Rosuvastatin
FDA Drug Information • Also known as: Crestor, Ezallor Sprinkle, Rosuvastatin
- Brand Names
- Crestor, Ezallor Sprinkle, Rosuvastatin
- Drug Class
- HMG-CoA Reductase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Rosuvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)-reductase inhibitor. The chemical name for rosuvastatin calcium is bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino] pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt with the following structural formula: The empirical formula for rosuvastatin calcium is (C 22 H 27 FN 3 O 6 S) 2 Ca and the molecular weight is 1,001.14. Rosuvastatin calcium is a white or almost white, hygroscopic powder that is slightly soluble in water, freely soluble in methylene chloride, practically insoluble in ethanol. Rosuvastatin calcium has a partition coefficient (octanol/water) of 2.20 at pH of 7.3. Rosuvastatin for oral use contain rosuvastatin 5 mg, 10 mg, 20 mg or 40 mg (equivalent to 5.2 mg, 10.4 mg, 20.8 mg, and 41.6 mg rosuvastatin calcium) and the following inactive ingredients: anhydrous lactose, lactose monohydrate, anhydrous dibasic calcium phosphate, microcrystalline cellulose (101, 102), crospovidone, magnesium stearate, hypromellose 2910, titanium dioxide, triacetin, D&C yellow #10 aluminium lake, FD&C red #40/allura red AC aluminium lake, FD&C blue #2/ indigo carmine aluminium lake, FD&C yellow #6/ sunset yellow FCF aluminium lake. Image
What Is Rosuvastatin Used For?
1 INDICATIONS AND USAGE Rosuvastatin tablets is indicated: To reduce the risk major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L, and at least one additional CV risk factor. As an adjunct to diet to: Reduce low-density lipoprotein cholesterol (LDL-C) in adults with primary hyperlipidemia. Reduce 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. Rosuvastatin tablets is an HMG Co-A reductase inhibitor (statin) indicated: ( 1 ) To reduce the risk of major adverse cardiovascular (CV) events (CV death, nonfatal myocardial infarction, nonfatal stroke, or an arterial revascularization procedure) in adults without established coronary heart disease who are at increased risk of CV disease based on age, high-sensitivity C-reactive protein (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. to reduce LDL-C and slow the progression of atherosclerosis in adults. to 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.
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Take orally with or without food, at any time of day. ( 2.1 ) Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating rosuvastatin tablets, and adjust dosage if necessary. ( 2.1 ) Adults : Recommended dosage range is 5 to 40 mg once daily. ( 2.1 ) Pediatric Patients with HeFH : Recommended dosage range is 5 to 10 mg once daily for patients aged 8 to less than 10 years of age, and 5 to 20 mg once daily for patients aged 10 years and older. ( 2.2) Pediatric Patients with HoFH : Recommended dosage is 20 mg once daily for patients aged 7 years and older. ( 2.2 ) Asian Patients : Initiate at 5 mg once daily. Consider risks and benefits of treatment if not adequately controlled at doses up to 20 mg once daily. ( 2.4 ) Patients with Severe Renal Impairment (not on hemodialysis) : Initiate at 5 mg once daily; do not exceed 10 mg once daily. ( 2.5 ) See full prescribing information for rosuvastatin tablets dosage and administration modifications due to drug interactions. ( 2.6 ) 2.1 General Dosage and Administration Information Administer rosuvastatin tablets orally as a single dose at any time of day, with or without food. Swallow the tablets 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. 