Lescol Information
Lescol ()
Lescol () dosage And Administration
Dose range: 20 mg to 80 mg/ day.
Lescol () /Lescol () XL can be administered orally as a single dose, with or without food.
Do not break, crush or chew Lescol () XL tablets or open Lescol () capsules prior to administration.
Do not take two Lescol () 40 mg capsules at one time.
Since the maximal effect of a given dose is seen within 4 weeks, periodic lipid determinations should be performed at this time and dosage adjusted according to the patient’s response to therapy and established treatment guidelines.
For patients requiring LDL-C reduction to a goal of ≥25%, the recommended starting dose is 40 mg as one capsule in the evening, 80 mg as one Lescol () XL tablet administered as a single dose at any time of the day or 80 mg in divided doses of the 40 mg capsule given twice daily. For patients requiring LDL-C reduction to a goal of
Adult patients can be started on either Lescol () or Lescol () XL. The recommended starting dose for Lescol () is one 40 mg capsule in the evening, or one Lescol () 40 mg capsule twice daily. Do not take two Lescol () 40 mg capsules at one time.
The recommended starting dose for Lescol () XL is one 80 mg tablet administered as a single dose at any time of the day.
The recommended starting dose is one 20 mg Lescol () capsule. Dose adjustments, up to a maximum daily dose administered either as Lescol () capsules 40 mg twice daily or one Lescol () XL 80 mg tablet once daily should be made at 6 week intervals. Doses should be individualized according to the goal of therapy. [ ]
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Pediatrics.
Lescol () dosage Forms And Strengths
• Lescol () 20 mg capsules are brown and light brown imprinted twice with “” and “20” on one half and “Lescol () ” and the Lescol () (fluvastatin sodium) logo twice on the other half of the capsule.
• Lescol () 40 mg capsules are brown and gold imprinted twice with “” and “40” on one half and “Lescol () ” and the Lescol () (fluvastatin sodium) logo twice on the other half of the capsule.
• Lescol () XL 80 mg tablets are yellow, round, slightly biconvex film-coated tablet with beveled edges debossed with “Lescol () XL” on one side and “80” on the other.
Lescol () contraindications
Lescol () and Lescol () XL are contraindicated in women who are pregnant or may become pregnant Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Lescol () and Lescol () XL may cause fetal harm when administered to pregnant women. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia.
Lescol () and Lescol () XL should be administered to women of childbearing age only when such patients are highly unlikely to conceive and have been informed of the potential hazardsIf the patient becomes pregnant while taking this drug, Lescol () and Lescol () XL should be discontinued and the patient should be apprised of the potential hazard to the fetus. []
Lescol () warnings And Precautions
Lescol () /Lescol () XL should be prescribed with caution in patients with predisposing factors for myopathy. These factors include advanced age (>65 years), renal impairment, and inadequately treated hypothyroidism.
The risk of myopathy and/or rhabdomyolysis with statins is increased with concurrent therapy with cyclosporine, erythromycin, fibrates or niacin. Myopathy was not observed in a clinical trial in 74 patients involving patients who were treated with Lescol () /Lescol () XL together with niacin. Isolated cases of myopathy have been reported during post-marketing experience with concomitant administration of Lescol () /Lescol () XL and colchicine. No information is available on the pharmacokinetic interaction between Lescol () /Lescol () XL and colchicine.
Uncomplicated myalgia has also been reported in Lescol () -treated patients [see ]. In clinical trials, uncomplicated myalgia has been observed infrequently in patients treated with Lescol () at rates indistinguishable from placebo. Myopathy, defined as muscle aching or muscle weakness in conjunction with increases in CPK values to greater than 10 times the upper limit of normal, was
Lescol () /Lescol () XL therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. Lescol () /Lescol () XL therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Increases in serum transaminases (aspartate aminotransferase [AST]/serum glutamic-oxaloacetic transaminase, or alanine aminotransferase [ALT]/serum glutamic-pyruvic transaminase) have been reported with HMG-CoA reductase inhibitors, including Lescol () /Lescol () XL. In most cases, the elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy.
