Emergency Treatment for Antihistamine Overdose: What to Do Right Away

When someone takes too much antihistamine, minutes matter. It’s not just about feeling drowsy - it can mean a racing heart, seizures, trouble breathing, or even cardiac arrest. Antihistamine overdoses are more common than most people think, especially with kids getting into medicine bottles or adults doubling up on doses out of confusion. The good news? If you act fast, survival rates are nearly 100%. The key is knowing exactly what to do before emergency help arrives.

Recognizing the Signs of an Overdose

Not all antihistamine overdoses look the same. First-generation antihistamines like diphenhydramine (Benadryl), chlorpheniramine, and promethazine are the most dangerous. They cross the blood-brain barrier and block acetylcholine, leading to anticholinergic toxicity. Symptoms usually show up within 30 minutes to 2 hours after ingestion.

• Extreme drowsiness or unresponsiveness
• Fast or irregular heartbeat (over 120 bpm)
• Blurred vision or dilated pupils
• Dry mouth, flushed skin, no sweating
• Difficulty urinating
• Confusion, hallucinations, or agitation
• Seizures or loss of consciousness

Second-generation antihistamines like cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra) are much safer. Even large doses rarely cause life-threatening effects. But if someone takes more than 10 times the recommended dose - say, 100 mg of cetirizine or 1,000 mg of fexofenadine - they can still develop dizziness, tachycardia, or QT prolongation on an EKG.

The most critical red flag? A QRS complex wider than 100 milliseconds on an electrocardiogram. That’s a sign of sodium channel blockade, which can lead to ventricular arrhythmias. Diphenhydramine is the biggest culprit here - it’s involved in 83% of serious pediatric overdoses and 62% of all severe cases.

Immediate First Aid Steps

If you suspect an overdose, don’t wait for symptoms to get worse. Time is your most valuable resource.

1. Call Poison Control immediately. In the U.S., dial 1-800-222-1222. This is free, confidential, and staffed by toxicology experts 24/7. They’ll ask for the person’s age, weight, the medication name, how much was taken, and when. Don’t guess - bring the bottle with you.
2. Do NOT induce vomiting. This is a common mistake. If the person is drowsy or unconscious, vomiting can cause aspiration - meaning stomach contents enter the lungs, which can be fatal. The American Association of Poison Control Centers says 98% of cases are managed safely without vomiting.
3. Remove any remaining pills or liquid from the mouth. If it’s a child who swallowed a tablet, gently wipe out the mouth with a damp cloth. Don’t force anything.
4. If the substance got on the skin or in the eyes, rinse immediately. For skin contact, wash with soap and water for at least 15 minutes. For eye exposure, flush with cool running water for 20 minutes. Don’t rub.
5. Keep the person awake and sitting up. If they’re drowsy, lay them on their side to prevent choking. Don’t let them sleep until medical help arrives.

Parents often think, “They’re just sleepy - I’ll watch them for a bit.” But symptoms can spike suddenly. One Reddit user shared that their 2-year-old took 50 mg of Benadryl - five times the dose - and seemed fine for an hour. Then they started having seizures. Poison control told them to go to the ER right away. That delay could have cost them everything.

What Happens at the Hospital

Once you get to the emergency room, the team will assess the situation fast. They’ll check vital signs, run an EKG, and ask for details about the medication. If it’s a first-generation antihistamine overdose, they’ll likely start these interventions:

• Activated charcoal. Given within 1-2 hours of ingestion, it binds to the drug in the gut and stops more from being absorbed. Adults get 25-100 grams; kids get 0.5-1 gram per kilogram of body weight.
• Continuous EKG monitoring. For doses over 300 mg of diphenhydramine, or any case with QRS widening, the patient will be monitored for at least 6 hours - sometimes up to 24.
• Benzodiazepines. If the person is agitated, having seizures, or in delirium, lorazepam or midazolam are given. These calm the central nervous system without worsening heart problems. Physostigmine, once used to reverse anticholinergic effects, is no longer recommended - it can trigger dangerous heart rhythms.
• Sodium bicarbonate. If the QRS interval is over 120 ms and the heart rate is above 120 bpm, doctors may give IV sodium bicarbonate. This helps narrow the QRS complex and stabilize the heart. A 2022 study in the New England Journal of Medicine showed it cuts arrhythmia risk by nearly half.
• IV fluids. Used to maintain blood pressure and support kidney function. Antihistamines are highly protein-bound (70-95%), so dialysis or urine alkalinization won’t help.

