It is available in generic and brand versions. These side effects may go away during treatment as your body adjusts to the medicine. The occurrence of side effects will become more pronounced, and the chances for the user to experience some of the more severe side effects are also significantly increased. The undesirable effects of Benadryl can be minimized and managed so that patients can continue with their day-to-day activities in an efficient manner. In the case of interacting with alcohol, Benadryl and Zyrtec are quite similar, even though the second one is a second-generation non-sedative antihistamine. There are side effects associated with using Benadryl for dogs that all dog owners should be aware of. In a study of older adults, diphenhydramine reduced awakenings but didn't improve sleep latency, total sleep time, or sleep quality. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Side Effects of Benadryl. Common long-term side effects of prolonged diphenhydramine use include: Dependence. Continued diphenhydramine use can cause long-term adverse side effects that result in permanent damage. The following tips can be followed to manage these side effects: Nevertheless, morning side effects such as residual sleepiness or hangover can occur, though this typically improved after about four nights of use. Taking Benadryl with Zyrtec may increase the risk of certain side effects such as sleepiness, dry mouth, fatigue, and headache. Not only will prolonged use cause harm, but it can lead to other aspects such as dependence on the medication. Long-Term Side Effects of Diphenhydramine Abuse. Diphenhydramine (Benadryl, Diphenhist, Unisom, Zzzquil) is an antihistamine used to treat symptoms of seasonal allergies including sneezing, runny nose, and itching or watering eyes.It is also used as an over-the-counter sleep aid. Minimizing Side Effects of Diphenhydramine. Benadryl (diphenhydramine) is an antihistamine used to treat symptoms of seasonal allergies including sneezing, runny nose, and itching or watering eyes.It works by blocking the action of histamine which causes allergic symptoms.It is available over-the-counter, and also sold as generic diphenhydramine. Benadryl Injection (diphenhydramine hydrochloride) is an antihistamine used to treat life-threatening allergic reactions (anaphylaxis) along with epinephrine and other treatments.Benadryl Injection is also used to relieve symptoms of household allergies, hay fever and the common cold when medication cannot be given by mouth. Benadryl (diphenhydramine hydrochloride) is a brand name antihistamine drug with anticholinergic (drying) and sedative side effects manufactured by McNeil Healthcare, a division of Johnson & Johnson. 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