Which of the following medications is most likely to cause myalgias: empagliflozin (Jardiance), lisinopril, or amlodipine?

Which Medication is Most Likely to Cause Myalgias?

Amlodipine is most likely to cause myalgias among these three medications, followed by empagliflozin (Jardiance), with lisinopril being the least likely culprit.

Evidence-Based Analysis

Amlodipine and Myalgias

Amlodipine, a dihydropyridine calcium channel blocker, has documented associations with severe neuromuscular complications:

• Case reports demonstrate severe, progressive myopathy, myalgias, arthralgias, and weakness directly linked to amlodipine therapy, with complete symptom resolution within 4 days of discontinuation 1
• The temporal relationship between amlodipine dosage increases and worsening symptoms, followed by rapid improvement after cessation, strongly supports causality 1
• Myalgias and arthralgias appear to be adverse effects common to the entire dihydropyridine calcium-channel antagonist class, not just amlodipine specifically 1

Empagliflozin (Jardiance) and Myalgias

Empagliflozin has emerging evidence of myopathy risk, though less commonly reported:

• A documented case of myopathy with muscle pain, weakness, and wasting persisted for 1 year after starting empagliflozin, with symptoms resolving within weeks of discontinuation 2
• Resistance testing confirmed muscle weakness, and MRI changes reversed after stopping the medication 2
• The FDA label for Jardiance does not list myalgias or myopathy as common adverse effects, with the most common side effects being urinary tract infections and yeast infections 3
• This suggests myopathy is a rare but recognized complication requiring high clinical suspicion 2

Lisinopril and Myalgias

Lisinopril, an ACE inhibitor, has the weakest association with myalgias:

• ACE inhibitors are not typically associated with myalgias or myopathy in clinical practice 4
• The European Society of Hypertension guidelines extensively discuss lisinopril's use in various cardiovascular conditions without mentioning myalgias as a concern 5
• While any medication can theoretically cause muscle symptoms, lisinopril lacks substantial evidence linking it to this adverse effect

Clinical Approach to Drug-Induced Myalgias

When evaluating suspected drug-induced myalgias 4:

• Assess temporal relationship: Symptoms typically begin weeks to months after drug initiation
• Check creatine kinase levels: Can range from mild elevations to fulminant rhabdomyolysis
• Look for proximal muscle weakness in addition to pain
• Exclude endocrine disorders and inflammatory etiologies before attributing symptoms to medications
• Consider drug-drug interactions, particularly with medications metabolized by cytochrome P450 enzymes 4

Important Caveats

• Discontinuation of the offending drug typically improves symptoms in drug-induced myopathy, making this both diagnostic and therapeutic 2, 4
• A high degree of suspicion is required, as myalgias may not be listed as common adverse effects even when causally related 2, 1
• Referral to a neuromuscular subspecialist is warranted if symptoms persist after drug discontinuation 4