Alcohol and other CNS depressants including barbiturates, tranquilizers, hypnotics, sedatives, antianxiety agents, and narcotic analgesics: have additive effects with antihistamines. Dosage adjustments of CNS depressants may be necessary to avoid profound CNS depression.
Monoamine oxidase inhibitors (MAOI) (phenelzine, tranylcypromine, isocarboxazid, furazolidone, procarbazine): may prolong and intensify the anticholinergic and CNS depressant effects of diphenhydramine. Diphenhydramine should be used with caution with MAOIs or within two weeks of stopping a MAOI.
Anticholinergic drugs (e.g., atropine): may potentiate diphenhydramine's anticholinergic side effects.
β-blockers (metoprolol, carvedilol, labetalol, propranolol, timolol): Diphenhydramine increases the plasma concentrations and cardiovascular effects of these drugs.
PAS (4-aminosalicylic acid): Diphenhydramine administration significantly reduces absorption of the antituberculosis agent PAS from the GI tract.