Taking Benadryl With Zofran

In our latest question and answer, the pharmacist discusses whether or not there is an interaction between Benadryl and Zofran.


I was prescribed Zofran for severe nausea from migraines. it is safe to take it with Benadryl?

Asked by Sammi On Jun 09, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jun 09, 2018

Benadryl TabletsZofran and Benadryl have a moderate drug interaction with one another. Zofran may enhance the QTc-prolonging effect of Benadryl when used together, leading to an increased risk of arrhythmias. 

Concurrent use of Benadryl and Zofran and should be used with caution, especially in susceptible patients such as those greater than the age of 65, females, and patients with heart disease. Be sure to ask your doctor if the use of Benadryl is safe for your particular medical situation.

Benadryl (Diphenhydramine)

Benadryl is an antihistamine used for the relief of seasonal allergies, colds, and minor allergic reactions. The active ingredient in Benadryl is diphenhydramine.

Benadryl works by competing with histamine for the H1 (histamine) receptors in the body such as in blood vessels and the respiratory tract. Benadryl is a "first-generation" antihistamine and is well known to cause increased sedation and drowsiness. Benadryl should be avoided in the elderly due to an increased risk of falls. Individuals participating in activities requiring full mental and physical attention should avoid Benadryl as it may impair these abilities.

Zofran (Ondansetron)

Zofran (ondansetron) is an anti-emetic and used primarily to prevent chemotherapy and radiation induced nausea and vomiting. It is also used to treat postoperative nausea and vomiting that is severe or refractory to other therapies.

Zofran works by selectively blocking the serotonin receptor in the central nervous system. Individuals at high risk of arrhythmias, such as the elderly, should be monitored with an ECG prior to the initiation of therapy.

Zofran should be avoided in individuals taking apomorphine or those with a history of an allergic reaction to Zofran. Additionally, patients with heart failure, abnormally low levels of magnesium or potassium, or bradyarrhythmias should be monitored with and ECG during therapy.

About the Pharmacist

Dr. Hayden Gharibyar

Dr. Hayden Gharibyar is a Doctor of Pharmacy graduate from the University of Colorado. His areas of expertise include pharmacovigilance and drug safety.

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