Usage
Ezetimibe is prescribed to lower high cholesterol levels. It’s used as adjunctive therapy to diet for the reduction of elevated total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and triglycerides (TG), and to increase high-density lipoprotein cholesterol (HDL-C). It is specifically indicated for:
- Primary Hypercholesterolemia (Heterozygous Familial and Non-Familial): In adults and adolescents (10 to 17 years of age).
- Homozygous Familial Hypercholesterolemia (HoFH): In adults and adolescents (10 to 17 years of age), usually administered with a statin.
- Homozygous Sitosterolemia: To reduce elevated sitosterol and campesterol levels.
Ezetimibe’s pharmacological classification is a cholesterol absorption inhibitor. It works by selectively inhibiting the intestinal absorption of cholesterol and related plant sterols.
Alternate Names
Ezetimibe is the generic name. Brand names include Zetia and Ezetrol.
How It Works
Pharmacodynamics: Ezetimibe primarily acts on the small intestine’s brush border, where it inhibits the Niemann-Pick C1-Like 1 (NPC1L1) protein. NPC1L1 is a transporter responsible for cholesterol absorption. By inhibiting this transporter, ezetimibe reduces the amount of cholesterol absorbed from the diet, thereby lowering plasma cholesterol levels.
Pharmacokinetics:
- Absorption: Ezetimibe is absorbed after oral administration and is extensively metabolized in the small intestine and liver to its pharmacologically active glucuronide metabolite (ezetimibe-glucuronide).
- Metabolism: Ezetimibe undergoes enterohepatic recirculation, which contributes to its long half-life.
- Elimination: Both ezetimibe and ezetimibe-glucuronide are primarily eliminated in the feces (approximately 80%), with a smaller portion excreted in the urine (approximately 10%).
Mode of Action: Ezetimibe targets the NPC1L1 transporter at the brush border of enterocytes. This inhibition effectively blocks the uptake of cholesterol and plant sterols from the intestinal lumen.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Ezetimibe does not bind to receptors or modulate neurotransmitters. Its primary mechanism is selective inhibition of the NPC1L1 transporter protein.
Dosage
Standard Dosage
Adults:
The standard dosage for adults is 10 mg orally once daily, taken with or without food.
Children (10 years and older):
The standard dosage for children 10 years and older is 10 mg orally once daily, taken with or without food.
Special Cases:
- Elderly Patients: No dosage adjustment is necessary.
- Patients with Renal Impairment: No dosage adjustment is necessary.
- Patients with Hepatic Dysfunction (Mild): No dosage adjustment is required. Ezetimibe is not recommended for patients with moderate or severe hepatic impairment.
- Patients with Comorbid Conditions: Dosage adjustments may be required depending on the specific comorbidity. Refer to a specialist for guidance.
Clinical Use Cases
Ezetimibe is not typically used in acute clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It’s primarily indicated for chronic management of hypercholesterolemia.
Side Effects
Common Side Effects:
Upper respiratory tract infections, diarrhea, joint pain, muscle pain, and fatigue.
Rare but Serious Side Effects:
Liver problems (abdominal pain, yellowing of skin and eyes), myopathy/rhabdomyolysis (unexplained muscle pain, weakness), hypersensitivity reactions (angioedema, anaphylaxis), pancreatitis, and severe cutaneous adverse reactions (SJS, TEN, DRESS).
Contraindications
- Hypersensitivity to ezetimibe.
- Active liver disease or unexplained persistent elevations in serum transaminases (especially when used in combination with a statin).
- Pregnancy and lactation when used in combination with a statin.
- Moderate or severe hepatic impairment.
- Concurrent use with a statin, fenofibrate, or other LDL-C lowering therapy when such therapy is contraindicated.
Drug Interactions
- Cyclosporine: Increased exposure of ezetimibe and cyclosporine.
- Fibrates (other than fenofibrate): Increased risk of gallstones.
- Bile acid sequestrants: Administer ezetimibe at least 2 hours before or 4 hours after bile acid sequestrants.
- Statins: Increased risk of myopathy.
- Anticoagulants (e.g., Warfarin): Close monitoring is required.
Pregnancy and Breastfeeding
- Pregnancy: Ezetimibe is generally avoided during pregnancy, especially when combined with a statin. If absolutely necessary, use only if the potential benefit outweighs the risk to the fetus.
- Breastfeeding: While limited data exists, ezetimibe is generally considered acceptable during breastfeeding. However, using Ezetimibe in combination with a statin is not recommended.
Drug Profile Summary
- Mechanism of Action: Inhibits intestinal cholesterol absorption.
- Side Effects: Common: Upper respiratory tract infection, diarrhea, joint pain, and fatigue. Serious: Liver damage, myopathy, hypersensitivity reactions.
- Contraindications: Hypersensitivity, active liver disease, pregnancy/lactation with statins, moderate/severe hepatic impairment.
- Drug Interactions: Cyclosporine, fibrates, bile acid sequestrants, statins.
- Pregnancy & Breastfeeding: Avoid during pregnancy (especially with statins). Generally acceptable during breastfeeding (avoid with statins).
- Dosage: 10 mg once daily, with or without food.
- Monitoring Parameters: Lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides), liver function tests.
Popular Combinations
- Ezetimibe + Statin: This combination is frequently used to achieve greater LDL-C reduction than either drug alone.
Precautions
- Monitor liver function tests.
- Monitor for muscle pain or weakness (especially with statins).
- Evaluate for gallbladder disease (especially with fibrates).
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ezetimibe?
A: 10 mg orally once daily for adults and children 10 years and older.
Q2: How does Ezetimibe work?
A: It selectively inhibits the intestinal absorption of cholesterol.
Q3: What are the common side effects of Ezetimibe?
A: Upper respiratory tract infection, diarrhea, joint pain, and muscle aches.
Q4: Can Ezetimibe be taken with statins?
A: Yes, but with caution, as it may increase the risk of myopathy. Close monitoring is necessary.
Q5: Is Ezetimibe safe during pregnancy?
A: Ezetimibe should generally be avoided during pregnancy, particularly when combined with a statin.
Q6: What are the contraindications to Ezetimibe?
A: Hypersensitivity, active liver disease, pregnancy/lactation with statins, moderate/severe hepatic impairment.
Q7: How should Ezetimibe be taken with bile acid sequestrants?
A: Administer Ezetimibe at least 2 hours before or 4 hours after a bile acid sequestrant.
Q8: What should I monitor in patients taking Ezetimibe?
A: Monitor lipid profile and liver function tests. If taken with a statin, closely monitor for muscle symptoms.
Q9: Can Ezetimibe be used in children?
A: Yes, in children 10 years and older at the same dose as adults. It is not recommended for children under 10 years old.
Q10: Does Ezetimibe interact with alcohol?
A: There are no known direct interactions, but alcohol may worsen some side effects like diarrhea, dizziness, and fatigue. Excessive alcohol intake can damage the liver.
