FLUVASTATIN ER (Generic for LESCOL XL)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-Administer fluvastatin with or without meals.

-If administered concomitantly with cholestyramine, a bile-acid resin, administration times should be staggered by at least 4 hours to avoid impairing fluvastatin bioavailability.

Oral Solid Formulations
-Immediate-release Capsules: For once daily dosing regimen, administer immediate-release capsules in the evening. Do not open fluvastatin capsules.
-Extended-release Tablets: Administer extended-release tablets once daily at any time during the day. Swallow whole; do not break, crush or chew fluvastatin extended-release tablets prior to administration.

Gastrointestinal (GI) effects such as dyspepsia (3.5% to 7.9%), diarrhea (3.3% to 4.9%), abdominal pain (3.7% to 6.3%), constipation (3.3%), flatulence (1.4% to 2.6%), and nausea (2.5% to 3.2%) were reported in adult clinical trials of fluvastatin. Postmarketing, pancreatitis, anorexia, and vomiting were noted.

HMG-CoA reductase inhibitors have been associated with toxicity to the skeletal muscle system. Myopathy and elevations of CPK to greater than 10 times normal have been reported during fluvastatin therapy (less than 0.1% of adults in clinical trials; incidence in children unknown). Myalgia was noted in 2.2 to 5% of adult patients. Rhabdomyolysis with acute renal failure secondary to myoglobinuria has also been associated with statins. Postmarketing, muscle cramps, myalgia, myopathy, rhabdomyolysis, muscle spasms, muscle weakness, and myositis were noted. Discontinue fluvastatin if markedly elevated CPK concentrations occur or if myopathy is diagnosed or suspected. Any evidence of unexplained myalgia, myasthenia (muscle weakness), or elevated CPK values may indicate myopathy, particularly if symptoms include fever, lethargy/drowsiness, asthenia/weakness, and/or malaise. Instruct patients to promptly report such symptoms. Statin-induced myopathy is generally dose-related. Rhabdomyolysis may occur anytime during drug treatment, and the risk may be increased by a number of confounding factors including age, concomitant drug therapy, renal dysfunction, and concomitant disease states. Many cases result in hospitalization and a need for dialysis for treatment.

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as fluvastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.

Arthralgia (2.1%), arthritis (1.3% to 2.1%), and arthropathy (3.2%) have been reported in adult clinical trials of fluvastatin.

Elevated hepatic enzymes (transaminases, alkaline phosphatase, gamma-glutanyl transpeptidase, billirubin) have been reported with fluvastatin. In most cases, these changes appeared soon after initiation, were transient, were not associated with symptoms, and resolved or improved on continued therapy or after temporary discontinuation of therapy. In very rare cases, possibly drug-related hepatitis was observed in patients receiving fluvastatin that resolved upon discontinuation. Postmarketing, hepatitis including chronic active hepatitis, cholestatic jaundice (cholestasis), fatty change in liver, cirrhosis, fulminant hepatic necrosis, hepatoma, and fatal and non-fatal hepatic failure have been noted. Assess hepatic enzymes prior to initiating fluvastatin and repeat as clinically indicated. Instruct patients and caregivers to promptly report any symptoms of hepatic injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice). Discontinue fluvastatin if serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs. If an alternate etiology is not found, do not restart fluvastatin.

Rash, dermatitis including bullous dermatitis, eczema, alopecia, pruritus, lichen planus-like eruption, and a variety of general skin changes (e.g., nodules, discoloration, dryness of skin or mucous membranes, changes to hair/nails) have been reported during postmarketing use of fluvastatin. An apparent hypersensitivity syndrome has rarely been reported with HMG-CoA reductase inhibitors and has included one or more of the following features: anaphylaxis (anaphylactoid reactions), angioedema, lupus-like symptoms, polymyalgia rheumatica, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome.

Dizziness was reported in 3.9% of adults during fluvastatin clinical trials. Tremor, vertigo, paresthesias, hypoesthesia, dysesthesia, peripheral nerve palsy, and peripheral neuropathy have been reported during postmarketing use. An association between HMG-CoA reductase inhibitors (statins), including fluvastatin, and peripheral neuropathy has been reported in the literature (case series, case-control studies, cohort studies). Case reports and series indicate that the onset of neuropathy is typically 1 year or more after drug initiation and is reversible with drug discontinuation. However, cases describing irreversible neuropathy are also reported. The adverse effect appears to be a class effect because in all cases, when a patient is either re-challenged or treated with a different statin, the symptoms of neuropathy return. While the data appear to support an association between HMG-CoA reductase inhibitors and peripheral neuropathy, the incidence is rare and estimated to be approximately 1 per 14,000 person-years. Furthermore, a causal relationship cannot be definitively established based on the observational nature of the available data. The benefits of statin therapy far outweigh any risk of peripheral neuropathy; however, until more information is available, health care providers should be aware of this adverse effect.