Most patients stay in the hospital for 24-48 hours. The median length of stay is just over 22 hours, according to a 2022 study in the Journal of Medical Toxicology. Recovery is usually complete, but complications like prolonged QT interval or respiratory depression can linger.

Why Some Antihistamines Are Far More Dangerous

Not all antihistamines are created equal. The difference between first and second-generation drugs isn’t just about sedation - it’s about toxicity.

Comparison of Antihistamine Overdose Risks

Antihistamine	Generation	Typical Toxic Dose	Major Risks	Severity Rate in Children
Diphenhydramine (Benadryl)	First	> 7.5 mg/kg or 300 mg	QRS widening, seizures, cardiac arrest	1.8% serious outcomes
Chlorpheniramine	First	> 4 mg/kg	Respiratory depression, coma	1.5% serious outcomes
Promethazine	First	> 25 mg	Sudden infant death, hypotension	High risk in infants
Cetirizine (Zyrtec)	Second	> 100 mg	Mild tachycardia, dizziness	0.2% serious outcomes
Loratadine (Claritin)	Second	> 100 mg	Very rare severe effects	0.1% serious outcomes
Fexofenadine (Allegra)	Second	> 1,000 mg	Minimal risk	0.05% serious outcomes

Here’s the kicker: diphenhydramine makes up only 28% of all antihistamine sales, but causes 62% of serious overdoses. Why? It’s cheap, widely available, and often used as a sleep aid. Many adults don’t realize how little it takes to overdose - just 10 tablets of 25 mg can be toxic. And in kids, a single dose of children’s liquid Benadryl (12.5 mg) can be dangerous if they get two or three.

Preventing Overdose in the First Place

Most antihistamine overdoses aren’t intentional. They’re accidents.

• Keep all meds out of reach. The AAPCC reports 67% of pediatric cases involve children under 6 who found bottles on counters or in purses.
• Use child-resistant caps - and keep them closed. Even with child-resistant packaging, 42% of pediatric exposures happen because caregivers misread dosing cups.
• Don’t mix medications. Many cold and sleep aids contain diphenhydramine. Taking Tylenol PM with Benadryl doubles your dose without realizing it.
• Check labels for active ingredients. “Non-drowsy” doesn’t mean safe in overdose. Always look for “diphenhydramine,” “chlorpheniramine,” or “doxylamine.”
• Don’t use antihistamines to sedate kids. The FDA banned this for children under 2 in 2008. Promethazine has a black box warning for sudden infant death.

One mother on Reddit said she used Benadryl to help her toddler sleep on a long flight. Her child ended up in the ER. She didn’t know the dose was for adults. That’s the problem - most people think antihistamines are harmless because they’re sold over the counter.

What to Do After the Emergency

Once the crisis is over, don’t assume everything’s fine. Follow up with your doctor or a poison control specialist.

• Ask for a copy of the hospital’s treatment notes - especially the EKG results.
• Review all medications in your home. Get rid of expired or unnecessary antihistamines.
• If the overdose was accidental, talk to your pharmacist about safer alternatives. For allergies, consider second-generation options like fexofenadine or loratadine.
• If it was intentional (even once), seek mental health support. Only 18% of adult overdoses are suicide attempts, but that number rises sharply in people with depression or anxiety.

The bottom line? Antihistamine overdoses are preventable. They’re treatable. But they’re not harmless. If you ever suspect someone has taken too much - even if they seem fine - call poison control. Don’t wait. Don’t guess. Just call.