Phenergan vs. Zofran: Differences, Similarities, and Which One is Better For You

In this article:

• What are the main differences between Phenergan and Zofran?
• Conditions treated by Phenergan and Zofran
• Is Phenergan or Zofran more effective?
• Coverage and cost comparison of Phenergan vs. Zofran
• Common side effects of Phenergan vs. Zofran
• Drug interactions of Phenergan vs. Zofran
• Warnings of Phenergan and Zofran
• Frequently asked questions about Phenergan vs. Zofran

In this article

• What are the main differences between Phenergan and Zofran?
• Conditions treated by Phenergan and Zofran
• Is Phenergan or Zofran more effective?
• Coverage and cost comparison of Phenergan vs. Zofran
• Common side effects of Phenergan vs. Zofran
• Drug interactions of Phenergan vs. Zofran
• Warnings of Phenergan and Zofran
• Frequently asked questions about Phenergan vs. Zofran

Phenergan and Zofran are prescription antiemetic agents often used to treat nausea and vomiting. People may experience nausea due to various causes, including movement, stress, pregnancy, medications, or certain health conditions. Although many cases of nausea can be relieved through non-medication methods, more severe cases may require an antiemetic agent. For example, chemotherapy or radiation for cancer treatment can cause nausea and vomiting. People who undergo surgery may receive anesthesia, which can also cause nausea and vomiting. 

While they have similar uses for nausea and vomiting, Phenergan and Zofran have important differences in their mechanism of action, their dosages, and side effects. Continue reading to learn about the similarities and differences between Phenergan and Zofran. 

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What are the main differences between Phenergan and Zofran?

Phenergan and Zofran differ in several ways. A healthcare provider may prescribe one drug over the other, depending on a person’s condition and other factors. Consult a healthcare provider to determine the best treatment for nausea and vomiting.

They contain different active ingredients

Phenergan is a brand-name drug that contains promethazine, an antihistamine. It works by blocking H1 receptors in the chemoreceptor trigger zone (CTZ), an area of the brain involved with nausea and vomiting. Other examples of antihistamines that can be used to treat nausea and vomiting include meclizine and diphenhydramine. 

Zofran is a brand-name drug that contains ondansetron, a serotonin receptor antagonist. It helps reduce the nausea-related activity of serotonin by blocking serotonin receptors in the CTZ. Other serotonin receptor antagonists used to treat nausea and vomiting include granisetron, palonosetron, and dolasetron. 

They have different dosage forms

Phenergan is only available as a generic medication, as the brand name has been discontinued. The generic version of Phenergan is promethazine, and it can be administered as an oral tablet, oral solution, injection, or suppository. The recommended dosage for nausea and vomiting is 12.5 to 25 mg every four to six hours as needed. The maximum recommended dose is 100 mg per day. 

Zofran is only available as an oral solution. The generic version, ondansetron, is available as an oral solution, oral tablet, orally disintegrating tablet, and injection. The recommended dosage is 8 mg, 16 mg, or 24 mg, given before chemotherapy, radiation, or anesthesia. Subsequent doses may be given every eight to 12 hours after the completion of the procedure for one to two days. The maximum recommended dose is 24 mg per day. 

They have different age restrictions

Phenergan and Zofran have different age limits. Phenergan is approved for use in adults and children aged two years and older. It is not approved for children younger than two due to the risk of severe respiratory depression or slowed breathing. 

The Zofran oral solution and all oral dosage forms of ondansetron are only approved for adults and children aged four years and older. However, the injectable form can be administered to children and infants as young as one month, depending on what it is being used for. 

