What Should You Avoid While Taking Diphenhydramine?

October 10, 2025 •

4 min read

According to the FDA, misusing over-the-counter medications can lead to serious problems, highlighting the need for caution even with common drugs. To ensure safety, it is critical to know what you should avoid while taking diphenhydramine, the active ingredient in products like Benadryl.

Quick Summary

Taking diphenhydramine requires avoiding alcohol, other CNS depressants, and anticholinergic drugs to prevent amplified sedation and side effects. Activities like driving should be halted, and specific medical conditions warrant consulting a doctor before use.

Key Points

Avoid Alcohol: Combining diphenhydramine with alcohol dangerously increases sedation, dizziness, and impairment.
Limit Other Sedating Medications: Steer clear of other CNS depressants like opioids, benzodiazepines, and sleep aids, as these amplify drowsiness and other side effects.
Do Not Drive or Operate Machinery: Due to its sedative effects, diphenhydramine impairs judgment and coordination, making driving and operating machinery unsafe.
Check for Drug Duplication: Many combination cold and flu products contain diphenhydramine or other antihistamines; always read labels carefully to avoid double-dosing.
Consider Pre-Existing Conditions: Individuals with conditions like glaucoma, enlarged prostate, respiratory problems, or heart disease should consult a doctor before taking diphenhydramine.
Be Cautious with Age: The elderly are more susceptible to side effects like falls, while children may experience paradoxical hyperactivity.

Diphenhydramine is a first-generation antihistamine widely available over-the-counter to treat allergies, common cold symptoms, and insomnia. However, its effectiveness comes with significant side effects and a high risk of interactions with other substances and health conditions. Because it easily crosses the blood-brain barrier, it can cause marked drowsiness and other central nervous system (CNS) effects. To use this medication safely, it is crucial to understand what should be avoided.

Alcohol and other CNS Depressants

Combining diphenhydramine with other CNS depressants is one of the most significant risks and is strongly advised against. Both diphenhydramine and alcohol depress the central nervous system, and taking them together amplifies their sedative effects to dangerous levels.

Alcohol: Even small amounts of alcohol can significantly increase drowsiness, dizziness, and impaired coordination when combined with diphenhydramine. This combination can also increase the risk of respiratory depression, where breathing becomes dangerously slow.
Opioids: These are powerful CNS depressants often prescribed for pain relief. Combining them with diphenhydramine can lead to extreme sleepiness, respiratory depression, and an increased risk of overdose. Examples include oxycodone, morphine, and fentanyl.
Benzodiazepines: Prescribed for anxiety and insomnia (e.g., Xanax, Valium), these medications, when mixed with diphenhydramine, can cause profound sedation and impaired coordination.
Sedative-Hypnotics (Sleep Aids): Many over-the-counter and prescription sleep aids, like zolpidem (Ambien), eszopiclone (Lunesta), and even melatonin, have sedative effects. Combining them with diphenhydramine, especially since many OTC sleep aids contain diphenhydramine itself, is a direct path to excessive sedation and overdose.
Cannabis Products: Cannabis also has CNS depressant properties. Its concurrent use with diphenhydramine can lead to heightened drowsiness, confusion, and difficulty concentrating, with risks being especially high for the elderly.

Other Medications and Supplements

Carefully checking medication labels is vital, as many products contain antihistamines or ingredients that interact with diphenhydramine.

Other Antihistamines: Do not combine diphenhydramine with other antihistamines, even seemingly 'non-drowsy' ones like cetirizine (Zyrtec) or loratadine (Claritin), or other first-generation types like hydroxyzine. This can lead to an overdose of antihistamines, increasing side effects like dry mouth, blurry vision, and heart problems.
Combination Cold and Flu Products: Many multi-symptom cold and flu remedies contain diphenhydramine or other antihistamines. Always read labels to avoid double-dosing. Some products also contain decongestants like pseudoephedrine, which can increase blood pressure and counteract diphenhydramine's sedative effects, causing a mixed and unpredictable reaction.
Anticholinergic Medications: Diphenhydramine itself has strong anticholinergic properties. Combining it with other anticholinergic drugs, such as certain antidepressants (e.g., amitriptyline) and medications for bladder control or Parkinson's disease, can worsen side effects like dry mouth, constipation, blurred vision, and confusion.
Herbal and Natural Supplements: Be aware of supplements with sedative properties. Melatonin, valerian root, kava, and ashwagandha can all increase drowsiness when taken with diphenhydramine.

