It is expected that low doses of diphenhydramine taken occasionally will not cause any adverse effects on breastfed infants. Large doses or long-term use may affect the baby or reduce breast milk supply, especially when combined with sympathomimetic drugs such as pseudoephedrine or before the establishment of lactation. A single bedtime dose after the last feeding of the day may minimize any harmful effects of the medication on the baby and on the milk supply. Still, non-sedating antihistamines are the preferred alternative.Paradoxical reactions to diphenhydramine have been documented, in particular among children, and it may cause excitation instead of sedation.Topical diphenhydramine is sometimes used especially for people in hospice. This use is without indication and topical diphenhydramine should not be used as treatment for nausea because research does not indicate this therapy is more effective than alternatives.There were no documented cases of clinically apparent acute liver injury caused by normal doses of diphenhydramine. Adverse effects
The most prominent side effect is sedation. A typical dose creates driving impairment equivalent to a blood-alcohol level of 0.10, which is higher than the 0.08 limit of most drunk-driving laws.Diphenhydramine is a potent anticholinergic agent and potential deliriant in higher doses. This activity is responsible for the side effects of dry mouth and throat, increased heart rate, pupil dilation, urinary retention, constipation, and, at high doses, hallucinations or delirium.
Overdose symptoms may include:

Acute poisoning can be fatal, leading to cardiovascular collapse and death in 2–18 hours, and in general is treated using a symptomatic and supportive approach. Diagnosis of toxicity is based on history and clinical presentation, and in general specific levels are not useful. Several levels of evidence strongly indicate diphenhydramine (similar to chlorpheniramine) can block the delayed rectifier potassium channel and, as a consequence, prolong the QT interval, leading to cardiac arrhythmias such as torsades de pointes. No specific antidote for diphenhydramine toxicity is known, but the anticholinergic syndrome has been treated with physostigmine for severe delirium or tachycardia. Benzodiazepines may be administered to decrease the likelihood of psychosis, agitation, and seizures in people who are prone to these symptoms. Interactions
Alcohol may increase the drowsiness caused by diphenhydramine. Pharmacology
Pharmacodynamics
Diphenhydramine, while traditionally known as an antagonist, acts primarily as an inverse agonist of the histamine H1 receptor. It is a member of the ethanolamine class of antihistaminergic agents. By reversing the effects of histamine on the capillaries, it can reduce the intensity of allergic symptoms. It also crosses the blood–brain barrier and inversely agonizes the H1 receptors centrally. Its effects on central H1 receptors cause drowsiness. Like many other first-generation antihistamines, diphenhydramine is also a potent antimuscarinic (a competitive antagonist of muscarinic acetylcholine receptors) and, as such, at high doses can cause anticholinergic syndrome. The utility of diphenhydramine as an antiparkinson agent is the result of its blocking properties on the muscarinic acetylcholine receptors in the brain.