Percocet Versus Other Painkillers

By Lauren Smith

Last updated: 16 February 2024 & medically reviewed by Dr. Jenni Jacobsen

How is Percocet different from other opioids?

Percocet is distinguished from other opioids because the pills include both oxycodone and a fixed dose of acetaminophen (paracetamol), a common medicine cabinet analgesic popularly known as Tylenol. Acetaminophen amplifies the painkilling effects of oxycodone.

Percocet is available in four doses:^[1]

• 2.5mg oxycodone/325mg acetaminophen

• 5mg oxycodone/325 mg acetaminophen

• 7.5mg oxycodone/325mg acetaminophen

• 10mg oxycodone/325mg acetaminophen

Other opioids offer oxycodone on its own, or a slightly less potent drug called hydrocodone. They may offer these opioids in other combinations, such as with aspirin or ibuprofen. Other opioids, such as tramadol, act both on opioid receptors and other neurotransmitters in the brain.

Vicodin vs Percocet

While Percocet is the brand name for a combination of oxycodone and acetaminophen, Vicodin is the brand name of a combination pill including hydrocodone bitartrate and acetaminophen. The hydrocodone/acetaminophen combination is also sold under the trade names Lorcet, Lortab, and Norco, among others.

Oxycodone and hydrocodone are similar; both are semi-synthetic opioids, synthesized from substances from the opium poppy. Oxycodone is usually produced from thebaine, while hydrocodone is typically converted from codeine.

Use

Both oxycodone and hydrocodone relieve pain by acting on opioid receptors in the body and are prescribed for pain after surgery and injuries. They're also both occasionally used for chronic pain, although this use has been restricted in recent years amid concerns about addiction. Hydrocodone is also an antitussive, meaning it's used to treat coughs.

Strength

The hydrocodone in Vicodin is somewhat less potent than oxycodone in Percocet. While hydrocodone is about as strong as morphine, oxycodone is thought to be around 50% stronger.^[2] One study comparing the two found that it took 50% more hydrocodone to produce the same degree of miosis (pupil contraction)—a side effect of opiates/opioids.^[3] A survey of opioid users seeking treatment found that more (44.7%) preferred oxycodone to hydrocodone (29.4%), with users citing the superior high oxycodone supposedly produces.^[4]

However, studies among emergency room patients given either hydrocodone or oxycodone have found no difference in the level of pain relief they deliver.^[5][6]

Vicodin is available in three strengths:^[7]

• Vicodin: 5mg hydrocodone/300mg acetaminophen

• Vicodin ES: 7.5mg hydrocodone/300mg acetaminophen

• Vicodin HP: 10mg hydrocodone/300mg acetaminophen 

Side effects

Both Percocet and Vicodin cause the typical side effects of opioids, including drowsiness, nausea, constipation, and itching. However, hydrocodone (Vicodin) has been associated with a somewhat higher frequency of constipation, while oxycodone (Percocet) was more likely to cause nausea, headache, dizziness, and fatigue.^[5][6]

Rate of abuse and addiction

In a study of more than 500,000 patients given a first prescription of oxycodone or hydrocodone in the state of Oregon between 2015 and 2017, patients given oxycodone were more likely to develop chronic use (3.3%) than those given hydrocodone (2.2%).^[8] 

However, both drugs come with a significant risk of abuse and addiction. The American Medical Association (AMA) estimates that between 3% and 19% of people prescribed any type of narcotic pain medication go on to become addicted to them.^[9]

Risk of overdose

Both Vicodin and Percocet can cause opioid overdoses if taken in excess, with symptoms including respiratory depression (slow, shallow breathing), unresponsiveness, and blue or gray skin. Opioid overdoses can be fatal and are a medical emergency. 

The study of 500,000 Oregonians found that oxycodone, contained in Percocet,, was associated with a slightly higher likelihood of opioid overdose (0.38% of patients) than hydrocodone (0.24%).^[8]

Additionally, overdoses of acetaminophen in both Vicodin and Percocet can cause severe liver damage. Patients should limit themselves to a maximum of 4g of acetaminophen a day at the most (or 2g if they’re also drinking alcohol), which is 13 Vicodin pills and 12 Percocets.^[10]

Oxycodone vs Percocet

Oxycodone is the opioid present in Percocet. It’s also sold on its own, under the brand names Roxicodone and OxyContin (an extended-release formulation), among others.

