Diphenhydramine Overdose – Symptoms, Dosage, Effects, Diagnosis and Treatments

Diphenhydramine hydrochloride is an antihistamine belonging to the ethanolamines class. Diphenhydramine is an H1- receptor antagonist which blocks the binding of histamine to the receptor sites thereby preventing allergic symptoms and inflammation. H1 receptor antagonists are associated with many cases of poisoning as compared to the other antihistamines.

H1 receptor antagonist aside from competing with histamine receptor sites, also competitively inhibits the muscarinic receptors yielding anti-cholinergic effects such as dry skin, dry mouth, tachycardia, urinary retention and delirium. Since diphenhydramine blocks neurotransmission through sodium block, it also causes sedation and other CNS effects.

Diphenhydramine hydrochloride is present in drug preparations such as Nytol, Benadryl, Tylenol PM and Sominex. This drug is usually indicated in allergic reactions and sedation of pediatric clients.

benadryl overdose, Side effects

Antihistamine overdose is the 11th reason for drug toxicities with diphenhydramine as the leading antihistamine that causes drug overdose.

Overdose Levels for Diphenhydramine

The therapeutic level of diphenhydramine depends on the age of the patient. Adults may receive 150-300 mg in divided doses (25-50 mg per orem every 4 hours) in a day, whereas children may receive 75 to 150 mg in a day in divided doses (12.5-25 mg per orem three to four times a day). Intake of diphenhydramine of doses exceeding the therapeutic dose will result in antihistamine toxicity.

Lethal levels of diphenhydramine in the blood include higher than 19 mg/L, 7 mg/L and 1.5 mg/L in adults, children and infants respectively. Overdose of the drug can yield diphenhydramine hydrochloride overdose symptoms.

Diphenhydramine Overdose Symptoms

Symptoms of diphenhydramine hydrochloride overdose can be divided into anti-cholinergic effects, CNS effects, cardiac toxicity, pulmonary toxicity and skin and musculoskeletal symptoms.

1. Anti-cholinergic symptoms

  • Dry mucous membranes
  • Flushed, dry, hot skin
  • Low-grade fever
  • Absence of sweating
  • Dilated pupils
  • Blurred vision
  • Intestinal ileus
  • Sinus tachycardia
  • Urinary retention
  • Anti-cholinergic delirium as evidenced by agitation, disorientation, confusion, poor short- term memory, meaningless motor movements and incoherent speech

2. CNS effects

  • Repeated seizures in patients with epilepsy
  • Somnolence
  • Lethargy
  • Catatonic stupor
  • Coma
  • Toxic psychosis
  • Heightened anxiety
  • Extrapyramidal symptoms
  • Withdrawal-like symptoms such as insomnia, restlessness, excessive blinking and irritability

3. Cardiac effects

4. Pulmonary Symptoms

  • Pulmonary edema

5. Musculoskeletal Symptoms

6. Integumentary symptoms

  • Rare skin eruptions

7. Others

  • Diarrhea
  • Nausea
  • Abdominal pain

Long-term effects of Diphenhydramine Overdose

Diphenhydramine hydrochloride overdose can lead to complications or long-term effects such as:

Heart blocks

This long-term effect accounts to most of the deaths from diphenhydramine hydrochloride overdose. This effect results from the blocking of the sodium pump which slows down the myocardial contractility leading to cardiac arrest.


Seizures are uncommon diphenhydramine hydrochloride overuse effect. This is observed in patients with epilepsy, but normal individuals who have overdose of the drug can also experience it rarely.


The result of nerve impulse transmission blockage is a coma due to slowed nerve activity in the brain. The level of consciousness gradually decreases from lethargy to stupor to coma.

Causes and Risk Factors of Diphenhydramine Overdose

The main cause of diphenhydramine hydrochloride overdose is excessive oral or parenteral administration of the drug exceeding the therapeutic level. However, certain risk factors arise such as:


Patients younger than 6 years old are more at risk for drug overdose because of treatments for otitis media and upper respiratory infections. The elderly population are also at risk in the drug overdose because of inadvertent use of the drug without rational cause.


Caucasians have a higher sensitivity to the effects of diphenhydramine than Asians because the Asian population have faster acetylation of diphenhydramine. Acetylation involves the conversion of diphenhydramine into its non-toxic byproduct.


Diagnostic tests for diphenhydramine overdose include:

Toxicology screens

This test involves determining the level of diphenhydramine through blood tests.

Blood tests for other drugs

Acetaminophen and salicylates are checked in the blood because antihistamines are combined with antipyretic and analgesics in some colds and cough medications.

