Can Zetia (Ezetimibe) cause a chronic cough?

From the Guidelines

Ezetimibe (Zetia) is not typically associated with causing chronic cough, and other causes such as acid reflux, asthma, or allergies should be considered first. This medication works in the digestive tract to reduce cholesterol absorption and has minimal systemic effects, which is why respiratory side effects like chronic cough are not commonly reported 1. The most common side effects of ezetimibe include diarrhea, joint pain, and fatigue. If you're experiencing a chronic cough while taking ezetimibe, it's more likely due to another cause, and a thorough evaluation should be done to determine the underlying cause of the cough.

According to the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines, the most common causes of chronic cough are upper airway secretions (UACS), asthma, and gastroesophageal reflux disease (GERD) 1. These conditions may present alone or in combination and may be clinically silent apart from the cough itself.

Some key points to consider in the evaluation of chronic cough include:

• The patient's medical history and physical examination are crucial in determining the cause of the cough 1
• The timing and characteristics of the cough are of little diagnostic value 1
• UACS, asthma, and GERD should be considered as potential causes of chronic cough, even if the patient has no other symptoms apart from the cough 1
• Other medications, such as ACE inhibitors, can cause cough and should be considered as a potential cause 1

It is essential to consult with a healthcare provider to determine the underlying cause of the cough and to develop an appropriate treatment plan. The healthcare provider can evaluate the patient's symptoms, medical history, and physical examination to determine the best course of action. Don't stop taking any prescribed medication without discussing it with your doctor first.

From the FDA Drug Label

Adverse reactions reported in ≥2% of patients treated with ezetimibe tablets and at an incidence greater than placebo in placebo-controlled studies of ezetimibe tablets are shown in Table 1 The following additional adverse reactions have been identified during post-approval use of ezetimibe tablets: Blood Disorders: thrombocytopenia Gastrointestinal Disorders: abdominal pain; pancreatitis; nausea Hepatobiliary Disorders: elevations in liver transaminases, including elevations more than 5 X ULN; hepatitis; cholelithiasis; cholecystitis Immune System Disorders: Hypersensitivity reactions including: anaphylaxis, angioedema, rash, and urticaria Musculoskeletal Disorders: elevated creatine phosphokinase; myopathy/rhabdomyolysis Nervous System Disorders: dizziness; paresthesia; depression; headache Skin and Subcutaneous Tissue Disorders: erythema multiforme Respiratory disorders are not explicitly mentioned in the post-marketing experience section, however upper respiratory tract infection is mentioned in the clinical trials section.

Chronic cough is not explicitly mentioned in the drug label as an adverse reaction. However, upper respiratory tract infection is reported in the clinical trials section. It can be inferred that while Zetia (Ezetimibe) may cause upper respiratory tract infections, there is no direct evidence to suggest that it causes chronic cough. Given the information available, a conservative clinical decision would be to monitor patients for any respiratory symptoms, including cough, when taking Zetia (Ezetimibe) 2.

From the Research

Drug-Induced Chronic Cough

• Chronic cough is defined as a cough lasting for ≥8 weeks with a normal chest radiograph 3
• Drug-induced chronic cough refers to a chronic cough caused by certain drugs, with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) being common causes 3, 4
• Other drugs such as omeprazole and leflumide have also been reported to cause cough 3

Ezetimibe and Chronic Cough

• Ezetimibe is a lipid-lowering agent used to treat primary hypercholesterolaemia, either as monotherapy or in combination with other hypolipidaemic drugs 5
• There is no direct evidence in the provided studies to suggest that ezetimibe (Zetia) can cause a chronic cough 5
• The studies on ezetimibe focus on its side effects, such as mild elevations of liver transaminases and myopathy, but do not mention chronic cough as a potential side effect 5, 6, 7

Management of Chronic Cough

• The management of chronic cough involves identifying and treating the underlying cause, which can be challenging 7
• Recent advances have been made in the comprehension of refractory chronic cough pathophysiology as well as its pharmacologic and non-pharmacologic treatment 7
• Symptomatic antitussives, such as centrally acting opioids, may be used to suppress cough, but their efficacy and safety need to be carefully evaluated 6