Fentanyl vs. oxycodone: Differences, similarities & risks

In this article:

• Key differences
• Conditions treated
• Is fentanyl stronger than oxycodone?
• Coverage and cost
• Side effects
• Interactions and warnings

In this article

• Key differences
• Conditions treated
• Is fentanyl stronger than oxycodone?
• Coverage and cost
• Side effects
• Interactions and warnings

Fentanyl and oxycodone are two potent opioid medications used to treat severe pain. These prescription drugs work by binding to opioid receptors in the brain and body to reduce pain signals. If you go through a serious injury or experience chronic pain that won’t respond to regular painkillers, a healthcare provider may prescribe one of these medications.

Both fentanyl and oxycodone are generic opioid pain relievers that are also available in brand-name versions. They’re meant to be used for a short time. Both drugs are classified as Schedule II controlled substances, which means they have a high potential for abuse, misuse, and dependence. Therefore, it’s important to use them only with guidance from a healthcare provider.

Read on to learn more about the similarities and differences between fentanyl and oxycodone. 

Fentanyl vs. oxycodone: Key differences

Although fentanyl and oxycodone work similarly as opioid analgesics (painkillers), they have several differences. Fentanyl is a generic synthetic opioid that was first approved in 1968 by the Food and Drug Administration (FDA). It’s available as a lozenge, patch, injection, and sublingual (placed under the tongue) or buccal (placed inside the cheek) tablet. 

Oxycodone is a generic semi-synthetic opioid first approved by the FDA in 1950. It’s typically taken as an immediate-release or extended-release tablet or capsule. Oxycodone is also available as a liquid oral solution.

The dosages of fentanyl and oxycodone can vary depending on the type of pain being treated and how a person responds to treatment. Fentanyl is considered more potent than oxycodone and is one of the strongest opioids available. It also has a longer duration of action than oxycodone: A fentanyl patch can last up to 72 hours, while an oxycodone immediate-release tablet lasts for around three to four hours. However, oxycodone is also available in extended-release versions that can last for up to 12 hours.

Compare fentanyl vs. oxycodone key differences
	Fentanyl	Oxycodone
Drug class	Opioid	Opioid
Brand/generic status	Brand and generic available	Brand and generic available
What is the brand name?	Actiq, Duragesic, Fentora, Sublimaze	Roxybond, Roxicodone, Percodan, Oxycontin, Xtampza ER
What forms does the drug come in?	Lozenge, sublingual tablet, buccal tablet, patch, injection	Tablet, capsule, extended-release tablet, extended-release capsule, liquid oral solution
What is the standard dosage?	Dosage depends on pain severity, response to treatment, previous use of other pain relievers, and potential risk for addiction or misuse	Dosage depends on pain severity, response to treatment, previous use of other pain relievers, and potential risk for addiction or misuse
How long is the typical treatment?	Short-term or long-term with medical supervision	Short-term or long-term with medical supervision
Who typically uses the medication?	Adults	Adults

Fentanyl vs. oxycodone: Conditions treated

Fentanyl and oxycodone are approved by the FDA to treat moderate to severe pain that doesn’t get better with non-opioid medications. They are usually reserved for situations when other pain relievers, like nonsteroidal anti-inflammatory drugs (NSAIDs), aren’t effective enough. Fentanyl, in particular, is often prescribed for patients who have already been using other opioids like morphine or oxycodone for at least a week. 

These drugs are commonly used to manage acute pain following surgery or a major injury. In addition to postoperative pain, they may also be prescribed for chronic pain associated with conditions like cancer. However, they are not generally recommended for long-term use due to the risk of addiction and potential overdose. Healthcare providers try to prescribe the smallest effective dose for pain control and for the shortest time necessary to minimize risks.

Compare fentanyl vs. oxycodone conditions treated
Condition	Fentanyl	Oxycodone
Pain so severe that it requires the use of an opioid, and when other treatments are inadequate	Yes	Yes

Is fentanyl stronger than oxycodone?

Both opioids are potent and effective for pain relief. However, fentanyl may have a stronger analgesic effect than oxycodone. For comparison, oxycodone is up to two times stronger than morphine. On the other hand, fentanyl is around 50–100 times stronger than morphine. Therefore, after doing the math, fentanyl could be 25 to 50 times stronger than oxycodone. 

Still, some studies suggest that fentanyl and oxycodone provide similar pain relief in real-world applications. In one study, patients who used oxycodone for pain relief after laparoscopic cholecystectomy, a procedure to remove the gallbladder, required less medication than those who used fentanyl. However, the oxycodone group experienced more nausea between six and 24 hours post-operation. Despite these differences, there were no significant differences in overall patient satisfaction or other side effects between the two groups.

