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Drug vs. Drug

Tramadol vs. oxycodone: Differences, similarities, and which is better for you

Tramadol and oxycodone both treat severe pain, but work differently. Here’s what to know.
Tramadol vs Oxycodone drug comparison

Key takeaways

  • Tramadol and oxycodone are both prescription opioid pain relievers used in the treatment of severe pain and persistent severe pain that has not responded to non-opioid treatments.

  • Tramadol and oxycodone are CNS depressant medications that can have dangerous and addictive side effects. They are both categorized as controlled substances by the Drug Enforcement Administration (DEA).

  • Opioids are generally meant for very short-term and limited use in acute severe pain. However, tramadol and oxycodone can be used for an extended period when necessary for persistent severe pain.

  • There can be very dangerous interactions with other medications, so your doctor and pharmacist need to be aware of all other medications you take and any other medical conditions you may have.

Tramadol and Oxycodone are prescription pain relievers that may be prescribed to you for moderate to severe pain when other treatments have not worked. Tramadol and oxycodone interact with opioid receptors in the brain to reduce pain signal transmission. They may be used to treat various pain types, including musculoskeletal pain and post-surgical pain. While they may be used in similar pain types, these two drugs are unique and different from each other.

Main differences between tramadol and oxycodone
Tramadol Oxycodone
Drug class Mu-opioid analgesic Opioid analgesic
Brand/generic status Brand and generic available Brand and generic available
What is the brand name? Ultram, Ultram ER, ConZip, Ryzolt, Rybix Roxicodone, OxyOR, Oxycontin, Oxaydo, Xtampza ER
What form(s) does the drug come in? Immediate-release and extended-release tablet Immediate-release and extended-release tablet, oral liquid concentrate
What is the standard dosage? 50 mg every 4-6 hours 5 mg to 15 mg every 4-6 hours
How long is the typical treatment? 7 days or less 7 days or less
Who typically uses the medication? Children 12 years of age and older, adults Infants, children, adults

What are the main differences between tramadol and oxycodone?

Tramadol is a prescription opioid analgesic used to treat pain described as severe for which over-the-counter or other non-opioid options have failed to help. It can also be used in acute traumatic pain, such as post-operative pain, where it is reasonable to assume that less potent options would leave the patient in unreasonable pain. While the use of opioid pain relievers generally tends to be for a short and limited time, tramadol can be used for extended treatment in someone with persistent severe pain for which other non-opioid options are inadequate. Tramadol interacts with mu-opioid receptors in the central nervous system (CNS). This alters the body’s perception and response to pain through the ascending pain pathways. Tramadol also inhibits the reuptake of norepinephrine and serotonin neurotransmitters, which are also in the descending pathway. 

When tramadol originally came to market, it was not classified as a controlled substance. In 2014, the Drug Enforcement Administration (DEA) re-classified tramadol as a Schedule IV controlled substance. Tramadol has the potential to be abused or misused, and its use should be monitored closely. 

Tramadol is available as an oral tablet in both immediate-release and extended-release formulations. It is also available in a tablet in combination with acetaminophen, the active ingredient in over-the-counter Tylenol. 

Oxycodone is also a prescription opioid pain reliever. Like tramadol, it can be used in severe and persistent severe pain for which other options have failed to provide relief. Oxycodone binds to opioid receptors in the CNS pathway, causing inhibition in the ascending pain pathway. This alters perception and response to pain and causes generalized CNS depression.

Oxycodone is a Schedule II controlled substance. It has a very high potential for addiction, abuse, and misuse.

Oxycodone is available as an oral tablet in both immediate-release and extended-release formulations. It is also available in formulations that combine it with acetaminophen, aspirin, ibuprofen, naloxone, or naltrexone.

Conditions treated by tramadol and oxycodone

Tramadol is indicated for the management of moderate to severe pain. It can be used in acute pain, such as postoperative pain, though its use should be limited to short-term use, typically three to seven days. Tramadol can also be used in chronic pain management for persistent, severe pain, though it is not typically a first choice for this indication.

Tramadol has been used to relieve restless leg syndrome in patients who have had little or no success with traditional treatments. This use is considered off-label, meaning it has not been approved by the Food and Drug Administration (FDA) for this type of use.

Oxycodone is also indicated in the management of pain classified as severe. It can be used in acute pain but should be limited to three to seven days. Oxycodone can be used in chronic pain as well. Due to its severe CNS depressive effects, oxycodone must be titrated slowly up in dose.

