7 Promethazine Interactions You Should Know About

You may have heard of promethazine — an antihistamine used for nausea and vomiting. But you may not be aware it’s FDA-approved for other conditions as well. This includes motion sickness and allergies. It’s also used for sedation before and/or after certain types of surgery. You can find it as an oral tablet or liquid, injection, and rectal suppository. 

Many medications can interact with promethazine. And alcohol can, too. Several interactions can result in excessive drowsiness. Others might cause side effects like dry mouth, constipation, or fast heartbeat. 

Some promethazine interactions may be mild, while others may be serious. So, it’s important to know what to avoid — and watch out for — when taking it.

7 promethazine interactions to know about

This list reviews some of the important interactions with promethazine. But there are other medications that can also interact with it, too. Always check with your healthcare provider or pharmacist before starting a new medication. They can help determine if there are any possible issues.

1. Opioids

Opioids are a type of pain medication. All opioids are controlled substances. Some examples include hydrocodone and oxycodone. They work by changing how the brain responds to pain and how your body experiences it. Most commonly, they can cause sedation (drowsiness or sleepiness). 

Combining opioids and promethazine can cause too much drowsiness. And it could also slow your breathing to a dangerous level. If you need to take them together, your healthcare provider may lower the dosage of your pain medication.

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You may be surprised that promethazine is available in combination with codeine (an opioid). This combination is an FDA-approved cough and cold medication. In this case, it’s important to follow your healthcare provider’s instructions for use to minimize side effects.

2. Benzodiazepines

Benzodiazepines (BZDs) are often used to treat anxiety, panic disorder, and other conditions. BZDs are also controlled substances. Common examples are lorazepam (Ativan) and alprazolam (Xanax).

BZDs affect chemicals in the brain to slow down the nervous system and relax muscles. And like promethazine, they can cause drowsiness. So, this side effect can be more severe if they’re taken together. 

Some people take BZDs every day, while others only take them as needed. Talk to your healthcare provider about how to manage this interaction with your specific regimen.

3. Tricyclic antidepressants

Tricyclic antidepressants (TCAs) treat depression and anxiety. They can also treat insomnia and help prevent migraines. Examples include amitriptyline, nortriptyline (Pamelor), and imipramine (Tofranil).  

TCAs are thought to work by raising the levels of certain chemicals in the brain. This causes changes in mood and drowsiness, among other effects. Combining them with promethazine can cause excessive drowsiness. Dizziness, blurred vision, and dry mouth may also become worse.

Your healthcare provider may recommend a lower TCA dose, or an alternative to promethazine.

4. Phenobarbital

Phenobarbital is a barbiturate medication that’s used to treat seizures. Like opioids and BZDs, it’s also a controlled substance. 

Phenobarbital works by slowing down electrical activity in the brain, which can cause sedation. Taking it with promethazine can worsen this side effect. Your healthcare provider may recommend an alternative medication that doesn’t interact with phenobarbital.

5. Alcohol

Alcohol also has sedative properties. It’s thought to affect some of the same chemicals and receptors in the brain as promethazine and BZDs. 

Drinking alcohol while taking promethazine can make you feel too drowsy or sleepy. This can be even more dangerous if you’re driving or operating machinery. 

It’s usually best to avoid or minimize alcohol while taking promethazine. Your healthcare provider can tell you how much alcohol may be safe for you to drink.

6. Anticholinergic medications

Anticholinergic medications treat several medical conditions, including bladder, eye, and lung problems. A few examples are hyoscyamine (Levsin), oxybutynin (Ditropan), and solifenacin (Vesicare).

Because of how they work, anticholinergics can cause many side effects. Common ones include dry mouth, less sweating, and difficulty going to the bathroom. Severe side effects, like confusion and agitation, are also possible. Side effects tend to happen more in older adults.

Promethazine can also have anticholinergic effects. Combining it with other anticholinergic medications can worsen these side effects. You shouldn’t take these medications together unless your healthcare provider tells you to.

7. Monoamine oxidase inhibitors 

Monoamine oxidase inhibitors (MAOIs) treat Parkinson’s disease and depression. Examples include selegiline (Zelapar), rasagiline (Azilect), and phenelzine (Nardil).

MAOIs aren’t used as often as other treatments. This is due to lots of side effects and drug interactions. You also have to follow a special diet when taking them.

Promethazine can interact with MAOIs to cause uncontrollable body movements. These are known as extrapyramidal symptoms (EPS). And MAOIs can cause drowsiness and anticholinergic side effects, too. So, these may be worse when combined with promethazine.

Your healthcare provider will determine if you can take promethazine if you’re already taking an MAOI.

When should I contact my healthcare provider about a promethazine interaction?

​​If you're concerned about a promethazine interaction, contact your healthcare provider. Even though you may not need to change your medications, it doesn’t hurt to check.

They may already be aware of possible interactions with promethazine. Medications are sometimes still prescribed even if there may be an interaction. Not all interactions are harmful and just need extra monitoring. But some interactions can be serious and may require you to change medications.

Talk to your healthcare provider if you’re experiencing side effects that bother you. This could include too much sleepiness, dry mouth, or agitation. If your drowsiness is severe, or if you feel like your breathing is too slow, get medical attention right away.

How can I avoid or manage potential interactions with promethazine?

Talking to your healthcare provider or pharmacist is the best way to manage interactions. They can check your medications for any potential issues. They can also suggest safe medication changes, if needed.

It’s also a good idea to have your medication list with you anytime you’re starting a new medication. This can help your healthcare provider avoid serious interactions when prescribing a new medication. They may already have a list of your medications. But sometimes it’s missing things like over-the-counter products or supplements. 

You should also always be honest with them about how much alcohol you drink. This will help them know when there might be an issue with your medication. 

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

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