Another study looked at the use of oxycodone and fentanyl after laparoscopic hysteromyomectomy, a minimally invasive surgery to remove uterine fibroids. Both medications provided similar pain scores, but more patients were more satisfied with oxycodone (73.3%) than fentanyl (36.7%). In addition, patients taking oxycodone had fewer headaches after the surgery.

Effectiveness can also depend on the amount of fentanyl or oxycodone taken and how each person reacts to the medication. It’s important to use these opioids only with medical guidance to ensure they are safe and effective.

Fentanyl vs. oxycodone: Insurance coverage and cost comparison

Fentanyl and oxycodone are available in both generic and brand-name forms. Many insurance and Medicare plans usually cover these drugs, but coverage can vary based on the insurance plan. Prices may also vary depending on the pharmacy location and whether a person has met their deductible. Patients may need prior authorization from their healthcare provider, especially for fentanyl, due to its high potency.

Retail prices for prescription opioids can change based on the pharmacy, dosage form, and the quantity purchased. Without insurance, the cost of oxycodone is roughly $310 per month, while fentanyl’s average cost can hover around $178. The availability of these medicines can depend on the demand and supply at your local pharmacy.

You may be able to save on retail prescription costs with discount cards like SingleCare. These cards often provide helpful savings on pain medicine, especially for those without insurance. With your SingleCare card or the SingleCare app, you can access coupons for fentanyl or oxycodone to bring the cost down to $39 and $77, respectively. 

Compare fentanyl vs. oxycodone cost & coverage
	Fentanyl	Oxycodone
Typically covered by insurance?	Yes	Yes
Typically covered by Medicare Part D?	Yes	Yes
Quantity	2 boxes of 5 patches each	20, 5 mg tablets
SingleCare cost	$39	$77

 

Fentanyl vs. oxycodone side effects

As part of the same drug class, fentanyl and oxycodone share many of the same side effects. The most common side effects of opioid pain medications include central nervous system (CNS) depressant effects like drowsiness, dizziness, insomnia, weakness, fatigue, and headaches. These medications can also cause gastrointestinal side effects such as nausea, vomiting, constipation, and diarrhea. In addition, increased sweating and itching are possible while using opiates like fentanyl and oxycodone.

Compare fentanyl vs. oxycodone side effects
	Fentanyl		Oxycodone
Side effect	Applicable?	Frequency	Applicable?	Frequency
Nausea	Yes	>5%	Yes	>3%
Vomiting	Yes	>5%	Yes	>3%
Drowsiness	Yes	>5%	Yes	>3%
Dizziness	Yes	>5%	Yes	>3%
Insomnia	Yes	>5%	Yes	>3%
Itching	Yes	3%	Yes	>3%
Constipation	Yes	>5%	Yes	>3%
Increased sweating	Yes	>5%	Yes	N/A
Weakness	Yes	2%	Yes	>3%
Headache	Yes	>5%	Yes	>3%
Fatigue	Yes	>5%	Yes	N/A
Diarrhea	Yes	>5%	Yes	N/A

Source: DailyMed (Fentanyl), DailyMed (Oxycodone)

This may not be a complete list of adverse effects that can occur. Please refer to your healthcare provider to learn more.

Fentanyl and oxycodone drug interactions

Fentanyl and oxycodone can interact with similar medications, including the following:

• Liver enzyme inhibitors or inducers: Both fentanyl and oxycodone are processed by the liver enzyme CYP3A4. Certain medications, like certain macrolide antibiotics and azole-antifungal drugs, can slow this process, leading to higher opioid levels in the body and an increased risk of an opioid overdose. Other drugs, like certain anticonvulsants, speed up metabolism, potentially making these opioids less effective or causing withdrawal symptoms.
• CNS depressants: Combining fentanyl or oxycodone with other CNS depressants, such as benzodiazepines, muscle relaxants, or antipsychotics, can increase the risk of extreme drowsiness, slowed breathing, coma, or death. If these drugs need to be used together, dosages should be carefully managed by a healthcare provider.
• Serotonergic drugs: Both opioids can increase the risk of serotonin syndrome, a dangerous condition that affects mood and nervous system function, especially when taken with certain antidepressants. These antidepressants may include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or tricyclic antidepressants (TCAs). Symptoms include confusion, rapid heart rate, and high blood pressure.
• Monoamine oxidase inhibitors (MAOIs): Using fentanyl or oxycodone with MAOIs, such as phenelzine or tranylcypromine, can lead to severe side effects, such as dangerous changes in blood pressure or respiratory depression. These opioids should not be used with MAOIs or within 14 days of stopping an MAOI.
• Diuretics: Opioids can make diuretics less effective by increasing the release of antidiuretic hormone, which reduces urination. Those on diuretics should be monitored for fluid retention.
• Anticholinergic drugs: Medications that affect the nervous system, such as those used for bladder issues or allergies, can increase the risk of severe constipation and urinary retention when taken with fentanyl or oxycodone.

