What is the recommended stepwise pharmacologic management for an adult with shoulder pain, including NSAIDs, topical NSAIDs, acetaminophen, oral corticosteroids, opioids, muscle relaxants, and neuropathic agents, and how should therapy be modified for contraindications such as peptic ulcer disease, severe renal impairment, uncontrolled hypertension, or cardiovascular risk?

Pharmacologic Management of Shoulder Pain in Adults

Start with acetaminophen up to 3000-4000 mg daily or topical NSAIDs as first-line therapy, then escalate to oral NSAIDs (ibuprofen 400-800 mg every 6 hours, maximum 2400 mg/day) with proton pump inhibitor co-therapy if needed, reserving opioids and corticosteroid injections for severe refractory pain. 1, 2

First-Line Pharmacologic Therapy

Acetaminophen should be offered initially for pain relief with regular dosing as needed. 1 The maximum daily dose is 3000-4000 mg, though lower doses should be used in patients with hepatic disease, malnutrition, or severe alcohol use disorder. 2, 3 Acetaminophen provides comparable pain relief to NSAIDs for musculoskeletal pain with fewer gastrointestinal side effects, making it the preferred first-line agent particularly in elderly patients and those with comorbidities. 4, 3

Topical NSAIDs should be considered before oral NSAIDs for localized shoulder pain, as they provide effective analgesia with minimal systemic absorption and significantly reduced risk of gastrointestinal, renal, and cardiovascular toxicity. 1, 2 Topical preparations are particularly valuable when oral NSAIDs are contraindicated or to minimize duration of systemic exposure. 2

Second-Line Therapy: Oral NSAIDs

If acetaminophen or topical NSAIDs provide insufficient pain relief, oral NSAIDs should be prescribed at the lowest effective dose for the shortest possible duration, typically not exceeding 5-10 days for acute pain. 1, 2

Standard NSAID Dosing

• Ibuprofen 400-800 mg every 6 hours, with a maximum daily dose of 2400 mg 1, 2
• All oral NSAIDs have similar analgesic efficacy but vary in their toxicity profiles 1

Mandatory Risk Assessment Before Prescribing NSAIDs

High-risk patients requiring either NSAID avoidance or mandatory gastroprotection include: 1, 2

• Age >60 years (5-fold increased risk of serious GI bleeding) 2, 4
• History of peptic ulcer disease (5% risk of recurrent bleeding within 6 months even with protective measures) 2
• Concurrent anticoagulant use (5-6 times increased GI bleeding risk) 2
• Concomitant corticosteroid or SSRI use 5, 4
• Cardiovascular disease or risk factors 1, 6
• Renal impairment (creatinine clearance significantly reduced) 1, 7
• Uncontrolled hypertension (NSAIDs increase blood pressure by mean 5 mmHg) 1, 7, 6
• Heart failure (NSAIDs cause sodium/water retention and worsen heart failure) 7, 6

Modified Therapy for High-Risk Patients

For Patients with Peptic Ulcer Disease or GI Risk

Use one of the following regimens: 1

• Acetaminophen alone (up to 3000 mg daily) 2, 4
• Topical NSAIDs 1, 2
• COX-2 selective inhibitor PLUS proton pump inhibitor 1
• Standard NSAID PLUS proton pump inhibitor (choosing the PPI with lowest acquisition cost) 1

Discontinue NSAIDs immediately if peptic ulcer or gastrointestinal hemorrhage develops. 1

For Patients with Severe Renal Impairment

Avoid NSAIDs entirely in patients with compromised fluid status, interstitial nephritis, or concomitant nephrotoxic drugs. 1, 7 Consider acetaminophen as a safer alternative. 2, 4

Discontinue NSAIDs immediately if BUN or creatinine doubles, or if signs of acute kidney injury appear (decreased urine output, rising creatinine, fluid retention). 1, 2

For Patients with Uncontrolled Hypertension or Cardiovascular Risk

NSAIDs should be avoided in patients with cardiovascular disease, as they attenuate the effects of diuretics, beta-blockers, ACE inhibitors, and AT-2 blockers, leading to uncontrolled hypertension or heart failure aggravation. 6, 8 COX-2 inhibitors may increase the rate of myocardial infarction and stroke. 6, 8

Discontinue NSAIDs immediately if hypertension develops or worsens. 1, 5

If NSAIDs are unavoidable in cardiovascular patients, use naproxen with proton pump inhibitor or misoprostol, though complete NSAID avoidance is preferred. 8

Mandatory Monitoring for Extended NSAID Use

If shoulder pain requires NSAID therapy beyond 2 weeks, mandatory monitoring every 3 months must include: 1, 2, 5

• Blood pressure
• BUN and creatinine
• Liver function tests (alkaline phosphatase, LDH, SGOT, SGPT)
• Complete blood count
• Fecal occult blood

Discontinue NSAIDs if: 1, 2

• Liver function tests increase above normal limits
• BUN or creatinine doubles
• Hypertension develops or worsens
• Any gastrointestinal bleeding occurs

Third-Line Therapy: Corticosteroids and Opioids

Intra-articular Corticosteroid Injections

Consider intra-articular corticosteroid injections for moderate to severe shoulder pain unresponsive to oral analgesics. 1 These provide effective short-term pain relief (1-3 weeks) without systemic toxicity. 1

Oral Corticosteroids

The evidence provided does not specifically address oral corticosteroids for shoulder pain. Based on general musculoskeletal pain principles, oral corticosteroids are typically reserved for inflammatory conditions and used cautiously due to systemic side effects.

Opioid Analgesics

Opioids should be reserved for severe or refractory acute shoulder pain when first-line and second-line therapies are inadequate. 1, 4, 3 They are safer alternatives than NSAIDs in high-risk patients with bleeding disorders, severe renal impairment, or age >60 years with multiple comorbidities. 1, 4

For severe pain, consider tramadol (works on opioid and monoamine receptors) as a bridge before traditional opioids, or use acetaminophen/opioid combinations. 3, 9 Prescribe opioids at the lowest effective dose for the shortest duration (typically 5-10 days maximum for acute pain), with attention to minimizing addiction risk. 3

Muscle Relaxants and Neuropathic Agents

Muscle relaxants are not specifically recommended for shoulder pain in the provided guidelines, though they may be useful as adjuncts for acute low back pain. 3

Neuropathic agents (gabapentin or pregabalin) should be added if there is a neuropathic pain component rather than increasing NSAID doses. 2 These are appropriate when shoulder pain has radicular features or nerve involvement.

Critical Pitfalls to Avoid

• Never combine multiple NSAIDs (including aspirin) simultaneously, as this increases toxicity without improving efficacy 5, 4
• If taking low-dose aspirin for cardioprotection, ibuprofen must be taken at least 30 minutes AFTER immediate-release aspirin or at least 8 hours BEFORE aspirin to avoid interfering with cardioprotection 2
• Account for "hidden sources" of NSAIDs in combination medications to prevent excessive dosing 2
• If 2 NSAIDs are tried successively without efficacy, switch to another analgesic approach rather than trying additional NSAIDs 1, 5
• Avoid NSAIDs entirely in heart failure, as they cause sodium/water retention and worsen cardiac function 7, 6