ZzzQuil With Lactulose Interaction

In our latest question and answer, the pharmacist discusses the potential interaction between ZzzQuil and lactulose.


Hello. I took lactulose at 6pm. May I take Zzzquil tonight at 11pm? Thanks for your answer!!

Asked by Joe On Jul 20, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Jul 22, 2018

There are no drug interactions between lactulose and Zzzquil (diphenhydramine). However, lactulose can decrease the absorption of some drugs due to the rapid increase in gut motility. In other words, it increases the speed at which drugs and food move through your GI tract. Examples of these medications include hydrocodone and fosfomycin.  There is no evidence to suggest diphenhydramine absorption is affected by lactulose. Read more about both lactulose and diphenhydramine below.


Information About Lactulose

Lactulose is FDA approved for the treatment of constipation and hepatic encephalopathy, a mental condition resulting from liver damage. Lactulose was first approved by the FDA in 1976.

For treatment of constipation, lactulose is typically dosed at 15 to 30 mL once daily and can be increased up to 60 mL once daily. Response varies, but generally begins to work within 24 to 48 hours. Dosing can vary based on the reason for being prescribed the medication.

For the treatment of hepatic encephalopathy, dosing is more frequent at 30 to 45 mL up to 4 times daily. Many times, lactulose dosing and frequency is adjusted based on the number of soft stools per day. Lactulose works to improve the mental status in patients with hepatic encephalopathy by reducing blood ammonia levels.


Information About Diphenhydramine

Diphenhydramine (Benadryl) is a first-generation antihistamine. Antihistamines are widely used for self-care of allergy symptoms including runny nose, watery eyes, sneezing, and itching of the nose, throat, or eyes. Benadryl may also be used for symptoms of the common cold, allergic reactions, occasional insomnia, and more.

Because Benadryl is a first-generation antihistamine, it is more likely to cause sedation and drowsiness. Other first-generation antihistamines include Dramamine (dimenhydrinate), Chlor-Trimeton (chlorpheniramine), Tavist (clemastine), and Phenergan (promethazine), among others.

These medications cross the blood-brain barrier and have CNS effects like drowsiness and dizziness. First generation antihistamines can also cause urinary retention, GI upset, and blurry vision.

The first generation antihistamines are also listed as medications to avoid in elderly adults by the Beers Criteria due to the increased risk of confusion, dry mouth, and drowsiness.

Second generation antihistamines include Claritin (loratadine), Cetirizine (Zyrtec), and Allegra (fexofenadine) and are much less sedating. These antihistamines are generally only used for treatment of allergy symptoms, whereas Benadryl can be used for a variety of reasons including allergies, insect bites, poison ivy, sleep, and motion sickness.

About the Pharmacist

Dr. Kevin Davis Pharm.D

Dr. Kevin Davis is a licensed pharmacist with experience in retail and hospital pharmacy. He graduated from the University of Florida with a Doctor of Pharmacy degree in 2015 and a Master of Healthcare Administration degree from Adventist University in 2017. He is also a Board Certified Pharmacotherapy Specialist since 2016.

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