Fluvastatin Er (fluvastatin sodium)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Fluvastatin sodium, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (i.e., statin), is an antilipemic agent.
Fluvastatin is a competitive inhibitor of 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonate (an early and rate-limiting step in cholesterol biosynthesis). Fluvastatin is pharmacologically related to other statins (e.g., atorvastatin, lovastatin, pravastatin, simvastatin, pitavastatin, rosuvastatin). Fluvastatin, like atorvastatin, is a synthetic compound that differs structurally from mevinic acid-derivative statins (e.g., lovastatin, pravastatin, simvastatin) and is not fungus-derived.
Unlike the lactone prodrugs lovastatin and simvastatin, fluvastatin exists as an active hydroxy acid and does not require hydrolysis in vivo. The fluorophenyl indole moiety of fluvastatin is similar structurally to HMG-CoA and competes with this compound for HMG-CoA reductase.
Fluvastatin reduces elevated low-density lipotrotein (LDL)-cholesterol concentrations. Therapeutic response is expected within 4 weeks. The mechanism of the LDL-lowering effect may involve both reduction of very low-density lipoprotein (VLDL) concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-cholesterol.
Triglyceride and apolipoprotein B may decrease and high-density lipoptotein (HDL)-cholesterol concentrations may increase during treatment with fluvastatin. Other favorable effects of statins (pleiotropic effects) include an antiproliferative influence on smooth muscle cells, reconstruction of endothelial activity, antioxidant, antithrombotic, anticancer, and anti-inflammatory effects.
Fluvastatin is lipophilic and has variable absolute bioavailability (24%, range 9-50%). Peak plasma concentrations are reached in less than 1 hour following administration of a 10-mg dose (immediate-release preparation). At steady state, administration of immediate-release fluvastatin with the evening meal results in a 50% decrease in peak plasma concentration, 11% decrease in AUC, and a more than 2-fold increase in time to peak plasma concentration as compared to administration 4 hours after the evening meal; no significant differences in the lipid-lowering effects were observed.
After single or multiple doses above 20 mg, immediate-release fluvastatin exhibits saturable first-pass metabolism resulting in more than dose proportional plasma fluvastatin concentrations.
The mean relative bioavailability of the extended-release preparation is approximately 29% (range, 9-66%) compared to the fluvastatin immediate-release preparation administered under fasting conditions; peak concentration is reached in approximately 3 hours under fasting conditions or 2.5 hours after a low-fat meal. Administration with a high-fat meal delayed absorption (time to peak concentration 6 hours) and increased bioavailability of the extended-release preparation by approximately 50%. However, the maximum concentration following administration of the extended-release preparation after a high-fat meal is less than the peak concentration following a single dose or twice daily dose of immediate-release fluvastatin 40 mg.
Fluvastatin has 2 enantiomers; both enantiomers are metabolized in a similar manner. Fluvastatin is metabolized in the liver, primarily via hydroxylation to metabolites that have some pharmacologic activity, but do not circulate in the blood. Fluvastatin is metabolized principally by cytochrome P-450 (CYP) 2C9 (approximately 75%) and to a lesser extent by CYP2C8 and CYP3A4 (approximately 5 and 20%, respectively).
Fluvastatin is 98% bound to plasma proteins and is primarily (about 90%) excreted in the feces as metabolites, with less than 2% present as unchanged drug; approximately 5% of a radiolabeled oral dose is recovered in urine. The elimination half-life of immediate-release and extended-release fluvastatin is approximately 3 and 3-5 hours, respectively. The AUC of fluvastatin is approximately 30% higher in females 21-49 years of age compared to males of the same age group; adjusting for body weight decreases the magnitude of the observed differences.
There were no significant differences in fluvastatin exposures between males and females in other age groups. Fluvastatin AUC increases 67% and 77% for women compared to men under fasted and high-fat meal conditions, respectively, following administration of the extended-release preparation. .
USES: Fluvastatin is used along with a proper diet to help lower "bad" cholesterol and fats (such as LDL, triglycerides) and raise "good" cholesterol (HDL) in the blood. It belongs to a group of drugs known as "statins." It works by reducing the amount of cholesterol made by the liver. Lowering "bad" cholesterol and triglycerides and raising "good" cholesterol decreases the risk of heart disease and helps prevent strokes and heart attacks.
In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.
Generic name: fluvastatin sodium
Pronunciation: (FLEW-vuh-stat-in)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Fluvastatin Er
Indications
The following indications are listed for Fluvastatin Er:
- Atherosclerotic Cardiovascular Disease
- Heterozygous Familial Hypercholesterolemia
- Hypercholesterolemia
- Hyperlipidemia
- Mixed Hyperlipidemia
- Treatment To Slow Progression Of Coronary Artery Disease
Also known as: Atherosclerosis, Atherosclerotic Vascular Disease, Cardiovascular Disease Related To Atherosclerosis, Combined Hypercholesterolemia And Hypertriglyceridemia, Elevated Blood Cholesterol Level, Familial Heterozygous Hypercholesterolemia, Heterozygous Familial Elevated Blood Cholesterol, Hyperlipoidemia, Lipemia, Lipidemia, Lipoidemia, Mixed Dyslipidemia, Treatment To Slow Progression Of Cad.
Dosing
Dosage of fluvastatin sodium is expressed in terms of fluvastatin and must be carefully adjusted according to individual requirements (i.e., percent reduction in LDL-cholesterol concentrations) and response.
In patients receiving cyclosporine or fluconazole, the manufacturer recommends that fluvastatin dosage not exceed 20 mg twice daily.
