Usage
Fenofibrate + Rosuvastatin is a combination medication prescribed to manage mixed dyslipidemia, a condition characterized by elevated levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and apolipoprotein B (Apo B), along with decreased high-density lipoprotein cholesterol (HDL-C). This combination therapy is considered when statin monotherapy (e.g., Rosuvastatin alone) fails to achieve optimal lipid control. It belongs to the pharmacological class of lipid-lowering agents, specifically combining a statin (Rosuvastatin) with a fibrate (Fenofibrate).
Rosuvastatin inhibits HMG-CoA reductase, an enzyme crucial for cholesterol synthesis in the liver. This action reduces the production of cholesterol, leading to lower LDL-C levels. Fenofibrate, a PPAR-α agonist, increases lipoprotein lipase activity, facilitating the breakdown and clearance of triglycerides. It also enhances HDL-C levels.
Alternate Names
While “Fenofibrate + Rosuvastatin” is the standard generic name, the specific brand name can vary depending on the manufacturer and region. Some common brand names include Rosufen.
How It Works
Pharmacodynamics: Rosuvastatin competitively inhibits HMG-CoA reductase, reducing cholesterol biosynthesis in the liver. This, in turn, lowers circulating LDL-C levels. Fenofibrate activates PPAR-α, leading to increased lipoprotein lipase activity. This action promotes triglyceride hydrolysis and lowers VLDL-C levels. It also increases Apo A-I and Apo A-II synthesis, thereby increasing HDL-C.
Pharmacokinetics: Both Rosuvastatin and Fenofibrate are administered orally. Rosuvastatin reaches peak plasma concentration in about 5 hours, while Fenofibrate achieves peak levels in 2 to 4 hours. Rosuvastatin is primarily metabolized by CYP2C9, and Fenofibrate is hydrolyzed to fenofibric acid, which is mainly glucuronidated. Both drugs are primarily excreted through the biliary route, with some renal excretion.
Mode of Action: Rosuvastatin acts through competitive inhibition of HMG-CoA reductase, a rate-limiting enzyme in cholesterol synthesis. Fenofibrate exerts its effect by activating PPAR-α, a nuclear receptor involved in lipid metabolism. This activation upregulates lipoprotein lipase and increases Apo A-I and Apo A-II production.
Elimination Pathways: Rosuvastatin is primarily excreted in bile, with a minor fraction undergoing renal excretion. Fenofibrate’s active metabolite, fenofibric acid, is mostly glucuronidated and excreted in bile, with some renal elimination.
Dosage
Standard Dosage
Adults: The recommended starting dose is one tablet containing 10 mg of Rosuvastatin and 145 mg of Fenofibrate once daily, taken orally after dinner. The dose can be adjusted based on individual response and tolerability, but the maximum recommended dose of Rosuvastatin is 40 mg and Fenofibrate is 160 mg.
Children: This combination is not recommended for pediatric patients.
Special Cases:
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Elderly Patients: Dose adjustments may be necessary based on renal function.
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Patients with Renal Impairment: For moderate renal impairment (creatinine clearance <60 mL/min), the initial Rosuvastatin dose should not exceed 5mg, and the 40 mg dose is contraindicated. The combination product may not be suitable for these patients. Fenofibrate requires dose adjustment in moderate renal impairment. The combination is contraindicated in severe renal impairment.
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Patients with Hepatic Dysfunction: Dose adjustment is needed for patients with hepatic impairment. Rosuvastatin should be used cautiously, starting with a lower dose (5-10 mg) in patients with moderate to severe hepatic impairment. The use of Fenofibrate + Rosuvastatin is contraindicated in patients with active liver disease or unexplained persistent liver function abnormalities.
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Patients with Comorbid Conditions: Caution is advised in patients with diabetes, hypothyroidism, and other metabolic disorders.
Clinical Use Cases
The combination of Fenofibrate and Rosuvastatin is specifically indicated for managing mixed dyslipidemia as an adjunct to diet and lifestyle modifications. It is not typically used in the context of intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments are based on individual response to therapy, renal function, hepatic function, and concomitant medications. Regular monitoring of lipid levels and liver function tests is essential.
Side Effects
Common Side Effects: Myalgia, gastrointestinal discomfort (constipation, diarrhea, abdominal pain), headache, back pain, elevated liver enzymes.
