Difference Between Unisom and Benadryl


Main Difference

The main difference between Unisom and Benadryl is that Unisom contains Doxylamine succinate as an active drug, and Benadryl contains Diphenhydramine hydrochloride as an active drug.

Unisom vs. Benadryl

Unisom is the trade name of Doxylamine succinate on the other hand Benadryl is the trade name of Diphenhydramine hydrochloride. Unisom treats allergies and used as a sleep aid, while Benadryl is used to treat allergies and hives. Unisom half-life is 2.4-9.3hrs; on the other hand, Benadryl half-life is 4.3 hrs. Unisom increases risks of fall so should not be used by elderly patients while Benadryl does not increase risks of fall, so can be used by elderly patients. Unisom has a long duration of action, while Benadryl has a short duration of action. Unisom is available as a pill, chewable tablet and liquid, on the other hand, Benadryl is available as tablets, capsules, liquid, and quick-dissolving tablet, creams, gel, and ointments.


Comparison Chart

Unisom contains Doxylamine.Benadryl contains diphenhydramine.
Drug Group
H1 antagonistH1 antagonist
Doxylamine succinateDiphenhydramine hydrochloride
Mechanism of Action
Blocks actions of the Histamine and acetylcholineBlocks actions of the Histamine
2.4 – 9.3 hrs4.3 hrs
Side Effects
dry mouth, urinary retention, and ataxia, inability to concentrate, drowsiness, hallucinations, and memory problemsdry mouth, fatigue, tiredness, sleepy feel, dizziness, and disturbed coordination
Use in Pregnancy
Safe to use in pregnancySafe to use in pregnancy

What is Unisom?

Unisom contains Doxylamine succinate. Unisom is the first-generation antihistamine. The active moiety of the Unisom is the H1 antagonist of the ethanolamine class. Unisom treats symptoms of hay fever, allergy, and the common cold. Unisom shows pharmacological actions by blocking the actions of histamine and acetylcholine and hence treats watery eyes, sneezing and runny nose. Unisom cannot be given to children younger than six years of age, and 25 mg Unisom tablets cannot be given to children who are younger than 12 years of age. Unisom does not treat the short length common cold and serious unwanted effects. When a patient is using Unisom, then make it sure that the patient is not using any cough and cold preparation that contains a similar active moiety. Unisom can be taken with or without food, and if there is a stomach upset, then Unisom can be taken with the milk or food to avoid further problem.


Unisom is also used to induce sleep in insomnia. For the treatment of insomnia, Unisom is an OTC drug. Unisom sleep gels are non-habit forming. For insomnia, the Unisom oral tablets are given 25minutes before going to bed. Unisom can be taken for insomnia for two weeks only if insomnia persists after two weeks of the treatment with Unisom then the patient should stop taking this medicine and should be evaluated for insomnia. Unisom although provide a good night sleep, but if the patient does not sleep for enough time, then he may get the problem to get up. The active ingredient of the Unisom is a potent anticholinergic and causes severe side effects which include the dry mouth, urinary retention and ataxia, inability to concentrate, drowsiness, hallucinations, and memory problems. Unisom causes extreme sensitivity to external stimuli. Oral tablets of Unisom have a strength of 25mg.

What is Benadryl?

Benadryl contains diphenhydramine. Benadryl belongs to the antihistamine. Benadryl salt name is diphenhydramine hydrochloride. Benadryl can be taken from a drug store or pharmacy without a prescription. Benadryl treats symptoms of seasonal allergies including sneezing, itchy watery eyes, and itchy throat or some other allergies. Benadryl relieves symptoms of the common old and finds its use in itchy skin due to hives and insect bites. Benadryl is thought to be first-choice for hives. Benadryl preparations are oral or topical. Benadryl causes sleepy to feel and is not recommended in children younger than six years. Benadryl gel preparation contains a high concentration of the drug. Benadryl gel products cause the loss of consciousness or/and confusion when swallowed mistakenly. The inactive ingredients in Benadryl tablets are candelilla wax, crospovidone, hypromellose, polyethylene glycol, colloidal silicon dioxide, povidone, talc pregelatinized starch, titanium dioxide, microcrystalline cellulose starch, and stearic acid. Benadryl adult dose is 25-50mg, and children of age 12 and above are given calculated doses. Benadryl is prescribed 12.5mg to 25mg in patients of age 6-12. Benadryl dose in the children under the age of six is decided by a physician.12.5 mg strength is not found in the capsule form. Benadryl is light sensitive. Benadryl storage temperature is 59-77F. Benadryl is stored in a dry place. Different dosage forms of Benadryl are oral chewable tablets, oral tablets, topical cream, topical gel, topical spray, and topical stick, oral liquid fill capsules, oral liquid solution. Benadryl causes dry mouth, fatigue, tiredness, sleepy feel, dizziness, and disturbed coordination. Benadryl is safe to use in pregnancy although breastfeeding mother should take Benadryl after consultation of a physician. Benadryl can treat motion sickness. Benadryl can interact with benzodiazepines and sedatives, so use it with care with them.

Key Differences

  1. Unisom contains Doxylamine succinate as an active drug; on the other hand, Benadryl contains Diphenhydramine hydrochloride as an active drug.
  2. Unisom used for allergies and as sleeping aid whereas Benadryl is used for allergies.
  3. Unisom half-life is 2.4-9.3hrs; on the other hand, Benadryl half-life is 4.3 hrs.
  4. Unisom is associated with an increased risk of falls while Benadryl is not associated with such risk.
  5. Unisom is not recommended for elderly patients. On the other hand, Benadryl can be prescribed to elderly patients safely.
  6. Unisom duration of action is long, whereas Benadryl duration of action is short.
  7. Unisom pill, chewable tablet, and liquid, on the other hand, Benadryl is available as tablets, capsules, liquid and quick-dissolving tablet, creams, gels, and ointments.


The main conclusion of the above discussion is that Buspar and Xanax belong to two different drug groups and are used to treat different depression and anxiety disorders.

Janet White

Janet White is a writer and blogger for Difference Wiki since 2015. She has a master's degree in science and medical journalism from Boston University. Apart from work, she enjoys exercising, reading, and spending time with her friends and family. Connect with her on Twitter @Janet__White