What are alternative pain medications to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Alternative Pain Medications to NSAIDs

Acetaminophen (paracetamol) should be your first-line alternative to NSAIDs for mild to moderate pain, with a maximum daily dose of 4000 mg/day. 1

First-Line Non-NSAID Options

Acetaminophen/Paracetamol

• Use acetaminophen 650-1000 mg every 4-6 hours (maximum 4000 mg/day) as the preferred first-line pharmacologic treatment for mild to moderate pain. 1
• Acetaminophen provides pain relief comparable to NSAIDs without gastrointestinal, cardiovascular, or renal toxicity risks. 1, 2
• It is particularly suitable for patients with liver disease, kidney disease, cardiovascular disease, gastrointestinal disorders, asthma, or older adults. 2
• Important caveat: Lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder. 3
• No routine dose reduction is needed for older adults unless they have decompensated cirrhosis or advanced kidney failure. 2

Topical Analgesics

• For localized pain, use topical NSAIDs (such as diclofenac gel) or capsaicin cream as effective alternatives. 1
• Topical formulations including methyl salicylate, capsaicin cream, or menthol can be beneficial for mild to moderate localized pain. 1
• Topical NSAIDs are specifically recommended for non-low back musculoskeletal injuries. 3

Second-Line Options for Moderate Pain

Weak Opioids and Tramadol

• For moderate pain not controlled by acetaminophen, consider tramadol or combination products containing acetaminophen plus codeine (up to 4000 mg acetaminophen and 240 mg codeine daily). 1
• Tramadol appears useful for patients who don't receive adequate pain relief with acetaminophen and are at risk for NSAID-related side effects. 4
• Other weak opioids include codeine, dihydrocodeine, or low doses of strong opioids like morphine or oxycodone. 1
• Controlled-release formulations of codeine, dihydrocodeine, and tramadol are available for moderate pain. 1

Combination Therapy

• Fixed-dose combinations of ibuprofen/acetaminophen provide pain relief similar to or better than opioids with fewer adverse events. 5
• Continue acetaminophen alongside second-line treatments for multimodal analgesia. 1

Third-Line Options for Severe Pain

Strong Opioids

• For severe pain, use morphine (oral route preferred), hydromorphone, or oxycodone in both immediate-release and modified-release formulations. 1
• Transdermal fentanyl is reserved for patients with stable opioid requirements, those unable to swallow, or those with poor tolerance to morphine. 1
• Methadone is an alternative but requires initiation by physicians with expertise due to marked inter-individual differences in half-life. 1
• Opioids should be used judiciously with careful assessment of benefits versus risks, particularly for aberrant drug-related behaviors with long-term use. 1

Condition-Specific Alternatives

Neuropathic Pain

• For neuropathic pain (diabetic neuropathy, postherpetic neuralgia), use duloxetine (SNRI antidepressant) or anticonvulsants pregabalin, gabapentin, or oxcarbazepine. 1, 6
• Tricyclic antidepressants are also effective but potentially inappropriate for older adults (≥65 years) due to anticholinergic effects. 1
• Topical lidocaine and capsaicin patches can be used, though evidence is limited. 1

Fibromyalgia

• For fibromyalgia, use duloxetine, milnacipran (SNRI antidepressants), or pregabalin/gabapentin (anticonvulsants). 1, 6
• These medications provide small to moderate improvements in pain, function, and quality of life. 1

Osteoarthritis

• For osteoarthritis, duloxetine has small to moderate benefits and is more effective in older patients (>65 years) and those with knee osteoarthritis. 1
• Note that acetaminophen has limited evidence for effectiveness in osteoarthritis and is no longer considered first-line. 1

Low Back Pain

• For chronic low back pain with insufficient response to nonpharmacologic approaches, consider duloxetine or skeletal muscle relaxants. 1
• Skeletal muscle relaxants are diverse medications with unclear mechanisms, grouped by their FDA-approved indication for muscle-related pain. 1

Critical Prescribing Considerations

Dosing Strategy

• Schedule analgesics around-the-clock rather than as-needed for consistent pain control. 1
• Provide breakthrough doses (usually 10% of total daily dose) for transient pain exacerbations. 7
• If more than 4 breakthrough doses are needed daily, increase the baseline analgesic regimen. 7

Monitoring and Safety

• Monitor for and manage opioid side effects including constipation, nausea, and drowsiness. 7
• Failure to respond to a time-limited course of opioids should lead to reassessment and consideration of alternative therapies or referral. 1
• When using multimodal analgesia, ensure optimal dosing of each component rather than suboptimal doses of multiple agents. 7

Common Pitfalls to Avoid

• Do not withhold analgesics, as pain itself can trigger complications. 7
• Avoid propoxyphene, which may be no more effective—and perhaps less effective—than acetaminophen or ibuprofen. 4
• Be cautious with duloxetine and pregabalin regarding side effects: duloxetine causes nausea and sedation; pregabalin causes dizziness, somnolence, and weight gain. 1, 6
• Review FDA-approved labeling, including boxed warnings, before initiating any pharmacologic therapy. 1