Rare but Serious Side Effects: Rhabdomyolysis, myopathy, hepatotoxicity, pancreatitis, cholelithiasis.
Long-Term Effects: Potential long-term effects include muscle damage, liver damage, and gallbladder issues. Regular monitoring is crucial.
Adverse Drug Reactions (ADR): Serious ADRs include rhabdomyolysis, liver failure, and severe allergic reactions.
Contraindications
Absolute contraindications include hypersensitivity to either drug, severe renal impairment, active liver disease, gallbladder disease, and concurrent use of certain medications like gemfibrozil. Relative contraindications include moderate renal or hepatic impairment, hypothyroidism, and pregnancy.
Drug Interactions
Significant drug interactions can occur with cyclosporine, certain antibiotics (e.g., erythromycin, clarithromycin), antifungals (e.g., ketoconazole, itraconazole), HIV protease inhibitors, gemfibrozil, and other fibrates. Concomitant use of bile acid sequestrants can decrease the absorption of Rosuvastatin.
Pregnancy and Breastfeeding
This combination is contraindicated during pregnancy and breastfeeding due to the potential for fetal harm.
Drug Profile Summary
- Mechanism of Action: Rosuvastatin: HMG-CoA reductase inhibition; Fenofibrate: PPAR-α activation.
- Side Effects: Myalgia, gastrointestinal discomfort, headache, rhabdomyolysis (rare), hepatotoxicity (rare).
- Contraindications: Hypersensitivity, severe renal/hepatic impairment, gallbladder disease, pregnancy, breastfeeding.
- Drug Interactions: Cyclosporine, azole antifungals, macrolide antibiotics, gemfibrozil.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: Rosuvastatin 10-40 mg + Fenofibrate 145 mg once daily; dosage adjusted based on individual patient characteristics.
- Monitoring Parameters: Lipid panel, liver function tests, renal function, creatine kinase.
Popular Combinations
Fenofibrate + Rosuvastatin is itself a popular combination used when statin monotherapy is insufficient.
Precautions
General precautions include monitoring liver and renal function, especially in elderly patients and those with pre-existing conditions. Assess for muscle pain and weakness. Alcohol should be limited. Caution is advised in pregnant/breastfeeding women, and pediatric patients.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fenofibrate + Rosuvastatin?
A: The standard starting dose is Rosuvastatin 10 mg + Fenofibrate 145 mg once daily, taken after dinner. Dosage may be adjusted based on individual patient response and tolerability, up to a maximum of Rosuvastatin 40 mg + Fenofibrate 160 mg daily.
Q2: What are the main side effects of this combination?
A: Common side effects include myalgia, gastrointestinal discomfort, headache, and elevated liver enzymes. Rare but serious side effects include rhabdomyolysis and hepatotoxicity.
Q3: Who should not take Fenofibrate + Rosuvastatin?
A: Contraindications include hypersensitivity to either drug, severe renal/hepatic impairment, gallbladder disease, pregnancy, and breastfeeding.
Q4: What are the key drug interactions to be aware of?
A: Important drug interactions can occur with cyclosporine, certain antibiotics (e.g., erythromycin), antifungals (e.g., ketoconazole), HIV protease inhibitors, gemfibrozil, and other fibrates.
Q5: How does this combination affect patients with renal impairment?
A: Dosage adjustments are necessary for patients with renal impairment. The combination may not be suitable for those with moderate to severe impairment.
Q6: Is this combination safe during pregnancy and breastfeeding?
A: No. Fenofibrate + Rosuvastatin is contraindicated during pregnancy and breastfeeding due to the potential for fetal harm.
Q7: What monitoring parameters are essential for patients on this therapy?
A: Regular monitoring of lipid panel, liver function tests, renal function, and creatine kinase is essential.
Q8: What is the mechanism of action of this drug combination?
A: Rosuvastatin inhibits HMG-CoA reductase, decreasing cholesterol synthesis, while Fenofibrate activates PPAR-α, leading to increased triglyceride breakdown and enhanced HDL-C levels.
Q9: Why is this combination prescribed?
A: Fenofibrate + Rosuvastatin is prescribed for managing mixed dyslipidemia, particularly when statin monotherapy is insufficient to achieve optimal lipid control.
