Can Nexlizet (bempedoic acid and ezetimibe) cause tendon problems?

Nexlizet and Tendon Problems

Yes, Nexlizet (bempedoic acid and ezetimibe) can cause tendon problems, including tendinitis and tendon rupture, and patients should be monitored for these complications. 1

Mechanism and Risk

Bempedoic acid, one component of Nexlizet, has been associated with tendon disorders in clinical studies. The 2022 ACC Expert Consensus specifically lists tendon rupture as a warning/precaution for both bempedoic acid alone and the combination product with ezetimibe (Nexlizet). 1

The risk appears to be related to the bempedoic acid component rather than ezetimibe, as ezetimibe alone does not carry specific warnings about tendon disorders. 2

Incidence and Comparison with Other Medications

In the CLEAR Outcomes study, which evaluated bempedoic acid in patients at high cardiovascular risk:

• Tendinopathies including tendon rupture occurred in 2% of patients in both the bempedoic acid and placebo groups 3

While this suggests a similar rate to placebo, the FDA-approved labeling still includes tendon rupture as a warning, indicating that individual cases have been documented and the risk is considered clinically relevant.

Drug-induced tendinopathy has been most commonly associated with:

• Fluoroquinolone antibiotics
• Statins
• Glucocorticoids
• Aromatase inhibitors 4, 5

Monitoring and Management

The ACC Expert Consensus provides clear guidance on managing this risk 1:

1. Immediate discontinuation if tendon rupture occurs

2. Consider discontinuation if the patient experiences:

   • Joint pain
   • Swelling
   • Inflammation

3. Patient education:

   • Advise patients to rest at the first sign of tendinitis or tendon rupture
   • Instruct patients to contact their healthcare provider if symptoms occur

4. Risk assessment:

   • Consider alternative therapy in patients with a history of tendon disorders or tendon rupture

Special Populations at Higher Risk

Patients with the following characteristics may be at increased risk for tendon problems with Nexlizet:

• History of previous tendon disorders
• History of tendon rupture
• Concurrent use of medications also associated with tendinopathy (such as fluoroquinolones)
• Advanced age

Clinical Approach

When prescribing Nexlizet:

1. Before starting therapy:

   • Screen for history of tendon disorders or rupture
   • Consider alternative therapy if positive history exists

2. During therapy:

   • Monitor for signs and symptoms of tendinitis or tendon rupture
   • Educate patients about warning signs
   • Ensure patients know to rest and contact their provider if symptoms develop

3. If tendon symptoms develop:

   • Immediately discontinue Nexlizet if tendon rupture occurs
   • Consider discontinuation for less severe tendon symptoms
   • Evaluate for alternative lipid-lowering therapy

Benefit-Risk Assessment

Despite the tendon-related risks, Nexlizet offers significant LDL-C reduction benefits:

• Combination therapy with statins provides approximately 38% additional LDL-C reduction 1
• Beneficial for patients with ASCVD or heterozygous familial hypercholesterolemia requiring additional LDL-C lowering 1

The decision to use Nexlizet should weigh these cardiovascular benefits against the potential risk of tendon problems, particularly in patients with pre-existing tendon disorders.