Rosuvastatin Calcium

ROSUVASTATIN CALCIUM — rosuvastatin calcium tablet, film coated
A-S Medication Solutions

1 INDICATIONS AND USAGE

Rosuvastatin tablets are indicated:

• To reduce the risk of stroke, myocardial infarction, and arterial revascularization procedures in adults without established coronary heart disease who are at increased risk of cardiovascular (CV) disease based on age, hsCRP ≥2 mg/L, and at least one additional CV risk factor.
• As an adjunct to diet to:
  • Reduce LDL-C in adults with primary hyperlipidemia.
  • Reduce low-density lipoprotein cholesterol (LDL-C) and slow the progression of atherosclerosis in adults.
  • Reduce LDL-C in adults and pediatric patients aged 8 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 7 years and older with homozygous familial hypercholesterolemia (HoFH).
• As an adjunct to diet for the treatment of adults with:
  • Primary dysbetalipoproteinemia.
  • Hypertriglyceridemia.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosage and Administration Information

• Administer rosuvastatin tablets orally as a single dose at any time of day, with or without food. The tablet should be swallowed whole.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating rosuvastatin tablets, and adjust the dosage if necessary.
• If a dose is missed, advise patients not take an extra dose. Resume treatment with the next dose.

2.2 Recommended Dosage in Adult Patients

• The dosage range for rosuvastatin tablets is 5 to 40 mg orally once daily.
• The recommended dose of rosuvastatin tablets depends on a patient’s indication for usage, LDL-C, and individual risk for cardiovascular events.

2.3 Recommended Dosage in Pediatric Patients

Dosage in Pediatric Patients 8 Years of Age and Older with HeFH

The recommended dosage range is 5 mg to 10 mg orally once daily in patients aged 8 years to less than 10 years and 5 mg to 20 mg orally once daily in patients aged 10 years and older.

Dosage in Pediatric Patients 7 Years of Age and Older with HoFH
The recommended dosage is 20 mg orally once daily.

2.4 Dosing in Asian Patients

Initiate rosuvastatin tablets at 5 mg once daily due to increased rosuvastatin plasma concentrations. Consider the risks and benefits of rosuvastatin tablets when treating Asian patients not adequately controlled at doses up to 20 mg once daily [see Warnings and Precautions (5.1), Use in Specific Populations (8.8), and Clinical Pharmacology (12.3)].

2.5 Recommended Dosage in Patients with Renal Impairment

In patients with severe renal impairment (CL_cr less than 30 mL/min/1.73 m²) not on hemodialysis, the recommended starting dosage is 5 mg once daily and should not exceed 10 mg once daily [see Warnings and Precautions (5.1) and Use in Specific Populations (8.6)].

There are no dosage adjustment recommendations for patients with mild and moderate renal impairment.

2.6 Dosage and Administration Modifications Due to Drug Interactions

Rosuvastatin Tablets Dosage Modifications Due to Drug Interactions

Table 1 displays dosage modifications for rosuvastatin tablets due to drug interactions [see Warnings and Precautions (5.1) and Drug Interactions (7.1)].

Table 1: Rosuvastatin Tablets Dosage Modifications Due to Drug Interactions

Concomitantly Used Drug	Rosuvastatin Tablets Dosage Modifications
Cyclosporine	Do not exceed 5 mg once daily.
Teriflunomide	Do not exceed 10 mg once daily.
Capmatinib	Do not exceed 10 mg once daily.
Fostamatinib	Do not exceed 20 mg once daily.
Febuxostat	Do not exceed 20 mg once daily.
Gemfibrozil	Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily.
Tafamidis	Avoid concomitant use. If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily.
Antiviral Medications
Sofbuvir/velpatasvir/voxilaprevir Ledipasvir/sofosbuvir	Concomitant use not recommended.
Simeprevir Dasabuvir/ombitasvir/paritaprevir/ritonavir Elbasvir/Grazoprevir Sofosbuvir/Velpatasvir Glecaprevir/Pibrentasvir Atazanavir/Ritonavir Lopinavir/Ritonavir	Initiate at 5 mg once daily. Do not exceed 10 mg once daily.
Darolutamide	Do not exceed 5 mg once daily.
Regorafenib	Do not exceed 10 mg once daily.

Rosuvastatin Tablets Administration Modifications Due to Drug Interactions

When taking rosuvastatin tablets with an aluminum and magnesium hydroxide combination antacid, administer rosuvastatin tablets at least 2 hours before the antacid [ see Drug Interactions (7.2)].

3 DOSAGE FORMS AND STRENGTHS

Rosuvastatin tablets, USP:
5 mg of rosuvastatin: Pink, oval shaped, biconvex film-coated tablets debossed with ‘I’ on one side and ‘29’ on the other side.
10 mg of rosuvastatin: Pink, round, biconvex film-coated tablets debossed with ‘I’ on one side and ‘30’ on the other side.
20 mg of rosuvastatin: Pink, round, biconvex film-coated tablets debossed with ‘I’ on one side and ‘31’ on the other side.40 mg of rosuvastatin: Pink, oval shaped, biconvex film-coated tablets debossed with ‘I’ on one side and ‘32’ on the other side.

4 CONTRAINDICATIONS

Rosuvastatin tablets are contraindicated in the following conditions:

• Acute liver failure ​or decompensated cirrhosis [see Warnings and Precautions (5.3)].
• Hypersensitivity to rosuvastatin ​or any excipients in rosuvastatin tablets. Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin [see Adverse Reactions (6.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Myopathy and Rhabdomyolysis

Rosuvastatin may cause myopathy [muscle pain, tenderness, or weakness associated with elevated creatine kinase (CK)] and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis with statins, including rosuvastatin.

Risk Factors for Myopathy

Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher rosuvastatin dosage. Asian patients on rosuvastatin may be at higher risk for myopathy [ see Drug Interactions (7.1) and Use in Specific Populations (8.8)]. The myopathy risk is greater in patients taking rosuvastatin 40 mg daily compared with lower rosuvastatin dosages.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis

The concomitant use of rosuvastatin with cyclosporine or gemfibrozil is not recommended. rosuvastatin dosage modifications are recommended for patients taking certain antiviral medications, darolutamide, and regorafenib [ see Dosage and Administration (2.6)]. Niacin, fibrates, and colchicine may also increase the risk of myopathy and rhabdomyolysis [see Drug Interactions (7.1)].

Discontinue rosuvastatin if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if rosuvastatin is discontinued. Temporarily discontinue rosuvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the rosuvastatin dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.