Opioids

Tramadol vs. Oxycodone: 6 Differences You Should Know

Written by Austin Ulrich, PharmD, BCACP | Reviewed by Alyssa Billingsley, PharmD

Published on October 23, 2023

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Key takeaways:

Tramadol (ConZip, Qdolo) and oxycodone (Roxicodone, Oxycontin) are both opioid pain medications. Although they have many similarities, there are some key differences that set them apart.
Both medications minimize pain by attaching to opioid receptors. But tramadol also affects certain chemicals, which may also help with pain control.
Tramadol and oxycodone are both controlled substances. They can both lead to dependence and misuse, though tramadol is considered less likely to be misused.

Tramadol (ConZip, Qdolo) and oxycodone (Roxicodone, Oxycontin) are two prescription pain medications. At first glance, they might seem quite similar. They’re both opioids and they both treat severe pain not relieved by other treatments. Both medications are also controlled substances. But there are some important distinctions that your healthcare provider may consider when deciding which option is best for you. Below, we’ll cover six key differences between tramadol versus oxycodone.

1. Tramadol and oxycodone are both opioids, but they work in different ways

Opioid medications treat pain by attaching to areas of the body called opioid receptors. These receptors exist throughout the body, including in the brain and stomach. When tramadol or oxycodone attaches to opioid receptors, they block your body’s pain signals. This means that even if you’re in pain, you won’t feel it as intensely.

The difference in how tramadol versus oxycodone works is that oxycodone only affects opioid receptors. But tramadol has other effects on the body. It increases the activity of two chemicals: norepinephrine and serotonin. This may also help lower pain intensity. Additionally, tramadol impacts other bodily processes and chemicals. This may further contribute to its pain-relieving properties.

2. Tramadol is a Schedule 4 medication and oxycodone is a Schedule 2 medication

Both tramadol and oxycodone are controlled substances. This means they have a risk for dependence and misuse. There’s also restrictions around how they’re prescribed and refilled.

The Drug Enforcement Administration designates five different levels of controlled substances. These are called “schedules.” Schedule 1 substances are illegal. They’re the most likely to cause dependence and misuse. Schedule 5 medications are deemed the least likely to cause dependence and misuse.

Tramadol is a Schedule 4 controlled substance. Oxycodone is a Schedule 2 controlled substance. This means that tramadol is considered to have a lower risk of misuse than oxycodone. But tramadol still has the potential to be misused.

If you take an opioid, regardless of which one, it’s important to take the lowest effective dose for the shortest amount of time to minimize your risks.

Good to know: Laws around prescribing and refilling controlled substances may vary from state to state. But in general, schedule 4 controlled substances such as tramadol can only be refilled a maximum of 5 times within 6 months. After 6 months (or five refills), a new prescription will be needed. Schedule 2 prescriptions such as oxycodone can’t be refilled at all. This means each time you need more oxycodone, you’ll need a new prescription from your healthcare provider.

3. Oxycodone and tramadol come in different forms

Oxycodone and tramadol are both oral medications. But they come in different dosage forms. Oxycodone and tramadol are also available in combination pills with other medications.

4. Tramadol and oxycodone may have different side effects

All opioids have possible side effects. These include:

Dizziness
Drowsiness
Constipation
Nausea

More seriously, opioids can slow down your breathing, especially if taken in a way they aren’t prescribed. Slowed breathing is a warning sign of an opioid overdose, which can be fatal. Overdoses are more likely to happen with high doses of opioids, or when they’re combined with other substances that can lead to overdose, such as benzodiazepines or alcohol. While any opioid can cause overdose, this risk may be lower with tramadol than with oxycodone. However, it’s still possible. Overdoses and tramadol-related deaths have increased in recent years.

There are also two serious side effects that are more likely with tramadol than oxycodone:

Seizure risk: The risk for seizures, especially in people who have an existing seizure condition, is higher with tramadol. And the risk is even higher if tramadol is combined with other medications that also raise the risk of seizures.
Serotonin syndrome: Tramadol is more likely than oxycodone to increase the risk of a condition called serotonin syndrome. This is a rare condition that can happen when serotonin levels are too high in the body. It’s usually mild, but can become a medical emergency in some cases. It’s highly unlikely to occur with tramadol alone. Rather, it’s more likely to occur when tramadol is combined with other medications that also affect serotonin.

Good to know: If you take an opioid, it’s a good idea to keep naloxone (Narcan, Zimhi) on hand. This is a life-saving medication that can reverse the effects of an opioid overdose. You can find it over the counter. If you or someone you know struggles with substance use, help is available. Call SAMHSA’s National Helpline at 1-800-662-4357 to learn about resources in your area.

5. Tramadol and oxycodone may have different drug interactions

Tramadol and oxycodone can both interact with other medications and substances. For example, both medications can interact with:

Alcohol
Benzodiazepines like alprazolam (Xanax)
Sleep medications like zolpidem (Ambien)
Some OTC medications like diphenhydramine (Benadryl)
Opioid antagonists like naltrexone (Vivitrol)

But tramadol may be more likely to react with medications that increase serotonin, since it increases serotonin itself. This includes a variety of antidepressants, such as fluoxetine (Prozac), escitalopram (Lexapro), and sertraline (Zoloft). It’s also more likely to interact with medications that increase your seizure risk, such as bupropion (Wellbutrin) and clozapine (Clozaril).

Check out our other GoodRx articles for a more in-depth look at tramadol interactions and oxycodone interactions.

Can you take tramadol and oxycodone together?

Generally, you shouldn’t combine opioid medications like tramadol and oxycodone. This raises the risk for side effects, including overdose and difficulty breathing. And, it can increase the risk for misuse and dependence.

However, in some medical conditions, combining opioids may be necessary for pain relief. For example, people with pain from cancer may need a long-acting and short-acting opioid. But this should only be done under the close supervision of a healthcare provider.

The bottom line

Tramadol and oxycodone are both opioid medications. They’re approved to treat pain that can’t be relieved by non-opioid treatments. But when comparing tramadol versus oxycodone, there are several differences your healthcare provider may consider.

Tramadol and oxycodone work in slightly different ways and come in different forms. And while they share common side effects, tramadol is more likely to cause seizures and serotonin syndrome in some cases. Tramadol is also considered to have a lower risk of misuse and dependence compared to oxycodone. However, these risks are possible with any opioid. That’s why it's best to take the lowest effective dose for the shortest amount of time possible.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. Ulrich’s experience includes direct patient care in hospital and community pharmacies.

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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References

Baldo, B. A. (2018). Opioid analgesic drugs and serotonin toxicity (syndrome): Mechanisms, animal models, and links to clinical effects. Archives of Toxicology.

Barakat, A. (2019). Revisiting tramadol: A multi-modal agent for pain management. Central Nervous System Drugs.

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.