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Fluvastatin

Pronunciation

Pronunciation

(FLOO va sta tin)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Lescol: 20 mg [DSC], 40 mg [DSC]

Generic: 20 mg, 40 mg

Tablet Extended Release 24 Hour, Oral:

Lescol XL: 80 mg

Generic: 80 mg

Brand Names: U.S.

  • Lescol XL
  • Lescol [DSC]

Pharmacologic Category

  • Antilipemic Agent, HMG-CoA Reductase Inhibitor

Pharmacology

Acts by competitively inhibiting 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonate; this is an early rate-limiting step in cholesterol biosynthesis. HDL is increased while total, LDL, and VLDL cholesterols; apolipoprotein B; and plasma triglycerides are decreased. In addition to the ability of HMG-CoA reductase inhibitors to decrease levels of high-sensitivity C-reactive protein (hsCRP), they also possess pleiotropic properties including improved endothelial function, reduced inflammation at the site of the coronary plaque, inhibition of platelet aggregation, and anticoagulant effects (de Denus 2002; Ray 2005).

Distribution

Vdss: 0.35 L/kg

Metabolism

Hepatic to inactive and active metabolites (oxidative metabolism via CYP2C9 [~75%], CYP2C8 [~5%], and CYP3A4 [~20%] isoenzymes); active forms do not circulate systemically; extensive (saturable) first-pass hepatic extraction

Excretion

Excretion: Feces (~90%; <2% unchanged); urine (~5%)

Onset of Action

Peak effect: Maximal LDL-C reductions achieved within 4 weeks

Time to Peak

Immediate-release: <1 hour (delayed more than 2-fold when administered with food as compared to administering 4 hours after the evening meal)

Extended-release: ~3 hours (minimally affected by low-fat meals; however, with a high-fat meal, delayed by 2-fold)

Half-Life Elimination

Immediate-release: ~3 hours; Extended-release: 7.3 to 10.5 hours (due to prolonged absorption time) (Barilla 2004)

Protein Binding

98%

Special Populations: Renal Function Impairment

In moderate to severe renal impairment (CrCl 10 to 40 mL/min), AUC and Cmax increased ~1.2-fold after administration of a single dose of 40 mg immediate-release fluvastatin; in ESRD on hemodialysis, the AUC increased ~1.5-fold.

Special Populations: Hepatic Function Impairment

AUC and Cmax increase ~2.5-fold after administration of a single dose of 40 mg immediate-release fluvastatin.

Use: Labeled Indications

Dyslipidemias:

Heterozygous familial and nonfamilial hypercholesterolemia and mixed dyslipidemia: Adjunct to diet to reduce elevated total cholesterol (total-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride, and apolipoprotein B (apo-B) levels and to increase HDL-C in adults with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb)

Heterozygous familial hypercholesterolemia: As an adjunct to diet to reduce total-C, LDL-C, and apo B levels in children ≥10 years and adolescents ≤16 years of age (female patients must be at least 1 year postmenarche) with heterozygous familial hypercholesterolemia and an LDL-C that remains ≥190 mg/dL or ≥160 mg/dL (with ≥2 cardiovascular risk factors or a positive family history of premature cardiovascular disease).

Prevention of cardiovascular disease (CVD):

Secondary prevention of CVD: To slow the progression of coronary atherosclerosis in patients with coronary heart disease; reduce risk of coronary revascularization procedures in patients with coronary heart disease

Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) according to the American College of Cardiology/American Heart Association: To reduce the risk of ASCVD in patients with clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) who are greater than 75 years of age or not a candidate for high-intensity statin therapy; in patients without clinical ASCVD if LDL-C is 190 mg/dL or greater and not a candidate for high-intensity statin therapy; in patients without clinical ASCVD who have type 1 or type 2 diabetes and are between 40 and 75 years of age; in patients with an estimated 10-year ASCVD risk 7.5% or greater and who are between 40 and 75 years of age (Stone 2013). Specific recommendations from the Kidney Disease: Improving Global Outcomes (KDIGO) organization have also been released for patients with chronic kidney disease (KDIGO [Tonelli 2013]).

