Hypercholesterolemia usually refers to abnormally high levels of cholesterol, mainly low-density lipoprotein cholesterol in the blood, contributing to high total cholesterol. Drugs can increase cholesterol by disturbing liver function, lipid excretion, and/or the hormones that process lipids. Drug-induced hypercholesterolemia fits into a broader category of dyslipidemia, which indicates abnormal levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides. Most cases are inherited. The other 30%-40% of cases are considered secondary, with drug-induced dyslipidemia being a common cause. Other secondary causes of hypercholesterolemia include hypothyroidism, nephrotic syndrome, primary biliary cholangitis, obstructive jaundice, diabetes, Cushing syndrome, and pheochromocytoma. Drug-induced weight gain may also contribute to increased cholesterol in affected individuals.

Detection occurs with lipid panel testing. Adult fasting lipid panel reference ranges (some patients may require lower targets based on medical history and risk factors):

• Total cholesterol: Below 200 mg/dL
  • Borderline high: 200-239 mg/dL
  • High: Above 240 mg/dL
• HDL cholesterol: Above 60 mg/dL. Less than 60 mg/dL is low.
• LDL cholesterol: Below 100 mg/dL
  • Diabetic patients: Below 70 mg/dL
• Triglycerides: Below 150 mg/dL

There are usually no signs or symptoms of hypercholesterolemia until complications occur. Complications include atherosclerosis, coronary artery disease, acute coronary syndrome, peripheral artery disease, and stroke.

Common drugs causing hypercholesterolemia include:

Hormones

• Progesterone 
• Testosterone 
• Anabolic steroids
• Danazol
• Glucocorticoids
• Growth hormone

Cardiovascular drugs

• Thiazide diuretics (chlorthalidone)
• Amiodarone

Antidiabetic agents

• SGLT2 inhibitors
• Thiazolidinediones

Immunosuppressants

• Calcineurin inhibitors (cyclosporine, tacrolimus)

Antiviral agents

• Protease inhibitors (ritonavir, indinavir) 
• Direct acting antivirals 

Antineoplastics

• mTOR inhibitors (sirolimus, everolimus) 

Neurologic / psychiatric drugs

• Anticonvulsants (carbamazepine) 
• Antipsychotics (especially atypical antipsychotics, eg, olanzapine, clozapine)

Vitamin A derivatives

• Retinoids (isotretinoin) 

Other risk factors for secondary dyslipidemia include smoking, stress, polypharmacy, excessive alcohol consumption, a poor diet high in saturated and trans fats, sedentary lifestyle, overweight, hypertension, liver disease, diabetes, and hypothyroidism. 

If possible, replace the causative drug. Monitor lipid levels if causative treatment must be continued. Advise lifestyle changes such as reducing saturated and trans fats intake, increasing physical activity, and weight loss. 

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