Usual Adult Dose for Hyperlipidemia

Initial dose: 10 mg to 20 mg orally once a day

• Lipid levels should be analyzed within 2 to 4 weeks of initiation or titration and the dosage adjusted accordingly

Maintenance dose: 5 mg to 40 mg orally once a day
Maximum dose: 40 mg (reserved for those who have not achieved their LDL-C goal with a 20 mg dose)

Comments:

• This drug is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, ApoB, nonHDL-C, triglycerides; and increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.
• This drug should be used in conjunction with a diet restricted in saturated fat and cholesterol.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Uses: For the treatment of hyperlipidemia and mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, and to slow the progression of atherosclerosis.

Usual Adult Dose for Hyperlipoproteinemia Type III (Elevated beta-VLDL + IDL)

Initial dose: 10 mg to 20 mg orally once a day

• Lipid levels should be analyzed within 2 to 4 weeks of initiation or titration and the dosage adjusted accordingly

Maintenance dose: 5 mg to 40 mg orally once a day
Maximum dose: 40 mg (reserved for those who have not achieved their LDL-C goal with a 20 mg dose)

Comments:

• This drug is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, ApoB, nonHDL-C, triglycerides; and increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.
• This drug should be used in conjunction with a diet restricted in saturated fat and cholesterol.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Uses: For the treatment of hyperlipidemia and mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, and to slow the progression of atherosclerosis.

Usual Adult Dose for Hypertriglyceridemia

Initial dose: 10 mg to 20 mg orally once a day

• Lipid levels should be analyzed within 2 to 4 weeks of initiation or titration and the dosage adjusted accordingly

Maintenance dose: 5 mg to 40 mg orally once a day
Maximum dose: 40 mg (reserved for those who have not achieved their LDL-C goal with a 20 mg dose)

Comments:

• This drug is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, ApoB, nonHDL-C, triglycerides; and increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.
• This drug should be used in conjunction with a diet restricted in saturated fat and cholesterol.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Uses: For the treatment of hyperlipidemia and mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, and to slow the progression of atherosclerosis.

Usual Adult Dose for Atherosclerosis

Initial dose: 10 mg to 20 mg orally once a day

• Lipid levels should be analyzed within 2 to 4 weeks of initiation or titration and the dosage adjusted accordingly

Maintenance dose: 5 mg to 40 mg orally once a day
Maximum dose: 40 mg (reserved for those who have not achieved their LDL-C goal with a 20 mg dose)

Comments:

• This drug is indicated as an adjunctive therapy to diet to reduce elevated total cholesterol, LDL-C, ApoB, nonHDL-C, triglycerides; and increase HDL-C in patients with primary hyperlipidemia or mixed dyslipidemia.
• This drug should be used in conjunction with a diet restricted in saturated fat and cholesterol.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Uses: For the treatment of hyperlipidemia and mixed dyslipidemia, hypertriglyceridemia, primary dysbetalipoproteinemia, and to slow the progression of atherosclerosis.

Usual Adult Dose for Homozygous Familial Hypercholesterolemia

Initial dose: 20 mg orally once a day
Maintenance dose: 5 mg to 40 mg orally once a day

Comments:

• Response to therapy should be estimated from preapheresis LDL-C levels.
• This drug may be used as an adjunctive therapy to other lipid-lowering treatments (e.g., LDL apheresis) or alone if such treatments are unavailable to reduce LDL-C, Total-C, and ApoB in adult patients with homozygous familial hypercholesterolemia.

Use: For patients with homozygous familial hypercholesterolemia.

Usual Adult Dose for Prevention of Cardiovascular Disease

Initial dose: 10 mg to 20 mg orally once a day

• Lipid levels should be analyzed within 2 to 4 weeks of initiation or titration and the dosage adjusted accordingly.

Maintenance dose: 5 mg to 40 mg orally once a day
Maximum dose: 40 mg (reserved for those who have not achieved their LDL-C goal with a 20 mg dose)

Comments:

• This drug is for the primary prevention of cardiovascular disease (CVD) in individuals without clinically evident coronary heart disease who are at an increased risk of CVD due to age (men, 50 years or older; women, 60 years or older), an elevated high-sensitivity C-reactive protein (hsCRP 2 mg/L or greater), and the presence of at least 1 additional CVD risk factor such as hypertension, low HDL-C, smoking, or family history of premature coronary heart disease.
• In these patients, this drug is intended to reduce the risk of: stroke, myocardial infarction, and arterial revascularization procedures.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Use: For the primary prevention of CVD.