Approximately 1.1% of patients treated with Lescol () capsules in worldwide trials developed dose-related, persistent elevations of serum transaminase levels to more than 3 times the upper limit of normal. Fourteen of these patients (0.6%) were discontinued from therapy. In all clinical trials, a total of 33/2969 patients (1.1%) had persistent transaminase elevations with an average Lescol () exposure of approximately 71.2 weeks; 19 of these patients (0.6%) were discontinued. The majority of patients with these abnormal biochemical findings were asymptomatic.
In a pooled analysis of all placebo-controlled studies in which Lescol () capsules were used, persistent transaminase elevations (>3 times the upper limit of normal [ULN] on two consecutive weekly measurements) occurred in 0.2%, 1.5%, and 2.7% of patients treated with daily doses of 20, 40, and 80 mg (titrated to 40 mg twice daily) Lescol () capsules, respectively. Ninety-one percent of the cases of persistent liver function test abnormalities (20 of 22 patients) occurred within 12 weeks of therapy and in all patients with persistent liver function test abnormalities there was an abnormal liver function test present at baseline or by Week 8.
In the pooled analysis of the 24-week controlled trials, persistent transaminase elevation occurred in 1.9%, 1.8% and 4.9% of patients treated with Lescol () XL 80 mg, Lescol () 40 mg and Lescol () 40 mg twice daily, respectively. In 13 of 16 patients treated with Lescol () XL the abnormality occurred within 12 weeks of initiation of treatment with Lescol () XL 80 mg.
It is recommended that liver function tests be performed prior to the initiation of therapy, at 12 weeks and when clinically indicated.
Patients who develop increased transaminase levels or signs and symptoms of active liver disease while taking Lescol () should be evaluated with a second liver function evaluation to confirm the finding and be followed thereafter with frequent liver function tests until the abnormalities return to normal. Should an increase in AST or ALT of 3 times the upper limit of normal or greater persist, withdrawal of Lescol () therapy is recommended.
In very rare cases, possibly drug-related hepatitis was observed that resolved upon discontinuation of treatment. Active liver disease or unexplained serum transaminase elevations are contraindications to the use of Lescol () and Lescol () XL. [] Caution should be exercised when Lescol () is administered to patients with a history of liver disease or heavy alcohol ingestion [] Such patients should be closely monitored.
Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production.
Lescol () /Lescol () XL exhibited no effect upon non-stimulated cortisol levels and demonstrated no effect upon thyroid metabolism as assessed by measurement of thyroid stimulating hormone (TSH). Small declines in total serum testosterone have been noted in treated groups, but no commensurate elevation in LH occurred, suggesting that the observation was not due to a direct effect upon testosterone production. No effect upon FSH in males was noted. Due to the limited number of premenopausal females studied to date, no conclusions regarding the effect of Lescol () /Lescol () XL upon female sex hormones may be made.
Two clinical studies in patients receiving fluvastatin at doses up to 80 mg daily for periods of 24 to 28 weeks demonstrated no effect of treatment upon the adrenal response to ACTH stimulation. A clinical study evaluated the effect of Lescol () at doses up to 80 mg daily for 28 weeks upon the gonadal response to HCG stimulation. Although the mean total testosterone response was significantly reduced (p
Patients treated with Lescol () /Lescol () XL who develop clinical evidence of endocrine dysfunction should be evaluated appropriately. Caution should be exercised if a statin or other agent used to lower cholesterol levels is administered to patients receiving other drugs (e.g. ketoconazole, spironolactone, cimetidine) that may decrease the levels of endogenous steroid hormones.