	Phenergan	Zofran
Drug class	Antihistamine	Serotonin receptor antagonist
Brand/generic status	Generic only	Brand and generic available
What is the generic name?	Promethazine	Ondansetron
What form(s) does the drug come in?	Solution for intramuscular (IM) injection  Solution for intravenous (IV) injection Rectal suppository  Oral tablet  Oral solution	Oral solution  Oral tablet  Orally disintegrating tablet  Solution for intramuscular (IM) injection Solution for intravenous (IV) injection
What is the standard dosage?	12.5 to 25 mg every 4 to 6 hours as needed Dosage depends on the purpose for use	8 to 24 mg given in a single dose before chemotherapy, radiation therapy, or anesthesia; then, every 8 to 12 hours for one to two days after, depending on the purpose for use
How long is the typical treatment?	Treatment is used as needed but usually no longer than 7 to 10 days in a row	Treatment is used as needed but usually no longer than 1 to 5 days in a row
Who typically uses the medication?	Adults and children aged 2 years and older	Adults, children, and infants aged 1 month and older

Conditions treated by Phenergan and Zofran

Phenergan has more approved uses than Zofran. As an antihistamine, Phenergan can be used to treat allergic conditions, including allergic reactions on the skin, allergic rhinitis, and allergic conjunctivitis (inflammation of the eye). Because of its sedative properties, it can be used to induce sleep before or after a procedure. It is also approved for the prevention of motion sickness and nausea or vomiting after surgery. On the other hand, Zofran is only FDA-approved for the treatment of nausea and vomiting caused by chemotherapy, radiation, or anesthesia. 

Phenergan may be used off-label to treat nystagmus or uncontrolled movements of the eyes. Zofran may be used off-label to treat alcohol dependence and itching that is caused by certain liver problems (cholestasis). Both Phenergan and Zofran may be used off-label for the treatment of nausea and vomiting in pregnant women. 

Condition	Phenergan	Zofran
Postoperative nausea and vomiting	Yes	Yes
Nausea and vomiting associated with chemotherapy	Off-label	Yes
Nausea and vomiting associated with radiation therapy	Off-label	Yes
Pregnancy-related nausea and vomiting	Off-label	Off-label
Motion sickness	Yes	No
Allergic conditions, including allergic rhinitis, allergic conjunctivitis, and allergic reactions	Yes	No
Sedation and relief of anxiety before or after a procedure	Yes	No
Peripheral vestibular nystagmus	Off-label	No
Itching caused by cholestasis	No	Off-label
Alcohol dependence	No	Off-label

Is Phenergan or Zofran more effective?

Phenergan and Zofran have been shown to be similarly effective in treating nausea. One randomized, double-blind clinical trial found that there was no significant difference between Phenergan and Zofran for treating nausea in the emergency department. However, Phenergan caused more sedation or drowsiness than Zofran. 

In some cases, Phenergan and Zofran may be used together. Some studies suggest that Phenergan, Zofran, and additional fluids are effective for improving nausea and vomiting. However, caution should be used when combining Phenergan and Zofran due to the potential risk of an irregular heart rhythm. 

Different factors will come into play when a healthcare provider determines the best treatment option, such as cost and potential side effects. Certain nausea medicines, including dopamine antagonists or other serotonin antagonists, may be more appropriate than others. 

Coverage and cost comparison of Phenergan vs. Zofran

Promethazine, the generic version of Phenergan, is usually covered by Medicare and commercial insurance plans. Without insurance, the cash price can vary depending on the pharmacy location and the quantity or strength prescribed. However, using a SingleCare card for Phenergan may help lower the retail price. 

Ondansetron, the generic version of Zofran, is usually covered by Medicare and commercial insurance plans. The average retail price for a typical supply of ondansetron tablets is around $125. A SingleCare coupon for ondansetron may help lower the cash price to a more affordable cost. 

	Phenergan	Zofran
Typically covered by insurance?	Yes (generic)	Yes (generic)
Typically covered by Medicare Part D?	Yes (generic)	Yes (generic)
Quantity	30 tablets (25 mg)	10 tablets (4 mg)
Typical Medicare copay	$0–$1	$0–$2
SingleCare cost	$1 for generic Phenergan	$5

Common side effects of Phenergan vs. Zofran

The most common side effect of Phenergan is drowsiness. Other side effects include dizziness, nervousness, confusion, blurred vision, dry mouth, and a stuffy or runny nose (nasal congestion).