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 ) ]. 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 CV 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 m 2 ) 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...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Myopathy and Rhabdomyolysis [see Warnings and Precautions ( 5.1 )] Immune-Mediated Necrotizing Myopathy [see Warnings and Precautions ( 5.2 )] Hepatic Dysfunction [see Warnings and Precautions ( 5.3 )] Proteinuria and Hematuria [see Warnings and Precautions ( 5.4 )] Increases in HbA1c and Fasting Serum Glucose Levels [see Warnings and Precautions ( 5.5 )] Most frequent adverse reactions (rate ≥2%) are headache, nausea, myalgia, asthenia, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Westminster Pharmaceuticals, LLC at 1-844-221-7294 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse reactions reported in ≥2% of patients in placebo-controlled clinical studies and at a rate greater than placebo are shown in Table 2. These studies had a treatment duration of up to 12 weeks. Table 2: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in Placebo-Controlled Trials Adverse Reactions Placebo N=382 % Rosuvastatin 5 mg N=291 % Rosuvastatin 10 mg N=283 % Rosuvastatin 20 mg N=64 % Rosuvastatin 40 mg N=106 % Total Rosuvastatin 5 mg-40 mg N=744 % Headache 5.0 5.5 4.9 3.1 8.5 5.5 Nausea 3.1 3.8 3.5 6.3 0 3.4 Myalgia 1.3 3.1 2.1 6.3 1.9 2.8 Asthenia 2.6 2.4 3.2 4.7 0.9 2.7 Constipation 2.4 2.1 2.1 4.7 2.8 2.4 Other adverse reactions reported in clinical studies were abdominal pain, dizziness, hypersensitivity (including rash, pruritus, urticaria, and angioedema) and pancreatitis. The following laboratory abnormalities have also been reported: dipstick-positive proteinuria and microscopic hematuria; elevated creatine phosphokinase, transaminases, glucose, glutamyl transpeptidase, alkaline phosphatase, and bilirubin; and thyroid function abnormalities. In the METEOR study, patients were treated with rosuvastatin 40 mg (n=700) or placebo (n=281) with a mean treatment duration of 1.7 years. Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 3. Table 3: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in the METEOR Trial Adverse Reactions Placebo N=281 % Rosuvastatin 40 mg N=700 % Myalgia 12.1 12.7 Arthralgia 7.1 10.1 Headache 5.3 6.4 Dizziness 2.8 4.0 Increased CPK 0.7 2.6 Abdominal pain 1.8 2.4 ALT greater than 3x ULN Frequency recorded as abnormal laboratory value. 0.7 2.2 In the JUPITER study, patients were treated with rosuvastatin 20 mg (n=8,901) or placebo (n=8,901) for a mean duration of 2 years. In JUPITER, there was a significantly higher frequency of diabetes mellitus reported in patients taking rosuvastatin (2.8%) versus patients taking placebo (2.3%). Mean HbA1c was significantly increased by 0.1% in rosuvastatin-treated patients compared to placebo-treated patients. The number of patients with a HbA1c >6.5% at the end of the trial was significantly higher in rosuvastatin-treated versus placebo-treated patients [see Clinical Studies ( 14 )] . Adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 4. Table 4: Adverse Reactions Reported in ≥2% of Patients Treated with Rosuvastatin and > Placebo in the JUPITER Trial Adverse Reactions Placebo N=8,901 % Rosuvastatin 20 mg N=8,901 % Myalgia 6.6 7.6 Arthralgia 3.2 3.8 Constipation 3.0 3.3 Diabetes mellitus 2.3 2.8 Nausea 2.3 2.4 Pediatric Patients with HeFH In a 12‑week controlled study in pediatric patients 10 to 17 years of age with HeFH with rosuvastatin 5 to 20 mg daily [see Use in Specific Populations ( 8.4 ) and Clinical Studies ( 14 )] , elevations in serum CK greater than 10 x...