Electrolyte determination

The electrolyte levels need to be assessed in patients exhibiting cardiac symptoms and CNS alterations. The blood sodium level is usually ordered.


ECG is taken to assess any cardiac dysrhythmias and heart blocks.

CT scan

Patient with CNS problems and seizure are often subjected to CT scan to determine any underlying conditions. Patients with good improvement and non-focal neurological symptoms are excluded from undergoing a CT scan.

Chest X-ray

This is performed in patients with cardiogenic affectation to determine pulmonary edema as a complication.

Treatment of Diphenhydramine Overdose

Paramedic Care

Patients are given intravenous fluids to prevent dehydration. Cardiac monitoring is started and benzodiazepines may be given to manage seizures

Hospital Care

The following managements are done to reduce diphenhydramine overdose

Administer activated Charcoal

This substance enhances the clinging of the drug on the surface of the charcoal in order not to be absorbed in the intestines. Activated charcoal may be taken by conscious patients by mouth. In patients with altered CNS condition, this can be administered through a nasogastric tube.

Administer Intravenous fluids

Normal saline solution is given by bolus to address hypotension. Dopamine may also be administered to elevate the blood pressure.

Endotracheal Intubation

Patient should be intubated immediately because patients may experience seizures and it may lead to respiratory collapse.


Physostigmine is the antidote for diphenhydramine overdose. This drug is an anticholinesterase inhibitor which passes through the blood-brain barrier to increase acetylcholine levels reversing the anti-cholinergic effects of diphenhydramine.

Sodium Bicarbonate Administration

Sodium bicarbonate is given to those who have cardiac toxicity to improve the heart contraction  The sodium level is taken into consideration before administering sodium bicarbonate.

Benzodiazepines & barbiturates Administration

These drugs are given to manage seizure activity. Valium and Phenobarbital are the most common drugs used to manage seizures caused by diphenhydramine overdose.

Treatments for diphenhydramine overdose should be instituted immediately to prevent life-threatening effects and help reduce the risk for mortality. Prevention of overdose include keeping the medication out of children’s reach and administer the medication as prescribed. Never take any antihistamine without a prescription in order to determine appropriate dosage.



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25 thoughts on “Diphenhydramine Overdose – Symptoms, Dosage, Effects, Diagnosis and Treatments

  • 31/07/2012 at 12:19 pm

    Antihistamines can really reduce the symptoms of alllergy like sneezing or skin itching but it can also make you very drowsy. “`'”.

  • 20/02/2013 at 12:57 am

    Antihistamines are most commonly used to control the symptoms of allergies such as hay fever.In these conditions they work by preventing the actions of histamine, which is a substance produced by the body as part of its natural defences.:

    Freshest article on our own blog

  • 28/04/2013 at 10:02 pm

    I believe you mean to say the patient needs a test of “Creatine Kinase”, not “Creatinine Kinase”. Thank you.

    • 17/07/2013 at 3:02 pm

      creatinine is a lab test to evaluate kidney fonction

      • 14/12/2015 at 4:09 pm

        Creatine; Creatinine and Creatine kinase are three different things.

        Creatine monohydrate (creatine) is an organic acid that helps provide energy to muscle cells. Creatinine is a byproduct of creatine metabolism.

        Creatine kinase (CK) aka creatine phosphokinase (CPK) is an enzyme that converts creatine to creatinine.
        A creatinine lab test along with a BUN (blood urea nitrogen) are used to elvalute kidney function
        CK (creatine kinase) lab tests are used to evalute tissue damage such as heart attacks; strokes and general tissue damage.

        Creatine kinase break down into 3 types CKMB (heart) CKBB (brain) and CKMM (muscle).
        The lab does not test for creatine monohydrate, only creatinine (the byproduct).

  • 20/07/2013 at 4:52 am

    This website is great 827270a565234ae9fccb740108abe40a

  • 26/12/2013 at 5:29 pm

    I took 8-12 25 mg benadryl tabs several times for a kind of high and now I have a heart block. Could it have been caused by the benadryl?? Is it a chronic problem now or can it heal its self?

    • 11/09/2015 at 5:26 pm

      It’s hard to say, it depends on the type of heart block you have 1st degree, 2nd degree, etc… It could have been caused by Benadryl , but , it’s hard to tell if your current serum levels of Benadryl are not within a normal value, Again it’s hard to tell if you will have a chronic heart block, if there is damage to the nodes sa or av, or bundle branches, then maybe, if not the heart block my just be temporary until serum levels reduce. you will need physicians to evaluate you and a cardiologist to properly identify the kind of heart block.

