Usage
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Fluvastatin is prescribed to lower high cholesterol and triglycerides (types of fat) in the blood. Specifically, it reduces low-density lipoprotein cholesterol (LDL-C), often referred to as “bad” cholesterol, and increases high-density lipoprotein cholesterol (HDL-C), known as “good” cholesterol. It also moderately reduces triglycerides.
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It is also used in secondary prevention of cardiovascular disease in patients with coronary heart disease (CHD), slowing the progression of atherosclerosis and reducing the risk of coronary revascularization procedures. It is prescribed for these conditions when dietary changes and other lifestyle modifications are insufficient.
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Pharmacological classification: HMG-CoA reductase inhibitor (statin).
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Mechanism of Action: Fluvastatin inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. This reduces hepatic cholesterol synthesis, upregulates LDL receptors, and increases hepatic LDL-C uptake, ultimately lowering plasma LDL-C and total cholesterol levels.
Alternate Names
- Fluvastatin sodium
- Brand Names: Lescol, Lescol XL
How It Works
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Pharmacodynamics: Fluvastatin primarily exerts its effects in the liver by lowering cholesterol production and increasing cholesterol clearance from the bloodstream. This leads to reduced levels of total cholesterol, LDL-C, and triglycerides, as well as increased levels of HDL-C. These changes positively impact the lipid profile, reducing cardiovascular risk.
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Pharmacokinetics:
- Absorption: Fluvastatin is rapidly and almost completely absorbed following oral administration, although it undergoes extensive first-pass metabolism, reducing its bioavailability to 24% (range 9-50%).
- Metabolism: Extensively metabolized in the liver, primarily by CYP2C9. It has no active metabolites.
- Elimination: Excreted mainly in the bile and feces, with a small portion excreted in the urine. It has a relatively short half-life of approximately 3 hours (immediate-release) and 9 hours (extended-release).
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Mode of Action: Fluvastatin selectively and competitively inhibits HMG-CoA reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, a critical step in cholesterol biosynthesis. By inhibiting this enzyme, fluvastatin reduces hepatic cholesterol production. The reduced hepatic cholesterol levels trigger an increase in LDL receptors on the surface of liver cells, enhancing the removal of LDL-C from the circulation.
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Receptor binding, enzyme inhibition, or neurotransmitter modulation: Fluvastatin’s primary mechanism is the competitive inhibition of HMG-CoA reductase.
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Elimination pathways: Primarily eliminated via hepatic metabolism and biliary excretion into feces. A minor portion is excreted renally.
Dosage
Standard Dosage
Adults:
- Immediate-release capsules: Initial dose is 20-40 mg orally once daily, preferably in the evening. The dose can be titrated up to a maximum of 80 mg/day, administered as 40 mg twice daily (morning and evening).
- Extended-release tablets: 80 mg orally once daily at any time of the day.
Children (10-16 years with heterozygous familial hypercholesterolemia):
- Immediate-release capsules: Initial dose: 20 mg orally once daily, preferably in the evening. The dose can be increased at 6-week intervals up to a maximum of 80 mg/day, administered as 40 mg twice daily.
- Extended-release tablets: 80 mg orally once daily. Fluvastatin is not recommended for dosage initiation in children because the lower starting doses cannot be achieved with the available formulation.
- Children (<10 years): Safety and efficacy not established.
Special Cases:
- Elderly Patients: No dose adjustment is typically required. However, initiate with caution at the lower end of the dosing range and monitor closely.
- Patients with Renal Impairment: No dose adjustment is generally necessary for mild to moderate renal impairment. Caution is advised in patients with severe renal impairment, and doses greater than 40 mg/day have not been extensively studied in this population.
- Patients with Hepatic Dysfunction: Contraindicated in patients with active liver disease or unexplained persistent elevations in hepatic transaminases.
- Patients with Comorbid Conditions: Consider individual patient factors and potential drug interactions when dosing patients with comorbidities such as diabetes or cardiovascular disease. When used concomitantly with cyclosporine or fluconazole, the maximum dose of fluvastatin should be limited to 20 mg twice daily.
Clinical Use Cases
Fluvastatin is not typically indicated for acute clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for chronic management of hyperlipidemia and secondary prevention of cardiovascular disease.
Dosage Adjustments
- Dosage adjustments should be made based on individual patient response and tolerance. Monitor lipid levels regularly (every 4 weeks initially) and adjust the dose as needed to achieve target LDL-C levels.
- Consider dose reductions in patients with severe renal impairment or when co-administered with drugs that inhibit CYP2C9 metabolism (e.g., cyclosporine, fluconazole).
