My spouse is allergic to penicillin is it safe for him to take azithromycin?

Yes: There is no relationship between the two In fact, likely 90%^ of patients with a history of penicillin allergy will turn out to be allergic with testing and challenge. This is not to say that you should take it without having been tested by an allergist. As for azithromycin, it does cause cardiac rhythm problem is a small % of the people and thus it is not entirely harmless.