Diphenhydramine

Is diphenhydramine safe?

An occasional label dose is low-risk for most healthy adults. Diphenhydramine has been sold since the 1940s, and its harms are predictable. The problem is that they are common: it sedates more than many people realise, it slows thinking in older adults, it hides in dozens of night-time combination products, and taken in large amounts it can stop the heart.

We score it 64, below cetirizine, the newer antihistamine most people could use for hay fever instead, and above zolpidem, the prescription sleeping pill with a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary.

US adults and children 12 and over take 25 to 50 mg every 4 to 6 hours for allergies, with no more than 6 doses in 24 hours. As a sleep aid (ZzzQuil, Unisom SleepGels, Nytol) the dose is 50 mg once at bedtime.

Does Benadryl affect driving?

Yes, and more than alcohol in one well-known test. In a 2000 trial in the Iowa driving simulator, 40 drivers with hay fever took 50 mg of diphenhydramine, a non-drowsy antihistamine, enough alcohol to reach about 0.1% blood alcohol, or placebo, a week apart. After diphenhydramine they were worse at keeping pace with the car ahead than after alcohol, and lane keeping suffered too. How sleepy drivers felt did not predict how badly they drove.

The label says to be careful driving or using machinery. A bedtime dose may still leave you drowsy and slower the next morning.

Why doctors avoid it in older adults

Diphenhydramine blocks acetylcholine as well as histamine. In older people that causes confusion, constipation, dry mouth, blurred vision and trouble passing urine, and it raises the risk of falls. The American Geriatrics Society's 2023 Beers Criteria list first-generation antihistamines such as diphenhydramine among medicines older adults should generally avoid.

There is also a long-term question. A 2015 study followed 3,434 people aged 65 and over in Seattle for about 7 years. Those with the heaviest use of strong anticholinergic drugs over 10 years had a 54% higher risk of dementia than non-users. First-generation antihistamines were the second most common class. The study cannot prove that the drugs caused the dementia, but it is one reason many doctors advise against nightly sleep aids in later life.

The label also asks you to check with a doctor first if you have glaucoma, chronic bronchitis or other breathing problems, or trouble urinating from an enlarged prostate.

What happens in an overdose

In September 2020 the FDA warned that taking more than the label dose can cause serious heart problems, seizures, coma or death, after reports of teenagers taking large amounts in the "Benadryl Challenge" shared on TikTok. The agency asked families to lock up medicines.

Diphenhydramine also turns up widely in US overdose deaths. A CDC review of 92,033 overdose deaths in 2019 and 2020 found it in the blood of 9,645 people and listed it as a cause in 2,226. Almost all of those deaths also involved other drugs, usually opioids; antihistamines alone accounted for 90. That is the pattern that matters: alone at label doses it is forgiving, but combined with other depressants or taken in large amounts it is not.

If someone has taken too much, call Poison Help on 1-800-222-1222 in the US or NHS 111 in the UK. Call 911 or 999 if they are hard to wake, confused, have a racing heart or a seizure.

Hidden doses and interactions

Diphenhydramine is in many products that do not lead with the word "Benadryl": PM pain relievers such as Tylenol PM and Advil PM, night-time cold and flu syrups, and anti-itch creams. The label says not to combine it with any other diphenhydramine product, even one used on the skin. Read the active ingredients of everything you take at night.

The interactions that matter most:

• alcohol, opioids, benzodiazepines, zolpidem and other sedatives, which deepen drowsiness and slow breathing
• other anticholinergic medicines, such as some bladder drugs and tricyclic antidepressants, which add to confusion and urine retention
• drugs cleared by the CYP2D6CYP450 enzymesA family of liver enzymes that break down many medicines. When another drug or supplement speeds them up or slows them down, drug levels change.More in the glossary enzyme, such as metoprolol and some antidepressants, whose levels it can raise

For sleep, a short course of melatonin is a common alternative people ask about; it carries different risks, so check with a pharmacist.

Who should be careful

Talk to your doctor or pharmacist before using diphenhydramine if you are over 65, have glaucoma, an enlarged prostate, asthma or COPD, or take sedatives, opioids or antidepressants, or if you are pregnant or breastfeeding. Do not give it to children to make them sleep. Keep it locked away from teenagers and children, and stick to one product that contains it at a time.

How we scored it

Track record (95) is the strongest factor: 80 years of wide use. Overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (50) is the weakest, reflecting the FDA's 2020 warning and the drug's frequent role in combined overdose deaths. Serious side effects (65) and interactions (55) reflect sedation, driving impairment and anticholinergic harm in older adults rather than rare reactions.