CNS effects, as evidenced by decreased activity, ataxia, loss of righting reflex, and ptosis were seen in the following animal studies: the 18-month mouse carcinogenicity study at 50 mg/kg/day, the 6-month dog study at 36 mg/kg/day, the 6-month hamster study at 40 mg/kg/day, and in acute, high-dose studies in rats and hamsters (50 mg/kg), rabbits (300 mg/kg) and mice (1500 mg/kg). CNS toxicity in the acute high-dose studies was characterized (in mice) by conspicuous vacuolation in the ventral white columns of the spinal cord at a dose of 5000 mg/kg and (in rats) by edema with separation of myelinated fibers of the ventral spinal tracts and sciatic nerve at a dose of 1500 mg/kg. CNS toxicity, characterized by periaxonal vacuolation, was observed in the medulla of dogs that died after treatment for 5 weeks with 48 mg/kg/day; this finding was not observed in the remaining dogs when the dose level was lowered to 36 mg/kg/day. CNS vascular lesions, characterized by perivascular hemorrhages, edema, and mononuclear cell infiltration of perivascular spaces, have been observed in dogs treated with other members of this drug class. No CNS lesions have been observed after chronic treatment for up to 2 years with fluvastatin in the mouse (at doses up to 350 mg/kg/day), rat (up to 24 mg/kg/day), or dog (up to 16 mg/kg/day).
Prominent bilateral posterior Y suture lines in the ocular lens were seen in dogs after treatment with 1, 8, and 16 mg/kg/day for 2 years.
Lescol () adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the label:
Because clinical studies on Lescol () /Lescol () XL are conducted in varying study populations and study designs, the frequency of adverse reactions observed in the clinical studies of Lescol () /Lescol () XL cannot be directly compared with that in the clinical studies of other statins and may not reflect the frequency of adverse reactions observed in clinical practice.
In the Lescol () placebo-controlled clinical trials database of 2326 patients treated with Lescol () (age range 18-75 years, 44% women, 94% Caucasians, 4% Blacks, 2% other ethnicities) with a median treatment duration of 24 weeks, 3.4% of patients on Lescol () and 2.3% patients on placebo discontinued due to adverse reactions regardless of causality. The most common adverse reactions that led to treatment discontinuation and occurred at an incidence greater than placebo were: transaminase increased (0.8%), upper abdominal pain (0.3%), dyspepsia (0.3%), fatigue (0.2%) and diarrhea (0.2%).
In the Lescol () XL database of controlled clinical trials of 912 patients treated with Lescol () XL (age range 21-87 years, 52% women, 91% Caucasians, 4% Blacks, 5% other ethnicities) with a median treatment duration of 24 weeks, 3.9% of patients on Lescol () XL discontinued due to adverse reactions regardless of causality. The most common adverse reactions that led to treatment discontinuation were abdominal pain (0.7%), diarrhea (0.5%), nausea (0.4%), dyspepsia (0.4%) and chest pain (0.3%).
Clinically relevant adverse experiences occurring in the Lescol () and Lescol () XL controlled studies with a frequency 2%, regardless of causality, included the following:
In the Lescol () Intervention Prevention Study (LIPS), the effect of Lescol () 40 mg, administered twice daily on the risk of recurrent cardiac events was assessed in 1677 patients with CHD who had undergone a percutaneous coronary intervention (PCI) procedure. This was a multicenter, randomized, double-blind, placebo-controlled study, patients were treated with dietary/lifestyle counseling and either Lescol () 40 mg (n=844) or placebo (n=833) given twice daily for a median of 3.9 years. [Also see section 14.3]
In patients aged
In two open-label, uncontrolled studies, 66 boys and 48 girls with heterozygous familial hypercholesterolemia ( 9-16 years of age, 80% Caucasian, 19% Other [ mixed ethnicity], 1% Asians) were treated with fluvastatin sodium administered as Lescol () capsules 20 mg -40 mg twice daily, or Lescol () XL 80 mg extended-release tablet.. [ ]
Because adverse reactions from spontaneous reports are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following effects have been reported with drugs in this class. Not all the effects listed below have necessarily been associated with fluvastatin sodium therapy.
