Zofran vs Phenergan

Listen to the article instead of reading through it.


For patients suffering from nausea or vomiting associated with certain medical treatments, there are effective drugs that influence specific receptors in the brain to suppress such symptoms. Zofran and Phenergan are two such medications often prescribed for nausea and vomiting. They each influence different receptors in the brain, but both have significant effects in managing these symptoms. Zofran is a selective 5-HT3 receptor antagonist, affecting serotonin levels in the brain and the gastrointestinal tract to reduce nausea and vomiting. On the other hand, Phenergan is classified as a H1 receptor antagonist, primarily affecting histamine levels in the body but also influencing other neurotransmitters. It is used not only as an antiemetic but also has antihistamine properties, making it useful for treating allergy symptoms as well.

What is Zofran?

Ondansetron (the generic name for Zofran) was a significant advancement in the class of antiemetics known as serotonin 5-HT3 receptor antagonists. Ondansetron, first approved by the FDA in 1991, functions by blocking the actions of chemicals in the body that can trigger nausea and vomiting. It is often prescribed to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, and surgery. Zofran has a selective effect on serotonin receptors, with virtually no effect on dopamine receptors, resulting in fewer side effects compared to other antiemetics that have stronger effects on dopamine. On the other hand, Promethazine (the generic name for Phenergan) belongs to a class of drugs called phenothiazines, working primarily by blocking dopamine receptors, and is therefore more likely to cause certain side effects, like drowsiness.

What conditions is Zofran approved to treat?

Zofran is approved for the treatment of several types of nausea and vomiting:

  • Postoperative nausea and vomiting
  • Nausea and vomiting related to chemotherapy or radiation therapy
  • Prevention of post-anesthesia shivering (in combination with another drug, propofol)

On the other hand, Phenergan is also used for managing various conditions including:

  • Allergic reactions such as seasonal allergies
  • Preoperative sedation
  • Treatment and prevention of motion sickness
  • Nausea or vomiting from any cause.

How does Zofran help with these illnesses?

Zofran functions to manage nausea and vomiting by blocking the actions of chemicals in the body that can trigger nausea and vomiting. It does this by being a selective antagonist of the serotonin 5-HT3 receptor, a type of serotonin receptor found predominantly in the brain's chemoreceptor trigger zone and the gastrointestinal tract. Serotonin is a neurotransmitter, a chemical that acts as a messenger in the brain and throughout the body. When serotonin binds to these 5-HT3 receptors, it can trigger a vomiting reflex. By blocking these receptors, Zofran can help prevent nausea and vomiting, particularly in patients receiving chemotherapy or after surgery. Similarly, Phenergan also works to prevent nausea and vomiting, but it does so by acting as an antagonist to histamine H1 receptors and muscarinic receptors. This mechanism of action is more broad and not as targeted as Zofran, which can result in more side effects such as drowsiness. Therefore, the choice between Zofran and Phenergan often depends on the specific needs and health condition of the patient.

What is Phenergan?

Phenergan is a brand name for promethazine, which is an antihistamine. It works by blocking histamines in the body that are produced during allergic reactions and thus reducing these symptoms. Promethazine also affects the neurotransmitter acetylcholine, acting as an antagonist at its receptors – this gives it additional sedative properties. First approved by the FDA in 1951, Phenergan has long been used to treat allergies, insomnia, and nausea or vomiting (including motion sickness). As with other medications that impact acetylcholine activity such as Zofran (ondansetron), some patients may experience side effects like dry mouth or sleepiness. However, unlike ondansetron which mainly targets serotonin receptors to prevent nausea and vomiting from chemotherapy or surgery, Phenergan's broader action means it can be useful for a wider variety of conditions including those not responsive to more selective treatments like Zofran.

What conditions is Phenergan approved to treat?

Phenergan is a renowned medication, approved by the FDA for various uses including:

  • Treatment and prevention of nausea and vomiting caused by anesthesia or surgery
  • Allergy symptoms such as itching, runny nose, sneezing and hives
  • Motion sickness Moreover, it's also used off-label to treat morning sickness during pregnancy.

How does Phenergan help with these illnesses?

Histamine is a compound that is released by cells in response to injury and in allergic and inflammatory reactions, causing contraction of smooth muscle and dilation of capillaries. It plays a significant role in causing nausea and vomiting. Phenergan, also known as promethazine, works by blocking the effects of histamine in the body, thus alleviating symptoms related to allergic reactions and also post-surgery nausea and vomiting. It may be a more suitable option than Zofran for patients who have allergic reactions alongside their nausea and vomiting. Furthermore, Phenergan's antihistaminic effects can also be beneficial in treating allergy symptoms, making it a more versatile medication. However, its use may be accompanied by side effects such as drowsiness or sedation, which should be taken into consideration when a patient is choosing between medications.

How effective are both Zofran and Phenergan?

