Lescol

• Novartis Pharmaceuticals Corporation

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Lescol and certain other medicines can interact causing serious side effects. Especially tell your doctor if you take medicines for:

• your immune system
• cholesterol
• infections
• heart failure
• seizures
• diabetes
• heartburn or stomach ulcers

Know all the medicines you take. Keep a list of all the medicines you take with you to show your doctor and pharmacist.

Before taking Lescol, tell your doctor if you:

• have muscle aches or weakness
• drink more than 2 glasses of alcohol daily
• have diabetes
• have a thyroid problem
• have kidney problems

Some medicines should not be taken with Lescol. Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. 

Lescol has been detected in human breast milk. Because of the possibility for adverse reactions in nursing infants from Lescol, a choice should be made whether to stop nursing or to stop use of this medication. The importance of the drug to the mother should be considered.

• Your doctor will prescribe the medicine that is right for you. Take Lescol exactly as prescribed.
• Lescol can be taken daily with or without food as a single dose. Sometimes a second dose is required.
• Do not change your dose or stop Lescol without talking to your doctor. Your doctor may do blood tests to check your cholesterol levels during treatment with Lescol. Your dose of Lescol may be changed based on these blood test results.

Fluvastatin is in a group of drugs called HMG CoA reductase inhibitors, or "statins." Fluvastatin reduces levels of "bad" cholesterol (low-density lipoprotein, or LDL) and triglycerides in the blood, while increasing levels of "good" cholesterol (high-density lipoprotein, or HDL).

Fluvastatin is used to lower cholesterol and triglycerides (types of fat) in the blood and to slow the build-up of plaque (fatty deposits) in your blood vessels.

Fluvastatin is also used to lower the risk of heart complications in certain people with coronary artery disease.

Fluvastatin is used in adults and children who are at least 10 years old.

Fluvastatin may also be used for purposes not listed in this medication guide.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take this medicine with a full glass of water.

Fluvastatin is usually taken once or twice daily, with or without food. Take the medicine at the same time each day.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Tell your doctor if you have trouble swallowing the pill.

While using fluvastatin, you may need frequent blood tests.

It may take up to 4 weeks before your cholesterol levels improve. Keep using this medicine as directed, even if you feel well. High cholesterol usually has no symptoms.

Fluvastatin is only part of a complete treatment program that may also include diet, exercise, and weight control. Follow your doctor's instructions very closely.

Store at room temperature away from moisture, heat, and light.

Many other drugs can increase your risk of muscle problems if you take them with fluvastatin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with fluvastatin. Give a list of all your medicines to any healthcare provider who treats you.

General

• Patients should be placed on a standard lipid-lowering diet before initiation of fluvastatin therapy and should remain on this diet during treatment with the drug.1 60

Monitoring during Antilipemic Therapy

• Manufacturer recommends obtaining lipoprotein concentrations periodically during fluvastatin therapy.1 ACC/AHA cholesterol management guideline recommends obtaining lipoprotein concentrations within 4–12 weeks following initiation of statin therapy (to assess response and adherence) and monitoring every 3–12 months thereafter as clinically indicated.350

• Periodically reinforce adherence to lifestyle modifications during statin therapy.350

Administration

Oral Administration

Administer orally without regard to meals.1

Administer conventional capsules once (in the evening) or twice daily;1 do not administer two 40-mg capsules at one time.72 Do not open capsules prior to administration.1

Administer extended-release tablets as a single dose at any time of day.1 Do not break, crush, or chew tablets.1

Dosage

Available as fluvastatin sodium; dosage expressed in terms of fluvastatin.1

Pediatric Patients

Children 10–16 years of age: Initially, 20 mg once daily.1

Adjust dosage at 6-week intervals until the desired effect on lipoprotein concentrations is observed or a daily dosage of 80 mg (administered as 40 mg twice daily as conventional capsules or 80 mg once daily as extended-release tablets) is reached.1 72