The most common side effects of Zofran are fatigue, headache, constipation, and diarrhea. Other side effects of Zofran include dizziness and nervousness.

Both Phenergan and Zofran can cause changes in blood pressure and heart rate. 

Serious side effects are possible while taking Phenergan or Zofran (see Warnings section). Phenergan can cause seizures, severe respiratory depression, and neuroleptic malignant syndrome, whereas Zofran can cause heart rhythm problems (QT prolongation) and serotonin syndrome.

See the following tablet for the most common side effects of Phenergan and Zofran. 

	Phenergan		Zofran
Side Effect	Applicable?	Frequency	Applicable?	Frequency
Drowsiness	Yes	N/A	No	–
Fatigue	Yes	N/A	Yes	13%
Dizziness	Yes	N/A	Yes	7%
Anxiety or nervousness	Yes	N/A	Yes	6%
Headache	No	–	Yes	24%
Constipation	No	–	Yes	9%
Diarrhea	No	–	Yes	6%
Confusion	Yes	N/A	No	–
Blurry vision	Yes	N/A	No	–
Dry mouth	Yes	N/A	No	–
Nasal congestion	Yes	N/A	No	–
Ringing in the ears	Yes	N/A	No	–
Changes in blood pressure	Yes	N/A	Yes	N/A
Fast or slow heart rate	Yes	N/A	Yes	N/A

Frequency is not based on data from a head-to-head trial. This may not be a complete list of adverse effects that can occur. Please refer to your doctor or healthcare provider to learn more.

Source: DailyMed (Phenergan), DailyMed (Zofran)

Drug interactions of Phenergan vs. Zofran

Phenergan can interact with other CNS depressants, such as opioids, tricyclic antidepressants, benzodiazepines, and barbiturates. Mixing Phenergan with CNS depressants can increase the risk of CNS side effects, such as drowsiness and dizziness. 

Taking Phenergan with anticholinergic drugs, such as benztropine or scopolamine, can lead to an increased risk of anticholinergic side effects, including confusion, blurred vision, and dry mouth. In addition, taking Phenergan with monoamine oxidase inhibitors (MAOIs), such as phenelzine or selegiline, can increase the risk of extrapyramidal side effects. Examples of extrapyramidal side effects include restlessness and uncontrolled muscle movements. 

Zofran can interact with serotonergic drugs, including opioids, tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors. Taking Zofran with a drug that affects serotonin levels may increase the risk of serotonin syndrome. 

Zofran is processed by the CYP liver enzymes, which can be affected by other drugs, such as certain antibiotics, antifungals, and anticonvulsants. Combining Zofran with CYP inhibitors or inducers can lead to increased levels or decreased effects of Zofran. 

Drug	Drug Class	Phenergan	Zofran
Tramadol Methadone Meperidine	Opioids	Yes	Yes
Clomipramine Imipramine Amitriptyline Nortriptyline	Tricyclic antidepressants (TCAs)	Yes	Yes
Fluoxetine Escitalopram Sertraline Paroxetine	Selective serotonin reuptake inhibitors (SSRIs)	Yes	Yes
Alprazolam  Clonazepam	Benzodiazepines	Yes	No
Phenobarbital Pentobarbital Secobarbital	Barbiturates	Yes	No
Benztropine Scopolamine Hyoscyamine	Anticholinergics	Yes	No
Phenelzine Selegiline Isocarboxazid	Monoamine oxidase inhibitors (MAOIs)	Yes	Yes
Fluconazole Itraconazole	Antifungals	Yes	Yes
Clarithromycin Erythromycin	Macrolide antibiotics	Yes	Yes
Phenytoin Carbamazepine	Anticonvulsants	Yes	Yes
Epinephrine	Sympathomimetic	Yes	No

Consult a healthcare professional for other possible drug interactions

Warnings of Phenergan and Zofran

The use of Phenergan is contraindicated in children under the age of two, due to potential risks of respiratory depression and death. Phenergan is also linked to a potential risk of neuroleptic malignant syndrome, a potentially fatal condition that can cause rigid muscles, increased body temperature, and confusion. In addition, the use of Phenergan can lower the seizure threshold and cause an increased risk of seizures. 

