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Rx pill bottles: Oxycodone acetaminophen alternatives
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Oxycodone acetaminophen (Endocet) alternatives: What can I take instead of oxycodone acetaminophen?

Endocet (oxycodone acetaminophen) doesn't work for everyone. Oxycodone, Tylenol Extra Strength, Xtampza ER, Naprosyn, and Neurontin are some oxycodone acetaminophen alternatives. Get the full list here.
Chad Shaffer, MD, medical writer and reviewer for SingleCare
By | Jul. 17, 2023

Compare oxycodone acetaminophen alternatives | Oxycodone | Tylenol Extra Strength | Xtampza ER | Naprosyn | Neurontin | Natural alternatives | How to switch meds

Risks abound when you take Endocet or Percocet, the combination tablets of oxycodone with acetaminophen. Black box warnings alone from the Food and Drug Administration are extensive. Addiction, life-threatening respiratory depression, accidental overdose, hazards with other sedating substances like alcohol, and liver toxicity are some warnings slapped on oxycodone-acetaminophen. Couple these with common side effects like constipation, drowsiness, and unsteadiness, and you have ample reasons to look for alternatives.

What can I take in place of oxycodone acetaminophen?

Oxycodone and a long-acting form, Oxycontin, are opiate pain relievers that have been at the center of the opioid epidemic in America, according to the Centers for Disease Control and Prevention (CDC). The rising use of opioids has led to increased overdose deaths since 1999, with rapidly escalating rates at times. The opiate class has several other members who share similar risks. Nonetheless, you could still consider them alternative options to Endocet or Percocet.

The other active ingredient in the combination drug is acetaminophen, the same pain-relieving, free-reducing drug in Tylenol. Acetaminophen is not habit-forming or sedating but can be highly toxic to the liver in overdose. Still, an option for replacing your oxycodone-acetaminophen combination tablet is to take one component or the other separately.

Stepping away from the opiate class, you could pick a non-steroidal anti-inflammatory drug (NSAID). This popular class has members available over-the-counter (OTC) and by prescription. Alternatively, among non-opioid medications, you could choose from local anesthetics, like topical lidocaine; anticonvulsants, such as gabapentin; or antidepressants, namely amitriptyline or Cymbalta. These other options have their pros and cons too. Your best bet is to inform yourself about the painkillers on the market.

Compare Endocet (oxycodone acetaminophen) alternatives
Drug name Uses Dosage Savings options
Endocet (oxycodone-acetaminophen) Moderate to severe pain 2.5 mg/325 mg to 10 mg/325 mg every 6 hours as needed Endocet coupons
Percocet (oxycodone-acetaminophen) Moderate to severe pain 2.5 mg/325 mg to 10 mg/325 mg every 6 hours as needed Percocet coupons
Oxaydo (oxycodone) Severe pain 5 to 15 mg every 6 hours as needed Oxaydo coupons
Oxycontin (oxycodone extended-release) Severe chronic pain 10 to 80 mg every 12 hours Oxycontin coupons
Xtampza ER (oxycodone extended-release) Severe chronic pain 9 to 36 mg every 12 hours Xtampza ER coupons
Tylenol Extra Strength (acetaminophen) Pain reliever, fever reducer 500 to 1000 mg every 6 hours as needed Tylenol Extra Strength coupons
Acetaminophen-codeine #3 Mild to moderate pain 300 mg/30 mg every 6 hours as needed Acetaminophen-codeine #3 coupons
Hydrocodone-acetaminophen Moderate to severe pain 2.5 mg/325 mg to 10 mg/325 mg every 6 hours as needed Hydrocodone-acetaminophen coupons
Fentanyl patch Severe chronic pain 12 to 100 mcg/hour patch changed every 3 days Fentanyl patch
Butrans (buprenorphine patch) Moderate to severe pain 5 to 20 mcg/hour patch changed every 7 days  Butrans coupons
Qdolo (tramadol) Moderate to severe pain 50 to 100 mg every 6 hours as needed Qdolo coupons
Naprosyn (naproxen) Osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute gout, mild to moderate pain 250 to 500 mg twice daily Naprosyn coupons
Celebrex (celecoxib) Acute pain, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, dysmenorrhea 100 to 200 mg once or twice daily Celebrex coupons
Neurontin (gabapentin) Neuropathic pain (off-label), seizure, post-herpetic neuralgia 300 to 1200 mg three times daily Neurontin coupons
Lyrica (pregabalin) Diabetic neuropathic pain, post-herpetic neuralgia, fibromyalgia, partial seizures, spinal cord injury-associated neuropathic pain 50 to 100 mg three times daily Lyrica coupons
Lidocaine 5% patch Post-herpetic neuralgia One patch applied for up to 12 hours once daily Lidocaine 5% patch coupons

Other alternatives to oxycodone acetaminophen

Top 5 oxycodone acetaminophen alternatives

The following are some of the most common alternatives to oxycodone acetaminophen.