Usual Pediatric Dose for Heterozygous Familial Hypercholesterolemia

8 to less than 10 years: 5 mg to 10 mg orally once a day

• Safety and efficacy of doses greater than 10 mg/day have not been studied

10 to 17 years: 5 mg to 20 mg orally once a day

• Safety and efficacy of doses greater than 20 mg/day have not been studied

Comments:

• Dose adjustments should be made at intervals of 4 weeks or more.
• Doses should be based on recommended goal of therapy for each individual patient.
• This drug is intended as an adjunct to diet to reduce Total-C, LDL-C, and ApoB levels in pediatric patients with heterozygous familial hypercholesterolemia whose LDL-C is greater than 190 mg/dL or greater than 160 mg/dL with a positive family history of premature cardiovascular disease (CVD) or 2 or more other CVD risk factors after an adequate trial of diet therapy.

Use: For the treatment of heterozygous familial hypercholesterolemia.

Usual Pediatric Dose for Homozygous Familial Hypercholesterolemia

7 years or older: 20 mg orally once a day

Comments:

• Dose adjustments should be made at intervals of 4 weeks or more.
• Doses should be based on recommended goal of therapy for each individual patient.
• This drug is intended to reduce LDL-C, Total-C, nonHDL-C and ApoB in pediatric patients 7 years or older with homozygous familial hypercholesterolemia, either alone or with other lipid lowering treatments (e.g., LDL apheresis).

Use: For the treatment of homozygous familial hypercholesterolemia.

Renal Dose Adjustments

Severe renal dysfunction (CrCl less than 30 mL/min and not on hemodialysis):

• Initial dose: 5 mg orally once a day
• Maximum dose: 10 mg orally once a day

Liver Dose Adjustments

Active liver disease or persistent elevations of hepatic transaminase levels: Contraindicated

Use caution in patients who consume substantial quantities of alcohol and/or have a history of chronic liver disease

Dose Adjustments

Asian Patients:

• Initial dose: Consider an initial dose of 5 mg orally once a day
• Maintenance dose: Increased systemic exposure should be taken into consideration when treating Asian patients not adequately controlled at doses up to 20 mg/day

Concomitant therapy with cyclosporine and darolutamide:

• Maximum dose: 5 mg orally once a day

Concomitant therapy with gemfibrozil: Avoid concomitant use, if use cannot be avoided:

• Initial dose: 5 mg orally once a day
• Maximum dose: 10 mg orally once a day

Concomitant therapy with regorafenib:

• Maximum dose: 10 mg orally once a day

Concomitant therapy with atazanavir and ritonavir, lopinavir and ritonavir, simeprevir or combination of dasabuvir/ombitasvir/paritaprevir/ritonavir, elbasvir/grazoprevir, sofosbuvir/velpatasvir and glecaprevir/pibrentasvir:

• Initial dose: 5 mg orally once a day
• Maximum dose: 10 mg orally once a day

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients; hypersensitivity reactions have included rash, pruritus, urticaria, and angioedema
• Active liver disease, which may include unexplained persistent elevations of hepatic transaminase levels
• Pregnancy
• Lactation

Safety and efficacy have been not established in patients younger than 7 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available; hemodialysis does not significantly enhance clearance of this drug

Other Comments

Administration advice:

• Take orally once a day, at any time; preferably at the same time every day
• Swallow whole with or without food
• Do not take 2 doses within 12 hours of each other
• If an antacid containing the combination of aluminum and magnesium is needed, take antacid at least 2 hours after taking this drug

Storage requirements:

• Protect from moisture

General:

• This drug should be used in addition to a diet restricted in saturated fat and cholesterol.
• When switching from another HMG-CoA reductase inhibitor, patients should start with the initial recommended dose and titrate according to response and individual goals of therapy.
• The 40 mg dose should be reserved for patients who have not achieved their LDL-C goal utilizing the 20 mg dose.
• This drug has not been studied in Fredrickson Type I and V dyslipidemias.

Monitoring:

• Lipid levels: Analyze within 2 to 4 weeks of initiation or dose titration; adjust dose accordingly
• Hepatic: Measure liver enzymes prior to initiation and if signs/symptoms of liver injury occur

Patient advice:

• Patients should be instructed to read the US FDA-approved patient labeling (Patient Information).
• Patients should be instructed to immediately report any unexplained muscle pain, tenderness, or weakness, especially if accompanied by malaise or fever; patients should understand the risks of consuming excess alcohol.
• Patients should be instructed to report any signs/symptoms indicative of liver injury (e.g., fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice).
• Patients should be instructed to tell healthcare provider about all prescription, over-the-counter medicines, vitamins, and herbal supplements they are taking or plan to start.
• Females of childbearing potential should use effective contraception during treatment.