Limitations of use: Has not been studied in conditions where the major abnormality is elevation of chylomicrons, very low-density lipoprotein (VLDL), or intermediate density lipoprotein (IDL) (ie, hyperlipoproteinemia types I, III, IV, or V).

Contraindications

Hypersensitivity to fluvastatin or any component of the formulation; active liver disease; unexplained persistent elevations of serum transaminases; pregnancy or women planning to become pregnant; breast-feeding

Dosing: Adult

Heterozygous familial and nonfamilial hypercholesterolemia: Oral:

Immediate release: 40 mg once daily in the evening or 40 mg twice daily

Extended release: 80 mg once daily (anytime)

Mixed dyslipidemia: Oral:

Immediate release: 40 mg once daily in the evening or 40 mg twice daily

Extended release: 80 mg once daily (anytime)

Patients requiring ≥25% decrease in LDL-C: Oral:

Immediate release: Initial: 40 mg once daily in the evening or 40 mg twice daily

Extended release: Initial: 80 mg once daily (anytime)

Patients requiring <25% decrease in LDL-C: Oral: Initial: Immediate release: 20 mg once daily in the evening; may increase based on tolerability and response to a maximum recommended dose of 80 mg/day, given in 2 divided doses (immediate release) or as a single daily dose (extended release)

Prevention of cardiovascular disease: ACC/AHA Blood Cholesterol Guideline recommendations to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Stone 2013): Adults ≥21 years: Oral:

Primary prevention:

LDL-C ≥190 mg/dL: High-intensity therapy necessary; use alternate statin therapy (eg, atorvastatin, rosuvastatin)

Type 1 or 2 diabetes and age 40 to 75 years: Moderate intensity therapy:

Immediate release: 40 mg twice daily.

Extended release: 80 mg once daily.

Type 1 or 2 diabetes, age 40 to 75 years, and an estimated 10-year ASCVD risk ≥7.5%: High-intensity therapy necessary; use alternate statin therapy (eg, atorvastatin, rosuvastatin).

Age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy:

Immediate release: 40 mg twice daily or consider using high-intensity statin therapy (eg, atorvastatin, rosuvastatin).

Extended release: 80 mg once daily or consider using high-intensity statin therapy (eg, atorvastatin, rosuvastatin).

Secondary prevention:

Patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG (AHA [Kulik 2015]) and:

Age ≤75 years: High-intensity therapy necessary; use alternate statin therapy (eg, atorvastatin, rosuvastatin).

Age >75 years or not a candidate for high-intensity therapy: Moderate-intensity therapy:

Immediate release: 40 mg twice daily.

Extended release: 80 mg once daily.

Concomitant use with cyclosporine or fluconazole: Immediate release: Do not exceed fluvastatin 20 mg twice daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Heterozygous familial hypercholesterolemia: Children ≥10 years and Adolescents ≤16 years: Oral: Initial: 20 mg once daily; may increase every 6 weeks based on tolerability and response to a maximum recommended dose of 80 mg/day, given in 2 divided doses (immediate release) or as a single daily dose (extended release)

Concomitant use with cyclosporine or fluconazole: Immediate release: Do not exceed fluvastatin 20 mg twice daily

Dosing: Renal Impairment

Mild to moderate renal impairment: No dosage adjustment necessary.

Severe renal impairment: There are no dosage adjustments provided in the manufacturer's labeling; use with caution, particularly at doses >40 mg/day (has not been studied).

Dosing: Hepatic Impairment

Use is contraindicated in active liver disease or unexplained transaminase elevations.

Dosing: Adjustment for Toxicity

Severe muscle symptoms or fatigue: Promptly discontinue use; evaluate CPK, creatinine, and urinalysis for myoglobinuria (Stone 2013).