Side Effects
Common Side Effects
- Headache, dizziness
- Gastrointestinal upset (nausea, diarrhea, abdominal pain, constipation)
- Muscle aches or weakness
- Insomnia
- Elevated liver enzymes
Rare but Serious Side Effects
- Rhabdomyolysis (muscle breakdown)
- Hepatitis (liver inflammation)
- Myopathy (muscle disease)
- Peripheral neuropathy
Long-Term Effects
- Chronic muscle pain or weakness with prolonged use (rare)
Adverse Drug Reactions (ADR)
- Angioedema (severe allergic reaction)
- Hepatotoxicity
- Rhabdomyolysis
Contraindications
- Hypersensitivity to fluvastatin
- Active liver disease or unexplained persistent elevations in hepatic transaminases
- Pregnancy and breastfeeding
Drug Interactions
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CYP450 interactions: Fluvastatin is primarily metabolized by CYP2C9. Inhibitors of CYP2C9 (e.g., cyclosporine, fluconazole, amiodarone, azole antifungals) can increase fluvastatin concentrations and risk of myopathy. Inducers of CYP2C9 (e.g., rifampin) may decrease fluvastatin efficacy.
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Other drug interactions:
- Gemfibrozil and other fibrates increase the risk of myopathy when combined with fluvastatin.
- Bile acid sequestrants (e.g., cholestyramine) can bind to fluvastatin, reducing its absorption. Administer fluvastatin at least 4 hours after a bile acid sequestrant.
- Nicotinic acid can increase the risk of myopathy when combined with fluvastatin. Monitor closely.
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Food and lifestyle factors: Avoid excessive alcohol consumption while taking fluvastatin as it can increase the risk of liver damage. Grapefruit juice can inhibit CYP2C9 and increase fluvastatin concentrations, so concurrent use should be avoided.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X. Fluvastatin is contraindicated during pregnancy due to the risk of fetal harm.
- Breastfeeding: Fluvastatin is contraindicated during breastfeeding. It is unknown if fluvastatin is excreted in human milk.
Drug Profile Summary
- Mechanism of Action: HMG-CoA reductase inhibitor, reducing cholesterol biosynthesis.
- Side Effects: Headache, GI upset, muscle aches, insomnia, elevated liver enzymes; rarely, rhabdomyolysis, hepatitis, myopathy, peripheral neuropathy.
- Contraindications: Hypersensitivity, active liver disease, pregnancy, breastfeeding.
- Drug Interactions: CYP2C9 inhibitors (e.g., cyclosporine, fluconazole), fibrates, bile acid sequestrants, nicotinic acid.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 20-80 mg/day; Children (10-16 years): 20-80 mg/day.
- Monitoring Parameters: Lipid panel (total cholesterol, LDL-C, HDL-C, triglycerides), liver function tests (LFTs), creatine kinase (CK) if muscle symptoms occur.
Popular Combinations
Fluvastatin can be combined with other lipid-lowering medications such as ezetimibe or bile acid sequestrants when monotherapy is insufficient to achieve target lipid levels. However, combination therapy should be carefully considered, weighing the potential benefits against the increased risk of side effects.
Precautions
- General Precautions: Monitor liver function tests and CK levels. Discontinue if significant elevations occur. Screen patients for muscle pain or weakness.
- Specific Populations:
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Contraindicated.
- Children & Elderly: Initiate with caution and adjust dosage as needed.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluvastatin?
A: Adults: Immediate-release: 20-40 mg initially, up to 80 mg/day (40 mg twice daily). Extended-release: 80 mg once daily. Children (10-16 yrs): Similar to adults, but not for initial therapy. Children <10 yrs: Not established.
Q2: What are the common side effects of Fluvastatin?
A: The common side effects are headache, gastrointestinal issues (nausea, diarrhea, abdominal pain, constipation), muscle aches or weakness, insomnia, and elevated liver enzymes.
Q3: What are the serious side effects of Fluvastatin?
A: The serious side effects, though rare, include rhabdomyolysis (muscle breakdown), liver damage (hepatitis), and peripheral neuropathy.
Q4: Is Fluvastatin safe during pregnancy or breastfeeding?
A: No, Fluvastatin is contraindicated during pregnancy and breastfeeding. It belongs to pregnancy category X.
Q5: Can Fluvastatin interact with other medications?
A: Yes, Fluvastatin interacts with several drugs, most importantly CYP2C9 inhibitors, fibrates, and bile acid sequestrants.
Q6: How does Fluvastatin work to lower cholesterol?
A: It inhibits HMG-CoA reductase, a key enzyme in cholesterol synthesis, thus reducing cholesterol production in the liver.
Q7: What should be monitored in patients taking Fluvastatin?
A: Liver function tests, lipid profiles, and creatine kinase levels if muscle symptoms occur should be monitored.
Q8: What should patients do if they experience muscle pain while taking Fluvastatin?
A: Patients should immediately report any muscle pain or weakness to their doctor, as these could be signs of serious side effects.
A: Yes, it is available as immediate-release capsules and extended-release tablets.
Q10: Can Fluvastatin be used with other cholesterol-lowering drugs?
A: It can be used in combination with other lipid-lowering medications when monotherapy is insufficient, but this should be carefully assessed by a physician.