Condition Tramadol Oxycodone
Acute pain is classified as moderate to severe Yes Yes
Chronic pain Yes Yes
Premature ejaculation Off-label No
Restless leg syndrome Off-label Off-label
Diabetic neuropathy Off-label Off-label
Osteoarthritis Off-label No

Is tramadol or oxycodone more effective?

Oxycodone has long been regarded as more potent than tramadol. Pain relievers are commonly compared based on morphine-equivalent dosing. Oxycodone is 1.5 times more potent than morphine, while tramadol has negligible potency compared to morphine. 

One study compared pain control after facial surgery using tramadol and oxycodone. In this study, the drugs were administered intravenously through a patient-controlled device. Pain control was similar between the two groups, with no statistical difference. Tramadol does not cause respiratory depression to the degree that oxycodone does. However, patients experienced more nausea with tramadol. Researchers concluded that tramadol provided pain relief comparable to oxycodone without the risk of severe respiratory depression.

Coverage and cost comparison of tramadol vs. oxycodone

Medicare and commercial drug insurance plans typically cover Tramadol, though some limitations may apply. In response to the opioid epidemic, many prescribing limitations and guidelines went into effect in 2019 and have been updated as recently as January 2025. Medicare Part D beneficiaries who are opiate naive are limited to a seven-day prescription upon an initial fill of an opiate. Opiate naive is defined as not having taken an opiate in the past 60 days. After seven days, if additional medication is needed, prescribers may prescribe a longer-term. There are exceptions to these rules, such as hospice and cancer-related care. Some chronic pain diagnoses qualify for prescribing exceptions as well. Many commercial insurance plans have adopted similar limitations for their beneficiaries. Pharmacies may also have their own specific policies for the filling of opiate medications.

Tramadol can cost as much as $33 for 30 tablets of the 50 mg strength. However, with a coupon from SingleCare, you could purchase this prescription generically for as little as $8.

The average retail price for Oxycodone can be over $35 for 300 tablets of the 5 mg strength. With a coupon from SingleCare, you can fill this prescription for under $9 at select pharmacies.

Tramadol Oxycodone
Typically covered by insurance? Yes, with limitations Yes, with limitations
Typically covered by Medicare? Yes, with limitations Yes, with limitations
Standard dosage 60, 50mg tablets 120, 10mg tablets
Typical Medicare copay Typically less than $10 Typically less than $10
SingleCare cost $12-$30 $37-$52

Common side effects of tramadol and oxycodone

The side effects of tramadol and oxycodone are primarily due to their interaction with the central nervous system. Both drugs are likely to cause headaches, drowsiness, and dizziness due to their CNS depressive effects. The adverse events can be severe and may inhibit normal daily activity.

Opiate pain relievers are known to cause constipation, sometimes severe. It may be necessary to take preventative medications for constipation while on pain relievers. Prolonged constipation may require more harsh laxatives.

The following chart is not intended to be a comprehensive list of side effects. Please consult a medical professional such as your doctor or pharmacist for a complete list.

Norco Vicodin
Side effect Applicable? Frequency Applicable? Frequency
Somnolence Yes 16%-25% Yes Not defined
Headache Yes 18%-32% Yes Not defined
Dizziness/ Lightheadedness Yes 26%-33% Yes Not defined
Constipation Yes 24%-46% Yes Not defined
Nausea Yes 24%-40% Yes Not defined
Vomiting Yes 9%-17% Yes Not defined
Pruritus Yes 8%-11% Yes Not defined
Sweating Yes 6%-9% Yes Not defined
Dyspepsia Yes 5%-13% Yes Not defined
Dry mouth Yes 5%-10% Yes Not defined
Diarrhea Yes 5%-10% Yes Not defined

Source: Tramadol (DailyMed) Oxycodone (DailyMed)

Drug interactions of Tramadol vs. Oxycodone

The use of tramadol and oxycodone with other CNS depressant drugs should be avoided when possible. Drugs such as alprazolam and diazepam, as well as other opiate painkillers, may cause a dangerous level of CNS depression when used with tramadol or oxycodone. Patients may exhibit severe respiratory depression, profound sedation, low blood pressure, coma, or even death.

Drugs that affect the serotonergic receptors, such as fluoxetine or sertraline, should be used cautiously in patients who take tramadol or oxycodone. There is the potential for an increased likelihood of serotonin syndrome, which can be characterized by increased heart rate, high blood pressure, confusion, and tremors. This may be more likely when being treated chronically with tramadol or oxycodone.

The following table is not intended to be a complete list of potential drug interactions. Consult a medical professional for a complete list and advice on interactions.