Both ondansetron (Zofran) and promethazine (Phenergan) have well-established histories of success in treating nausea and vomiting, with their initial FDA approval only 12 years apart. Since they act on different receptors - Zofran inhibiting the action of serotonin at the 5-HT3 receptor sites while Phenergan antagonizes H1 receptors - they may be prescribed under varying circumstances.

The effectiveness of both drugs was directly studied in a randomized clinical trial in 1997; both exhibited similar efficacy managing symptoms related to postoperative nausea and vomiting, with promising safety profiles. Patient satisfaction scores were similar between the groups receiving either drug.

A 2006 review showed that Zofran starts being effective within first couple hours of treatment for chemotherapy-induced nausea and vomiting, has fewer side effects compared to many other antiemetics, particularly extrapyramidal symptoms such as akathisia and dystonia associated with Phenergan use. It is also well-tolerated among pediatric patients undergoing chemotherapy or surgery.

A comprehensive analysis from several studies conducted up until 2014 indicated that Phenergan provides significant relief from motion sickness symptoms but its usage is limited due to sedative effect which can impair daily activities requiring alertness like driving. Typically considered a second-line treatment option after non-sedating antihistamines for motion sickness prevention or when there's need for additional sedation during surgical procedures where anxiety plays a role. Its unique pharmacology makes it an optimal choice for those who did not respond adequately to first-line treatments or have specific needs to avoid certain side effects such as headache often seen with Zofran use.

abstract image of a researcher studying a bottle of drug.

At what dose is Zofran typically prescribed?

Oral dosages of Zofran range from 4–24 mg/day, but studies have indicated that a single dose of 8 mg before anesthesia or right after surgery is sufficient for preventing nausea and vomiting in most people. Children older than one month may be started on 0.1 to 0.15 mg/kg per dose for up to four times per day. In either population, dosage can be adjusted based on the severity of symptoms and response to treatment. The maximum dosage that should not be exceeded in any case is 24 mg/day.

On the other hand, Phenergan's oral dosages range from 12.5-25 mg every four to six hours as needed; however, this needs medical guidance since it varies greatly by individual need and context (i.e., whether being used for allergy relief or as a preoperative sedative). For children over two years old, lower doses are generally recommended with careful supervision by a healthcare provider due to potential serious side effects.

At what dose is Phenergan typically prescribed?

Phenergan treatment usually begins at a dosage of 12.5–25 mg, taken every four to six hours as needed. The dose can be increased if necessary, up to a maximum daily dose of 100 mg. This is divided into several doses throughout the day with no single dose exceeding more than 25 mg and spaced apart by 4-6 hours depending on your body's response and tolerance level. If there is no significant relief or response after taking Phenergan at these dosages for a period of time, it may necessitate an adjustment in the dosage or a switch to another medication under doctor's advice.

What are the most common side effects for Zofran?

Common side effects of Zofran include:

  • Headache
  • Lightheadedness or dizziness
  • Drowsiness or fatigue
  • Constipation

Whereas, common side effects of Phenergan are slightly more extensive and can include:

  • Dry mouth, nose, and throat
  • Decreased sweating
  • Increased sensitivity to sunlight
  • Reduced appetite (anorexia)
  • Nausea or vomiting
  • Constipation or diarrhea
  • Low blood pressure (hypotension) leading to light-headedness on standing up too quickly.

Remember that if you experience any severe reactions like difficulty breathing; swelling of your face, lips, tongue, or throat; rash; hives; uncontrollable movements; slow heartbeat. Seek immediate medical attention as these could be signs of a serious allergic reaction.

abstract image of a patient experiencing side effect

Are there any potential serious side effects for Zofran?

In rare instances, Zofran can cause serious side effects such as:

  • Serotonin syndrome symptoms: hallucinations, fever, shivering or shaking, muscle stiffness or twitching, loss of coordination and nausea
  • Blurry vision or temporary vision loss (lasting from only a few minutes to several hours)
  • Severe lightheadedness leading to fainting
  • Fast or pounding heartbeats
  • Jaundice (yellowing of the skin or eyes)
  • High levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate

Phenergan on the other hand has been known to occasionally lead to side effects including:

  • Signs of an allergic reaction: hives; difficult breathing; swelling in your face/lips/tongue/throat
  • Uncontrollable movements in your face/chewing movements/sticking out tongue/eye movement/blinking -Seizure (convulsions) -Slow heartbeat/pounding neck or ears/slow breathing/breathing may stop causing you to feel like you might pass out. -A light-headed feeling that may lead you to pass out

If any severe reactions occur while taking either medication it is crucial that immediate medical attention is sought.

What are the most common side effects for Phenergan?

