Difference Between Zofran and Phenergan


Main Difference

The main difference between Zofran and Phenergan is that Zofran has Ondansetron HCL as an active pharmaceutical ingredient while Phenergan has Promethazine as an active pharmaceutical ingredient.

Zofran vs. Phenergan

Zofran contains Ondansetron HCL as therapeutic moiety while Phenergan contains Promethazine as therapeutic moiety. Zofran is the 5-HT3-Receptor Antagonist; on the other hand, Phenergan is a first-generation antihistamine. Zofran costs more while Phenergan is cheap. Zofran does not cause drowsiness, whereas Phenergan causes drowsiness. Zofran if used in high doses, causes disturbances in heart beats; on the other hand, Phenergan does not cause such effects in high doses. Zofran can be used in patents of age six months while Phenergan cannot be used in patients of age under two years. Zofran is available as a pill, disintegrating liquid, liquid, and sublingual film while Phenergan is available as a pill, liquid, and suppository. Zofran has the onset of action of 30minutes, whereas Phenergan has the onset of action from 15-60 minutes. Zofran shows mild side effects; on the other hand, Phenergan shows severe side effects relatively.


Comparison Chart

Zofran is the 5-HT3-Receptor Antagonis, which is used to treat nausea and vomiting.Phenergan is the first generation antihistamine, which is used to treat nausea and vomiting.
Drug Group
5-HT3-Receptor AntagonistFirst-generation antihistamine
Active Therapeutic Agent
Ondansetron HCLPromethazine
Onset of Action
Adverse Effects
Dosage Forms
Pill, disintegrating liquid and sublingual filmPill, liquid, and suppository
Main therapeutic use
Use in chemotherapy to avoid nausea and vomitingAllergies, Nausea and vomiting

What is Zofran?

Zofran is the brand name of Ondansetron HCL, which is the 5-HT3-Receptor Antagonist. Zofran is widely used to treat the chemotherapy-induced emesis and nausea, which is secondary to upper abdominal irradiation. 5-HT3-Receptor are present in different sites which are involved in the emesis. Zofran shows its antiemetic effects even after the drug disappears from the circulation. Zofran is administered effectively just once a day. Zofran is absorbed orally and extensively metabolized by the drug-metabolizing enzymes of the liver, followed by the conjugation reaction involving glucuronidation and sulfate conjugation. When Zofran is taken by the patients who have an abnormal liver function, then these patients have reduced plasma clearance of the drug, so the dose is adjusted in such patients. Elderly patients also have reduced Zofran clearance, but dose adjustment is not required in elderly patients. Zofran is also used by pregnant women for the treatment of the hyperemesis in pregnancy. Zofran is taken 30minutes before the start of the treatment through chemotherapy to avoid nausea and vomiting. Zofran is taken 1-2 hr before the start of radiation treatment to avoid nausea. Zofran is taken 1before the start of surgery to avoid nausea and vomiting after surgery. When Zofran is used in liquid form, then use the special measuring spoon or device to measure the dose correctly and do not use the regular household spoon for this purpose as it would lead to the less or more measurement of dose.


What is Phenergan?

Phenergan is the brand name of Promethazine, which is a first-generation antihistamine and is a phenothiazine derivative. Phenergan also possesses some anticholinergic properties. Phenergan has sedative effects, but it is primarily used for antiemetic effects. Phenergan is available as Promethazine hydrochloride. Phenergan is used to treat different medical conditions like allergies, nausea, and also used to induce sleep. Phenergan also helps to mitigate the symptoms of the common cold. Phenergan sedates those patients who are anxious or agitating. Phenergan cab is taken with or without food three to five times a day. To avoid motion, sickness takes Phenergan 30-60 minutes before the start of travel. To treat allergies, Phenergan is taken at bedtimes to avoid the drowsiness of day. When Phenergan is taken to avoid vomiting after surgery then, in that case, Phenergan is taken a night before the surgery or just before the medical procedure, and its dose should be then continued according to the prescription of the doctor. Phenergan has different side effects like blurred vision, dry mouth, constipation, and dizziness; some patients may suffer from fainting, slow heartbeat, or some mental changes including hallucinations, irritability, and nervousness. Phenergan should not be taken if patients are allergic to promethazine or any other phenothiazine. Patients who are going to use Phenergan must tell their doctors if they have any respiratory disorder including asthma, COPD or sleep apnea and immune system problems, including bone marrow depression. Do not operate heavy machinery after taking Phenergan. Phenergan use leads to sunlight sensitivity, so use shades or any protective clothing. Phenergan is available as tablets and suppositories.

Key Differences

  1. Zofran has Ondansetron HCL while Phenergan has
  2. Zofran is classified as 5-HT3-Receptor Antagonist; on the other hand, Phenergan is classified as a first-generation antihistamine.
  3. Zofran is expensive relatively while Phenergan is cheap relatively.
  4. Zofran does not induce sleep; on the other hand, Phenergan induces sleep.
  5. Zofran interferes with cardiac rhythms in high doses, on the other hand, Phenergan does not interfere with cardiac rhythms
  6. Zofran can be used in patients from 6 months to onwards while Phenergan can be used in patients from 2 years to onwards.
  7. Zofran is found as a pill, disintegrating liquid, liquid, and sublingual film, on the other hand, Phenergan is found as a pill, liquid, and suppository
  8. Zofran starts its pharmacological action in 30 minutes, whereas Phenergan starts its pharmacological action in 15minutes to 1 hr.
  9. Zofran does not show a serious side effect; on the other hand, Phenergan shows serious side effects.


The main conclusion of the above discussion is that Zofran and Phenergan belong to different drug groups, but they are used to treat nausea and vomiting.

Janet White

Janet White is a writer and blogger for Difference Wiki since 2015. She has a master's degree in science and medical journalism from Boston University. Apart from work, she enjoys exercising, reading, and spending time with her friends and family. Connect with her on Twitter @Janet__White