Drug Drug Class Tramadol Oxycodone
Alprazolam

Clonazepam

Diazepam

Midazolam

Triazolam

Temazepam

Benzodiazepines Yes Yes
Cannabidiol (CBD)

Cannabis

Dronabinol

Cannabinoids Yes Yes
Carbamazepine

Phenobarbital

Anti-epileptics Yes Yes
Dabrafenib

Erdafitinib

Immunosuppressive agents Yes Yes
Desmopressin Vasopressor Yes Yes
Aprepitant

Fosaprepitant

Antiemetics Yes Yes
Granisetron

Dolasetron

Ondansetron

Palonosetron

Ramosetron

Tropisetron

5HT3 Antagonists Yes No
Hydrochlorothiazide

Furosemide

Torsemide

Spironolactone

Diuretics Yes Yes
Isoniazid Antitubercular  No Yes
Naltrexone Opiate antagonist Yes Yes
Phenelzine

Linezolid

Monoamine oxidase inhibitors Yes Yes
Oxycodone Opiate Yes Yes
Pramipexole

Ropinirole

Dopamine agonists Yes Yes
Probenecid Uricosuric No Yes
Ritonavir

Ombitasvir

Paritaprevir

Dasabuvir

Antivirals Yes Yes
Zolpidem Sedative Yes Yes
Fluoxetine

Sertraline

Paroxetine

Selective serotonin reuptake inhibitors Yes Yes

Warnings of tramadol and oxycodone

1. Alcohol

Alcohol use should be avoided in patients who take oxycodone. Alcohol could increase the serum concentration of oxycodone and, therefore, enhance the CNS depressant effects. This could lead to dangerous levels of respiratory depression.

2. Liver and Kidney Function

Prescribers may need to adjust the dose or dosing interval of both tramadol or oxycodone in patients who have liver damage or impaired kidney function. Renal and hepatic impairment will affect how these drugs are processed and allow them to remain in the bloodstream longer.

3. Pregnancy and Breastfeeding

Tramadol and oxycodone are pregnancy category C, meaning there are no human studies proving harm or safety in pregnant patients. The use of these drugs should be limited to only absolutely necessary use. Oxycodone is present in the breast milk of lactating mothers, and breastfeeding mothers should only use oxycodone when the benefit clearly outweighs the risk. Tramadol should not be used in breastfeeding mothers as its active metabolite is more potent and can result in opioid withdrawal in infants.

4. Use in Children

Opiate pain relievers should only be used in children when absolutely necessary, typically in an in-patient setting where they can be monitored. The severe risk of respiratory depression makes these drugs very dangerous in children.

5. History of Substance Abuse

Tramadol and oxycodone each have a high potential for abuse, misuse, physical dependence, and addiction. They should only be used when all other non-opiate treatment options have been exhausted. Their use should be limited to as short of a term as possible. If a patient has been taking opiate pain relievers for an extended period, they may be prone to withdrawal symptoms if they stop abruptly. Discontinuation after high doses and long-term use of opioid analgesics should be done with physician oversight.

Frequently asked questions about tramadol vs. oxycodone

Are tramadol and oxycodone the same?

While both tramadol and oxycodone are opiate pain relievers, they are not the same. Oxycodone is a Schedule II narcotic and causes significant CNS depression, including respiratory depression. Tramadol is a Schedule IV controlled substance and does not cause a significant amount of respiratory depression.

Is tramadol or oxycodone better?

Oxycodone is 1.5 times the potency of morphine, while tramadol is only a fraction of the potency of morphine. However, a study done on post-surgical patients found similar pain relief with both drugs. Tramadol causes less respiratory depression, but other side effects, such as nausea, may be worse with Tramadol.

Can I use tramadol or oxycodone while pregnant?

The use of tramadol or oxycodone when pregnant should be limited to only when absolutely necessary, as there have been no randomized, controlled human trials to prove their safety. The benefits of use must outweigh the risks, and infants should be monitored for opioid withdrawal syndrome if these drugs are used long-term.

Can I use tramadol or oxycodone with alcohol?

Patients taking tramadol or oxycodone should avoid alcohol use. Alcohol may enhance the CNS depressive effects of these drugs, which can lead to serious adverse events such as respiratory depression, coma, or death.

Which is stronger: tramadol or oxycodone? 

The potency of opioids is measured in morphine equivalent dosing. Oxycodone is 1.5 times the potency of morphine, while tramadol is only a fraction of the potency of morphine. Clinically, despite this difference, their pain relief of some acute pain symptoms may be similar.