Is it safe to take benedryl and allegra (fexofenadine) in the same day?

In general, yes,: Most common potential side effect would be sedation, however, Allegra is the least sedating antihistamine, so unless you are taking extra high dose of benadryl, (diphenhydramine) it would be quite safe. Often in patients with difficult to control chronic hives, we have to use combination, sometime high dose, of antihistamines to treat the condition.

Depends: Allegra 60 mg has about a 12 hour duration of action. Benedryl at bedtime may provide relief of symptoms and help with sleep. I have used Allegra 180 mg at 8 am and zyrtec or Claritin (loratadine) at 8 pm in patients with difficult to control hives.