Diphenhydramine is extensively metabolized in the liver, hepatic impairment may lead to a decrease in metabolism, a subsequent increase in drug levels, and an added risk of toxicity. Because of anticholinergic effects, diphenhydramine should be used with extreme caution in patients with bladder obstruction, GI obstruction, prostatic hypertrophy, or urinary retention. Diphenhydramine should be used with caution in patients with hyperthyroidism or hypertension since it can exacerbate these conditions. Antihistamines should be used with caution in patients undertaking tasks requiring mental alertness. Drowsiness can be severe in some patients.
Adverse effects are more likely to occur in geriatric patients.
Patients should exercise extreme caution until the effects are known. Alcohol can add to sedation caused by diphenhydramine. In addition, antihistamines can mask signs of allergic reactions, thus delaying the diagnosis of a hypersensitivity reaction. If diphenhydramine is used concomitantly with other CNS depressants, additive CNS effects, such as drowsiness and sedation, can occur. MAOIs can increase and prolong anticholinergic and CNS depressant effects of diphenhydramine.