Taking ZzzQuil With Lipitor (Atorvastatin)

There is no interaction between ZzzQuil (diphenhydramine) and Lipitor (atorvastatin).

Aug 30, 2018

grftnlrd asked

Is it safe to take ZzzQuil, a nighttime sleep-aid, while I am taking Atorvastatin before bedtime?

At a glance

  • There is no known drug interaction between ZzzQuil (diphenhydramine) and Lipitor (atorvastatin).


There are no drug interactions between Zzzquil (diphenhydramine) and atorvastatin (Lipitor).

They can be taken at the same time with no concerns. Read more about both diphenhydramine and atorvastatin below.

Diphenhydramine Info

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 the treatment of allergy symptoms, whereas Benadryl can be used for a variety of reasons including allergies, insect bites, poison ivy, sleep, and motion sickness.

Atorvastatin Info

Lipitor (atorvastatin) is a statin medication, otherwise known as an HMG-CoA reductase inhibitor.

Lipitor gradually decreases the amount of total cholesterol, LDL cholesterol (known as “bad” cholesterol), and triglycerides.

Atorvastatin can reduce LDL levels by up to 45-60%. Atorvastatin 40-80 mg is considered a high-intensity statin per the American College of Cardiology and American Heart Association.

Lipitor is metabolized by several processes, especially CYP3A4, P-glycoprotein, and OATP1B1.

The most significant drug interactions with Lipitor come with medications that reduce or increase the activity of CYP3A4. CYP3A4 is the most common enzyme responsible for breaking down medications. Many drug interactions are due to inhibition or induction of CYP3A4 and other CYP enzymes.

Inhibiting the enzyme allows for drugs that require CYP metabolism to stay in the body longer at a higher concentration.

Inhibitors can increase the effect of Lipitor, which may lead to side effects like muscle pain and a severe condition known as rhabdomyolysis. Examples of CYP3A4 inhibitors include diltiazem, digoxin, grapefruit, and many HIV medications. Diphenhydramine does not inhibit CYP3A4.

Per the Lipitor package insert, one study showed that drinking one glass of grapefruit juice (8 ounces) with atorvastatin resulted in an increased drug concentration of 37%.

Drinking excessive amounts of grapefruit (approximately 1 L/day) increased drug concentrations 250%. Avoid grapefruit juice to avoid the risk of side effects.

  1. Lipitor Prescribing Information. AccessFDA
  2. ACC/AHA Release Updated Guideline on the Treatment of Blood Cholesterol to Reduce ASCVD Risk. AAFP
  3. American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Wiley Online Library

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