Phenergan, as compared to Zofran, can cause a variety of side effects. These may include:

  • Dry mouth and throat
  • Constipation or diarrhea
  • Blurred vision or eye sensitivity to light
  • Drowsiness and sleep problems (insomnia)
  • Ringing in the ears
  • Feeling restless, nervous, or irritable
  • Skin rash or hives
  • Slow heart rate or low blood pressure
  • Increased urination -Tremors, confusion, hallucinations -Loss of coordination and dizziness

Please remember it's crucial to consult with your healthcare provider about potential side effects before starting any medication regimen.

Are there any potential serious side effects for Phenergan?

Although Phenergan is generally well-tolerated, it's important to be aware of potential serious side effects. These may include:

  • Signs of an allergic reaction such as hives; difficulty breathing; swelling of your face, lips, tongue or throat
  • Possible signs of a severe skin reaction including fever, sore throat, burning in your eyes, skin pain followed by a red or purple rash that spreads and causes blistering and peeling
  • Unusual bleeding (nosebleeds, bleeding gums), easy bruising
  • Little or no urination
  • Hallucinations
  • Jaundice (yellowing of the skin or eyes)
  • Seizure (convulsions) If any of these symptoms occur while taking Phenergan stop using the medication immediately and seek medical attention right away.

Contraindications for Zofran and Phenergan?

Both Zofran and Phenergan, along with most other antiemetic medications, may cause some severe side effects. If you experience symptoms such as an irregular heartbeat, difficulty breathing or swallowing, vision changes or excessive drowsiness after taking these drugs, please seek immediate medical attention.

Neither Zofran nor Phenergan should be taken if you are using apomorphine due to the risk of severely low blood pressure and loss of consciousness. Always tell your physician which medications you are taking; apomorphine will require a washout period before starting either Zofran or Phenergan to prevent dangerous interactions. Other drugs that can interact adversely include certain antidepressants, antipsychotics and heart medicines among others. Always provide your healthcare provider with a full list of all the prescription and non-prescription drugs you take.

How much do Zofran and Phenergan cost?

For the brand-name versions of these drugs:

  • The price for 30 tablets of Zofran (8 mg) averages around $725, which works out to about $24-$48/day depending on your dose.
  • The price for 12 suppositories of Phenergan (25mg) averages about $125, working out to approximately $10.42/day.

Thus, if you are in the higher dosage range for Zofran (i.e., 16 mg/day or higher), then brand-name Phenergan is less expensive on a per-day treatment basis. Please note that cost should not be a primary consideration in determining which of these drugs is right for you.

For the generic versions of Zofran (ondansetron) and Phenergan (promethazine), costs are significantly lower:

  • Ondansetron is available in packs from 10 up to 1000 tablets, with approximate costs between $0.40 and $1.20 per day for dosages ranging from 8 mg/day to 24 mg/day.
  • Promethazine comes as tablets or rectal suppositories at various quantities with prices starting as low as $0.20 per day and not exceeding about $2.00/day depending on form and quantity purchased upfront.

Popularity of Zofran and Phenergan

Promethazine, also known by the brand name Phenergan, was prescribed to approximately 3 million people in the U.S. in 2020. This medication is an antihistamine primarily used to treat allergies and motion sickness, though it can also be used as a sedative or for postoperative pain relief.

On the other hand, Ondansetron - more commonly recognized as Zofran - was estimated to have been prescribed to about 6.5 million individuals across the country within that same year. Primarily utilized as an antiemetic (a drug that suppresses nausea and vomiting), this medication is particularly popular amongst patients undergoing chemotherapy or radiotherapy treatment.

Though both drugs are capable of alleviating symptoms of nausea and vomiting, they belong to different classes with unique mechanisms of action which may make one more suitable than another depending on individual patient needs. The use of these medications has remained steady over recent years but consult your health care provider for what's best suited for you.


Both Zofran (ondansetron) and Phenergan (promethazine) are commonly used to prevent nausea and vomiting, with a long-standing record of usage in patients undergoing surgery or those receiving chemotherapy. Their effectiveness is supported by numerous clinical studies indicating that they are more effective than placebo treatments. Both drugs can be used together under the careful supervision of a physician due to potential interactions between them.

Zofran works primarily by blocking serotonin receptors, while Phenergan acts as an antihistamine. Because of these different mechanisms, they may be prescribed under varying circumstances. For instance, Zofran's potential for fewer side effects often makes it a first-line treatment option for postoperative or chemotherapy-induced nausea and vomiting whereas Phenergan could usually be considered as an alternative if Zofran isn't suitable or doesn't bring about the desired effect.

Both medications have generic versions available which significantly reduces cost especially for patients who pay out-of-pocket. The onset time varies; thus, some individuals may not immediately notice the effects.

Side effects differ slightly between these two medications but both are generally well-tolerated. However, sedation is more prevalent with use of Phenergan compared to Zofran making it less desirable in situations where alertness is required such as driving or operating machinery. As always when starting new medication therapy, seek medical help promptly if there's worsening symptoms or new unusual symptoms.