizziness and headache are the most
commonly reported side effects associated with its use. There have been no significant drug interactions
reported with this drug's use. 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.

What is this medicine?

ONDANSETRON (on DAN se tron) is used to treat nausea and vomiting caused by chemotherapy. It is also used to
prevent or treat nausea and vomiting after surgery.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:

 liver disease
 an unusual or allergic reaction to ondansetron, granisetron, other medicines, foods, dyes, or preservatives
 pregnant or trying to get pregnant
 breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on your prescription label. Take your doses
at regular intervals. Do not take your medicine more often than directed.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency
room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take
double or extra doses.
What may interact with this medicine?

 carbamazepine
 rifabutin
 rifampin
 rifapentine
 St. John's wort
 tramadol

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs,
non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal
drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Check with your doctor or health care professional right away if you have any sign of an allergic reaction.

Do not drink alcohol while taking this medicine.

What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:

 difficulty breathing, wheezing, shortness of breath

 fast or irregular heartbeat
 fever and chills
 tightness in the chest
 skin rash, itching
 swelling of the face, tongue, throat, hands and feet

Side effects that usually do not require medical attention (report to your doctor or health care professional if they
continue or are bothersome):

 constipation or diarrhea
 dizziness
 headache

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may
report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store between 2 and 30 degrees C (36 and 86 degrees F). Throw away any unused medicine after the expiration
date.

NOTE:This sheet is a summary. It may not cover all possible information. If you have questions about this medicine,
talk to your doctor, pharmacist, or health care provider.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with
others, and use this medication only for the indication prescribed

Read more: http://www.healthline.com/goldcontent/ondansetron#ixzz1DiefbWrk 
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