The difference between oxycodone and Percocet is the presence of 325mg of acetaminophen in every Percocet tablet. This can amplify the painkilling effects of Percocet but makes no difference in the high that drug users chase and can cause liver damage in overdose.

Use

Both Percocet and oxycodone are prescribed for moderate to severe pain, including:

• Acute pain after surgery and medical procedures

• Acute pain after accidents and injuries

• Chronic cancer pain

• End-of-life pain

• Chronic pain unresponsive to non-opioid analgesics, although this use has been restricted in recent years.

Starting in the late 1990s, OxyContin, an extended-release form of oxycodone, was aggressively marketed by manufacturer Purdue Pharma for chronic pain, including back pain, with the drug company minimizing the risk of abuse and addiction.^[11] The liberal prescribing of OxyContin is now acknowledged to have been a major factor in the opioid crisis.^[12]

Strength

Immediate-release oxycodone is usually available in the following strengths:^[13]

• 5mg

• 10mg

• 15mg

• 20mg

• 30mg

 Extended-release oxycodone (OxyContin) is available in the following strengths:^[14]

• 10mg

• 15mg

• 20mg

• 30mg

• 40mg

• 60mg (for opioid-tolerant patients only)

• 80mg (for opioid-tolerant patients only)

• 160mg (for opioid-tolerant patients only)

These doses are higher than those available in Percocet, which tops out at 10mg of oxycodone.

Side effects

Oxycodone and Percocet have largely the same side effects associated with opioids:

• Nausea and vomiting

• Drowsiness

• Itching

• Constipation

• Stomach discomfort

The only difference is that Percocet comes with the possible side effects of acetaminophen. These are usually minimal, but a very small number of people may have an allergic reaction to it, with symptoms including:^[15]

• Rash

• Itching and swelling of the face, throat, and tongue

• Difficulty breathing

• Severe dizziness

Rate of abuse and addiction

Oxycodone and Percocet are largely the same drugs and have similar risk profiles, including for abuse and addiction. Patients using oxycodone may be at somewhat higher risk of developing dependence, because oxycodone comes in higher doses than Percocet.

Risk of overdose 

Oxycodone pills come in higher strengths than Percocet, increasing the risk of overdose. In a national sample of Veterans Health Administration patients with chronic pain treated with opioids, the mean prescribed daily dose among those who died of an opioid overdose was 98 morphine milligram equivalents (MME), compared to 48 among those who didn’t experience a fatal overdose.^[16] 98 MMEs is 65mg of oxycodone—the amount contained in some single pills of oxycodone, while you’d have to take 6.5 to 26 pills of Percocet to reach this level.

However, Percocet has the added risk of overdose from acetaminophen, which can cause severe liver damage at doses of just 4g (12 Percocet).

Percocet vs hydrocodone

Hydrocodone is an opioid, available as standalone, extended-release pills branded Hysingla ER and Vantrela ER.^[17] Meanwhile, Percocet is a combination pill of the similar opioid oxycodone and acetaminophen.

Use

Hydrocodone and Percocet are both used to relieve moderate to severe pain. However, standalone hydrocodone is used somewhat rarely. Combinations of hydrocodone with other drugs are preferred, such as with acetaminophen (Vicodin, Lortab, Norco). 

Hydrocodone is primarily available in extended-release formulations, designed to be taken once or twice a day, and offers hours of pain relief. Because of the higher dose and greater risk of overdose and death, these should only be given to patients for whom non-opioid analgesics and immediate-release opioids aren’t sufficient.^[18]

Additionally, hydrocodone is used, at low doses, to relieve cough under the brand name Hycodan.