Activities to Avoid

Due to its powerful sedative effects, diphenhydramine can significantly impair coordination, judgment, and reaction time. The following activities should be strictly avoided until you know how the medication affects you.

Driving: Even moderate doses can impair driving ability more than alcohol. The National Highway Traffic Safety Administration (NHTSA) highlights the dangers of driving while drowsy, with many over-the-counter drugs being a culprit.
Operating Heavy Machinery: Tasks requiring alertness and motor skills, such as operating construction equipment, tools, or even kitchen appliances, pose a serious risk.

Health Conditions Requiring Caution

Certain health conditions can be worsened by diphenhydramine or increase the risk of adverse side effects.

Glaucoma: The anticholinergic effects can increase pressure in the eyes and worsen narrow-angle glaucoma.
Enlarged Prostate: Men with benign prostate hyperplasia (BPH) may experience difficulty urinating or urinary retention due to diphenhydramine's effects.
Respiratory Problems: For individuals with asthma, emphysema, or chronic bronchitis, diphenhydramine can thicken mucus in the lungs, making it harder to clear.
Heart Disease or High Blood Pressure: Diphenhydramine can cause tachycardia (fast heartbeat) and changes in blood pressure, which can be dangerous for those with existing cardiovascular conditions.
Liver or Kidney Disease: These organs are responsible for metabolizing and eliminating diphenhydramine. Impaired function can lead to a buildup of the drug in the system, increasing the risk of toxicity and prolonged side effects.
Elderly Patients: Individuals over 65 are more susceptible to side effects like dizziness, sedation, confusion, and low blood pressure, which increases the risk of falls.
Children: Diphenhydramine is not recommended for children under 6 without medical supervision and is contraindicated in infants. In some children, it can cause paradoxical excitement instead of drowsiness.

Comparison of Antihistamines: Diphenhydramine vs. Newer Options


Feature	Diphenhydramine (Benadryl)	Second-Generation Antihistamines (Zyrtec, Allegra, Claritin)
Sedation	High; crosses the blood-brain barrier easily.	Minimal; less likely to cross the blood-brain barrier.
Performance Impact	Significant impairment of driving and operating machinery.	Generally lower risk, though Zyrtec may still cause some drowsiness.
Speed of Action	Works relatively quickly, with effects in 30 minutes to 1 hour.	Can take a bit longer to reach peak effectiveness compared to diphenhydramine.
Duration of Effect	Shorter duration (4-6 hours), requiring more frequent dosing.	Longer duration (up to 24 hours), allowing for once-daily dosing.
Use Cases	Allergies, cold symptoms, sleep aid, motion sickness.	Best for daily, ongoing allergy management without significant drowsiness.

Conclusion

While diphenhydramine is a readily available and effective medication for allergies and other conditions, it is not without risks. Understanding what you should avoid while taking diphenhydramine is essential for preventing serious side effects and dangerous interactions. This includes avoiding alcohol, other CNS depressants, specific medical conditions, and activities requiring mental alertness. Always consult your healthcare provider or pharmacist, especially if you have other health conditions or take other medications, to ensure safe use. For more safety information from a trusted source, review the MedlinePlus Drug Information.

Frequently Asked Questions

No, you should not drink alcohol while taking diphenhydramine. Both are central nervous system depressants, and combining them can cause severe drowsiness, dizziness, impaired coordination, and a greater risk of accidents.

No, it is not safe to drive or operate machinery after taking diphenhydramine until you know how the medication affects you. The medication can cause significant drowsiness, impaired judgment, and slowed reaction times.

You should avoid other sedating medications, including other antihistamines (like Zyrtec or Claritin), opioids, benzodiazepines, and sleep aids. Additionally, be cautious with certain antidepressants, blood pressure medications, and anticholinergic drugs.

Yes, some herbal supplements, especially those used for sleep or anxiety, can interact with diphenhydramine. These include melatonin, valerian root, and kava, which can increase drowsiness and sedation.

Individuals with conditions such as glaucoma, enlarged prostate, asthma, heart disease, high blood pressure, and liver or kidney problems should be cautious and consult a doctor. The elderly and young children also face higher risks of adverse effects.

Symptoms of a diphenhydramine overdose can include extreme drowsiness, confusion, agitation, hallucinations, seizures, a fast heartbeat, dilated pupils, and coma. If you suspect an overdose, seek immediate medical attention.

Long-term use is not recommended because the American Academy of Sleep Medicine suggests it is not effective for sleep over a prolonged period and the risk of side effects, such as dementia in older adults, increases with continued use.