Neurological:
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
Psychiatric:
Hypersensitivity Reactions:
Gastrointestinal:
Skin:
Reproductive:
Eye:
Lescol () Use In Specific Populations
Pregnancy Category X
Lescol () /Lescol () XL is contraindicated in women who are or may become pregnant. [ ]
Lipid lowering drugs are contraindicated during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Serum cholesterol and triglycerides increase during normal pregnancy. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy
There are no adequate and well-controlled studies of use with Lescol () /Lescol () XL during pregnancy. Rare reports of congenital anomalies have been received following intrauterine exposure to other statins. In a review of about 100 prospectively followed pregnancies in women exposed to other statins, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. The number of cases is adequate only to exclude a 3- to 4-fold increase in congenital anomalies over background incidence. In 89% of prospectively followed pregnancies, drug treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.
Teratology studies with fluvastatin in rats and rabbits showed maternal toxicity at high dose levels, but there was no evidence of embryotoxic or teratogenic potential [].
Lescol () or Lescol () XL should be administered to women of child-bearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If a woman becomes pregnant while taking Lescol () or Lescol () XL, the drug should be discontinued and the patient advised again as to the potential hazards to the fetus.
Lescol () overdosage
To date, there has been limited experience with overdosage of fluvastatin. If an overdose occurs, it should be treated symptomatically with laboratory monitoring and supportive measures should be instituted as required. The dialyzability of fluvastatin sodium and of its metabolites in humans is not known at present. [See ]
In the pediatric population, there have been reports of overdosage with fluvastatin sodium in children including a 2 year-old and the other 3 years of age, either of whom may have possibly ingested fluvastatin sodium. The maximum amount of fluvastatin sodium that could have been ingested was 80 mg (4 x 20 mg capsules). Vomiting was induced by ipecac in both children and no capsules were noted in their emesis. Neither child experienced any adverse symptoms and both recovered from the incident without problems.
In the postmarketing experience there have been reports of accidental ingestion of Lescol () tablets in infants up to 3 years of age. In one case, increased serum CPK values were noted. There have been reports of intentional overdose in adolescents with the development of hepatic enzyme elevations, convulsions and gastroenteritis/vomiting/diarrhea. One case of intentional overdose as suicide attempt in a 15 year-old female reported ingestion of 2,800 mg Lescol () XL with hepatic enzyme elevation.
Lescol () description
Lescol () is a water-soluble cholesterol lowering agent which acts through the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase.
Fluvastatin sodium is [*,*-()]-(±)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1-indol-2-yl]-3,5-dihydroxy-6-heptenoic acid, monosodium salt. The empirical formula of fluvastatin sodium is CHFNO•Na, its molecular weight is 433.46 and its structural formula is:
This molecular entity is the first entirely synthetic HMG-CoA reductase inhibitor, and is in part structurally distinct from the fungal derivatives of this therapeutic class.
Fluvastatin sodium is a white to pale yellow, hygroscopic powder soluble in water, ethanol and methanol. Lescol () is supplied as capsules containing fluvastatin sodium, equivalent to 20 mg or 40 mg of fluvastatin, for oral administration. Lescol () XL is supplied as extended-release tablets containing fluvastatin sodium, equivalent to 80 mg of fluvastatin, for oral administration.
Lescol () clinical Pharmacology
Following oral administration of the capsule, fluvastatin reaches peak concentrations in less than 1 hour. The absolute bioavailability is 24% (range 9%-50%) after administration of a 10 mg dose.
At steady state, administration of fluvastatin with the evening meal results in a 50% decrease in C, a 11% decrease in AUC, and a more than two-fold increase in t as compared to administration 4 hours after the evening meal. No significant differences in the lipid-lowering effects were observed between the two administrations. After single or multiple doses above 20 mg, fluvastatin exhibits saturable first-pass metabolism resulting in more than dose proportional plasma fluvastatin concentrations.