No dosing information is available for this tab.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Fluvastatin is metabolized principally by cytochrome P450 isoenzyme (CYP) 2C9 (approximately 75%); CYP2C8 and CYP3A4 (approximately 5 and 20%, respectively) also contribute to fluvastatin metabolism. Fluvastatin is also a CYP2C9 inhibitor.
Fluvastatin is a substrate of organic anion transporter protein (OATP) 1B1, 1B3, and 2B1.
Drug interaction studies have not been performed with extended-release fluvastatin.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Hypersensitivity to fluvastatin or any component of the formulation; anaphylaxis, angioedema, and Stevens-Johnson syndrome have been reported.
*Immediate-release capsules: Active liver disease or unexplained, persistent elevations of serum transaminases.
*Extended-release tablets: Acute liver failure or decompensated cirrhosis.
*Immediate-release capsules: Nursing mothers. The manufacturer states that this formulation is contraindicated in women who are pregnant or may become pregnant; however, because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in >=2% of patients, and greater than placebo, receiving immediate-release fluvastatin include headache, dyspepsia, myalgia, abdominal pain, and nausea.
Adverse effects reported in >=2.5% of patients, and greater than placebo, receiving extended-release fluvastatin include influenza-like symptoms, sinusitis, dyspepsia, urinary tract infection, bronchitis, and nausea.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and effectiveness of fluvastatin in pediatric patients >=10 years of age (adolescent boys and girls at least one year post-menarche) with heterozygous familial hypercholesterolemia (HeFH) have been established in open-label, uncontrolled studies of 2 years' duration. The most common adverse effects observed were influenza and infections. There were no detectable effects on growth or sexual maturation in boys or on duration of menstrual cycle in girls. The manufacturer states that pediatric patients receiving fluvastatin in adolescence should be re-evaluated in adulthood, with appropriate adjustments in the antilipemic regimen, to achieve adult treatment goals. Adolescent girls should be advised to use appropriate contraceptive methods during fluvastatin therapy. Safety and efficacy of fluvastatin have not been evaluated in children <10 years of age with HeFH or in children with other types of hyperlipidemia. However, experts state that statins may be considered in patients as young as 8 years of age in the presence of concerning family history, extremely elevated LDL-cholesterol level, or elevated lipoprotein (a), in the context of informed shared decision-making and counseling with the patient and family.
Pharmacokinetic data in the pediatric population are not available.
All statins were previously contraindicated in pregnant women because the fetal risk with these drugs was thought to outweigh any possible benefit. This determination was based on several factors including safety signals from animal data. Fluvastatin produced delays in skeletal development in rats at doses of 12 mg/kg daily and in rabbits at doses of 10 mg/kg daily (approximately 2 and 5 times, respectively, the human exposure after a 40-mg dose based on mg/m2 surface area). Malaligned thoracic vertebrae were observed in rats at 36 mg/kg, a dose that produced maternal toxicity. Maternal mortality at or near term and postpartum, as well as fetal and neonatal lethality, were observed in female rats receiving fluvastatin 12 and 24 mg/kg daily during the third trimester of pregnancy.
In addition, congenital anomalies including severe CNS defects and unilateral limb deficiencies were reported in a case series of pregnant women who were exposed to a lipophilic statin during the first trimester. Because statins decrease synthesis of cholesterol and possibly other products of the cholesterol biosynthetic pathway, there is also a concern that these drugs can potentially cause fetal harm. More recent data from case series and observational cohort studies have not shown evidence of an increased risk of major birth defects with statin use during pregnancy, and this was observed after controlling for potential confounders such as maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use. The overall evidence from animal studies suggests limited potential for statins to cause malformations or other adverse fetal effects. While an increased risk of miscarriage has been reported in pregnant women exposed to statins, it is not clear whether this effect is related to the drugs or to other confounding factors. FDA conducted a comprehensive review of all available clinical and nonclinical data related to statin use in pregnant women and concluded that the totality of evidence suggests limited potential for statins to cause malformations and other adverse embryofetal effects. Because statins may prevent serious or potentially fatal cardiovascular events in certain high-risk patients who are pregnant, FDA has requested that the contraindication in pregnant women be removed from the prescribing information for all statins. While FDA still advises that most pregnant patients discontinue statins because of the possibility of fetal harm, there may be some patients (e.g., those with homozygous familial hypercholesterolemia or established cardiovascular disease) in whom continued therapy may be beneficial; therefore, decisions should be individualized based on the patient's risks versus benefits. Patients who become pregnant or suspect that they are pregnant while receiving a statin should notify their clinician who can advise them on the appropriate course of action.
Fluvastatin is distributed into milk in animals, with a milk-to-plasma ratio of 2:1. Because of the potential for serious adverse reactions from fluvastatin in nursing infants, the drug is contraindicated in nursing women; women who require fluvastatin therapy should not breast-feed their infants. Many patients can stop statin therapy temporarily until breast-feeding is complete; patients who require ongoing statin treatment should not breast-feed and should use alternatives such as infant formula.
Select dosage with caution in geriatric patients,considering the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy.
Fluvastatin generally is well tolerated in geriatric patients. Fluvastatin exposures were not substantially different between geriatric patients (65 years of age or older) and younger patients. However, because advanced age is a predisposing factor for myopathy, fluvastatin should be used with caution in geriatric patients.
Because patients older than 75 years of age may have a higher risk of adverse effects and lower adherence to therapy, the expected benefits versus adverse effects should be considered before initiating statin therapy in this population.
Fluvastatin plasma levels are not significantly different in patients > 65 years of age compared to patients 21-49 years of age.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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