SUPERSTAT PLUS

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, 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.

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.

LDL-C and slow the progression of atherosclerosis in adults.

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.

Rosuvastatin tablets is an HMG

Co-A reductase inhibitor (statin) indicated: 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).

History of hepatopathies History of myopathy

History of acquired myopathy due to statin or fibrate Family history of myopathy Significant alcohol consumption KPC > 5 times the normal upper limit Child under 6 years of age Uncontrolled epilepsy Hypotension Hypothyroidism Severe acute infection Renal impairment: creatinine clearance < 60 ml/min Major surgery Myasthenia Endocrine pathology Patient at risk for diabetes High dose treated patient Genetic polymorphism Subject at risk of rhabdomyolysis Asian subject Subject over 70 years Subject with intense sporting activity Nephrotic syndrome Extended treatment Trauma Hydroelectrolytic disorder Metabolic disorder.

Mechanism of Action Rosuvastatin is an inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3‑hydroxy‑3‑methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. 12.2 Pharmacodynamics Inhibition of HMG-CoA reductase by rosuvastatin accelerates the expression of LDL-receptors, followed by the uptake of LDL-C from blood to the liver, leading to a decrease in plasma LDL-C and total cholesterol.

Sustained inhibition of cholesterol synthesis in the liver also decreases levels of very-low-density lipoproteins.

The maximum

LDL-C reduction of rosuvastatin is usually achieved by 4 weeks and is maintained after that. 12.3 Pharmacokinetics Absorption In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached to 5 hours following oral dosing.

Both C max and

AUC increased in approximate proportion to rosuvastatin dose.

The absolute bioavailability of rosuvastatin is approximately 20%.

AUC of rosuvastatin does not differ following evening or morning drug administration.

Effect of food

Administration of rosuvastatin with food did not affect the AUC of rosuvastatin.

Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters.

Rosuvastatin is 88% bound to plasma proteins, mostly albumin.

This binding is reversible and independent of plasma concentrations.

Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite.

The major metabolite is

N-desmethyl rosuvastatin, which is formed principally by cytochrome P450.

\ 2C9, and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG‑CoA reductase inhibitory activity of the parent compound.

Overall, greater than 90% of active plasma HMG‑CoA reductase inhibitory activity is accounted for by the parent compound.

Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%).

After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route.

The elimination half-life of rosuvastatin is approximately 19 hours.

There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥65 years).

In a population pharmacokinetic analysis of two pediatric trials involving patients with HeFH to 17 years of age and to 17 years of age, respectively, rosuvastatin exposure appeared comparable to or lower than rosuvastatin exposure in adult patients.

There were no differences in plasma concentrations of rosuvastatin between males and females.

A population pharmacokinetic analysis revealed no clinically relevant differences in pharmacokinetics among White, Hispanic or Latino ethnicity, and Black or Afro-Caribbean groups.

However, pharmacokinetic studies, including one conducted in the US, have demonstrated an approximate 2‑fold elevation in median exposure (AUC and C max ) in Asian subjects when compared with a White control group.

Mild to moderate renal impairment (CL cr ≥30 mL/min/1.73 m 2 ) had no influence on plasma concentrations of rosuvastatin.

However, plasma concentrations of rosuvastatin increased to a clinically significant extent (about 3‑fold) in patients with severe renal impairment (CL cr <30 mL/min/1.73 m 2 ) not receiving hemodialysis compared with healthy subjects (CL cr >80 mL/min/1.73 m 2 ).

Steady-state plasma concentrations of rosuvastatin in patients on chronic hemodialysis were approximately 50% greater compared with healthy volunteer subjects with normal renal function.

In patients with chronic alcohol liver disease, plasma concentrations of rosuvastatin were modestly increased.

In patients with

Child‑Pugh A disease, C max and AUC were increased by 60% and 5%, respectively, as compared with patients with normal liver function.

Child‑Pugh B disease, C max and AUC were increased 100% and 21%, respectively, compared with patients with normal liver function.

Rosuvastatin clearance is not dependent on metabolism by cytochrome P450 3A4 to a clinically significant extent.

Rosuvastatin is a substrate for certain transporter proteins including the hepatic uptake transporter organic anion-transporting polyprotein 1B1 (OATP1B1) and efflux transporter breast cancer resistance protein (BCRP).

Concomitant administration of rosuvastatin with medications that are inhibitors of these transporter proteins (e.g. cyclosporine, certain HIV protease inhibitors and ticagrelor ) may result in increased rosuvastatin plasma concentrations.