Zofran can cause a heart rhythm problem (arrhythmia) called QT prolongation. People with a history of heart rhythm problems, congestive heart failure, or electrolyte imbalances should use Zofran with caution. Zofran affects serotonin levels, which can lead to serotonin syndrome. Symptoms of serotonin syndrome include hallucinations, sweating, tremors, and diarrhea. 

People who have a history of an allergic reaction to Phenergan or Zofran should avoid using either drug. Signs and symptoms of an allergic reaction include itching, hives, and trouble breathing.

Consult a healthcare provider for other possible warnings and precautions before starting treatment with Phenergan or Zofran. 

Frequently asked questions about Phenergan vs. Zofran

What is Phenergan?

Phenergan is a prescription drug that contains promethazine. It is used to treat allergic conditions, motion sickness, and nausea or vomiting. It can also be used to induce sleep before or after surgery. The Phenergan brand name has been discontinued. It is only available as a generic. 

What is Zofran?

Zofran is a prescription drug that contains ondansetron. It is approved to treat nausea and vomiting caused by chemotherapy, radiation, or anesthesia. Zofran is available in brand-name and generic versions.

Are Phenergan and Zofran the same?

Phenergan and Zofran can both be used as antiemetic agents to prevent or treat nausea and vomiting. However, they have different active ingredients, dosage forms, and side effects. Phenergan is an antihistamine, while Zofran is a serotonin receptor antagonist. They also have different age restrictions; Phenergan can be used in adults and children older than two years of age, while Zofran can be used in adults and children as young as one month old. 

Is Phenergan or Zofran better?

Phenergan and Zofran are similarly effective for the treatment of nausea and vomiting. The best treatment option will depend on other factors, such as the age of the person, other health conditions, and other medications being taken. For example, someone with a history of seizures may be better off taking Zofran instead of Phenergan. Consult a healthcare provider about the best treatment for nausea and vomiting based on your individual situation. 

Can I use Phenergan or Zofran while pregnant?

Zofran is in Pregnancy Category B, while Phenergan is in Pregnancy Category C. In other words, Zofran has a lower risk of causing problems in an unborn baby than Phenergan. However, most research is needed to determine the exact effects of Phenergan or Zofran during pregnancy. Consult a healthcare provider to weigh the benefits and risks of using Phenergan or Zofran to treat nausea or vomiting while pregnant or breastfeeding. 

Can I use Phenergan or Zofran with alcohol?

It is recommended to avoid alcohol with Phenergan. Drinking alcohol with Phenergan may increase drowsiness. Zofran is not known to interact with alcohol. However, certain side effects of Zofran may overlap with the effects of alcohol, such as dizziness and headache. Consult a healthcare provider before drinking alcohol during treatment with Phenergan or Zofran. 

Can you take Phenergan and Zofran together? 

In some cases, Phenergan and Zofran may be used together to prevent nausea and vomiting after surgery. Studies suggest that Phenergan and Zofran are effective for reducing nausea and vomiting when used together. However, in rare cases, taking Phenergan and Zofran together may increase the risk of heart rhythm problems. Consult a healthcare provider before taking Phenergan and Zofran together. 

What should not be taken with Zofran?

Taking Zofran with certain medications can increase the risk of side effects. Zofran should not be taken with serotonergic drugs, such as antidepressants and opioids, due to an increased risk of serotonin syndrome. Drugs that affect the CYP liver enzymes, such as certain antibiotics, antifungals, and anticonvulsants, can lead to increased levels or decreased effects of Zofran. Before using Zofran, tell a healthcare provider about any medications you take, including prescription drugs, over-the-counter medicines, and herbal supplements.