1. Oxycodone

A relatively simple switch away from Endocet or Percocet would be to take only oxycodone or its brand-name Oxaydo. All of the risks and adverse effects of an opioid pain medication would still be a concern of course. The danger of overdosing on acetaminophen would be alleviated, and this is not a trivial hazard. It is easy to forget that acetaminophen is in Endocet and Percocet, and many people make the mistake of taking Tylenol in addition to Endocet or Percocet. The result can be an accidental overdose and potentially life-threatening liver damage. The same danger exists for hydrocodone-acetaminophen, which went under the brand name Vicodin in the past.

Oxycodone may be a better choice than other opiates in some circumstances. While it certainly has a long list of potential side effects, oxycodone does avoid the ultra-rapid metabolism warning from the FDA. Both tramadol and codeine carry this warning due to the hazard seen with their use in children.

2. Tylenol Extra Strength

You may be interested in avoiding the opiate category altogether, in which case, you may want to try acetaminophen alone, either via a brand-name Tylenol product or a generic. Limiting the daily amount to the level approved by your healthcare provider will still be important. Avoiding higher doses can help you avoid liver complications.

3. Xtampza ER

Another reason you may be looking for an alternative to oxycodone-acetaminophen is that the duration of action may be insufficient. If you have a long-term need for opiate analgesics and have already been taking short-acting narcotics like oxycodone, then you may want to inquire about a long-acting option. Xtampza ER capsules are manufactured to release oxycodone gradually to provide pain relief for about 12 hours or more. They are made to reduce the risk of abuse compared to Oxycontin. For safety reasons, these long-acting options are not initially used for pain management. If their expense seems too much, try presenting your SingleCare discount card at your local pharmacy.

4. Naprosyn

NSAIDs, such as Naprosyn, have the potential for significant analgesia. Experts and studies have suggested that combining an NSAID with acetaminophen may be just as effective as an opiate medication for pain treatment. Naprosyn, which is a brand-name form of naproxen, and its fellow NSAIDs, such as Aleve, also reduce inflammation in the body. Accordingly, they may provide more therapeutic than just pain relief. 

The downside to the NSAID class is the chance of side effects. While they are not prone to abuse or withdrawal problems, they can be detrimental to some individuals’ kidney function or the gastrointestinal tract. Fortunately, if this is a concern for you, topical NSAID formulations, such as Voltaren gel and the Flector patch, are available to minimize these risks. Celebrex is one of the COX-2 inhibitors, a variety of NSAIDs with less risk of adverse effects on the stomach.

5. Neurontin

As more and more emphasis is placed on limiting the use of opiates, non-opioid alternatives have consequently been in higher demand. The anticonvulsant Neurontin has been prescribed more often as a result. It is only FDA-approved for seizures and post-herpetic neuralgia, the pain syndrome that follows shingles. However, off-label use is relatively common for neuropathic pain, especially for nerve pain from diabetic neuropathy. 

Proof of effectiveness and safety for some of its off-label uses is still needed. Sedation effects and a chance of abuse are more reasons to be cautious before starting Neurontin. It can also cause dangerous respiratory depression if combined with opiates.

Natural alternatives to oxycodone acetaminophen

All of this talk of risks, hazards, and warnings could rightfully have you frightened and wanting to keep up the search for other options. Non-drug approaches such as physical therapy, chiropractic care, and acupuncture could be considered. Natural alternatives such as supplements may come to mind too. 

A 2022 review of natural alternatives to prescription pain medicine highlighted topical options, such as rosemary and lavender, and oral options, like peppermint, ginger, and turmeric, because they have some study data to support their use. However, the clinical trial evidence is minimal, and the review mentions that their use would be more appropriate for chronic, persistent pain than acute, short-term pain.

How to switch to a oxycodone acetaminophen alternative

So, maybe there is no perfect painkiller to treat pain. You may still have found one that sounds more appealing than Endocet, Percocet, or generic oxycodone-acetaminophen. You need to take your concerns about oxycodone-acetaminophen to the prescribing provider. You can go over your concerns regarding certain medications and discuss your ideas about an alternative. Making changes without getting medical advice is a bad idea. A healthcare provider can check your list of other prescription drugs and OTC medicines and review your medical history before helping you make the best decision.