Mild to moderate muscle symptoms: Discontinue use until symptoms can be evaluated; evaluate patient for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases). Upon resolution, resume the original or lower dose of fluvastatin. If muscle symptoms recur, discontinue fluvastatin use. After muscle symptom resolution, may then use a low dose of a different statin; gradually increase if tolerated. In the absence of continued statin use, if muscle symptoms or elevated CPK continues after 2 months, consider other causes of muscle symptoms. If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose (Stone 2013).

Administration

Oral: Patient should be placed on a standard cholesterol-lowering diet before and during treatment. Administer without regard to meals. Do not break, chew, or crush extended release tablets; do not open immediate-release capsules. Do not administer two 40 mg immediate-release capsules at once.

Dietary Considerations

Generally, patients should be placed on a standard cholesterol-lowering diet and other lifestyle modifications for 3 to 6 months prior to the initiation of drug therapy. The diet should be continued during drug therapy. However, for patients with advanced risk factors (eg, known coronary heart disease), drug therapy may be initiated concurrently with diet modification.

Red yeast rice contains variable amounts of several compounds that are structurally similar to HMG-CoA reductase inhibitors, primarily monacolin K (or mevinolin) which is structurally identical to lovastatin; concurrent use of red yeast rice with HMG-CoA reductase inhibitors may increase the incidence of adverse and toxic effects (Lapi 2008; Smith 2003).

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Acipimox: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Amiodarone: May decrease the metabolism of HMG-CoA Reductase Inhibitors. Management: Dose of HMG-CoA reductase inhibitor may need to be reduced (limit simvastatin adult maximum dose to 20 mg/day, limit lovastatin adult maximum dose to 40 mg/day). Consider therapy modification

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

Antacids: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Asunaprevir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Atazanavir: May increase the serum concentration of Fluvastatin. Consider therapy modification

Bezafibrate: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Bezafibrate may increase the serum concentration of HMG-CoA Reductase Inhibitors. More specifically, bezafibrate may increase the serum concentration of fluvastatin Management: Monitor patients closely for myopathy with concomitant use of bezafibrate and HMG-CoA reductase inhibitors. Concomitant use is contraindicated in patients predisposed to myopathy and alternative therapy should be considered. Consider therapy modification

Boceprevir: May increase the serum concentration of Fluvastatin. Monitor therapy

Bosentan: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Bosentan. Management: Concomitant use of both a CYP2C9 inhibitor and a CYP3A inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. See monograph for details. Monitor therapy

Cannabis: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Monitor therapy

Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy

Cholestyramine Resin: May decrease the serum concentration of Fluvastatin. Management: Administer fluvastatin at least 1 hour or greater (particularly with extended-release form) before, or at least 4 hours after cholestyramine to minimize the risk for any significant interaction. Consider therapy modification

Ciprofibrate: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Avoid the use of HMG-CoA reductase inhibitors and ciprofibrate if possible. If concomitant therapy is considered, benefits should be carefully weighed against the risks, and patients should be monitored closely for signs/symptoms of muscle toxicity. Consider therapy modification

Colchicine: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Colchicine may increase the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

CycloSPORINE (Systemic): May increase the serum concentration of Fluvastatin. Management: Limit fluvastatin to 20 mg twice daily in patients who are also receiving cyclosporine. Consider therapy modification

CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Monitor therapy

Cyproterone: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Management: Avoid use of statins metabolized by CYP3A4 (eg, simvastatin) and consider avoiding fluvastatin as well in patients receiving high dose cyproterone (300 mg/day). Consider use of pravastatin, rosuvastatin, or pitavastatin if statin therapy is needed. Consider therapy modification