Fluvastatin administered as Lescol () XL 80 mg tablets reaches peak concentration in approximately 3 hours under fasting conditions, after a low-fat meal, or 2.5 hours after a low-fat meal. The mean relative bioavailability of the XL tablet is approximately 29% (range: 9%-66%) compared to that of the Lescol () immediate-release capsule administered under fasting conditions. Administration of a high-fat meal delayed the absorption (T: 6h) and increased the bioavailability of the XL tablet by approximately 50%. However, the maximum concentration of Lescol () XL seen after a high-fat meal is less than the peak concentration following a single dose or twice daily dose of the 40 mg Lescol () capsule.
Fluvastatin is 98% bound to plasma proteins. The mean volume of distribution (VD) is estimated at 0.35 L/kg. At therapeutic concentrations, the protein binding of fluvastatin is not affected by warfarin, salicylic acid and glyburide.
Fluvastatin is metabolized in the liver, primarily via hydroxylation of the indole ring at the 5- and 6-positions. N-dealkylation and beta-oxidation of the side-chain also occurs. The hydroxy metabolites have some pharmacologic activity, but do not circulate in the blood. Fluvastatin has two enantiomers. Both enantiomers of fluvastatin are metabolized in a similar manner.
In vitro data indicate that fluvastatin metabolism involves multiple Cytochrome P450 (CYP) isozymes. CYP2C9 isoenzyme is primarily involved in the metabolism of fluvastatin (approximately 75%), while CYP2C8 and CYP3A4 isoenzymes are involved to a much less extent, i.e. approximately 5% and approximately 20%, respectively.
Following oral administration, fluvastatin 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 were recovered in urine. The elimination half-life (t) of fluvastatin is approximately 3 hours.
In patients with moderate to severe renal impairment (CL 10-40 mL/min), AUC and C increased approximately 1.2-fold after administration of a single dose of 40 mg fluvastatin compared to healthy volunteers. In patients with end-stage renal disease on hemodialysis, the AUC increased by approximately 1.5-fold. Lescol () XL was not evaluated in patients with renal impairment. However, systemic exposures after administration of Lescol () XL are lower than after the 40 mg immediate release capsule.
In patients with hepatic impairment due to liver cirrhosis, fluvastatin AUC and C increased approximately 2.5- fold compared to healthy subjects after administration of a single 40 mg dose. The enantiomer ratios of the two isomers of fluvastatin in hepatic impairment patients were comparable to those observed in healthy subjects.
Plasma levels of fluvastatin are not significantly different in patients age > 65 years compared to patients age 21 to 49 years.
Gender:
In a study evaluating the effect of age and gender on fluvastatin pharmacokinetics, there was there was no significant differences in fluvastatin exposures between males and females, except between younger females and younger males (both ages 21-49 years), where there was an approximate 30% increase in AUC in females. Adjusting for body weight decreases the magnitude of the differences seen. For Lescol () XL, the AUC increases 67% and 77% for women compared to men under fasted and high- fat meal fed conditions, respectively.
Pediatric:
Pharmacokinetic data in the pediatric population are not available.
Drug-Drug Interactions:
Data from drug-drug interactions studies involving coadministration of gemfibrozil, niacin, itraconazol, erythromycin, or tolbutamide indicate that the PK disposition of fluvastatin is not significantly altered when fluvastatin is coadministered with either of these drugs.
The below listed drug interaction information is derived from studies using Lescol () . Similar studies have not been conducted using the Lescol () XL tablet.
*Single dose unless otherwise noted
**Mean ratio (with/without coadministered drug and no change = 1-fold) or % change (with/without coadministered drug and no change = 0%); symbols of ↑ and ↓ indicate the exposure increase and decrease, respectively.
† Considered clinically significant
Data from drug-drug interaction studies involving fluvastatin and coadministration of either gemfibrozil, tolbutamide or lorsartan indicate that the PK disposition of either gemfibrozil, tolbutamide or lorsartan is not significantely altered when coadministered with fluvastatin.