Strength

 Hydrocodone by itself is available in the following doses, in extended-release formulations:

• Hysingla ER: 20mg, 30mg, 40mg, 60mg, 80mg, 100mg, and 120mg. Doses above 80mg/day are only for opioid-tolerant patients.^[18]

• Vantrela ER: 15 mg, 30 mg, 45 mg, 60 mg, and 90 mg ^[19]

Oxycodone, as in Percocet, is thought to be 50% stronger than hydrocodone.

Side effects

The side effects of Percocet and hydrocodone are largely the same and follow those of opioids. However, hydrocodone has been associated with a higher risk of constipation and stomach discomfort, while oxycodone, as in Percocet, is more likely to cause nausea, headache, dizziness, and fatigue.^[5][6] 

Rate of abuse and addiction

The most common standalone versions of hydrocodone, Hysingla ER and Vantrela ER, are extended-release formulations, meaning they come in higher doses—tempting for people who abuse opioids. To mitigate this, they have abuse-deterrent design features. Hysingla ER has a coating that makes the pill difficult to crush, grind, and chew. When dissolved, the pill becomes a thick gel that is difficult to inject. Vantrela employs another method that also makes crushing or IV injection difficult. This means the full dose can’t be accessed at once and is instead slowly released when it’s ingested.^[20]

However, people can and do get around these defenses. They also use pills that combine hydrocodone with other painkillers and don’t have abuse deterrents.

In general, however, hydrocodone is associated with somewhat lower risks of abuse than oxycodone (2.2% vs 3.3% of opioid-naive patients given a prescription), according to a population-level study.^[8]

Risk of overdose

Hydrocodone comes in higher strengths than are available with Percocet: up to 120mg of hydrocodone in a single pill. These are extended-release formulations, so not all the drug is released at once when it’s ingested. They’re also designed with abuse deterrents. But the risk of overdose is still present and is one of the reasons these ER formulations are only given to patients for whom immediate-release pills aren’t suitable.

In general, patients given hydrocodone are somewhat less likely than those given oxycodone to go on to have an opioid overdose (0.38% vs 0.24%).^[8]

Percocet vs Norco

Norco is another trade name for the combination of hydrocodone and acetaminophen also known as Vicodin. The only difference between Norco and Vicodin is that the former contains 325mg of acetaminophen while the latter uses 300mg. 

For information about how Percocet differs from Norco, see the section above about Percocet vs Vicodin.

OxyContin vs Percocet

OxyContin is an extended-release form of oxycodone, designed to release medication over a 12- to 24-hour period once ingested. Percocet also contains oxycodone but combines it with acetaminophen and doesn’t have the controlled-release design, so it requires regular dosing (typically once every 6 hours).

Use

Both Percocet and OxyContin are used to treat moderate to severe pain. However, because OxyContin has an extended-release design, it’s ideal for people who need round-the-clock pain relief, rather than pain relief as needed, and may struggle with the regular dosing required by Percocet and other immediate-release alternatives. It’s also recommended that extended-release formulations like OxyContin are only given to patients who are opioid-tolerant, meaning they’ve taken opioids for at least one week and are accustomed to them.^[21]

Strength

OxyContin comes with much higher amounts of oxycodone (up to 160mg) than are available with Percocet (up to 10mg). This is because of the extended-release design of OxyContin, designed to deliver medication over a 12 to 24-hour period. The highest doses of OxyContin (60, 80, and 160mg) are supposed to be reserved for patients with some tolerance for opioids.

Side effects

 With the same active ingredient (oxycodone), OxyContin and Percocet have the same potential side effects, those shared by all opioids:

• nausea

• vomiting

• drowsiness

• constipation

• itching

Rate of abuse and addiction

When OxyContin was launched, manufacturers Purdue Pharma claimed it was less liable to abuse and tolerance and less addictive than other opioids. Advertising for OxyContin claimed that fewer than 1% of patients went on to be addicted. This claim was drawn from an obscure, brief letter to the editor, published in the New England Journal of Medicine in the 1980s and describing outcomes of patients given opioids in hospitals, not those taking them out of that setting.^[22] This marketing convinced doctors to prescribe the drug for patients with chronic pain, rather than reserving it for acute pain, as opioids typically had been.^[23]