Daclatasvir: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

DAPTOmycin: HMG-CoA Reductase Inhibitors may enhance the adverse/toxic effect of DAPTOmycin. Specifically, the risk of skeletal muscle toxicity may be increased. Management: Consider temporarily stopping HMG-CoA reductase inhibitor therapy prior to daptomycin. If used together, regular (i.e., at least weekly) monitoring of CPK concentrations is recommended. Consider therapy modification

Dronabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Dronabinol. Monitor therapy

Elbasvir: May increase the serum concentration of Fluvastatin. Monitor therapy

Eltrombopag: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Etravirine: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. This applies to atorvastatin, lovastatin and simvastatin. Conversely, levels of fluvastatin may be increased. Management: Dose adjustment of the HMG-CoA reductase inhibitor may be warranted. No interaction is expected with rosuvastatin, pravastatin, or pitavastatin. Monitor therapy

Fenofibrate and Derivatives: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Fluconazole: May increase the serum concentration of Fluvastatin. Management: Limit fluvastatin maximum adult dose to 20 mg twice daily, and monitor for toxic effects of fluvastatin (e.g., myalgia, rhabdomyolysis, liver function test abnormalities), during concomitant treatment. Consider therapy modification

Fosphenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Fusidic Acid (Systemic): May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Specifically, the risk for muscle toxicities, including rhabdomyolysis may be significantly increased. Management: Avoid concurrent use whenever possible. Use is listed as contraindicated in product characteristic summaries in several countries, although UK labeling suggests that use could be considered under exceptional circumstances and with close supervision. Avoid combination

Gemfibrozil: May enhance the myopathic (rhabdomyolysis) effect of Fluvastatin. Avoid combination

Grazoprevir: May increase the serum concentration of Fluvastatin. Monitor therapy

Lanthanum: HMG-CoA Reductase Inhibitors may decrease the serum concentration of Lanthanum. Management: Administer HMG-CoA reductase inhibitors at least two hours before or after lanthanum. Consider therapy modification

Mifepristone: May increase the serum concentration of Fluvastatin. Management: Use fluvastatin at the lowest recommended dose, and monitor closely for adverse effects (including myopathy), during and in the 2 weeks following mifepristone treatment. Consider therapy modification

Niacin: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Management: Greatest concern with niacin 1 g/d or greater. Avoid simvastatin 80 mg with niacin 1 g or greater in Chinese patients. Do not exceed 40 mg/d of simva or lovastatin with Niaspan. Use of niacin with rosuvastatin 40 mg is contraindicated (Canadian label). Consider therapy modification

Niacinamide: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir: May increase the serum concentration of Fluvastatin. Management: Canadian product labeling recommends use of the lowest fluvastatin dose with this combination. Monitor therapy

PAZOPanib: HMG-CoA Reductase Inhibitors may enhance the hepatotoxic effect of PAZOPanib. Specifically, the risk for increased serum transaminase concentrations may be increased. Management: Simvastatin is specifically implicated in this interaction. There is a lack of data regarding the risk with other statins, but caution appears warranted with any statins. Monitor therapy

Phenytoin: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Consider therapy modification

Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of HMG-CoA Reductase Inhibitors. Monitor therapy

Red Yeast Rice: May enhance the adverse/toxic effect of HMG-CoA Reductase Inhibitors. Avoid combination

Rifamycin Derivatives: May decrease the serum concentration of HMG-CoA Reductase Inhibitors. Management: Consider use of noninteracting antilipemic agents (note: pitavastatin concentrations may increase with rifamycin treatment). Monitor for altered HMG-CoA reductase inhibitor effects. Rifabutin and fluvastatin, or possibly pravastatin, may pose lower risk. Consider therapy modification

Sacubitril: May increase the serum concentration of HMG-CoA Reductase Inhibitors. Monitor therapy

Telaprevir: May increase the serum concentration of Fluvastatin. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/SLCO1B1 Substrates. Monitor therapy

Tetrahydrocannabinol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Tetrahydrocannabinol. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Trabectedin: HMG-CoA Reductase Inhibitors may enhance the myopathic (rhabdomyolysis) effect of Trabectedin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): HMG-CoA Reductase Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Adverse Reactions

As reported with fluvastatin capsules; in general, adverse reactions reported with fluvastatin extended release tablet were similar, but the incidence was less.