  • 28/12/2013 at 12:20 pm

    i recently overdosed on Benadryl and still feeling effects in my head confusion and stuttering,is that normal?

  • 27/02/2014 at 5:50 am

    I’ve been taking about 10 benadryl every night to help me sleep

  • 11/09/2014 at 4:43 pm

    Thanks a lot for sharing this with all folks you really understand what you are speaking approximately!

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    We could have a hyperlink alternate arrangement between us

  • 25/03/2015 at 3:23 am

    how many mgs could prove fatal for 35-y/o Caucasian male of 120 lbs/BMI ~19?

  • 23/04/2015 at 6:57 am

    I have been overdosing on IV Benadryl for over a year now. They are 50mg/ml bottles and I am taking at least 15-20 bottles a night to help me sleep. I started out with just a few and over time I needed more and more. I inject it right through my mediport.
    I don’t understand I stay away from pain meds and anxiety meds but rather use my Benadryl to go to sleep and get the high that I crave. Today I have this itching feeling throughout my body, like something is crawling on me. This also happened about a year ago.
    I threw away 180 vials because I know if I didn’t I’ll use the rest of them within a week

    • 19/03/2018 at 11:02 am

      Where in the world did you get IV Benadryl? Isn’t the IV dose
      available by script only?

  • 16/10/2015 at 1:16 am

    With out our worthwhile guests/users this hack could
    be eliminated off the net – long time ago.

    • 16/05/2016 at 6:21 pm

      Sounds like you have overdosed on something. Agitated state that you are in. Get the help you need and don’t criticize people looking for help. Nobody is perfect!

  • 13/09/2016 at 8:30 am

    My sister overdosed on benadryl and klonopin I called the er immediately and broke down her door. They came quickly but once there did NOTHING. They said it was best to let her process the medicines. She was dehydrated had elevated blood sugar and hallucinating. One male nurse pushed my 90 lb suicidal sister who had recently been raped by a male. His excuse was she was moving …hello ehes hallucinating! I felt they grossly mishandled this. I own activated charcoal dhpuld (I pray it never does)but should I ever be in a similar situation should I give charcoal before emts arrive?

    • 15/11/2016 at 10:38 am

      Activated charcoal (medical grade not barbecue) has to been given soon after the overdose (within 2 hours) to provide benefit but should not replace an ER visit. As soon as you learn of the OD, call 911 or head to the ER. Grab the charcoal and drink it on the way. Also grab the bottle of Benadryl and show it to the ER. Give an accurate estimate of how much was taken. Insist on quick charcoal administration. If medical care starts later than two hours after the OD, prepare for a tenuous and dangerous period lasting about 12 hours. Finally, start planning and preventing a second OD and don’t blame each other.

  • 13/02/2017 at 7:22 pm

    Sehe ich nicht unbedingt so. die meisten 1er sind langsam und werden von Leuten gespielt die keine Ahnung haben. Stehen dann nicht an stellen zum spotten sondern fahren idiotisch durch die Gegend.

  • 05/09/2017 at 6:13 am

    Great post! Have nice day ! 🙂 bxvxt

  • 25/09/2017 at 8:01 pm

    Two nights ago. I took 70 tablets of diphenahydramine, sleep aid, pills. I believe they are dosed at .25 MG each. I also swallowed that with whatever was left of the bottle of nyquil I had. That night was hell. Hallucinations, sweating, dry mouth, i locked myself in the bathroom for hours and eventually passed out. I couldn’t see anything and my motor skills were completely gone. Throughout the next day I was able to make out shapes, could not read or type so my cell phone was useless. Today is Monday, two days since. My body is acting very strangely. I’m so hyper but my mind is so tired. My nerves are complete shot. I’m drinking lots of water and forcing myself to eat.
    I feel as tho I am recovering but im worried about long term effects. I did not plan to live through this. Seeing as how I am tho… Should I go to the hospital? It can and most likely effect my career… So if im out of the woods. I’d like to just recoup on my own. Thoughts and advice welcome.

    • 16/12/2017 at 3:22 am

      Hi Zak, please see my message on this same website, I thought I was replying to you but unfortunately it seems that I was speaking to the world. My apologies for such a public message.
      Best wishes,

  • 04/04/2018 at 6:30 am

    Where do i find your response to zak

  • 11/06/2018 at 8:03 am

    So I drank 3 bottles of liquid sleep medicine that has diphenhydramine in it what should I do


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