Taking Benadryl With Levothyroxine

In our latest question and answer, the pharmacist discusses taking Bendaryl (diphenhydramine) with Synthroid (levothyroxine).

Apr 02, 2018

Sal asked

Is it okay to take Benadryl and levothyroxine together? I have heard that levothyroxine interacts with every medication.


While there is no drug-drug interaction between Synthroid (levothyroxine) and Benadryl (diphenhydramine), dosing of each should be separated by at least 30 to 60 minutes.

Synthroid (levothyroxine) should be taken by itself in the morning on empty stomach, at least 30 to 60 minutes before other medication or food to avoid fluctuations in absorption. 

It is very important to take Synthroid (levothyroxine) consistently as small changes in absorption (like when taken with food or other medication) can have a significant impact on thyroid levels due to how small the doses of levothyroxine are.

Synthroid (Levothyroxine) Information

Synthroid (levothyroxine), also known as T4, is a thyroid replacement medication for the treatment of hypothyroidism.

T4 is converted in the body to more biologically active, T3. For most individuals, using levothyroxine (T4) sufficient in to treat hypothyroidism but a small percentage of individuals don't efficiently convert T4 to T3. For these individuals, mixed T4/T3 products may be preferred.

Levothyroxine is generally well tolerated and side effects are often attributable to the wrong dosage, which can manifest as symptoms of either hypothyroidism or hyperthyroidism. If the dose of levothyroxine is too low, you may experience such symptoms as:

  • Fatigue
  • Lethargy
  • Chills
  • Dry skin
  • Poor memory
  • Weight gain

If the dose of levothyroxine is too high, you may experience symptoms of hyperthyroidism, which include:

  • Irritability
  • Sweating
  • Palpitations
  • Tremors
  • Diarrhea
  • Weight loss

Levothyroxine is known as a narrow therapeutic index drug, meaning there is a small window of effectiveness in regard to dose. It is important to stay on the same generic manufacturer of levothyroxine to reduce the variability between products. If your pharmacy is switching manufacturers of levothyroxine, be sure to speak with them about your concerns. 

Benadryl (Diphenhydramine) Information

Benadryl (diphenhydramine) is a first-generation antihistamine, and has a short duration of action (~4 to 8 hours) and, for most individuals, has significant sedating effects. Benadryl is most often used for the treatment of allergies and as a nighttime sleep aid.  In fact, it is a common ingredient in over the counter sleep products such as ZzzQuil.

Benadryl begins to work about 20 to 30 minutes after taking by mouth and maximum blood concentrations are reached after 1 to 2 hours.

Benadryl is generally well tolerated but can cause the following side effects:

  • Sedation
  • Dizziness
  • Constipation
  • Dry mouth
  • There is no interaction between Benadryl (diphenhydramine) and Synthroid (levothyroxine). 
  • However, Synthroid (levothyroxine) should be taken on an empty stomach in the morning, at least 30 to 60 minutes before food or other medications.

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