1% to 10%:

Central nervous system: Headache (9%), fatigue (3%), insomnia (3%)

Gastrointestinal: Dyspepsia (8%), diarrhea (5%), abdominal pain (5%), nausea (3%)

Genitourinary: Urinary tract infection (2%), cystitits (interstitial; Huang 2015)

Neuromuscular & skeletal: Myalgia (5%)

Respiratory: Sinusitis (3%), bronchitis (2%)

<1% (Limited to important or life-threatening) including additional class-related events (not necessarily reported with fluvastatin therapy): Alopecia, amnesia (reversible), anaphylaxis, angioedema, arthralgia, arthritis, cataracts, cholestatic jaundice, cirrhosis, cognitive impairment (reversible), confusion (reversible), depression, dermatomyositis, dyspnea, eosinophilia, erectile dysfunction, erythema multiforme, facial paresis, fatty liver, fever, fulminant hepatic necrosis, gynecomastia, hemolytic anemia, hepatitis, hepatoma, hypersensitivity reaction, immune-mediated necrotizing myopathy (IMNM), impotence, increased blood glucose, increased CPK (>10x normal), increased ESR, increased glycosylated hemoglobin (HbA1c), increased transaminases, interstitial lung disease, leukopenia, memory disturbance (reversible), memory impairment (reversible), muscle cramps, myopathy, nodules, ophthalmoplegia, pancreatitis, paresthesia, peripheral nerve palsy, peripheral neuropathy, photosensitivity, polymyalgia rheumatica, positive ANA, pruritus, psychic disturbance, purpura, rash, renal failure (secondary to rhabdomyolysis), rhabdomyolysis, skin discoloration, Stevens-Johnson syndrome, systemic lupus erythematosus-like syndrome, taste alteration, thrombocytopenia, thyroid dysfunction, toxic epidermal necrolysis, tremor, urticaria, vasculitis, vertigo

Warnings/Precautions

Concerns related to adverse effects:

• Diabetes mellitus: Increases in HbA1c and fasting blood glucose have been reported with HMG-CoA reductase inhibitors; however, the benefits of statin therapy (eg, reduction in the risk of MI or stroke) far outweigh the risk of dysglycemia. If a patient develops diabetes mellitus during therapy, continue use of fluvastatin and encourage patient to adhere to healthy lifestyle regimens (eg, heart healthy dietary pattern, engage in physical activity, achieve and maintain a healthy body weight) (ACC/AHA [Stone 2013]).

• Hepatotoxicity: Increased AST or ALT has been reported; in most cases, elevations were transient and resolved or improved on continued therapy or after a brief interruption in therapy. Postmarketing reports of fatal and nonfatal hepatic failure have been reported and are rare. If serious hepatotoxicity with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment, interrupt therapy promptly. If an alternate etiology is not identified, do not restart fluvastatin. Possible drug-related hepatitis (rare) was observed that resolved upon discontinuation of treatment. Liver enzyme tests should be obtained at baseline and as clinically indicated and if signs/symptoms of liver injury occur. Ethanol may enhance the potential of adverse hepatic effects; instruct patients to avoid excessive ethanol consumption. Use has been found to be safe in those with active hepatitis C (Kondo 2012; Kurincic 2014).

• Myopathy/rhabdomyolysis: Rhabdomyolysis with acute renal failure secondary to myoglobinuria and/or myopathy has been reported; patients should be monitored closely. This risk is dose related and is increased with concurrent use of cyclosporine, erythromycin, or other lipid-lowering medications (eg, fibrates, niacin at doses ≥1 g/day). Use caution in patients with inadequately treated hypothyroidism, and those taking other drugs associated with myopathy (eg, colchicine); these patients are predisposed to myopathy. Uncomplicated myalgia immune-mediated necrotizing myopathy (IMNM) associated with HMG-CoA reductase inhibitors use has also been reported. Patients should be instructed to report unexplained muscle pain, tenderness, weakness, or brown urine, particularly if accompanied by malaise or fever. Discontinue therapy if markedly elevated CPK levels occur or myopathy is diagnosed/suspected.

