6 Pregabalin Interactions to Watch Out for

Pregabalin (Lyrica) is a medication that’s used to treat several medical conditions. It’s FDA approved to treat fibromyalgia, nerve pain, and seizures in some people. It’s similar to its “sister” medication, gabapentin (Neurontin). 

Both medications work by mimicking the effects of a natural chemical in the body called gamma-aminobutyric acid (GABA). GABA relaxes the body and slows down the brian. This can help relieve nerve pain and prevent seizures. But pregabalin is a controlled substance in all U.S. states because it has a risk of dependence and addiction.

Pregabalin can interact with other medications and substances that have similar side effects. This includes those that can make you drowsy. Some interactions just need extra monitoring. But others may require a change in medications. Below, we’ve detailed some pregabalin interactions you should know about.

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1. Opioids

Opioids are medications that treat different types of pain. They work by changing the way the brain responds to pain. A couple examples include hydrocodone/acetaminophen and oxycodone (Oxycontin, Roxicodone). Like pregabalin, opioids are controlled substances.

Opioids are typically reserved for pain that can’t be controlled by non-opioid medications. This is because they can cause serious side effects and risks, especially with high doses and/or long-term use. These risks include dependence, addiction, and even overdose.

Pregabalin and opioids both affect the brain and cause tiredness, dizziness, and trouble with coordination. So these effects are more likely to happen if they’re taken together. 

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In serious cases, you may be more likely to develop trouble breathing with this combination. This is especially the case if you’re older and/or have underlying breathing problems. It can also make an opioid overdose more likely. This can be life-threatening. In fact, the FDA issued a warning about this interaction in 2019. 

It’s best to avoid combining opioids with pregabalin. But if your healthcare provider believes you need both, they may lower your doses. And they’ll ask you to monitor closely for symptoms of an interaction. This includes extreme sleepiness, confusion, and difficulty breathing. If you develop any of these symptoms, you should seek emergency help immediately.

2. Benzodiazepines

Benzodiazepines (BZDs) treat many health conditions, including anxiety, insomnia, and panic disorder. Like pregabalin, they work by affecting GABA. BZDs make GABA more active, which has a calming effect on the brain. Examples of BZDs include lorazepam (Ativan), diazepam (Valium), and alprazolam (Xanax).

Like pregabalin, BZDs are controlled substances. And they may interact in a way that's similar to pregabalin and opioids. The main concern is a risk for too much sedation, which can lead to trouble breathing.

It’s best to avoid taking BZDs with pregabalin, if possible. Your healthcare provider may recommend alternative medications to avoid this interaction. But, if they think both medications are needed, they may lower the doses. You should watch for symptoms of extreme drowsiness and slowed breathing. Seek emergency medical care if you notice these symptoms.

3. Antihistamines

Antihistamines are a group of medications that treat various medical conditions. This includes itching, allergies, and some symptoms of the common cold — just to name a few. Some antihistamines can be found in over-the-counter (OTC) sleep aids and motion sickness pills. 

Antihistamines work by blocking the effects of histamine. Histamine is a natural chemical in the body that causes many different effects. For example, it’s the driving force behind allergies. 

Some antihistamines are prescription-only. Others are available OTC. Examples include:

• Doxylamine (Unisom SleepTabs)

• Diphenhydramine (Benadryl, ZzzQuil)

• Meclizine (Antivert, Bonine, Dramamine Less Drowsy)

• Hydroxyzine

Some antihistamines are known to cause drowsiness. Sometimes they’re even used specifically for this reason, like doxylamine and diphenhydramine. Antihistamines that cause drowsiness can interact with pregabalin by causing too much sedation. 

Because many antihistamines are OTC, your healthcare provider may not know if you’re taking one. Always let them know what medications you're taking, including OTC products. If you need antihistamines for allergies or another condition, your provider may recommend one that doesn’t cause sleepiness. Examples might include loratadine or fexofenadine.

4. Other medications that cause drowsiness

Many other medications can cause drowsiness. This includes a broad group of medications called sedatives. They treat a wide range of medical conditions, including sleep problems and seizures. 

Sedative medications include sleep medications like zolpidem (Ambien, Edluar, and ZolpiMist). They also include barbiturates like phenobarbital. Benzodiazepines, which we discussed earlier, are also considered sedatives.

In general, any medication that causes drowsiness can interact with pregabalin. And many medications can cause sleepiness, even some you might not expect. For example, muscle relaxants — like cyclobenzaprine (Amrix) and baclofen (Ozobax) — can cause drowsiness. Antipsychotic medications, like olanzapine (Zyprexa) and quetiapine (Seroquel), can also cause drowsiness.

If you take pregabalin, your healthcare provider may want you to avoid medications that cause drowsiness. But it might not always be possible. If you're prescribed pregabalin and another medication that causes sleepiness, watch for symptoms of excess sedation. Seek emergency care if you experience extreme sleepiness or difficulty breathing.

5. Glitazones

Glitazones are a group of diabetes medications that include Avandia (rosiglitazone) and Actos (pioglitazone). These medications can cause fluid buildup (edema). This is also a potential side effect of pregabalin.

Research shows that when pregabalin and a glitazone are combined, edema and weight gain are more likely. In severe situations, this could lead to heart failure, or make existing heart failure worse. 

Talk to your healthcare provider about the risks and benefits of starting pregabalin if you take a glitazone. They may recommend avoiding this combination. 

6. Alcohol

While alcohol isn’t considered a medication, it can interact with many medications. In fact, it has multiple effects on almost every organ in the body, including the brain. Alcohol’s effects on the brain can affect your mood, alertness, and how well you breathe. 

Alcohol can also make you drowsy. If you drink alcohol and take pregabalin, it can cause excessive sleepiness. You could develop difficulty breathing in severe cases.

Avoiding alcohol while taking pregabalin is probably the safest bet. If you do drink alcohol, make sure your healthcare provider knows. They can weigh the risks and benefits of this combination with you.

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

If you’re worried about a pregabalin interaction, talk to your healthcare provider. It’s best to do this before starting pregabalin. It’s usually best to prevent an interaction rather than manage it when it happens.

Your provider and pharmacist can help you check for pregabalin interactions. They can do this by reviewing an up-to-date medication list. This is a list of all the medications you take. Make sure to include prescription and OTC medications and supplements. If you drink alcohol, talk to your healthcare provider about that too.

If you’re feeling more sleepy than usual while taking pregabalin, let your provider know. This could be a sign of an interaction. If you have severe symptoms, like excessive drowsiness or slowed breathing, seek immediate medical care.

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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:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed 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.

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