*Single dose unless otherwise noted
**Mean ratio (with/without coadministered drug and no change = 1-fold) or % change (with/without coadministered drug and no change = 0%); symbols of ↑ and ↓ indicate the exposure increase and decrease, respectively.
† Considered clinically significant
Lescol () clinical Studies
In 12 placebo-controlled studies in patients with primary hypercholesterolemia and mixed dyslipidemia, Lescol () was administered to 1621 patients in daily dose regimens of 20 mg, 40 mg, and 80 mg (40 mg twice daily) for at least 6 weeks duration (Table 5). After 24 weeks of treatment, treatment with Lescol () resulted in significantly reduced plasma LDL-C, TC, TG, and Apo B compared to placebo and was associated with variable increases in HDL-C across the dose range.
Lescol () XL has been studied in five controlled studies of patients with primary hypercholesterolemia and mixed dyslipidemia. Lescol () XL was administered to over 900 patients in trials from 4 to 26 weeks in duration. In the three largest of these studies, Lescol () XL given as a single daily dose of 80 mg significantly reduced Total-C, LDL-C, TG and Apo B. and resulted in increases in HDL-C (Table 5).
In patients with primary mixed dyslipidemia as defined by baseline plasma TG levels ≥200 mg/dL and
Lescol () was studied in two open-label, uncontrolled, dose-titration studies. The first study enrolled 29 pre-pubertal boys, 9-12 years of age, who had an LDL-C level >90th percentile for age and one parent with primary hypercholesterolemia and either a family history of premature ischemic heart disease or tendon xanthomas. The mean baseline LDL-C was 226 mg/dL (range: 137-354 mg/dL). All patients were started on Lescol () capsules 20 mg daily with dose adjustments every 6 weeks to 40 mg daily then 80 mg daily (40 mg b.i.d.) to achieve an LDL-C goal between 96.7 – 123.7 mg/dL. Endpoint analyses were performed at Year 2. Lescol () decreased plasma levels of Total-C and LDL-C by 21% and 27%, respectively. The mean achieved LDL-C was 161 mg/dL (range: 74-336 mg/dL).
The second study enrolled 85 male and female patients, 10 to 16 years of age, who had an LDL-C >190 mg/dL or LDL-C >160 mg/dL and one or more risk factors for coronary heart disease, or LDL-C >160 mg/dL and a proven LDL-receptor defect. The mean baseline LDL-C was 225 mg/dL (range: 148-343 mg/dL). All patients were started on Lescol () capsules 20 mg daily with dose adjustments every 6 weeks to 40 mg daily then 80 mg daily (Lescol () 80 mg XL tablet) to achieve an LDL-C goal of
The majority of patients in both studies (83% in the first study and 89% in the second study) were titrated to the maximum daily dose of 80 mg. At study endpoint, 26% to 30% of patients in both studies achieved a targeted LDL-C goal of
In the Lescol () Intervention Prevention Study (LIPS), the effect of Lescol () 40 mg administered twice daily on the risk of recurrent cardiac events (time to first occurrence of cardiac death, nonfatal myocardial infarction, or revascularization) was assessed in 1677 patients with CHD who had undergone a percutaneous coronary intervention (PCI) procedure (mean time from PCI to randomization=3 days). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with dietary/lifestyle counseling and either Lescol () 40 mg (n=844) or placebo (n=833) given twice daily for a median of 3.9 years. The study population was 84% male, 98% Caucasian, with 37% >65 years of age. Mean baseline lipid concentrations were: total cholesterol 201 mg/dL, LDL-C 132 mg/dL, triglycerides 70 mg/dL and HDL-C 39 mg/dL.
Lescol () significantly reduced the risk of recurrent cardiac events (Figure 1) by 22% (p=0.013, 181 patients in the Lescol () group vs. 222 patients in the placebo group). Revascularization procedures comprised the majority of the initial recurrent cardiac events (143 revascularization procedures in the Lescol () group and 171 in the placebo group). Consistent trends in risk reduction were observed in patients >65 years of age.