Headache (4.7% to 8.9%), fatigue (1.6% to 2.7%), and insomnia (0.8% to 2.7%) were reported in adults during fluvastatin clinical trials. Anxiety, psychic disturbances, and depression have been reported with postmarketing use.

Rare cases of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) have been associated with the use of all statins including fluvastatin. A review of available data by the FDA did not find an association between the event and a specific statin, statin dose, concomitant medication, or age of the patient. In general, post-marketing reports described patients over the age of 50 years who experienced notable, but ill-defined memory loss or impairment that was reversible upon statin discontinuation. The cases did not appear to be associated with progressive or fixed dementia. The time to symptom onset (1 day to years) and resolution (median 3 weeks) is variable.

Postmarketing, dysfunction of certain cranial nerves (including symptoms possibly indicative of cranial nerve palsies, such as alteration of taste (dysgeusia), impairment of extra-ocular movement, facial paresis), and peripheral nerve palsy was noted with fluvastatin. Amyotrophic lateral sclerosis (ALS, Lou Gehrig's Disease) has been reported to the FDA in a higher than expected number of patients taking statins like fluvastatin. ALS is a progressive motor neuron disorder with symptoms such as difficulty walking or standing, difficulty with fine motor skills, atrophy of tongue and hand muscles, dysphagia, dysarthria, and muscle paralysis. Due to the seriousness of ALS and the extensive use of statins, FDA further examined data from 41 long-term controlled clinical trials. The results of the review showed no increased incidence of ALS in patients treated with a statin compared with placebo. Specifically, 9 of approximately 64,000 patients treated with a statin (4.2 cases per 100,000 patient-years) and 10 of approximately 56,000 patients treated with placebo (5 case per 100,000 patient-years) were diagnosed with ALS. FDA is examining the feasibility of performing additional epidemiologic studies to further examine the incidence and clinical course of ALS in patients taking statins.

Increased hemoglobin A1c and fasting serum glucose (hyperglycemia) have been reported with HMG-CoA reductase inhibitors. A meta-analysis of 13 statin trials with 91,140 participants showed a 9% increase in the likelihood of the development of diabetes mellitus (OR 1.09; 95% CI 1.02 to 1.17). The incidence of diabetes was higher in high-risk patients (i.e., age 70 to 82 years with or at high risk of cardiovascular disease, myocardial infarction within the last 6 months, or heart failure) compared to patients with low diabetes risk (i.e., low BMI). Additionally, an analysis of the data from the Women's Health Initiative (WHI) trial found that statin use in postmenopausal individuals is associated with an increased risk of new-onset diabetes mellitus (multivariate-adjusted HR 1.48; 95% CI 1.38 to 1.59). No difference in the risk for diabetes between statins was detected in either analysis. Because the use of statins has been associated with significant benefit for cardiovascular risk reduction and all-cause mortality at comparable rates in people with and without diabetes, no changes to clinical practice guidelines have been recommended in either population. However, the increased risk of diabetes should be considered when initiating statin therapy in patients at low risk for cardiovascular events and in patient groups where the cardiovascular benefit of statin therapy has not been established.

Gynecomastia has been reported with statins. Statins interfere with cholesterol synthesis and lower circulating cholesterol concentrations and theoretically may blunt gonadal steroid hormone production. Small declines in total serum testosterone have been noted among adult male statin recipients, but no commensurate elevation in LH occurred, which suggests that the lowered total serum testosterone was not due to a direct effect upon testosterone production. No effect upon FSH in males was noted. In a study, fluvastatin 80 mg daily for 28 weeks reduced the mean total testosterone response after HCG stimulation relative to baseline. However, the mean total testosterone response after 80 mg was not significant in comparison to the changes noted in groups receiving either fluvastatin 40 mg or placebo. Evaluate patients who develop clinical evidence of endocrine dysfunction. Use caution if a statin or other agent used to lower cholesterol concentrations is administered to patients receiving other drugs that may decrease the concentrations of endogenous steroid hormones such as ketoconazole, spironolactone, and cimetidine.

Atrial fibrillation (2.4%), syncope (2.4%), hypertension (5.8%), intermittent claudication (2.3%), and peripheral edema (4.4%) were reported in adult patients receiving fluvastatin in clinical trials.

