Serotonin antagonists: Uses, common brands, and safety info

Serotonin antagonists are a class of prescription drugs used in the treatment and prevention of nausea and vomiting. This class is sometimes referred to as 5-HT3 receptor antagonists or serotoninblockers. 5-HT3 stands for 5-hydroxytryptamine, the chemical structure and name for serotonin. This class is used in cases of nausea and vomiting specifically related to chemotherapy treatment, radiation, and postoperative effects. Nausea and vomiting related to these conditions can be severe and further impact the health and safety of the patient, so effective treatment for nausea and vomiting in these cases is very important.

Other serotonin antagonists

• Kytril (granisetron)

• Granisol (granisetron)

What are serotonin (5HT3) antagonists?

Serotonin receptor antagonists are a class of medications known as antiemetics available by prescription only for the treatment of nausea and vomiting, particularly cases related to chemotherapy and radiation therapy, and postoperative treatment. Serotonin antagonists are also used for prophylaxis (prevention) of nausea and vomiting in these patients. There are different formulation types available within the class including oral tablets, dissolvable tablets, and intravenous solutions.

How do serotonin (5HT3) antagonists work?

You may be thinking of serotonin as one of the many neurotransmitters which affect your mood and energy. It is! Serotonin plays a key role in mood and energy along with dopamine, norepinephrine, histamine, and other neurotransmitters. What you may not realize is that there are many serotonin receptors in your gastrointestinal tract which have other effects as well.

Chemotherapy and radiation cause the release of serotonin from the tissue lining the gastrointestinal tract when it is damaged by the treatment. This now free serotonin interacts with nerve receptors in the stomach that send signals through the central nervous system (CNS) to the portion of the brain which triggers the vomit reflex. By blocking serotonin from interacting with those receptors, the signal is not sent and the likelihood of nausea and vomiting is reduced. It is not understood exactly how serotonin antagonists alleviate postoperative or other types of nausea, though it is presumed to be due to the same CNS signal inhibition.

What are serotonin (5HT3) antagonists used for?

• Nausea and vomiting

• Chemotherapy-induced nausea and vomiting

• Postoperative nausea and vomiting

• Radiation-induced nausea and vomiting

Types of serotonin (5HT3) antagonists

First-generation

These were the first serotonin receptor antagonists developed. They are available in oral tablets, orally disintegrating tablets, and injectable solutions. The first generation does have an affinity for other serotonin receptors in the body not related to the vomiting reflex. The clinical implications of these affinities are not understood. 

Examples: Zofran and Zofran ODT (ondansetron), Sancuso (granisetron), and Anzemet (dolasetron)

Second generation

There is only one second-generation serotonin antagonist. It has a much greater affinity for 5HT3 receptors and little to no affinity for any other serotonin receptor. This increases the duration of action for this second generation, making it useful in both acute and delayed nausea and vomiting related to chemotherapy.

Example: Aloxi (palonosetron)

Who can take serotonin (5HT3) antagonists?

Can men take serotonin (5-HT3) antagonists?

Men with no previous history of sensitivity to serotonin antagonists and who have healthy liver function can take serotonin antagonists for nausea and vomiting.

Can women take serotonin (5-HT3) antagonists?

Women may also take serotonin antagonists as long as there is no previous history of sensitivity to serotonin antagonists and healthy liver function has been established.

Can you take serotonin (5-HT3) antagonists while pregnant or breastfeeding?

Ondansetron is the serotonin antagonist utilized most frequently in pregnant patients. Valuable safety data is limited, though there have been suggestions that cleft palate and other malformations have occurred in babies born to mothers who used ondansetron. That incidence appears to be higher when it is taken in the first trimester. The American College of Obstetricians and Gynecologists (ACOG) considers the overall risk very low. In cases of severe or refractory nausea and emesis in pregnancy, the risk may outweigh the risks associated with dehydration due to vomiting. 

Can children take serotonin (5-HT3) antagonists?

Children can take serotonin antagonists, though they are generally not recommended for younger children under the age of 4.

Can seniors take serotonin (5-HT3) antagonists?

Seniors can take serotonin antagonists, though if they have impaired hepatic function, they may not be a good candidate for treatment with these drugs.

Are serotonin (5HT3) antagonists safe?

Recalls

• RXQ Compounding: Voluntary recall due to lack of sterility, June 2019

Restrictions

Serotonin antagonists should not be used in patients with a known sensitivity to this class of drugs. 

Serotonin antagonists are extensively metabolized in the liver. Increased serum plasma levels may occur in patients with hepatitis, hepatic disease, or elevated hepatic enzymes. This can lead to toxicity.

The use of serotonin antagonists may mask more serious gastrointestinal diseases such as adynamic ileus, GI obstruction, or distention after abdominal surgery. Ongoing gastrointestinal symptoms should be investigated to ensure it is nothing more serious.

Serotonin syndrome can occur when a patient is taking one or more serotonergic medications. Serotonin syndrome is characterized by confusion, headache, high blood pressure, and diarrhea. Combining a serotonin antagonist with antidepressants like selective serotonin reuptake inhibitors (SSRIs) may increase the risk of serotonin syndrome. 

Serotonin antagonists can cause QT prolongation, a type of arrhythmia. SSRIs like fluoxetine or antipsychotics like chlorpromazine can cause this as well. Combined treatment with two drugs that have this arrhythmia potential increases the likelihood it can happen.

Are serotonin (5HT3) antagonists controlled substances?

No, serotonin antagonists are not controlled substances.

Common serotonin (5HT3) antagonists side effects

• Headache

• Constipation

• QT prolongation

• Weakness

• Pruritus

• Bradycardia

• Anxiety

• Urinary retention

• Tinnitus

• Thrombocytopenia

• Rash

• Insomnia

• Hypotension

• Hypertension

• Hypersalivation

• Hyperglycemia

• Hiccups

• Flatulence

• Edema

• Diarrhea

• Dizziness

How much do serotonin (5HT3) antagonists cost?

Aloxi, the only second-generation serotonin antagonist, can be expensive if it is not covered by your insurance. It can cost up to $630. The generic version, palonosetron, is significantly cheaper, and a coupon from SingleCare can lower the price to less than $20.

Zofran, a common first-generation serotonin antagonist, can cost up to $300 without coverage. Thankfully, a coupon from SingleCare can give you significant savings, lowering the cost to less than $7 at participating pharmacies.