Fluvastatin Sodium (TEVA-FLUVASTATIN)

1. Health Canada Product Monograph — Fluvastatin Sodium

• Used as an adjunct to a cholesterol-lowering diet to treat elevated total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B in adults with primary hypercholesterolemia or mixed hyperlipidemia (Fredrickson type IIa and IIb) who have not responded adequately to diet and lifestyle changes alone.
• Used in patients with coronary heart disease who have undergone a percutaneous coronary intervention to help delay major adverse cardiac events such as cardiac death, nonfatal heart attack, or the need for repeat revascularization procedures.
• Not indicated for isolated elevations of chylomicrons, VLDL, or IDL (hyperlipoproteinemia types I, III, IV, or V), and has not been evaluated in rare homozygous familial hypercholesterolemia.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Contraindicated during pregnancy, because cholesterol and its biosynthetic products are essential for normal fetal development and statins may cause fetal harm.
• Should be given to women of childbearing age only when pregnancy is highly unlikely, and discontinued immediately if pregnancy occurs, with the patient counselled on potential harm to the fetus.

• Contraindicated in nursing mothers, since it is not known whether fluvastatin passes into human milk and there is potential for serious adverse effects in a nursing infant.

• Plasma concentrations of fluvastatin do not vary significantly with age, so no specific dose adjustment is required based on age alone.
• Older adults, particularly those over 70, may be more susceptible to muscle-related side effects such as myopathy, so caution and monitoring are advised.

• Safety and effectiveness in children have not been established, and experience with fluvastatin in pediatric patients is limited.

• Starting dose is 20 mg once daily for patients who need a smaller reduction in LDL cholesterol, or 40 mg once daily for those needing a greater reduction; the dose may be split to 40 mg twice daily if needed.
• Maximum recommended dose is 80 mg per day, given as 40 mg twice daily; in patients with coronary heart disease who have had a percutaneous intervention, the recommended dose is 40 mg twice daily without titration from a lower dose.
• Capsules may be taken with or without food, in the evening or at bedtime, and should be swallowed whole with a glass of water.
• Since maximal LDL lowering is seen within about 4 weeks, lipid levels should be checked periodically and the dose adjusted according to response.

• Dyspepsia (indigestion) may occur.
• Abdominal pain may occur.
• Diarrhea may occur.
• Constipation may occur.
• Flatulence may occur.
• Nausea may occur.
• Headache may occur.
• Muscle aches (myalgia) or joint pain may occur.
• Dizziness may occur.
• Insomnia or sleep disturbance may occur.
• Rash may occur.
• Fatigue may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Rare cases of myopathy and, very rarely, rhabdomyolysis with muscle breakdown and acute kidney injury may occur.
• Rare reports of immune-mediated necrotizing myopathy, an autoimmune muscle disease that persists even after stopping the statin, have occurred.
• Liver problems, including rare cases of fatal or non-fatal liver failure, have been reported; signs include nausea, vomiting, loss of appetite, jaundice, and easy bruising or bleeding.
• Severe hypersensitivity reactions, including angioedema, vasculitis, and a lupus-like syndrome, may occur rarely.
• Rare cases of interstitial lung disease have been reported, especially with long-term use.
• Rare cases of pancreatitis have been reported.
• Cognitive symptoms such as memory loss, confusion, or forgetfulness have been reported rarely and are generally reversible after stopping the drug.
• Statins may in rare instances trigger or worsen myasthenia gravis or ocular myasthenia.
• Seek prompt medical attention for unexplained muscle pain, tenderness, or weakness (especially with fever or malaise), signs of liver problems, or signs of a severe allergic reaction.

• Use with caution in patients with a personal or family history of hereditary muscle disorders or previous muscle toxicity with another statin.
• Use with caution in patients who consume substantial amounts of alcohol or who have a history of liver disease.
• Use with caution in patients with hypothyroidism, diabetes with fatty liver changes, or severe metabolic or electrolyte disturbances.
• Use with caution in patients over 70 years of age and in those with renal impairment.
• Use with caution during periods of sepsis, hypotension, major surgery, trauma, or uncontrolled seizures, all of which raise the risk of rhabdomyolysis.
• Use with caution in patients also taking a fibrate, niacin at lipid-lowering doses, or other drugs that raise fluvastatin levels.
• Use is not recommended in patients with severe renal insufficiency, since experience in this population is lacking.

• Contraindicated in patients with known hypersensitivity to fluvastatin or any ingredient in the capsule.
• Contraindicated in patients with active liver disease or unexplained, persistent elevations in liver transaminases.
• Contraindicated during pregnancy.
• Contraindicated in breastfeeding women.

• Cholestyramine reduces fluvastatin absorption; taking fluvastatin at least 4 hours after cholestyramine preserves the cholesterol-lowering effect.
• Concomitant fibrates (such as gemfibrozil or bezafibrate) or lipid-lowering doses of niacin increase the risk of myopathy and rhabdomyolysis.
• Cimetidine, ranitidine, omeprazole, and fluconazole can significantly increase fluvastatin blood levels.
• Rifampin can significantly lower fluvastatin blood levels and reduce its cholesterol-lowering effect.
• Cyclosporine can increase fluvastatin blood levels; isolated cases of myopathy have been reported with this combination.
• Concomitant use with drugs metabolized by CYP2C9, such as warfarin and other oral anticoagulants, phenytoin, and oral hypoglycemic agents (such as glyburide or tolbutamide), may require closer monitoring; fluvastatin can affect prothrombin time in patients on warfarin.
• NSAIDs such as diclofenac can increase fluvastatin blood levels.
• Concomitant colchicine has been anecdotally linked with muscle toxicity.

• May be taken with or without food; there is no clinically important difference in the cholesterol-lowering effect either way.
• Unlike some other statins, fluvastatin is not expected to interact significantly with grapefruit juice, since it is metabolized by a different liver enzyme.

• Taken once daily in the evening or at bedtime, since cholesterol synthesis is highest overnight; higher doses may be split into a twice-daily regimen.

• Store between 15 and 30 degrees C in a tightly closed container, protected from light and humidity.

• Fluvastatin is a statin used to lower cholesterol and triglycerides and to reduce cardiac risk after certain heart procedures.
• Take the capsule whole, once daily in the evening or at bedtime (or split into a twice-daily dose at higher strengths), with or without food.
• Common side effects include stomach upset, diarrhea, headache, and mild muscle or joint aches.
• Contact your doctor or pharmacist right away for unexplained muscle pain, weakness, or dark urine, or for signs of liver problems such as yellowing skin or eyes, unusual fatigue, or dark urine.
• This medication must not be used during pregnancy or breastfeeding; use effective birth control and tell your prescriber immediately if you become pregnant.
• Store at room temperature away from light and moisture, and have your cholesterol and liver function checked periodically as advised by your doctor.