Usage
- Ezetimibe + Rosuvastatin is prescribed to lower “bad” cholesterol (low-density lipoprotein cholesterol or LDL-C) levels in the blood. It is used as an adjunct to diet and exercise in patients with primary (non-familial) hyperlipidemia and homozygous familial hypercholesterolemia (HoFH), a genetic disorder causing very high cholesterol.
- Pharmacological classification: Lipid-lowering combination drug (HMG-CoA reductase inhibitor/statin + cholesterol absorption inhibitor)
- Mechanism of action: This combination therapy works through two distinct mechanisms. Rosuvastatin inhibits the enzyme HMG-CoA reductase in the liver, reducing cholesterol synthesis. Ezetimibe inhibits the absorption of cholesterol from the small intestine. The combined effect leads to a significant decrease in total and LDL-C levels.
Alternate Names
- The combination itself doesn’t have an international nonproprietary name (INN), as each component has its own INN (rosuvastatin and ezetimibe).
- Brand names: Roszet, Ridutrin, Ezetimibe + Rosuvastatin Composite Pack, Lypstaplus, and other regional brand names.
How It Works
- Pharmacodynamics: Rosuvastatin competitively inhibits HMG-CoA reductase, a key enzyme in the mevalonate pathway responsible for cholesterol synthesis in the liver. This leads to decreased hepatic cholesterol production, upregulation of LDL receptors, and increased clearance of LDL-C from the bloodstream. Ezetimibe inhibits the intestinal absorption of cholesterol by targeting the Niemann-Pick C1-Like 1 (NPC1L1) protein, a cholesterol transporter located on the brush border of enterocytes.
- Pharmacokinetics: Rosuvastatin is extensively metabolized by the liver, primarily by CYP2C9, and excreted mainly in the bile. Ezetimibe undergoes enterohepatic recirculation, is primarily glucuronidated in the liver and intestine, and is excreted both in feces and urine. The combined effect of reduced production and absorption of cholesterol significantly lowers LDL levels.
- Mode of Action: Rosuvastatin’s mode of action involves enzyme inhibition (HMG-CoA reductase). Ezetimibe acts by blocking the NPC1L1 cholesterol transporter. The combined effect reduces both endogenous cholesterol production and dietary cholesterol uptake.
- Elimination pathways: Rosuvastatin is predominantly eliminated via the hepatobiliary route, with minimal renal excretion. Ezetimibe is excreted in both urine and feces after glucuronidation.
Dosage
Standard Dosage
Adults:
- Initial dose: 10 mg rosuvastatin/10 mg ezetimibe once daily. Lower initial doses (e.g., 5 mg rosuvastatin/10 mg ezetimibe) are available for specific populations (e.g., Asian patients or those with renal impairment).
- Dosage range: 5 mg/10 mg to 40 mg/10 mg rosuvastatin/ezetimibe once daily.
- The dose can be titrated based on LDL-C levels and cardiovascular risk assessment.
- Maximum dose: 40 mg rosuvastatin/10 mg ezetimibe.
Children:
- Not recommended for use in children.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 5 mg rosuvastatin/10 mg ezetimibe) and monitor closely for myopathy.
- Patients with Renal Impairment: Mild to moderate renal impairment: no dosage adjustment is generally needed. Severe renal impairment (creatinine clearance < 30 mL/min): initiate at 5 mg/10 mg rosuvastatin/ezetimibe once daily; do not exceed 10 mg/10 mg once daily.
- Patients with Hepatic Dysfunction: Moderate to severe hepatic impairment: Ezetimibe + Rosuvastatin is not recommended.
- Patients with Comorbid Conditions: Dosage adjustments may be required based on individual patient considerations and potential drug interactions.
Clinical Use Cases
Ezetimibe + Rosuvastatin is indicated for the management of dyslipidemia, including primary hypercholesterolemia and homozygous familial hypercholesterolemia. It is not specifically indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments may be needed based on individual patient characteristics, such as renal or hepatic impairment, concomitant medications, and genetic factors affecting drug metabolism. Monitoring of liver function tests and creatine kinase levels is recommended, especially in patients at higher risk for myopathy.
Side Effects
Common Side Effects
Headache, nausea, muscle aches, weakness, constipation, diarrhea, dizziness, joint pain, abdominal pain, upper respiratory tract infection, and common cold.
Rare but Serious Side Effects
Myopathy (muscle pain, tenderness, or weakness, especially with fever), rhabdomyolysis (muscle breakdown), hepatitis, and allergic reactions.
Long-Term Effects
The long-term effects of Ezetimibe + Rosuvastatin primarily relate to its intended benefit of reducing cardiovascular risk. However, chronic use may be associated with a small increased risk of new-onset diabetes.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include myopathy, rhabdomyolysis, liver dysfunction, and allergic reactions. These require immediate intervention.
