11 Percocet Interactions To Watch For

Percocet is an opioid medication made up of two active ingredients: oxycodone and acetaminophen. It’s FDA approved to treat pain that can’t be managed by non-opioid medications.

Opioids like Percocet have many possible risks, including side effects and drug interactions. Here, we’ll discuss 11 possible Percocet interactions.

1. Acetaminophen-containing medications

Acetaminophen is an ingredient in several over-the-counter (OTC) medications. Examples include NyQuil Cold and Flu (acetaminophen / dextromethorphan / doxylamine) and Excedrin Migraine (acetaminophen / aspirin / caffeine).

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If you take Percocet with other medications that contain acetaminophen, you’ll want to make sure you’re not getting too much of this ingredient. Large amounts of acetaminophen can increase your risk of liver damage or cause an acetaminophen overdose.

Most adults can take up to 4,000 mg per day of acetaminophen. But if you’re taking it for more than 7 days in a row, 3,250 mg per day may be a safer dosage. An even lower dosage (or avoiding acetaminophen entirely) may be best if you have a history of liver problems.

If you take an OTC product with Percocet, make sure you read the medication label to check for acetaminophen. And ask your pharmacist to help you calculate how much acetaminophen you’re getting with the combination.

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2. Alcohol

Alcohol can cause drowsiness and impair your ability to think clearly. This is especially true if you drink it in large amounts or become intoxicated. Because of these effects, alcohol can interact with several medications.

Drowsiness and dizziness are common side effects of opioids like Percocet. More serious side effects, such as slowed breathing, coma, and overdose, can also occur with opioids. This risk of these serious side effects is much lower when Percocet is taken as prescribed. But when it’s combined with alcohol or medications that slow down breathing, the risks is much greater.

Additionally, drinking a lot of alcohol while taking acetaminophen can cause liver damage. This is another reason to completely avoid alcohol while taking Percocet.

Good to know: Alcohol is an ingredient in several OTC medications (especially liquid medications, such as Nyquil Cold and Flu). These medications should also be avoided if you take Percocet. Ask your pharmacist to help you check the label for alcohol anytime you pick up an OTC medication.

3. Benzodiazepines

Benzodiazepines are medications that treat several mental health conditions, including anxiety and panic disorders. Examples include Xanax (alprazolam) and Ativan (lorazepam).

Benzodiazepines and Percocet have several side effects in common, including drowsiness and dizziness. More seriously, they can both cause slowed breathing and overdose, especially when combined. Combining Percocet and benzodiazepines isn’t recommended in most cases. In fact, all opioids and benzodiazepines carry a boxed warning about the risks of this combination. A boxed warning is the most serious type of warning that the FDA can apply to a medication.

4. Non-benzodiazepine sleep medications

There are several medication options when it comes to treating insomnia (trouble sleeping). This includes prescription-only options like Ambien (zolpidem) and Lunesta (eszopiclone). It also includes OTC sleep medications like Unisom SleepTabs (Doxylamine) and Benadryl (diphenhydramine).

It’s best to avoid taking sleep medications while taking Percocet. Sleep medications can worsen drowsiness with Percocet. This could lead to trouble with coordination, slowed breathing, and overdose.

If you take Percocet and you’re experiencing insomnia, there are lifestyle modifications that may help. These include avoiding caffeine in the afternoon and evening, and trying to limit your naps to 15 to 20 minutes only. Additionally, creating a consistent bedtime routine may help you sleep more soundly.

If lifestyle modifications don’t help, talk to your prescriber about what else you can try. Melatonin supplements may be an option. While melatonin can still cause increased drowsiness when used taken opioids, it may be a safer option than other sleep medications.

5. Other medications that cause drowsiness

In addition to the medications and substances listed above, other types of medications can cause drowsiness. Some examples include:

• Hydroxyzine (Vistaril)

• Muscle relaxers, such as cyclobenzaprine (Amrix) and tizanidine (Zanaflex)

• Antidepressants like trazodone and mirtazapine (Remeron)

• Seizure medications like topiramate

Since several medications can cause drowsiness, it’s important to give your healthcare professional and pharmacist a list of all of the medications you take. This list should include any OTC products and supplements you take, as well. They can let you know if any of your medications may interact with Percocet.

6. Warfarin

Warfarin (Coumadin, Jantoven) is commonly used to prevent blood clots. As a result, one of its possible side effects is bleeding.

The acetaminophen in Percocet may increase the risk of bleeding with warfarin. Although there’s not a lot of research on this interaction, it is possible. So be sure to let your prescriber know if you’re taking warfarin. They may order more frequent blood tests to make sure that your warfarin dosage is appropriate.

If you’re taking warfarin with Percocet (or any other acetaminophen-containing product), watch for signs of unusual bleeding or bruising. This may include bruises that have no known cause, blood in the stool or urine, or more frequent nose bleeds. Contact your prescriber right away if you experience any of these symptoms. And if you have bleeding that is severe or won’t stop, seek immediate care by calling 911 or going to the emergency room.