Influenza and infection were the most common adverse reactions reported in uncontrolled clinical trials of pediatric patients (age 9 to 16 years) receiving fluvastatin. Respiratory and infectious adverse reactions reported in adult clinical trials include sinusitis (2.6% to 3.5%), bronchitis (1.8% to 2.6%), urinary tract infection (1.6% to 2.7%), influenza-like symptoms (5.1% to 7.1%), and naso-pharyngitis (2.8%). Interstitial lung disease has been reported with postmarketing use.

HMG-CoA reductase inhibitors (statins), such as fluvastatin, inhibit the synthesis of mevalonate and decrease Co-Enzyme Q-10 concentrations, which may lead to Co-Enzyme Q-10 deficiency. Supplementation with vitamin Co-Enzyme Q-10 may limit potential adverse reactions.

Statin therapy has been associated with rare reports of new-onset or exacerbation of myasthenia gravis (including ocular myasthenia gravis) and reports of recurrence when the same or different statin was administered. In a review of adult patients enrolled at a neuromuscular disease clinic over a 4-year time period, 6 of 54 myasthenia gravis patients (11%) receiving statin therapy experienced worsening myasthenia gravis. In a disproportionality analysis of the World Health Organization's VigiBase pharmacovigilance database, 169 of 3,967 (4.2%) of adverse reactions with the term 'myasthenia gravis and related conditions' were related to statin therapy. The reporting odds ratio (ROR) of myasthenia gravis relative to all other adverse reactions was 2.66 [95% CI: 2.28, 3.1] for statin therapy. In addition, the ROR was greater than 1 and statistically significant for all individual statins except lovastatin. The onset of symptoms following initiation of statin therapy has ranged from 1 week to 4 months for exacerbation and 6 months to 6 years for induction of myasthenia gravis. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents. Though this appears to be a rare adverse reaction, clinicians should closely monitor patients with myasthenia gravis for disease exacerbation and encourage them to report any muscle-related symptoms.

Fluvastatin extended-release is contraindicated in acute hepatic failure or decompensated cirrhosis (hepatic decompensation). Fluvastatin immediate-release is contraindicated in patients with active hepatic disease, including persistent elevations in serum aminotransferase concentrations. Individuals who consume substantial quantities of alcohol (alcoholism) and/or have a history of liver disease (e.g., hepatitis) may be at increased risk for liver injury. Assess hepatic enzymes prior to initiating fluvastatin and repeat as clinically indicated. Instruct patients and caregivers to promptly report any symptoms of hepatic injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice). Discontinue fluvastatin if serious hepatic injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs. If an alternate etiology is not found, do not restart fluvastatin.

Fluvastatin may cause myopathy and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including fluvastatin. Inform individuals and their caregivers of the risk of myopathy and rhabdomyolysis when initiating treatment. Instruct them to promptly report unexplained muscle pain, tenderness or weakness, especially if accompanied by malaise or fever. Temporarily discontinue fluvastatin in those experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., acute infection, including sepsis, shock, severe hypovolemia, hypotension major surgery, trauma, severe metabolic disorders, severe endocrine disease, severe electrolyte imbalance, or uncontrolled seizure disorder). Discontinue fluvastatin if myopathy is suspected or diagnosed and if markedly elevated CK concentrations occur. Risk factors for myopathy include age 65 years and older, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs, and higher statin dosage. Fluvastatin has not been evaluated at doses greater than 40 mg/day in adults with severe renal impairment. The risk in pediatric patients is not known.

Immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, has occurred rarely (1 to 3 of every 100,000 patients) with HMG-CoA reductase inhibitors, such as fluvastatin. Recurrence of IMNM has been reported following administration of the same or a different statin. IMNM is characterized by myalgia with symmetrical and proximal muscle weakness and elevated serum creatine phosphokinase, which persist despite discontinuation of HMG-CoA reductase inhibitor treatment. Some cases have occurred months to years after starting HMG-CoA reductase therapy and the myopathy progressed following therapy discontinuation. Other characteristics include positive anti-HMG-CoA reductase antibody, muscle biopsy showing necrotizing myopathy, and improvement with immunosuppressive agents. Dysphagia and respiratory failure have also been reported in patients with IMNM. Reported serum creatine phosphokinase levels have ranged from 576 to 35,000 International Units/L. Patients who develop IMNM may require additional neuromuscular and serologic testing. If IMNM develops, HMG-CoA reductase inhibitor therapy should be discontinued and treatment with immunosuppressants, such as high dose corticosteroids, intravenous immune globulin (IVIG), or other immunosuppressive agents, may be needed.