Always consult a healthcare provider before taking an opioid if you take other medications. Provide a list of prescription medications, over-the-counter drugs, and herbal supplements you may be taking. 

Compare fentanyl vs. oxycodone drug interactions
Drug	Drug class	Fentanyl	Oxycodone
Zithromax (azithromycin) Biaxin (clarithromycin) Ery-Tab (erythromycin)	Macrolide antibiotic	Yes	Yes
Diflucan (fluconazole) Nizoral (ketoconazole) Sporanox (itraconazole)	Azole antifungal	Yes	Yes
Norvir (ritonavir) Reyataz (atazanavir) Prezista (darunavir)	Protease inhibitor	Yes	Yes
Dilantin (phenytoin) Tegretol (carbamazepine) Depakote (valproate)	Anticonvulsant	Yes	Yes
Xanax (alprazolam) Valium (diazepam) Ativan (lorazepam)	Benzodiazepine	Yes	Yes
Flexeril (cyclobenzaprine) Soma (carisoprodol) Baclofen (baclofen)	Muscle relaxant	Yes	Yes
Abilify (aripiprazole) Zyprexa (olanzapine) Seroquel (quetiapine)	Antipsychotic	Yes	Yes
Prozac (fluoxetine) Zoloft (sertraline) Lexapro (escitalopram)	SSRI	Yes	Yes
Effexor XR (venlafaxine) Cymbalta (duloxetine) Pristiq (desvenlafaxine)	SNRI	Yes	Yes
Elavil (amitriptyline) Tofranil (imipramine) Norpramin (desipramine)	TCA	Yes	Yes
Imitrex (sumatriptan) Maxalt (rizatriptan) Zomig (zolmitriptan)	Triptan	Yes	Yes
Nardil (phenelzine) Parnate (tranylcypromine) Marplan (isocarboxazid)	MAOI	Yes	Yes
Lasix (furosemide) Hydrodiuril (hydrochlorothiazide) Aldactone (spironolactone)	Diuretic	Yes	Yes
Atrovent (ipratropium) Ditropan (oxybutynin) Bentyl (dicyclomine)	Anticholinergic	Yes	Yes

Consult a healthcare professional for other possible drug interactions.

Fentanyl and oxycodone drug warnings

Fentanyl and oxycodone carry many of the same warnings and precautions. You may need to work with a healthcare provider to watch for the following:

• Risk of addiction and dependence: Fentanyl and oxycodone have a high potential for addiction and dependence. Even when taken as prescribed, there is a risk of developing physical and psychological dependence when taking either drug. Always follow a healthcare provider’s instructions and discuss any history of substance abuse. 
• Neonatal opioid withdrawal syndrome (NOWS): The use of opioids during pregnancy can carry risks to an unborn child, such as NOWS. This condition can cause withdrawal symptoms in the newborn. Pregnant individuals should consult a healthcare provider to weigh the risks and benefits of pain medications.
• Opioid-induced hyperalgesia: In some cases, opioids can actually make pain worse instead of relieving it. If this happens, your healthcare provider may lower your dose or switch you to a different medication.  
• Breathing problems in certain individuals: Those with lung disease, who are frail, or who are of advanced age should be watched closely when starting an opioid or adjusting the dose. Opioids can cause respiratory depression, which is a serious condition in which breathing becomes inadequate, potentially leading to life-threatening complications.
• Adrenal gland issues: Opioids can cause adrenal insufficiency, which can lead to low blood pressure, fatigue, and weakness. If this happens, treatment with steroids may be needed.
• Severe low blood pressure (hypotension): Opioids can cause a dangerous drop in blood pressure, especially in people with circulatory problems. This can lead to complications such as dizziness or fainting if not managed.
• Risks with brain conditions: People with head injuries, brain tumors, or impaired consciousness may be more vulnerable to the sedative effects of opioids, which can increase the risk of breathing problems.

Consult a healthcare provider for other possible warnings and precautions before starting pain management with an opioid. Discuss any current or past medical conditions to decrease the risk of severe complications.