7. Isoniazid

Isoniazid is an antibiotic that’s prescribed to prevent and treat tuberculosis. Taking isoniazid with acetaminophen can cause acetaminophen to break down into a toxic chemical. This can increase your risk of liver damage.

If you’re taking isoniazid, talk to your prescriber about this potential interaction. They may recommend avoiding Percocet and other acetaminophen-containing medications entirely. Or they may monitor you for signs of liver damage, like extreme tiredness, dark urine, or yellowing of the skin and eyes (jaundice).

8. Medications that affect Percocet levels

Oxycodone and acetaminophen are metabolized by certain liver proteins. Medications and substances that block these proteins can increase levels of Percocet in the body. High oxycodone levels can raise your risk of drowsiness and slowed breathing, which can be life-threatening.

Medications and substances that can increase oxycodone levels when taken with Percocet include:

• Medications containing ritonavir (Norvir) 

• Some antibiotics, such as erythromycin (Ery-tab) and clarithromycin

• Some antidepressants, such as fluoxetine (Prozac) and paroxetine (Paxil) 

• Some antifungals, such as ketoconazole and itraconazole (Sporanox)

• Grapefruit juice

On the other hand, some medications can decrease oxycodone levels. This can make Percocet less effective. Examples include:

• Rifampin

• Phenobarbital

• Phenytoin (Dilantin, Phenytek)

• Carbamazepine (Tegretol)

Interestingly, phenobarbital, phenytoin, and carbamazepine can also increase acetaminophen levels. And high acetaminophen levels can increase your risk of liver damage.

Ask your pharmacist or prescriber to check for interactions anytime you start or stop a medication while taking Percocet. They can let you know whether you need to make any changes to your medication regimen.

9. Medications that increase serotonin levels

Certain medications, including the oxycodone in Percocet, can increase serotonin levels in your body. Serotonin is involved in many bodily processes, such as regulating your mood. But too much of this chemical can cause serotonin syndrome.

It’s rare for oxycodone to cause serotonin syndrome on its own. But taking it with other medications that increase serotonin can make this side effect more likely. Some medications that can increase serotonin levels include:

• Monoamine oxidase inhibitors (MAOIs), such as selegiline (Zelapar, Emsam)

• Tricyclic antidepressants, such as amitriptyline

• Triptans, such as sumatriptan (Imitrex)

• Selective serotonin reuptake inhibitors, such as fluoxetine

• Serotonin and norepinephrine reuptake inhibitors, such as Cymbalta (duloxetine)

• Other opioids, such as tramadol (Ultram, Conzip, Qdolo)

Your prescriber may recommend watching for symptoms of serotonin syndrome if you take Percocet with any of these medications. Possible symptoms include increased heart rate, sweating, and tremors. But in more severe cases, people may experience a high fever, hallucinations, and seizures.

10. Naltrexone

Opioid blockers (also called opioid antagonists) are used to block the effects of opioids and alcohol. Naltrexone (Vivitrol) is one example that’s used to treat alcohol use disorder and opioid use disorder.

If you take naltrexone, you shouldn’t take opioids. In fact, you may need to avoid opioids for a week or more before taking naltrexone. This is because taking naltrexone and Percocet together can lead to opioid withdrawal symptoms. Opioid withdrawal isn’t usually life-threatening, but it can be uncomfortable. Symptoms of opioid withdrawal include nausea, diarrhea, and anxiety.

Good to know: Don’t confuse naltrexone with naloxone (Narcan, Zimhi). Although naloxone is also an opioid blocker, it’s used to reverse the effects of an opioid overdose. If you’re prescribed Percocet, it’s a good idea to carry naloxone on you at all times. It’s available OTC without a prescription, but you can also ask your healthcare professional for a prescription and your insurance may cover the cost.

11. Anticholinergic medications

Anticholinergics are a broad group of medications. Examples include scopolamine (Transderm Scop) and dicyclomine (Bentyl). Benadryl and some antidepressants also have anticholinergic effects.

Anticholinergics can cause several side effects. And some of these side effects overlap with oxycodone side effects, like constipation and trouble peeing. While these side effects are often mild and manageable, they can be more severe for some people. This is especially true for older adults, who are more likely to experience these side effects in general.

If you’re taking Percocet, your prescriber may recommend avoiding anticholinergic medications. Or they may monitor you for signs of an interaction, including worsening constipation or difficulty peeing. Your prescriber can help you check whether any of your medications have anticholinergic effects, as can your pharmacist.

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Written by:

Alexa Mader, PharmD

Alexa Mader has been a practicing pharmacist since 2018. She earned her Doctor of Pharmacy degree from the University of Georgia College of Pharmacy.

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:

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.

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