HMG-CoA reductase inhibitors are known to have various endocrine effects that may be clinically significant in selected patients. Increased hemoglobin A1c, hyperglycemia, and worsening glycemic control have been reported during therapy with HMG-CoA reductase inhibitors. If fluvastatin is initiated in a patient with diabetes mellitus, increased monitoring of blood glucose control may be warranted. Optimization of lifestyle measures, including regular exercise, maintaining a healthy body weight, and making healthy food choices are recommended. In addition, because cholesterol synthesis is altered, fluvastatin may theoretically blunt adrenal and/or gonadal steroid production. Although data are very limited, in a small uncontrolled study of 85 adolescent males and females, there was no detectable effect on growth or sexual maturation in adolescent boys or on menstrual cycle length in girls (study length = 114 weeks). In adult trials, fluvastatin exhibited no effect on non-stimulated cortisol concentrations or thyroid metabolism. In males, small declines in serum testosterone were noted, but no commensurate elevation in LH occurred. Monitor patients carefully for any potential adverse effects on endocrine function and use caution if other drugs that affect endogenous steroid hormones are used concomitantly.

Safety and efficacy of fluvastatin have not been established in infants and children younger than 10 years of age. Because cholesterol plays a crucial role in growth and development, the clinical implications of using pharmacologic therapy to alter the normal production of cholesterol in young children is not clear. Due to these potential safety concerns and lack of safety data, most experts generally recommend delaying cholesterol-lowering medications until the child is at least 8 to 10 years old. In limited uncontrolled studies, there was no significant effect on growth or sexual maturation or on menstrual cycle length in individuals 9 years and older with HeFH. In some cases of severe familial hypercholesterolemia, however, HMG-CoA reductase inhibitors have been used in younger children with careful monitoring of growth and development.

Use fluvastatin with caution in persons with myasthenia gravis. Closely monitor for myasthenia gravis exacerbation and encourage reporting of any muscle-related symptoms. Exacerbation of myasthenia gravis, including ocular myasthenia gravis, has been reported during treatment with statins, including fluvastatin. Reports of recurrence have been noted when the same or a different statin was administered. The onset of symptom exacerbation following initiation of statin therapy has ranged from 1 week to 4 months. Partial or complete recovery has been reported following discontinuation of statin therapy; however, some patients have required treatment with pyridostigmine or immunosuppressive agents.

Description: Fluvastatin is a competitive HMG-CoA reductase inhibitor and was the first to be synthetically prepared. Fluvastatin is approved for use in pediatric patients with heterozygous familial hypercholesterolemia (HeFH). It has some similarities to lovastatin, simvastatin, and pravastatin, but it is structurally distinct, resulting in unique biopharmaceutic properties. Purported advantages of fluvastatin over the other HMG-CoA reductase inhibitors include short half-life with no active metabolites, extensive protein binding, and minimal CSF penetration, characteristics that suggest fluvastatin may be less likely to cause systemic adverse reactions than the other agents in this class. Fluvastatin is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B. It is one of the least potent HMG-CoA reductase inhibitors on the market in terms of LDL reduction, but it is also associated with a lower incidence of adverse effects compared to many agents. In pediatric clinical trials, fluvastatin 20 to 80 mg once daily was associated with a mean LDL reduction of 27% to 28%. Although evidence of beneficial long term effects on cardiovascular outcomes and mortality in pediatric patients is not available, statins are recommended as first-line for pharmacologic therapy of hyperlipidemia in pediatric patients based on evidence of short-term safety and efficacy. Fluvastatin is FDA-approved in pediatric patients as young as 10 years of age.

General Information
-Fluvastatin is FDA-approved for the treatment of heterozygous familial high cholesterol and is recommended for hyperlipidemia when either: 1) the LDL remains 190 mg/dL or more, or 2) the LDL remains 160 mg/dL or more and there is an increased risk for cardiovascular disease (e.g., positive family history of premature cardiovascular disease or 2 or more other risk factors are present).

For the treatment of hypercholesterolemia*, including heterozygous familial hypercholesterolemia, as an adjunct to dietary control:
Oral dosage (immediate-release capsules):
Children and Adolescents 10 to 17 years (at least 1 year post-menarche): 20 mg PO once daily initially. Adjust dosage at 6-week intervals to attain individual goals of therapy. Max: 40 mg PO twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Oral dosage (extended-release tablets):
Children and Adolescents 10 to 17 years (at least 1 year post-menarche): 80 mg PO once daily of the extended-release formulation may be used in individuals who have been titrated up to 40 mg PO twice daily of the immediate-release formulation. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Children
1 to 9 years: Safety and efficacy have not been established.
10 to 12 years: 80 mg/day PO.
-Adolescents
80 mg/day PO.