Outcome data for the Lescol () Intervention Prevention Study are shown in Figure 2. After exclusion of revascularization procedures (CABG and repeat PCI) occurring within the first 6 months of the initial procedure involving the originally instrumental site, treatment with Lescol () was associated with a 32% (p=0.002) reduction in risk of late revascularization procedures (CABG or PCI occurring at the original site >6 months after the initial procedure, or at another site).
In the Lipoprotein and Coronary Atherosclerosis Study (LCAS), the effect of Lescol () therapy on coronary atherosclerosis was assessed by quantitative coronary angiography (QCA) in patients with CAD and mild to moderate hypercholesterolemia (baseline LDL-C range 115-190 mg/dL). In this randomized double-blind, placebo- controlled trial, 429 patients were treated with conventional measures (Step 1 AHA Diet) and either Lescol () 40 mg/day or placebo. In order to provide treatment to patients receiving placebo with LDL-C levels ≥160 mg/dL at baseline, adjunctive therapy with cholestyramine was added after Week 12 to all patients in the study with baseline LDL-C values of ≥160 mg/dL which were present in 25% of the study population. Quantitative coronary angiograms were evaluated at baseline and 2.5 years in 340 (79%) angiographic evaluable patients.
Compared to placebo, Lescol () significantly slowed the progression of coronary atherosclerosis as measured by within-patient per-lesion change in minimum lumen diameter (MLD), the primary endpoint (Figure 3 below), percent diameter stenosis (Figure 4), and the formation of new lesions (13% of all fluvastatin patients versus 22% of all placebo patients). A significant difference in favor of Lescol () was found between all fluvastatin and all placebo patients in the distribution among the three categories of definite progression, definite regression, and mixed or no change. Beneficial angiographic results (change in MLD) were independent of patients’ gender and consistent across a range of baseline LDL-C levels.
Lescol () references
1. National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. . 89(3):495-501.1992.
2. Manson, J.M., Freyssinges, C., Ducrocq, M.B., Stephenson, W.P., Postmarketing Surveillance of Lovastatin and Simvastatin Exposure During Pregnancy, 10(6): 439-446, 1996.
Lescol () how Supplied/storage And Handling
Lescol () (fluvastatin sodium) Capsules
20 mg
Brown and light brown imprinted twice with “” and “20” on one half and “Lescol () ” and the Lescol () (fluvastatin sodium) logo twice on the other half of the capsule.
Bottles of 30 capsules………………………………………………………………….……………...NDC 0078-0176-15
Bottles of 100 capsules………………………………………………………………………………..NDC 0078-0176-05
40 mg
Brown and gold imprinted twice with “” and “40” on one half and “Lescol () ” and the Lescol () (fluvastatin sodium) logo twice on the other half of the capsule.
Bottles of 30 capsules……………………………………………………………………….………...NDC 0078-0234-15
Bottles of 100 capsules………………………………………………………………………………..NDC 0078-0234-05
Lescol () XL (fluvastatin sodium) Extended-Release Tablets
80 mg
Yellow, round, slightly biconvex film-coated tablet with beveled edges debossed with “Lescol () XL” on one side and “80” on the other.
Bottles of 30 tablets…………………………………………………………………………………...NDC 0078-0354-15
Bottle of 100 tablets…………………………………………………………………………………...NDC 0078-0354-05
Store at 25ºC (77ºF); excursions permitted to 15 -30ºC (59 -86ºF) [see USP Controlled Room Temperature]. Dispense in a tight container. Protect from light.
Lescol () patient Counseling Information
Patients taking Lescol () /Lescol () XL should be advised that high cholesterol is a chronic condition and they should adhere to their medication along with their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel to determine goal attainment.
Lescol ()
Lescol ()
Lescol ()
Lescol ()