Drug Interactions
7 DRUG INTERACTIONS See full prescribing information for details regarding concomitant use of rosuvastatin with other drugs that increase the risk of myopathy and rhabdomyolysis. ( 7.1 ) Aluminum and Magnesium Hydroxide Combination Antacids : Administer rosuvastatin at least 2 hours before the antacid. ( 7.2 ) Warfarin : Obtain INR prior to starting rosuvastatin. Monitor INR frequently until stable upon initiation, dose titration or discontinuation. ( 7.3 ) 7.1 Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin Rosuvastatin is a substrate of CYP2C9 and transporters (such as OATP1B1, BCRP). Rosuvastatin plasma levels can be significantly increased with concomitant administration of inhibitors of CYP2C9 and transporters. Table 5 includes a list of drugs that increase the risk of myopathy and rhabdomyolysis when used concomitantly with rosuvastatin and instructions for preventing or managing them [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )] . Table 5: Drug Interactions that Increase the Risk of Myopathy and Rhabdomyolysis with Rosuvastatin Cyclosporine Clinical Impact: Cyclosporine increased rosuvastatin exposure 7-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use of cyclosporine or gemfibrozil with rosuvastatin. Intervention: If used concomitantly, do not exceed a dose of rosuvastatin 5 mg once daily. Teriflunomide Clinical Impact: Teriflunomide increased rosuvastatin exposure more than 2.5-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking teriflunomide, do not exceed a dose of rosuvastatin 10 mg once daily. Enasidenib Clinical Impact: Enasidenib increased rosuvastatin exposure more than 2.4-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking enasidenib, do not exceed a dose of rosuvastatin 10 mg once daily. Capmatinib Clinical Impact: Capmatinib increased rosuvastatin exposure more than 2.1-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking capmatinib, do not exceed a dose of rosuvastatin 10 mg once daily. Fostamatinib Clinical Impact: Fostamatinib increased rosuvastatin exposure more than 2.0-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking fostamatinib, do not exceed a dose of rosuvastatin 20 mg once daily. Febuxostat Clinical Impact: Febuxostat increased rosuvastatin exposure more than 1.9-fold. The risk of myopathy and rhabdomyolysis is increased with concomitant use. Intervention: In patients taking febuxostat, do not exceed a dose of rosuvastatin 20 mg once daily. Gemfibrozil Clinical Impact: Gemfibrozil significantly increased rosuvastatin exposure and gemfibrozil may cause myopathy when given alone. The risk of myopathy and rhabdomyolysis is increased with concomitant use of gemfibrozil with...
Contraindications
4 CONTRAINDICATIONS Rosuvastatin tablets is 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 )] . Acute liver failure or decompensated cirrhosis. ( 4 ) Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Discontinue rosuvastatin when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Rosuvastatin decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, rosuvastatin may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology ( 12.1 )] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. 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 hyperlipidemia for most patients. Available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. Published data from prospective and retrospective observational cohort studies with rosuvastatin use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see Data) . In animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered rosuvastatin during the period of organogenesis at doses that resulted in systemic exposures equivalent to human exposures at the maximum recommended human dose (MRHD) of 40 mg/day, based on AUC and body surface area (mg/m 2 ), respectively (see Data) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data A Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic...
Overdosage
10 OVERDOSAGE No specific antidotes for rosuvastatin are known. Hemodialysis does not significantly enhance clearance of rosuvastatin. In the event of overdose, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Rosuvastatin tablets are supplied as: Strength How Supplied NDC Tablet Description 5 mg bottles of 30, 90, 100, 500 and 1000 tablets 69367-359-30 69367-359-09 69367-359-01 69367-359-05 69367-359-10 Yellow colored, round, biconvex film coated tablets, debossed with "RS" on one side and plain on the other side. 10 mg bottles of 30, 90, 100, 500 and 1000 tablets 69367-360-30 69367-360-09 69367-360-01 69367-360-05 69367-360-10 Pink colored, round, biconvex film coated tablets, debossed with "RS1" on one side and plain on the other side. 20 mg bottles of 30, 90, 100, 500 and 1000 tablets 69367-361-30 69367-361-09 69367-361-01 69367-361-05 69367-361-10 Pink colored, round, biconvex film coated tablets, debossed with "RS2" on one side and plain on the other side. 40 mg bottles of 30, 90, 100 and 500 tablets 69367-362-30 69367-362-09 69367-362-01 69367-362-05 Pink colored, oval, biconvex film coated tablets, debossed with "RS3" on one side and plain on the other side. Storage Store at controlled room temperature, 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from moisture.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.