Taking Benadryl With Tramadol

Use caution when using Benadryl with tramadol.


My doctor recently prescribed me tramadol. I take Benadryl to help me sleep every now and then. Are they safe together?

Asked by Top On Aug 10, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Aug 10, 2018


Additive Side Effects

Use of Benadryl (diphenhydramine) and tramadol together can cause additive side effects and therefore, caution is recommended when combining them. These potential side effects include (6):

  • Sedation
  • Drowsiness
  • Decreased motor function
  • Memory impairment

How Long To Wait Between Dosing

While tramadol and Benadryl generally shouldn't be taken together due to the additive side effects, in most cases they can be taken the same day, as long as they are separated by an appropriate amount of time.

  • Tramadol has a duration of action of around 6 hours, with peak effects occurring about 1.5-2 hours after taking a dose by mouth (1).
  • Benadryl has a duration of action around 4 to 6 hours (2). This can be prolonged in certain individuals, such as in those with liver dysfunction or in the elderly (3).

Based on how long each drug lasts, you should wait at least 6 hours after taking tramadol to take Benadryl to lessen the risk of additive effects. Similarly, you should wait at least 6 hours after taking Benadryl to take tramadol.

It is important to note that tramadol is the active ingredient in a variety of prescription products, many of them 'extended release'. These products include:

  • Ryzolt
  • Ultram ER
  • ConZip

If you are taking any of the extended release tramadol products, you will need to wait longer than 6 hours to avoid additive effects. To be safe, you may want to hold off on taking Benadryl the same day.

Other Recommendations

The above recommendations stem from how long the noticeable effects of each drug lasts. It takes considerably longer than the duration of action for them to be completely metabolized and eliminated from the body. If you wish to avoid having the two drugs in your system at the same time, you have to consider other characteristics, such as half-life.

The half-life of tramadol is around 6-7 hours for the immediate release dosage forms (e.g. Ultram). As it generally takes around 5-6 half-lives to be completely eliminated from the body, this correlates to 1 to 2 days (4).

The half-life of Benadryl is shorter than tramadol, around 2 to 3 hours for most individuals (although this is prolonged in certain populations) and nearly 100% of the drug is metabolized and eliminated with 24 hours (5).

Therefore, based on the half-lives for each drug, you will need to wait 1 to 2 days in most cases to avoid having both drugs in your body at the same time.

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of PharmacistAnswers.com. He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Brian.Staiger@PharmacistAnswers.com Office: 716-389-3076

About Tramadol

Tramadol is a centrally-acting analgesic with a unique, dual mechanism of action. It is both a mu-opioid receptor agonist and a weak inhibitor of norepinephrine and serotonin reuptake. Tramadol is a synthetic analog of codeine but has less potential for abuse or respiratory depression than other opiate agonists, but both may occur nonetheless. The onset of action of immediate release tramadol products is within 1 hour of administration, with effects lasting around 4 to 6 hours. The FDA approved oral, immediate-release tramadol (Ultram) in March 1995; an orally disintegrating tablet (Rybix) in May 2005; a once-daily, oral, extended-release tablet (Ultram ER) in September 2005; a second once-daily, oral, extended-release tablet with a different release formulation (Ryzolt) in December 2008; and a once-daily, extended-release capsule (ConZip) in May 2010; the ConZip product provides an immediate release component of tramadol, along with an extended-release component.

About Benadryl (Diphenhydramine)

Benadryl (diphenhydramine) is a first generation, sedating antihistamine (H1-blocker) of the ethanolamine class. It is available in oral, topical, and parenteral product forms. Benadryl is well known to cause significant sedation in most individuals and is commonly used in night-time sleep aids. Benadryl also has potent "drying" effects in most patients, which is why is causes dry mouth, dry eyes and constipation. The onset of action of Benadryl is around 15-30 minutes after taking by mouth, with peak effects occurring 1 to 3 hours later. The duration of action is around 4 to 6 hours, with this being prolonged in the elderly and in those with liver disease.

Recent Questions