Benadryl is very effective for hives because of the fast onset of the medication, but only lasts about four hours. Zyrtec tends to be slower in onset but lasts longer (24 hours). Both are antihistamines, of course, and most of the time you only need one of the other. On some occasions, however, when you have taken Zyrtec in the 24 hours, you can still get hives, so it is safe to take a dose of Benadryl. Benadryl does cause sedation, so please be careful if you need to drive.
If the hives don't clear up fairly quickly, or if they're accompanied by difficulty breathing, your wife should seek immediate medical attention. These can be the signs of a severe allergic reaction to something -- food, medication, etc.
If your wife gets hives occasionally (as some people do), and they are not accompanied by other symptoms, then I'd suggest she speak to her doctor about getting a prescription specifically for the hives. There are medications other than Benadryl that are used to treat hives.
In terms of combining antihistamines, I'd suggest you speak to a pharmacist. While Benadryl (diphenhydramine) has a different chemical composition than Zyrtec (cetirizine), they still are both the same class of medication. Generally, we try not to combine medications of the same class unless specifically directed to do so by a physician.
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