Patients with Hepatic Impairment Dosing
Contraindicated in patients with active liver disease or with unexplained or persistent hepatic transaminase elevations.

Patients with Renal Impairment Dosing
Specific recommendations for dosage adjustment in pediatric patients with renal impairment are not available. No initial dosage adjustment is recommended for adult patients with mild to moderate renal impairment. Fluvastatin has not been evaluated at doses more than 40 mg in patients with severe renal impairment; therefore, use caution when treating such patients at higher doses.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Fluvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, a hepatic enzyme responsible for the intracellular synthesis of cholesterol. HMG-CoA reductase is the rate-limiting enzyme in cholesterol biosynthesis and responsible for converting HMG-CoA to mevalonate, a precursor of sterols including cholesterol. Inhibition of HMG-CoA reductase decreases cholesterol concentrations within the hepatic cells, which induces expression of low-density lipoprotein receptors stimulating low-density lipoprotein cholesterol (LDL-C) uptake from the blood to the liver. Increased hepatic LDL-C uptake results in a reduction in plasma LDL-C and total cholesterol. Fluvastatin reduces plasma total cholesterol, LDL-C, and serum triglycerides; and it raises plasma high-density lipoprotein cholesterol (HDL-C) concentrations.

Pharmacokinetics: Fluvastatin is administered orally. The volume of distribution of fluvastatin is 0.35 L/kg, and it is highly protein bound (98%). Fluvastatin is hepatically metabolized, primarily via hydroxylation of the indole ring at the 5- and 6-positions. N-dealkylation and beta-oxidation of the side chain also occur. The active hydroxylated metabolites do not circulate systemically. Fluvastatin has 2 enantiomers; both are metabolized in a similar manner. Approximately 90% of an oral fluvastatin dose is excreted in the feces as metabolites, with less than 2% present as unchanged drug and approximately 5% excreted in the urine. The reported half-life of fluvastatin immediate-release capsules is 1 to 3 hours compared to 7.3 to 10.5 hours for fluvastatin extended-release tablets.

Affected cytochrome P450 isoenzymes: CYP2C8, CYP2C9, CYP3A4
Hepatic metabolism occurs primarily (75%) via CYP2C9 isoenzymes; other metabolic pathways include CYP2C8 (5%) and CYP3A4 (20%). Drugs that are CYP2C9 inhibitors or inducers have greater potential to alter fluvastatin plasma concentrations and cause potential toxicity relative to drugs that affect the CYP3A4 pathway. Fluvastatin also is a CYP2C9 inhibitor.


-Route-Specific Pharmacokinetics
Oral Route
Immediate-release formulation
Absorption is rapid reaching peak concentrations in less than 1 hour under fasting conditions. Due to a significant first-pass effect, the mean absolute bioavailability is only 24% after a 10 mg dose (range 9% to 50%). Fluvastatin immediate-release exhibits saturable first-pass metabolism resulting in more than dose proportional plasma fluvastatin concentrations as the dosage increases. At steady state, administration with the evening meal results in a 50% lower Cmax, 11% lower AUC, and more than a 2-fold increase in the time to peak concentration compared to administration 4 hours after the evening meal. However, no clinically significant differences in lipid-lowering effects have been noted between the 2 administration techniques.

Extended-release formulation
Following administration of fluvastatin extended-release tablets, peak concentrations are reached in approximately 3 hours in the fasting state or 2.5 hours after a low-fat meal. The mean relative bioavailability of fluvastatin extended-release is 29% (range 9% to 66%). Administration of fluvastatin extended-release tablets with a high-fat meal delayed the absorption (Tmax 6 hours) and increased the bioavailability by about 50%.


-Special Populations
Hepatic Impairment
Pharmacokinetic data in pediatric patients with hepatic impairment are not available. After a single 40 mg dose, adult patients with hepatic impairment due to liver cirrhosis experience AUC and Cmax values approximately 2.5-fold higher than those of healthy subjects.

Renal Impairment
Specific information regarding the pharmacokinetics of fluvastatin in pediatric patients with renal impairment is not available. The AUC and Cmax increased approximately 1.2-fold after administration of a single 40 mg oral dose of fluvastatin immediate-release to adult patients with severe renal impairment (CrCl 10 to 40 mL/minute). The AUC increased approximately 1.5-fold in adult patients with end-stage renal disease on hemodialysis. The pharmacokinetics of extended-release fluvastatin tablets have not been studied in patients with renal impairment.