How Long Does Benadryl Last And Shows Up On Drug Test?

Last Updated: July 16, 2020

Authored by Sharon Levy, MD, MPH

Diphenhydramine is an antihistamine that is used for treating allergies, hay fever, cold, flu, and other allergic symptoms. It is also prescribed for sleep problems and anxiety because of its sedative properties. The half-life of diphenhydramine (Benadryl) determines how long it stays in one’s system. Read further to find out about diphenhydramine half-life and how long does it take for Benadryl to wear off?

Benadryl Half-Life Period

The half-life determines the time after which 50% of the drug is flushed out of the system. The half-life of Benadryl ranges from 2.4 hours to 9.3 hours. The median half-life turns out to be 4.3 hours in healthy, young adults. Depending on this median value, it can be estimated that the drug will be completely flushed out of the system between 13.2 hours and 49 hours. The concentration of this drug is on a maximum level between 2 to 4 hours of taking a dose.

Male doctor with stethoscope looking at wrist watch

What Factors Can Influence Half-Life Duration?

50% of the common side effects of diphenhydramine start to wear off after this elimination half-life. The long-term effects of Benadryl, however, do not wear off this easily.

Variables That Have Influence On Period Diphenhydramine Stay In The System

How long Benadryl lasts in one’s system depends on the factors described below:


The amount of dose of diphenhydramine that one takes determines how long diphenhydramine stays in the system. A person who took a higher dose of Benadryl will most likely take more time to rid of the system from the drug than the person who took a lower dose. For example, a patient who took 100 mg of diphenhydramine will still have 50mg of the drug in his system after the elimination half-life time. Conversely, the patient who took a 50mg dose will have only 25 mg in his system after the same amount of time, so it will take less time for the patient who took the lower dose to flush his system out of diphenhydramine. According to this study about the pharmacokinetics of diphenhydramine at different doses, the elimination half-life of Benadryl increases when the dose is increased. Benadryl weight-based dosing ensures that patients are exposed to the side effects of the drug for the least amount of time as diphenhydramine will stay in the system for a lesser amount of time.


The frequency with which diphenhydramine is taken also determines the time for which it will stay in the system. The usual dosage of Benadryl suggests it be used every 4-6 hours. If it is taken once daily, its effects will start wearing off soon as compared to when taken several times a day. However, taking it once a day may not prove to be effective in treating the condition for which it was prescribed. Depending on its half-life, Benadryl will stay in the system longer if it is taken every 4 to 6 hours.

Interactions With Other Drugs

When diphenhydramine is taken in combination with other drugs, it affects how long Benadryl lasts in the system. Benadryl, when taken with antidepressants such as Monoamine Oxidase Inhibitors, increases the time it stays in the system. This results in more significant and prolonged side effects as well. Other drugs which interact with diphenhydramine by increasing the time it stays in the system include Lorazepam, hypertension medicines, and other cough and cold medicines. Taking Benadryl and Zyrtec together may also increase the time for the effects of Benadryl to wear off.

Diphenhydramine And Alcohol

Irrespective of the half-life of Benadryl, taking it together with alcohol can have extreme and dangerous side effects. This will also affect the time it takes Benadryl to stay in the system.


Age plays a crucial role in determining the half-life of diphenhydramine. Benadryl half-life in much shorter in kids and adults as compared to the elderly. In the case of children and young adults, their bodies can rid their system from diphenhydramine faster as compared to the bodies of individuals aged 65 and above.

Aged man reading Benadryl prescription bottleged

General Health And Metabolism

The overall health of an individual also determines the time for Benadryl to stay in the system. Since all medicines are metabolized in the liver and excreted via urine through the kidneys, the health of both the liver and the kidneys play a role in this regard. If they are healthy and functioning correctly, they would be able to flush Benadryl out of the system faster. If there is some problem in any one or both of them, it will lead to a higher time Benadryl stays in the system. Similarly, for the flushing of diphenhydramine, the metabolism of an individual also affects it. For Benadryl, metabolism rate, which is faster will lead to faster expulsion of the drug from the body as compared to individuals who have a slower metabolism.

Does Benadryl Show Up On A Drug Test?

According to this study on the cross-reactivity of diphenhydramine and methadone, it was concluded that a false positive for methadone could occur when patients have ingested diphenhydramine. Further detailed testing would then be required to disregard this as a false positive.

How Long Does Benadryl Stay In The Urine?

How long Benadryl is detectable in urine depends on its half-life. After 1 or 2 days, most of the diphenhydramine will be flushed out of the system. However, urine tests would still be able to detect diphenhydramine in the urine for up to 4 days after the last dose of diphenhydramine was taken.
A doctor holding a urine sample for Benadryl drug test

How Long Does Diphenhydramine Last In The Blood?

When a patient takes Benadryl, diphenhydramine reaches its peak level between 2 to 4 hours in the blood. After 4 hours, the level of diphenhydramine in the blood starts to decrease. After taking the final dose, it will take almost 3-4 days for diphenhydramine to last in the blood.

How Long Does Diphenhydramine Stay In The Saliva?

The time for which Benadryl stays in the saliva is the same amount that it stays in the blood or urine. This is approximately up to 3 to 4 days after discontinuing the drug as determined by the elimination half-life of diphenhydramine.

How To Flush Benadryl Out Of The System?

Several factors affect the time for which Benadryl stays in the body, as described in the previous sections. For how long Benadryl stays in the system depends on diphenhydramine half-life, but the following actions and precautions can help the body get rid of diphenhydramine faster:

woman searching information on How To Flush Benadryl Out Of The System

  • The drugs with which diphenhydramine interacts with should be avoided. These drug interactions increase the side effects as well as increase the time Benadryl stays in the system.
  • Some medicines such as antihistamines and other cold and cough medicines can result in an overdose which would make those drugs last in the system for longer. In such a case, Benadryl overdose treatment would be required.
  • Since medicines are flushed out of the system through urine, drinking plenty of fluids will help the body get rid of diphenhydramine a little faster.
  • How long does it take for Benadryl to wear off? In the case of long-term use is a bit different as patients also become dependent on it. To counter this dependency on Benadryl, detoxification would have to be carried out. Patients might experience diphenhydramine withdrawal symptoms, which should be professionally managed.

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Published on: June 5th, 2019

Updated on: July 16th, 2020

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.


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  • Andy
    I read everything but Found out it has alcohol in the Benadryl . I took it for three days how long does it take the alcohol to get out of my system for A urine test .