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Zofran vs. Phenergan: What's the Difference?

Edited by Janet White || By Harlon Moss || Updated on October 13, 2023
Zofran (ondansetron) and Phenergan (promethazine) are both medications used to treat nausea and vomiting, but they belong to different drug classes and have distinct mechanisms of action.

Key Differences

Zofran and Phenergan are both prescribed by healthcare professionals to manage and treat nausea and vomiting, but they differ in several key aspects. Their primary differences lie in their chemical composition, mechanism of action, and drug classification.
Zofran, whose generic name is ondansetron, is a member of the serotonin 5-HT3 receptor antagonists class of drugs. It primarily functions by blocking the action of serotonin, a chemical in the body that can cause vomiting. Often, Zofran is prescribed to patients undergoing surgery or chemotherapy to prevent nausea and vomiting associated with these procedures.
On the other hand, Phenergan, with its generic name being promethazine, belongs to the phenothiazine class of drugs. Its mechanism of action is more diversified, as it impacts several sites in the body, including the brain. Phenergan is not only prescribed for nausea and vomiting but also for allergy symptoms, sedation, and motion sickness.
While both Zofran and Phenergan are effective in treating nausea and vomiting, they do come with distinct side effect profiles. Doctors decide on their prescription based on the patient's specific condition, potential drug interactions, and the side effect profile that might be more acceptable for the patient.

Comparison Chart

Generic Name


Drug Class

Serotonin 5-HT3 receptor antagonists

Mechanism of Action

Blocks serotonin
Acts on multiple sites, including the brain

Common Uses

Nausea and vomiting (post-surgery, chemo)
Nausea, vomiting, allergies, sedation, motion sickness

Side Effect Profile

Generally well-tolerated
Can cause drowsiness and other CNS effects

Zofran and Phenergan Definitions


Zofran is a medication primarily used to prevent nausea and vomiting caused by chemotherapy or surgery.
After her chemotherapy session, Lisa was given Zofran to manage her nausea.


Phenergan can cause drowsiness, making it useful as a sedative in certain situations.
For his intense insomnia, Mark was occasionally prescribed Phenergan as a sedative.


Zofran's action is mainly centered around blocking chemical actions that trigger nausea and vomiting.
Zofran was a lifesaver for Jake, who always suffered from severe post-chemotherapy nausea.


Phenergan's generic name is promethazine, a drug that belongs to the phenothiazine class.
Phenergan, or promethazine, was prescribed to Stella for her persistent allergic reactions.


Zofran tablets are often prescribed post-operatively to reduce the risk of nausea.
Post her gallbladder surgery, Karen was given Zofran to ensure she didn't experience post-operative nausea.


Phenergan is a medication used for various purposes, including preventing nausea, vomiting, and treating allergies.
When traveling by boat, Marcy always took Phenergan to prevent motion sickness.


Zofran is a brand name for the generic drug ondansetron.
The doctor switched Robert from Zofran to generic ondansetron to save costs.


Besides its antiemetic properties, Phenergan also acts as an antihistamine.
After a bee sting, Alex was given Phenergan to manage the swelling and itching.


Zofran belongs to the class of drugs known as serotonin 5-HT3 receptor antagonists.
Due to its mechanism as a 5-HT3 antagonist, Zofran effectively prevents vomiting by blocking certain actions of serotonin.


Phenergan has a varied mechanism of action, impacting multiple sites in the body.
Due to Phenergan's diverse effects, it's crucial for patients to adhere to their doctor's recommended dose.


Antihistamine (trade name Phenergan) used to treat allergies; also an antiemetic used to treat motion sickness


Do both medications have generic versions?

Yes, Zofran's generic name is ondansetron and Phenergan's is promethazine.

Are Zofran and Phenergan used for the same conditions?

Both are used for nausea and vomiting, but Phenergan also treats allergies and can be used as a sedative.

Can I take Zofran and Phenergan together?

Only if prescribed together by a doctor; they can interact and cause unwanted side effects.

Is drowsiness a common side effect of Phenergan?

Yes, Phenergan can cause drowsiness, and patients should avoid driving when taking it.

Can I buy Phenergan over the counter?

In the US, Phenergan requires a prescription.

Are there any common side effects with Zofran?

Zofran is generally well-tolerated, but side effects can include headache, fatigue, and constipation.

Can I use Phenergan for my allergies?

Yes, Phenergan acts as an antihistamine and can treat allergy symptoms.

How do Zofran and Phenergan prevent nausea?

Zofran blocks serotonin, while Phenergan acts on multiple sites, including the brain.

How is Zofran administered?

It's available in oral tablets, orally disintegrating tablets, and as an injectable solution.

How quickly does Zofran work?

Zofran can start working within 30 minutes to 2 hours after consumption.

How often should I take Zofran for nausea?

Always follow the doctor's prescription, which usually depends on the cause of the nausea.

Are there any long-term side effects of using Phenergan?

Chronic use can lead to potential side effects; always consult with a doctor about prolonged usage.

Can Zofran cause an irregular heartbeat?

In rare cases, it can; always discuss any side effects with a healthcare professional.

What other medications should I avoid when taking Phenergan?

Always inform your doctor of all medications, as Phenergan can interact with several drugs, especially alcohol.

How should I store Phenergan tablets?

In a cool, dry place, away from light and out of the reach of children.

Can children take Zofran?

Zofran can be prescribed for children under certain conditions, always under a doctor's guidance.

Can Phenergan be used for anxiety?

It's not a primary use, but due to its sedative properties, it can be used off-label for anxiety under a doctor's prescription.

Is it safe to use Zofran during pregnancy?

Always consult a doctor, but some studies suggest caution in the first trimester.

Does Phenergan treat motion sickness?

Yes, Phenergan can be prescribed for motion sickness.

Is Phenergan used as a sleeping aid?

Occasionally, due to its sedative properties, but always under a doctor's guidance.
About Author
Written by
Harlon Moss
Harlon is a seasoned quality moderator and accomplished content writer for Difference Wiki. An alumnus of the prestigious University of California, he earned his degree in Computer Science. Leveraging his academic background, Harlon brings a meticulous and informed perspective to his work, ensuring content accuracy and excellence.
Edited by
Janet White
Janet White has been an esteemed writer and blogger for Difference Wiki. Holding a Master's degree in Science and Medical Journalism from the prestigious Boston University, she has consistently demonstrated her expertise and passion for her field. When she's not immersed in her work, Janet relishes her time exercising, delving into a good book, and cherishing moments with friends and family.

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