What non-opioid analgesics can be used to manage severe pain?

From the Guidelines

For severe pain, non-opioid options such as high-dose NSAIDs like ibuprofen (up to 800mg every 6 hours) or naproxen (500mg twice daily), often combined with acetaminophen (1000mg every 6 hours, not exceeding 4000mg daily), should be considered as first-line treatment. According to the most recent guideline evidence 1, nonopioid therapies are at least as effective as opioids for many common acute pain conditions.

Non-Opioid Analgesic Options

• High-dose NSAIDs like ibuprofen or naproxen can be used to reduce inflammation and pain
• Acetaminophen can be used to affect central pain pathways, with a maximum dose of 4000mg daily to avoid hepatic toxicity 1
• Adjuvant medications such as gabapentin or pregabalin can be effective for neuropathic pain, starting at a low dose and titrating up as needed
• Muscle relaxants like cyclobenzaprine can help with pain involving muscle spasm
• Ketamine, administered in controlled settings at sub-anesthetic doses, provides powerful analgesia for severe acute pain

Considerations for Use

• Clinicians should maximize the use of nonopioid pharmacologic and nonpharmacologic therapies as appropriate for the specific condition 1
• Opioid therapy should only be considered when nonopioid therapies are contraindicated or likely to be ineffective 1
• Patients should be aware of the expected benefits, common risks, and serious risks of nonopioid therapies, as well as alternatives to opioids 1

Monitoring and Side Effects

• Side effects of nonopioid therapies should be monitored, with NSAIDs carrying risks of gastrointestinal and renal issues, particularly with prolonged use 1
• Patients should be closely monitored for signs of hepatic toxicity when using acetaminophen, especially when exceeding the recommended daily dose 1

From the FDA Drug Label

After observing the response to initial therapy with naproxen tablets, the dose and frequency should be adjusted to suit an individual patient's needs. The recommended starting dose of naproxen is 500 mg, followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours as required. Onset of pain relief can begin within 1 hour in patients taking naproxen.

Naproxen can be used to manage severe pain. The recommended starting dose is 500 mg, followed by 500 mg every 12 hours or 250 mg every 6 to 8 hours as required. The initial total daily dose should not exceed 1250 mg of naproxen, and thereafter, the total daily dose should not exceed 1000 mg of naproxen 2.

From the Research

Non-Opioid Analgesics for Severe Pain Management

• Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line treatment options for most patients with acute mild to moderate pain 3
• Topical NSAIDs are recommended for non-low back, musculoskeletal injuries 3
• Selective cyclooxygenase-2 NSAIDs are a more expensive treatment alternative and are used to avoid the gastrointestinal adverse effects of nonselective NSAIDs 3
• For severe or refractory acute pain, treatment can be briefly escalated with the use of medications that work on opioid and monoamine receptors (e.g., tramadol, tapentadol) or with the use of acetaminophen/opioid or NSAID/opioid combinations 3

Over-the-Counter (OTC) Analgesics

• OTC analgesics, such as NSAIDs and the NSAID/acetaminophen combination, are safe and effective first-line options for managing acute dental pain 4
• The American College of Physicians supports the use of NSAIDs as first-line therapy for the treatment of low back pain 4
• The American Headache Society suggests that OTC NSAIDs and combination medications such as acetaminophen, aspirin, and caffeine are Level A recommendations for reducing migraine pain and other symptoms 4

Cancer Pain Management

• Non-opioid drugs, such as paracetamol (acetaminophen) and NSAIDs, are commonly used to treat cancer pain and are recommended for this purpose in the World Health Organization (WHO) cancer pain treatment ladder 5, 6
• There is no high-quality evidence to support or refute the use of paracetamol alone or in combination with opioids for the first two steps of the three-step WHO cancer pain ladder 5
• There is very low-quality evidence that some people with moderate or severe cancer pain can obtain substantial levels of benefit within one or two weeks with NSAIDs 6

Pharmacological Profile of Non-Opioid Analgesics

• All non-opioid analgesics are believed to act via inhibition of cyclo-oxygenase, but they differ in their inhibitory potency towards the enzyme 7
• The differences in inhibitory potency and pharmacokinetic parameters of non-opioid analgesics, such as aspirin, paracetamol (acetaminophen), ibuprofen, and phenazones, determine their suitability for over-the-counter (OTC) use and their profiles of effects and side effects 7