Adults

Select appropriate statin intensity to achieve optimal ASCVD risk reduction.350 Giving maximally tolerated statin intensity is preferred over giving lower statin dosages in combination with nonstatin drugs, a strategy not yet shown to reduce ASCVD risk.350

Although dosages of 20–40 mg once daily (as conventional capsules) or 80 mg once daily (as extended-release tablets) are FDA-labeled dosages, these dosages were not evaluated in randomized controlled studies reviewed by the ACC/AHA expert panel.350

ACC/AHA cholesterol management guideline recommends initiating high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

ACC/AHA cholesterol management guideline recommends moderate-intensity statin therapy (e.g., fluvastatin 40 mg twice daily [as conventional capsules], fluvastatin 80 mg once daily [as extended-release tablets]).350

If estimated 10-year ASCVD risk ≥7.5%, consider high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients <40 or >75 years of age, consider potential benefits, adverse effects, drug interactions, and patient preferences when deciding to initiate, continue, or intensify statin therapy.350

Estimated 10-year ASCVD risk ≥7.5%: ACC/AHA cholesterol management guideline recommends moderate- (e.g., fluvastatin 40 mg twice daily [as conventional capsules], fluvastatin 80 mg once daily [as extended-release tablets]) to high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin).350

Estimated 10-year ASCVD risk of 5 to <7.5%: ACC/AHA cholesterol management guideline states may consider moderate-intensity statin therapy.350

Consider potential benefits, adverse effects, drug interactions, and patient preferences before initiating statin therapy.350

ACC/AHA cholesterol management guideline recommends high-intensity statin therapy (i.e., with atorvastatin or rosuvastatin) unless contraindicated.350

In patients at increased risk for developing statin-associated adverse effects or in whom high-intensity statin therapy is inappropriate or contraindicated, consider moderate-intensity statin therapy (e.g., fluvastatin 40 mg twice daily [as conventional capsules], fluvastatin 80 mg once daily [as extended-release tablets]) if tolerated.350

Patients >75 years of age: Individualize therapy based on potential benefits, adverse effects, drug interactions, and patient preferences; may consider moderate-intensity statin therapy if tolerated.350

Patients who require reductions in LDL-cholesterol concentrations of <25%: Initially, 20 mg once daily in the evening.1

Patients who require reductions of >25% in LDL-cholesterol concentrations or patients with primary hypercholesterolemia or mixed dyslipidemia: Initially, 40 mg (as conventional capsules) once daily in the evening, 80 mg (as extended-release tablets) once daily at any time of day, or 40 mg (as conventional capsules) twice daily.1 72

Adjust dosage at intervals of ≥4 weeks until the desired effect on lipoprotein concentrations is observed.1

Usual maintenance dosage is 20–80 mg daily.1

ACC/AHA cholesterol management guideline states may consider decreasing statin dosage when LDL-cholesterol concentrations are <40 mg/dL on 2 consecutive measurements; however, no data to suggest that LDL-cholesterol concentrations <40 mg/dL increase risk of adverse effects.350

Prescribing Limits

Pediatric Patients

Children 10–16 years of age: Maximum 80 mg daily.1

Special Populations

Hepatic Impairment

Use with caution in patients who consume substantial amounts of alcohol and/or have a history of liver disease; monitor such patients closely.1

Contraindicated in patients with active liver disease or unexplained, persistent increases in serum aminotransferase concentrations.1

Renal Impairment

Dosage modification is not necessary in patients with mild to moderate renal impairment.1

Dosages >40 mg daily have not been studied in patients with severe renal impairment; use caution when administering higher dosages to such patients.1

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of fluvastatin in children 10 to 16 years of age. However, safety and efficacy have not been established in children younger than 10 years of age.