OxyContin quickly became a blockbuster and generated a reported $35 billion in revenue for Purdue. However, the pill was very prone to abuse and addiction, like other opioids and as the drug company well knew.^[24] As early as 2001, the DEA noted that “the strength, duration, and known dosage of OxyContin are the primary reasons the drug is attractive to both abusers and legitimate users.”^[25]

The actual number of patients who abused or became addicted to OxyContin is unknown, but a review estimated rates of misuse of all opioids at between 21% and 29% of patients and addiction at between 8% and 12%.^[26]

Risk of overdose

The extended-release coating on OxyContin can be easily thwarted, allowing users to access the entire contents of the pill at once. With doses of up to 160mg, this is potentially deadly. A single pill could cause an overdose in someone not accustomed to opioids.

The FDA notes that prescription overdoses and deaths rose sharply in the early 2000s, with opioids, especially OxyContin, “at the center of the problem.”^[27]

Tramadol vs Percocet

Like the oxycodone in Percocet, tramadol is an opioid. However, it’s a unique drug because it not only acts (weakly) on opioid receptors but also enhances the brain’s serotonin and norepinephrine systems, mimicking the action of SNRI antidepressants. It’s sold under the brand name Ultram in the U.S.

Use

Tramadol is used to treat moderate to moderately severe pain, especially after surgery. It’s also available in extended-release formulations for ongoing pain.^[28] Tramadol may be used off-label for the treatment of chronic pain in refractory cases of fibromyalgia.^[29]

Percocet is used for moderate to severe pain, usually acute.

Strength

Tramadol is a weak opioid, around one-tenth as strong as morphine.^[30] Additional pain relief is provided by its SNRI actions, and the drug has been found to be as effective as morphine in relieving mild to moderate pain, although less effective in the treatment of severe or chronic pain.^[31]

The oxycodone in Percocet is around 1.5 times the strength of morphine.

Side effects

Tramadol is a weak opioid, so is less likely to cause typical opioid side effects (nausea, drowsiness, constipation, itching, etc.) than Percocet, although they are still possible.

 Tramadol’s effect on serotonin and norepinephrine means it’s associated with additional potential side effects, including:^[32]

• Insomnia

• Nervousness

• Agitation

• Shaking

• Changes in mood

Rates of addiction and abuse

Tramadol was long thought to be less likely to cause abuse and addiction than other opioids. In the U.S., it was unscheduled until 2014, when it was made a Schedule IV controlled drug by the DEA.^[33] Other opioids such as oxycodone and hydrocodone are Schedule II and subject to tougher restrictions. 

However, more recent research has cast doubt on tramadol’s status as a low-risk opioid. An examination of the medical records of nearly 450,000 patients who underwent 20 common surgeries in the US between 2009 and 2018 found that those prescribed tramadol post-operatively were just as likely as those prescribed oxycodone and hydrocodone to continue using the pills past when their surgery pain should have ended.^[34]

Tramadol also appears to create the same pleasurable, reinforcing effects that other opioids do, making it liable for abuse. In a study, prescription opioid abusers reported that higher doses of tramadol (200mg and 400mg) produced a high and an effect they liked, giving it ratings comparable to those they gave high-dose codeine and slightly lower than they gave to oxycodone.^[35] In another study, recreational drug users favorably rated 50mg and 100mg of tramadol similar to 25mg of morphine, with a majority saying they “liked” the drug and would take it again.^[36]

Risk of overdose

Because it is dual-action, tramadol is associated with multiple adverse effects in overdose.^[31] First, it can cause opioid overdose much like oxycodone (e.g. Percocet), including respiratory depression.

Tramadol overdoses can also induce seizures. Seizures are also possible even at higher prescribed doses (100mg+).^[37] The potential of seizures can complicate the treatment of tramadol overdoses because the standard opioid overdose treatment, naloxone, can increase the risk of seizures.

 In overdose, tramadol can also cause serotonin syndrome, a serious condition resulting from an excess of serotonin in the body. Serotonin syndrome is also possible when tramadol is combined with other serotonergic drugs, such as the most common antidepressants.^[37]