Many customers who regularly buy first-generation antihistamines like diphenhydramine or chlorpheniramine understand not to take them with alcohol or other sedatives that increase drowsiness. Purchasers of newer antihistamines may need a pharmacist’s intervention to ensure that they receive the full benefit of the drug—without unexpected side effects.

A conversation that starts with “What do you drink for breakfast?” may seem odd, but it will quickly identify whether a customer purchasing a product with fexofenadine should use another antihistamine instead. Grapefruit, orange, and apple juice impair absorption of fexofenadine. Coffee? No problem. Fruit juice devotees could switch to another beverage until their congestion clears, or they might prefer to use another antihistamine in the same class—loratadine, which fruit juices do not affect.

Checking out with a bottle of Milk of Magnesia or complaining of heartburn? Fexofenadine also interacts with antacids that contain aluminum or magnesium if they are taken within 30 minutes of the antihistamine. The antacids reduce the bioavailability of fexofenadine, so they should be taken at least half an hour after the antihistamine.

Loratadine and cetirizine have similar interactions with a number of other medications. The antihistamines may increase the risk of ulcers associated with potassium citrate and potassium chloride, so asking about the use of salt substitutes in cooking as well as checking for a prescription could be warranted.

As anticholinergics, loratadine and cetirizine also intensify the effects of other drugs commonly used for severe congestion, chronic obstructive pulmonary disease, and asthma. While most anticholinergics can be modified or monitored when taken with loratadine or cetirizine, several should be avoided entirely, including aclidinium, cimetropium, glycopyrrolate, glycopyrronium, ipratropium, oxatomide, tiotropium, and umeclidinium. An intranasal corticosteroid might be a better alternative for relief of congestion in patients taking these drugs.

Loratadine and cetirizine may also increase the depressant effects of central nervous system depressants such as opioid agonists and benzodiazepines. They should not be combined with azelastine, benzodiazepines, bromperidol, orphenadrine, oxomemazine, and paraldehyde. If avoidance isn’t possible, dose modification should be suggested for buprenorphine, chlorphenesin, droperidol, flunitrazepam, methotrimeprazine, suvorexant, tapentadol, thalidomide, and zolpidem.

These antihistamines may also significantly reduce the effect of levosulpiride and should not be taken with this mood-elevating antipsychotic.

Individuals with irritable bowel syndrome who take eluxadoline might want to consider an alternative antihistamine to loratadine or cetirizine, as both can cause constipation when taken with this drug.

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