Disease-related concerns:

• Diseases reducing steroidogenesis: Use caution in patients with conditions or on medications that reduce steroidogenesis.

• Hepatic impairment and/or ethanol use: Use with caution in patients who consume large amounts of ethanol or have a history of liver disease. Use is contraindicated in patients with active liver disease or unexplained transaminase elevations.

• Renal impairment: Use with caution in patients with renal impairment; these patients are predisposed to myopathy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in patients with advanced age; these patients are predisposed to myopathy.

• Surgical patients: The manufacturer recommends temporary discontinuation for elective major surgery, acute medical or surgical conditions, or in any patient experiencing an acute or serious condition predisposing to renal failure secondary to rhabdomyolysis (eg, sepsis, hypotension, trauma, uncontrolled seizures, severe metabolic, endocrine, or electrolyte disorders). Based on current research and clinical guidelines, HMG-CoA reductase inhibitors should be continued in the perioperative period (ACC/AHA [Fleisher 2014]). Postoperative discontinuation of statin therapy is associated with an increased risk of cardiac morbidity and mortality.

Other warnings/precautions:

• Appropriate use: Drug therapy should be only one component of multiple risk factor intervention in patients at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. In patients with CHD or multiple risk factors for CHD, initiate therapy simultaneously with diet.

• Hyperlipidemia: Secondary causes of hyperlipidemia should be ruled out prior to therapy.

Monitoring Parameters

2013 ACC/AHA Blood Cholesterol Guideline recommendations (Stone 2013):

Lipid panel (total cholesterol, HDL, LDL, triglycerides): Baseline lipid panel; fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months (as clinically indicated) thereafter. If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.

Hepatic transaminase levels: Baseline measurement of hepatic transaminase levels (ie, ALT); measure hepatic function if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.

CPK: CPK should not be routinely measured. Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy). May measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).

Evaluate for new-onset diabetes mellitus during therapy; if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.

If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.

Manufacturer's labeling: Liver enzyme tests (at baseline and as clinically indicated); lipid panel at four weeks after initiation or dosage titration. Measure CPK when myopathy is being considered; discontinue therapy if markedly elevated CPK levels occur or myopathy is suspected or diagnosed.

Pregnancy Risk Factor

X

Pregnancy Considerations

Studies in pregnant women have shown evidence of fetal abnormalities and use is contraindicated in women who are or may become pregnant. There are reports of congenital anomalies following maternal use of HMG-CoA reductase inhibitors in pregnancy; however, maternal disease, differences in specific agents used, and the low rates of exposure limit the interpretation of the available data (Godfrey 2012; Lecarpentier 2012). Cholesterol biosynthesis may be important in fetal development; serum cholesterol and triglycerides increase normally during pregnancy. The discontinuation of lipid lowering medications temporarily during pregnancy is not expected to have significant impact on the long term outcomes of primary hypercholesterolemia treatment.

HMG-CoA reductase inhibitors should be discontinued prior to pregnancy (ADA 2013). If treatment of dyslipidemias is needed in pregnant women or in women of reproductive age, other agents are preferred (Berglund 2012; Stone 2013). The manufacturer recommends administration to women of childbearing potential only when conception is highly unlikely and patients have been informed of potential hazards.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dyspepsia, diarrhea, insomnia, or flu-like symptoms. Have patient report immediately to prescriber severe headache, edema of extremities, angina, urinary retention, oliguria, dysuria, signs of severe muscle problems, or signs of hepatic impairment (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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