Is Prednisone Safe To Take With Phenergan (Promethazine)?

In our latest question and answer, the pharmacist discusses whether or not there is a drug interaction between prednisone and Phenergan (promethazine).

Is Prednisone Safe To Take With Phenergan (Promethazine)?
Jan 18, 2020

Momma Hen asked

I am taking 20mg a day of prednisone for Bell’s Palsy. It is making me jittery and giving me mood swings. My doctor told me to take Phenergan. Is it safe to take Phenergan and Prednisone together?

At a glance

  • There is no known drug interaction between prednisone and Phenergan (promethazine). They do not appear to affect one another if taken together.


Two Pills Bottles Spilling With Text Prednisone With Phenergan

Hello and thank you for taking the time to reach out to us!

I'm sorry to hear that you are having to deal with some side effects from the prednisone that you are taking. Feeling jittery, anxious and having mood swings isn't all that uncommon with this drug, especially if you have been taking it for an extended period of time.

While Phenergan (promethazine) is not indicated or approved to be taken solely for the purpose of helping to decrease the severity of prednisone side effects, it could certainly help to calm you down since it has a fairly strong sedative effect (it is a sedating antihistamine after all).

The good news here is that no clinically significant drug interaction has been reported between prednisone and Phenergan (promethazine). They are considered to be safe to take together (unless there are any patient-specific contraindications).

I do want to point out that our own 'drug interaction checker', which pulls data from DrugBank, does list an interaction between these two drugs, and states:

The serum concentration of Prednisone can be increased when it is combined with Promethazine.

This interaction is only theoretical and is based on how each of these drugs interacts with a protein in our body known as 'p-glycoprotein'. P-glycoprotein is known as a 'transporter molecule' and, among other things, it transports drugs out of cells for elimination. It is even sometimes referred to as a 'drug pump'. It is a very important factor in the metabolism of many medications.

Now, not all drugs are affected by p-glycoprotein but if the actions of p-glycoprotein are altered in any way (like if another drug increases or decreases its activity), there is the potential for serious interactions.

The interaction comes up on our interaction checker because prednisone is listed in some sources as a 'P-glycoprotein substrate', meaning that it is affected by this protein, and promethazine may be a 'P-glycoprotein inhibitor', meaning it can decrease the activity of P-glycoprotein.

However, multiple studies report that prednisone metabolism isn't overly affected by the actions of P-glycoprotein and promethazine is a very weak inhibitor of it. This is likely why there have not been any interactions between these two drugs reported or even seen clinically.

All in all, based on current information, these drugs don't appear to affect one another.

  1. The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum. PubMed
  2. Identification of budesonide and prednisone as substrates of the intestinal drug efflux pump P-glycoprotein.PubMed
  3. Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells. PubMed
  4. DrugBank Promethazine Monograph. DrugBank

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