What is the treatment for myalgia potentially caused by Monjaro?

Monjaro and Myalgia: Treatment Approach

For myalgia potentially caused by Monjaro (tirzepatide), discontinue the medication immediately and initiate symptomatic management with acetaminophen or NSAIDs (if no contraindications exist), while ruling out serious muscle pathology through creatine kinase testing and clinical assessment.

Initial Assessment and Differential Diagnosis

The critical first step is distinguishing simple myalgia from serious myositis, as the latter requires urgent intervention:

• Check creatine kinase (CK) and aldolase levels to evaluate for muscle inflammation; transaminases (AST, ALT) and LDH may also be elevated in myositis 1
• Assess for muscle weakness versus pain alone: weakness suggests myositis, while pain without weakness is more consistent with simple myalgia or polymyalgia-like syndrome 1
• Obtain troponin levels to evaluate for myocardial involvement, as drug-induced myositis can affect the heart 1
• Perform a complete rheumatologic and neurologic examination including muscle strength testing and skin examination 1

Risk Stratification Based on Clinical Presentation

Grade 1: Mild Myalgia Without Weakness

• Continue monitoring if CK is normal and patient has only mild pain 1
• Initiate acetaminophen or NSAIDs for analgesia if there are no contraindications 1
• Consider holding statins if the patient is on concurrent statin therapy, as this may be contributing 1
• Reassess in 1-2 weeks with repeat CK if symptoms persist 1

Grade 2: Moderate Myalgia or Elevated CK (≥3x ULN)

• Hold Monjaro temporarily and do not resume until symptoms resolve and CK normalizes 1
• Escalate analgesia to diclofenac, naproxen, or etoricoxib if acetaminophen is insufficient 1
• Initiate prednisone 0.5-1 mg/kg/day if CK is elevated ≥3x upper limit of normal 1
• Refer to rheumatology or neurology for further evaluation 1
• Consider permanent discontinuation if objective findings of severe muscle involvement exist 1

Grade 3-4: Severe Weakness, Rhabdomyolysis, or Very High CK

• Permanently discontinue Monjaro 1
• Consider hospitalization for patients with severe weakness, respiratory involvement, dysphagia, or rhabdomyolysis 1
• Initiate methylprednisolone 1-2 mg/kg IV or higher dose bolus for severe compromise 1
• Urgent referral to rheumatology and/or neurology 1
• Consider plasmapheresis in patients with acute or severe disease 1
• Consider IVIG therapy, noting that onset of action is slower than plasmapheresis 1
• Add immunosuppressants (rituximab, TNFα antagonists, IL-6 antagonists) if no improvement after 2 weeks 1

Symptomatic Pain Management Algorithm

First-Line Analgesics

Acetaminophen is the safest initial choice for simple myalgia without inflammation 1

Second-Line: NSAIDs (Use With Caution)

• Ibuprofen 400-800 mg three times daily or naproxen 500 mg twice daily can be used if acetaminophen is insufficient 1, 2
• Monitor for cardiovascular risks: NSAIDs increase risk of MI, stroke, and heart failure, particularly in patients with existing CV disease 2
• Monitor for GI complications: NSAIDs cause ulceration and bleeding in 1% of patients at 3-6 months and 2-4% at one year 2
• Avoid in patients with recent MI, severe heart failure, or history of GI bleeding 2
• Check blood pressure regularly as NSAIDs can worsen hypertension 2

Third-Line: Neuropathic Pain Agents (If Pain Persists)

If myalgia persists despite discontinuing Monjaro and using simple analgesics, consider neuropathic pain medications:

• Pregabalin 75 mg twice daily, increasing to 150 mg twice daily within one week based on tolerance 3
• Gabapentin can be considered, though evidence is more limited 3
• Amitriptyline 10 mg at bedtime, increasing by 10 mg weekly to target 25-50 mg nightly 3
• Duloxetine 30 mg once daily for one week, then increase to 60 mg once daily 3

Medications to Avoid

Corticosteroids and strong opioids should not be used for simple myalgia without evidence of inflammatory myositis, as they lack efficacy and cause significant harm 1, 3

Additional Considerations

• Rule out metabolic causes: Check thyroid function, vitamin D levels, and iron stores, as these can perpetuate myalgia 4
• Assess for drug interactions: If patient is on statins or other myotoxic medications, these may be contributing 5
• Monitor for progression: If weakness develops or CK rises significantly, escalate management immediately 1, 6
• Do not rechallenge with Monjaro if severe myositis occurred, as caution is advised with rechallenging after immune-mediated muscle toxicity 1