Teenage girls taking fluvastatin should be counseled on appropriate birth control methods to prevent pregnancy.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of fluvastatin in the elderly. However, elderly patients are more likely to have age-related muscle problems, which may require caution in patients receiving fluvastatin.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Posaconazole

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atazanavir
• Bezafibrate
• Ceritinib
• Ciprofibrate
• Clofibrate
• Dalfopristin
• Danazol
• Daptomycin
• Darunavir
• Entacapone
• Fenofibrate
• Fenofibric Acid
• Fluconazole
• Fosphenytoin
• Gemfibrozil
• Phenytoin
• Pixantrone
• Quinupristin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Colchicine
• Eltrombopag
• Glyburide
• Mifepristone
• Oat Bran
• Pectin
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, or history of or
• Diabetes or
• Liver disease, history of—Use with caution. May cause side effects to become worse.

• Convulsions (seizures), not well-controlled or
• Electrolyte disorder, severe or
• Endocrine disorder, severe or
• Hypotension (low blood pressure) or
• Hypothyroidism (underactive thyroid), not adequately treated or
• Kidney disease, severe or
• Major surgery or
• Major trauma (injury) or
• Metabolic disorder, severe or
• Sepsis (severe infection in the blood)—Patients with these conditions may be at risk of developing muscle and kidney problems.

• Liver disease, active or
• Liver enzymes, persistently high levels—Should not be used in patients with these conditions.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Chills
• diarrhea
• fever
• general feeling of discomfort or illness
• joint pain
• loss of appetite
• muscle aches and pain
• nausea
• runny nose
• shivering
• sore throat
• sweating
• trouble sleeping
• unusual tiredness or weakness
• vomiting

• Bladder pain
• bloody or cloudy urine
• cough producing mucus
• dark-colored urine
• difficult, burning, or painful urination
• difficulty with breathing
• difficulty with moving
• difficulty with swallowing
• dizziness
• fast heartbeat
• frequent urge to urinate
• hives
• itching
• lower back or side pain
• muscle cramps, spasms, or stiffness
• muscular pain, tenderness, wasting, or weakness
• pain, swelling, or redness in the joints
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• skin rash
• tightness in the chest

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• headache
• heartburn
• indigestion
• stomach discomfort, upset, or pain

• Bloated or full feeling
• excess air or gas in the stomach or intestines
• pain or tenderness around the eyes and cheekbones
• passing gas
• unable to sleep

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad headache.
• Change in balance.
• Memory problems or loss.
• Feeling confused.
• Not able to pass urine or change in how much urine is passed.
• Pain when passing urine.
• This medicine may cause muscle pain, tenderness, or weakness. Sometimes, a very bad muscle problem may happen that may lead to kidney problems. Rarely, deaths have happened in people who get these problems when taking drugs like this one. Call your doctor right away if you have muscle pain, tenderness, or weakness that is not normal (with or without fever or feeling out of sorts). Call your doctor right away if you have muscle signs that last after your doctor has told you to stop taking Lescol (fluvastatin capsules).
• Liver problems have happened with drugs like this one. Sometimes, this has been deadly. Call your doctor right away if you have signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.

Therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. Drug therapy is indicated as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other non-pharmacologic measures alone has been inadequate.

     Hypercholesterolemia (Heterozygous Familial and Nonfamilial) and Mixed Dyslipidemia

Lescol and Lescol XL are indicated

• as an adjunct to diet to reduce elevated total cholesterol (Total-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG) and apolipoprotein B (Apo B) levels, and to increase high-density lipoprotein cholesterol (HDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Type IIa and IIb).
  
• as an adjunct to diet to reduce Total-C, LDL-C, and Apo B levels in adolescent boys and adolescent girls who are at least one year post-menarche, 10-16 years of age, with heterozygous familial hypercholesterolemia and the following findings are present:
  • LDL-C remains ≥ 190 mg/dL or
    
  • LDL-C remains ≥ 160 mg/dL and:
    • there is a positive family history of premature cardiovascular disease or
      
    • two or more other cardiovascular disease risk factors are present

The NCEP classification of cholesterol levels in pediatric patients with a familial history of hypercholesterolemia or premature CVD is summarized below.