Contraindications
- Active liver disease, including unexplained persistent elevations of serum transaminases.
- Pregnancy and breastfeeding.
- Hypersensitivity to rosuvastatin or ezetimibe.
Drug Interactions
- Cyclosporine, gemfibrozil, and certain drugs to treat hepatitis C (e.g., ledipasvir/sofosbuvir) significantly increase rosuvastatin exposure and should be avoided or used with caution.
- Bile acid sequestrants (e.g., cholestyramine) can reduce the absorption of Ezetimibe + Rosuvastatin. Administer the combination at least 2 hours before or 4 hours after a bile acid sequestrant.
- Antacids containing aluminum and magnesium can reduce the absorption of rosuvastatin. Administer the combination at least 2 hours before an antacid.
- Other potential interactions include those with fibrates, niacin, some antifungals, and certain medications metabolized by CYP2C9.
- Red yeast rice products should be avoided due to potential additive effects and increased risk of myopathy.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category X (contraindicated). HMG-CoA reductase inhibitors may cause fetal harm. Cholesterol and other products of cholesterol biosynthesis are essential for fetal development.
- Ezetimibe + Rosuvastatin should be discontinued if pregnancy is detected.
- Breastfeeding: Contraindicated. Rosuvastatin is excreted in breast milk and may pose a risk to the infant. Ezetimibe is also best avoided during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Inhibits HMG-CoA reductase (rosuvastatin) and cholesterol absorption (ezetimibe).
- Side Effects: Common: Headache, muscle aches, nausea. Serious: Myopathy, rhabdomyolysis, liver dysfunction.
- Contraindications: Active liver disease, pregnancy, breastfeeding, hypersensitivity.
- Drug Interactions: Cyclosporine, gemfibrozil, certain hepatitis C drugs, bile acid sequestrants, antacids.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 5 mg/10 mg to 40 mg/10 mg rosuvastatin/ezetimibe once daily. Not recommended for children.
- Monitoring Parameters: Liver function tests (LFTs), creatine kinase (CK), lipid panel.
Popular Combinations
Ezetimibe + Rosuvastatin itself is a popular combination. Combining it with other lipid-lowering agents may be considered in certain cases by specialists, but this needs careful evaluation of potential benefits and risks, including increased potential for drug interactions and adverse effects.
Precautions
- General Precautions: Monitor liver function and CK levels, especially at initiation and with dose increases. Assess for signs and symptoms of myopathy. Advise patients on lifestyle modifications.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Not recommended for children. Start elderly patients on a lower dose and monitor carefully.
- Menstruating Individuals: No specific precautions.
- Lifestyle Considerations: Emphasize the importance of diet, exercise, and weight management.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ezetimibe + Rosuvastatin?
A: The starting dose for adults is typically 10 mg/10 mg once daily. The dose can range from 5 mg/10 mg to 40 mg/10 mg once daily, adjusted based on individual patient response and lipid goals. Not recommended for children.
Q2: What are the most serious side effects?
A: Myopathy (muscle pain/weakness), rhabdomyolysis (severe muscle breakdown), and liver damage are rare but serious side effects. Patients should be advised to report any unexplained muscle pain or weakness, especially if accompanied by fever or dark urine.
Q3: Can this medication be used during pregnancy or breastfeeding?
A: No, Ezetimibe + Rosuvastatin is contraindicated during pregnancy and breastfeeding. Effective contraception should be used in women of childbearing potential.
Q4: What are the main drug interactions to be aware of?
A: Cyclosporine, gemfibrozil, and certain hepatitis C drugs can significantly increase rosuvastatin levels. Bile acid sequestrants and antacids can reduce absorption. Concomitant use of certain other medications (e.g., some antifungals, fibrates) requires careful monitoring.
Q5: How should this medication be taken?
A: Take one tablet by mouth once daily, with or without food, at the same time each day. Tablets should be swallowed whole and not crushed or chewed.
Q6: What should I monitor in patients taking this medication?
A: Monitor liver function tests (LFTs) and creatine kinase (CK) levels, particularly at the start of therapy and with dose adjustments. Regularly assess lipid panel to track treatment effectiveness.
Q7: Can this drug be used in patients with liver disease?
A: Ezetimibe + Rosuvastatin is contraindicated in patients with active liver disease or unexplained persistent elevations in liver enzymes. Use with caution in patients with mild hepatic impairment.
Q8: Is there a specific dosage adjustment for Asian patients?
A: Due to increased rosuvastatin plasma concentrations in Asian patients, a lower starting dose of 5 mg rosuvastatin/10 mg ezetimibe is recommended.
Q9: What if a patient forgets to take a dose?
A: If a dose is missed, the patient should take it as soon as remembered, unless it is almost time for the next dose. Do not double the dose.
