Can Zetia (ezetimibe) cause ptosis (lid drooping)?

Ezetimibe (Zetia) and Ptosis: No Direct Association

Ezetimibe (Zetia) is not known to cause ptosis (lid drooping) based on available evidence, and any lid drooping symptoms should prompt evaluation for other neurological conditions such as myasthenia gravis.

Mechanism of Action and Known Side Effects of Ezetimibe

Ezetimibe works by inhibiting intestinal uptake of dietary and biliary cholesterol without affecting the absorption of fat-soluble nutrients 1. It is primarily used as:

• An adjunct to diet for lowering LDL cholesterol in patients with hyperlipidemia
• A combination therapy with statins for enhanced cholesterol reduction
• A treatment option for patients who cannot tolerate statins 2

Common side effects of ezetimibe include:

• Upper respiratory tract infection
• Diarrhea
• Arthralgia
• Sinusitis
• Pain in extremities 2

Notably, ptosis or eyelid drooping is not listed among the known adverse effects of ezetimibe in any of the clinical guidelines or drug information.

Differential Diagnosis for Ptosis

When a patient presents with ptosis while taking ezetimibe, consider these potential causes:

1. Myasthenia Gravis

• Characterized by variable ptosis and strabismus that worsen with fatigue
• May present initially with only ocular symptoms in 50% of cases
• 50-80% of patients with ocular myasthenia develop generalized myasthenia within a few years 2
• Diagnostic tests include:
  • Ice pack test (application of ice over closed eyes for 2 minutes)
  • Rest test
  • Cogan lid-twitch sign
  • Anti-acetylcholine receptor antibody testing 2, 3

2. Oculomotor (Third) Nerve Palsy

• Second most common cranial neuropathy
• Presents with ptosis and misalignment with both horizontal and vertical components
• May be associated with vascular risk factors including hyperlipidemia, hypertension, and diabetes 2

3. Ocular Myokymia

• Benign condition with involuntary, fine contractions of the orbicularis oculi muscle
• Generally self-limiting 3

4. Other Causes

• Horner's syndrome
• Mechanical ptosis (aging)
• Post-surgical complication
• Contralateral lid drooping following ptosis repair on the opposite eye (Hering's law phenomenon) 4

Evaluation Algorithm for Ptosis in a Patient on Ezetimibe

1. Assess ptosis characteristics:

   • Unilateral vs bilateral
   • Constant vs variable/fatigable
   • Associated symptoms (diplopia, eye pain, weakness elsewhere)

2. Perform targeted examination:

   • Test for fatigability (sustained upgaze)
   • Check for Cogan's lid twitch sign
   • Perform ice pack test
   • Evaluate pupillary responses
   • Test extraocular movements

3. Consider diagnostic testing:

   • Anti-acetylcholine receptor antibodies
   • Anti-MuSK antibodies if AChR negative
   • Consider single fiber EMG (gold standard for myasthenia gravis diagnosis) 2
   • Neuroimaging if other neurological symptoms present

4. Management approach:

   • Do not discontinue ezetimibe based solely on ptosis, as there is no established causal relationship
   • Refer to ophthalmology and/or neurology for evaluation of ptosis
   • If myasthenia gravis is suspected, prompt referral is essential as this condition can progress to generalized myasthenia with potential respiratory complications 2

Important Considerations

1. Medication review: While ezetimibe is not associated with ptosis, review all medications as some can cause or exacerbate eye symptoms 3.

2. Monitoring: If continuing ezetimibe, monitor liver function as rare cases of serious hepatotoxicity have been reported 5.

3. Diagnostic pitfall: Failing to recognize ocular myasthenia gravis, which can precede generalized myasthenia in 50-80% of cases, can lead to delayed diagnosis of a potentially serious condition 2, 3.

4. Treatment timing: If myasthenia gravis is diagnosed, pyridostigmine (Mestinon) is the first-line treatment, starting at 30mg three times daily and gradually increasing as needed 3.

In conclusion, while patients may report ptosis while taking ezetimibe, there is no evidence supporting a causal relationship. Ptosis warrants thorough evaluation for neurological conditions, particularly myasthenia gravis, which can initially present with isolated ocular symptoms before progressing to a more generalized condition.