Children treated with fluvastatin in adolescence should be re-evaluated in adulthood and appropriate changes made to their cholesterol-lowering regimen to achieve adult treatment goals.

     Secondary Prevention of Cardiovascular Disease

In patients with clinically evident CHD, Lescol and Lescol XL are indicated to:

• reduce the risk of undergoing coronary revascularization procedures
  
• slow the progression of coronary atherosclerosis

     Limitations of Use

Neither Lescol nor Lescol XL have been studied in conditions where the major abnormality is elevation of chylomicrons, VLDL, or IDL (i.e., hyperlipoproteinemia Types I, III, IV, or V).

     Hypersensitivity to any Component of this Medication

Lescol and Lescol XL are contraindicated in patients with hypersensitivity to any component of this medication.

     Active Liver Disease

Lescol and Lescol XL are contraindicated in patients with active liver disease or unexplained, persistent elevations in serum transaminases [see Warnings and Precautions (5.2)].

     Pregnancy

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 hazards. If 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 [see Use In Specific Populations (8.1)].

     Nursing Mothers

Fluvastatin is secreted into the breast milk of animals and because HMG-CoA reductase inhibitors have the potential to cause serious adverse reactions in nursing infants, women who require treatment with Lescol or Lescol XL should be advised not to breastfeed their infants [see Use In Specific Populations (8.3)].

     Skeletal Muscle

Rhabdomyolysis with acute renal failure secondary to myoglobinuria have been reported with Lescol/Lescol XL and other drugs in this class.

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 Adverse Reactions (6)]. 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 <0.1% in fluvastatin clinical trials. Myopathy should be considered in any patient with diffuse myalgias, muscle tenderness or weakness, and/or marked elevation of CPK.

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.

All patients should be advised to promptly report to their physician unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing Lescol/Lescol XL.

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. 

     Liver Enzymes

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 enzyme tests be performed prior to the initiation of Lescol/Lescol XL, and if signs or symptoms of liver injury occur.

There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including fluvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with Lescol/Lescol XL, promptly interrupt therapy. If an alternate etiology is not found do not restart Lescol/Lescol XL.

In very rare cases, possibly drug-related hepatitis was observed that resolved upon discontinuation of treatment.1 Active liver disease or unexplained serum transaminase elevations are contraindications to the use of Lescol and Lescol XL [see Contraindications (4) and Warnings and Precautions (5.2)]. Caution should be exercised when Lescol is administered to patients with a history of liver disease or heavy alcohol ingestion [see Clinical Pharmacology (12.3)]. Such patients should be closely monitored.

     Endocrine Effects

Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including Lescol/Lescol XL.

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<0.05) relative to baseline in the 80 mg group, it was not significant in comparison to the changes noted in groups receiving either 40 mg of Lescol or placebo.

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 Toxicity

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 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 [R*,S*-(E)]-(±)-7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoic acid, monosodium salt. The empirical formula of fluvastatin sodium is C24H25FNO4•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.

Active Ingredient: fluvastatin sodium

Inactive Ingredients in capsules: calcium carbonate, gelatin, magnesium stearate, microcrystalline cellulose, pregelatinized starch (corn), red iron oxide, sodium bicarbonate, talc, titanium dioxide, yellow iron oxide, and other ingredients.

Capsules may also include: benzyl alcohol, black iron oxide, butylparaben, carboxymethylcellulose sodium, edetate calcium disodium, methylparaben, propylparaben, silicon dioxide, sodium lauryl sulfate, and sodium propionate.

Inactive Ingredients in extended-release tablets: microcrystalline cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, potassium bicarbonate, povidone, magnesium stearate, yellow iron oxide, titanium dioxide and polyethylene glycol 8000.

Many other drugs can increase your risk of muscle problems if you take them with Lescol. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all medicines you use, and those you start or stop using during your treatment with Lescol. Give a list of all your medicines to any healthcare provider who treats you.