Usage
Fenofibrate + Pitavastatin is a combination drug prescribed for the management of mixed dyslipidemia, characterized by elevated levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B, along with low levels of high-density lipoprotein cholesterol (HDL-C). It combines a fibrate (fenofibrate) and a statin (pitavastatin).
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Pharmacological Classification: Hypolipidemic agent (combination of a fibrate and a statin)
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Mechanism of Action: Fenofibrate activates peroxisome proliferator-activated receptor alpha (PPARα), leading to increased lipoprotein lipase activity, reduced hepatic very-low-density lipoprotein (VLDL) production, and enhanced triglyceride clearance. Pitavastatin inhibits 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis, lowering LDL-C.
Alternate Names
No widely recognized alternate names exist for the combination product itself. However, the individual components have various names:
- Fenofibrate: Tricor, Fenoglide, Antara, Lofibra
- Pitavastatin: Livalo, Zypitamag
How It Works
- Pharmacodynamics: Fenofibrate primarily affects triglyceride metabolism, while pitavastatin lowers cholesterol levels. Together, they improve overall lipid profiles.
- Pharmacokinetics:
- Fenofibrate: Well-absorbed orally, highly protein-bound, metabolized to fenofibric acid, primarily excreted in urine.
- Pitavastatin: Well-absorbed orally, extensively metabolized by glucuronidation, primarily excreted in feces.
- Mode of Action: Fenofibrate activates PPARα, regulating lipid metabolism. Pitavastatin competitively inhibits HMG-CoA reductase, reducing cholesterol synthesis.
- Receptor binding/Enzyme Inhibition: Fenofibrate binds to PPARα. Pitavastatin inhibits HMG-CoA reductase.
- Elimination Pathways: Fenofibrate mainly undergoes renal excretion, while pitavastatin undergoes hepatic excretion.
Dosage
Standard Dosage
Adults:
- Fenofibrate: Micronized formulation: 130-160 mg orally once daily.
- Pitavastatin: 2 mg orally once daily, adjustable up to 4 mg daily based on LDL-C goals and patient response.
Note that these are starting doses and should be adjusted after 4-8 weeks based on individual patient response and goals.
Children:
Pitavastatin is approved for children aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH), starting at 1-2 mg daily. Fenofibrate is generally not recommended for children.
Special Cases:
- Elderly Patients: Initiate with lower doses of both drugs and monitor closely.
- Patients with Renal Impairment:
- Fenofibrate: Contraindicated in severe renal impairment. Use with caution and dose reduction in moderate impairment.
- Pitavastatin: Initiate at 1 mg daily, maximum 2 mg daily in moderate to severe impairment.
- Patients with Hepatic Dysfunction:
- Fenofibrate: Use with caution and monitor liver function tests.
- Pitavastatin: Contraindicated in active liver disease or unexplained elevated liver enzymes.
- Patients with Comorbid Conditions: Individualized dosing and close monitoring are crucial in patients with diabetes, cardiovascular disease, or other relevant conditions.
Clinical Use Cases
The combination is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for chronic lipid management.
Dosage Adjustments
Adjustments are made based on lipid response, renal/hepatic function, drug interactions, and other patient-specific factors. Consult drug interaction checkers for potential interactions and necessary modifications.
Side Effects
Common Side Effects
- Myalgia, gastrointestinal upset (dyspepsia, abdominal pain), elevated liver enzymes, headache.
Rare but Serious Side Effects
- Rhabdomyolysis, myopathy, liver injury, pancreatitis, cholelithiasis.
Long-Term Effects
- Potential for muscle and liver damage with prolonged use.
Adverse Drug Reactions (ADR)
- Severe myopathy, rhabdomyolysis, acute renal failure.
Contraindications
- Severe renal dysfunction, active liver disease, gallbladder disease, hypersensitivity to either drug, pregnancy, breastfeeding, concomitant use with cyclosporine.
Drug Interactions
- Statins interact with numerous drugs including:
- CYP3A4 inhibitors (e.g., erythromycin, clarithromycin, some azole antifungals): Increase statin levels and myopathy risk.
- CYP3A4 inducers (e.g., rifampin): Decrease statin efficacy.
- Fibrates interact with:
- Bile acid sequestrants: Reduced fibrate absorption.
- Anticoagulants: Increased bleeding risk.
- The combination increases the risk of myopathy.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated.
- Breastfeeding: Contraindicated.
Drug Profile Summary
- Mechanism of Action: Fenofibrate: PPARα agonist; Pitavastatin: HMG-CoA reductase inhibitor.
- Side Effects: Myalgia, gastrointestinal upset, increased liver enzymes.
- Contraindications: Severe renal/liver disease, gallbladder disease, pregnancy, breastfeeding.
- Drug Interactions: CYP3A4 inhibitors/inducers, bile acid sequestrants, anticoagulants.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: Fenofibrate 130-160 mg/day, Pitavastatin 2-4 mg/day; individualize and adjust based on response.
- Monitoring Parameters: Lipid panel, liver function tests, renal function tests, creatine kinase.
Popular Combinations
This combination itself is increasingly used. Individual components may be combined with other lipid-lowering agents if needed.
Precautions
- Pre-screening for contraindications and drug interactions is essential.
- Monitor liver and kidney function.
- Counsel patients about myopathy risk and instruct them to report muscle pain or weakness.
- Avoid alcohol during treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fenofibrate + Pitavastatin?
A: Fenofibrate (micronized) 130-160 mg once daily + Pitavastatin 2 mg once daily (adjustable to 4 mg). Adjust based on individual patient response and tolerability after 4-8 weeks.
Q2: What are the main contraindications to this combination?
A: Severe renal dysfunction, active liver disease, gallbladder disease, pregnancy, and breastfeeding.
Q3: What are the most serious side effects of Fenofibrate + Pitavastatin?
A: Rhabdomyolysis, myopathy, severe liver injury.
Q4: How should I monitor patients on this combination therapy?
A: Monitor lipid panel, liver function tests (LFTs), renal function tests, and creatine kinase (CK) regularly. Assess for muscle symptoms (myalgia, weakness) at each visit.
Q5: Can this combination be used in patients with diabetes?
A: Yes, but it requires careful monitoring due to increased risk of myopathy and renal impairment. Glycemic control optimization is also crucial.
Q6: What are the key drug interactions to consider?
A: CYP3A4 inhibitors (e.g., erythromycin, clarithromycin), CYP3A4 inducers (e.g., rifampin), bile acid sequestrants, and anticoagulants.
Q7: What patient education points are important for this combination?
A: Counsel patients on the risk of myopathy, the importance of reporting muscle symptoms, adherence to lifestyle modifications (diet, exercise), regular monitoring, and avoidance of alcohol.
Q8: Is there a preferred time of day to administer Fenofibrate + Pitavastatin?
A: The combination can be administered at any time of the day, with or without food, preferably at the same time each day for consistent absorption.
Q9: What are the potential benefits of combining fenofibrate and pitavastatin?
A: The combination can address multiple lipid abnormalities simultaneously, improving overall lipid profiles beyond what either drug can achieve alone. This can lead to better cardiovascular risk reduction in patients with mixed dyslipidemia.
Q10: How does renal impairment affect the dosing of this combination?
A: Fenofibrate is contraindicated in severe renal impairment and requires dose reduction in moderate impairment. Pitavastatin should be initiated at a lower dose (1 mg) and limited to a maximum of 2 mg daily in moderate to severe renal impairment.