Table 8: Effect of Coadministered Drugs on Rosuvastatin Systemic Exposure Coadministered drug and dosing regimen Rosuvastatin Mean Ratio (ratio with/without coadministered drug) No Effect=1.0 Dose (mg) Single dose unless otherwise noted.

Change in AUC Change in C max Sofosbuvir/velpatasvir/voxilaprevir (400 mg -100 mg-100 mg) + Voxilaprevir (100 mg) once daily for 15 days 10 mg, single dose 7.39 Clinically significant Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7 = 30% decrease, 11=11‑fold increase in exposure) 18.88 Cyclosporine.

• stable dose required (75 mg - 200 mg BID) 10 mg, QD for 10 days 7.1 11 Darolutamide 600 mg BID, 5 days 5 mg, single dose 5.2 ~5 Regorafenib 160 mg QD, 14 days 5 mg, single dose 3.8 4.6 Atazanavir/ritonavir combination 300 mg/100 mg QD for 8 days 10 mg 3.1 7 Simeprevir 150 mg QD, 7 days 10 mg, single dose 2.8 3.2 Velpatasvir 100 mg once daily 10 mg, single dose 2.69 2.61 Ombitasvir 25 mg/paritaprevir 150 mg/ ritonavir 100 mg + dasabuvir 400 mg BID 5 mg, single dose 2.59 7.13 Teriflunomide Not available 2.51 2 2.65 Enasidenib 100 mg QD, 28 days 10 mg, single dose 2.44 3.66 Elbasvir 50 mg/grazoprevir 200 mg once daily 10 mg, single dose 2.26 5.49 Glecaprevir 400 mg/pibrentasvir 120 mg once daily 5 mg, once daily 2.15 5.62 Lopinavir/ritonavir combination 400 mg/100 mg BID for 17 days 20 mg, QD for 7 days 2.1 5 Capmatinib 400 mg BID 10 mg, single dose 2.08 3.04 Fostamatinib 100 mg BID 20 mg, single dose 1.96 1.88 Febuxostat 120 mg QD for 4 days 10 mg, single dose 1.9 2.1 Gemfibrozil 600 mg BID for 7 days 80 mg 1.9 2.2 Tafamidis 61 mg BID on Days 1 & 2, followed by QD on Days to 9 10 mg 1.97 1.86 Eltrombopag 75 mg QD, 5 days 10 mg 1.6 2 Darunavir 600 mg/ritonavir 100 mg BID, 7 days 10 mg, QD for 7 days 1.5 2.4 Tipranavir/ritonavir combination 500 mg/200 mg BID for 11 days 10 mg 1.4 2.2 Dronedarone 400 mg BID 10 mg 1.4 Itraconazole 200 mg QD, 5 days 10 mg or 80 mg 1.4 1.3 1.4 1.2 Ezetimibe 10 mg QD, 14 days 10 mg, QD for 14 days 1.2 1.2 Fosamprenavir/ritonavir 700 mg/100 mg BID for 7 days 10 mg 1.1 1.5 Fenofibrate 67 mg TID for 7 days 10 mg ↔ 1.2 Rifampicin 450 mg QD, 7 days 20 mg ↔ Aluminum & magnesium hydroxide combination antacidAdministered simultaneously.

Administered 2 hours apart 40 mg. 40 mg 0.5 0.8 0.5 0.8 Ketoconazole 200 mg BID for 7 days 80 mg 1.0 1.0 Fluconazole 200 mg QD for 11 days 80 mg 1.1 1.1 Erythromycin 500 mg QID for 7 days 80 mg 0.8 0.7 QD= Once daily, BID= Twice daily, TID= Three times daily, QID= Four times daily Table 9: Effect of Rosuvastatin Coadministration on Systemic Exposure to Other Drugs Rosuvastatin Dosage Regimen Coadministered Drug Mean Ratio (ratio with/without coadministered drug) No Effect=1.0 Name and Dose Change in AUC Change in C max 40 mg QD for 10 days Warfarin Clinically significant pharmacodynamic effects 25 mg single dose R.

• Warfarin 1.0 Mean ratio with 90% CI (with/without coadministered drug, e.g., 1= no change, 0.7=30% decrease, 11=11-fold increase in exposure) S-Warfarin 1.1 R-Warfarin 1.0 S-Warfarin 1.0 40 mg QD for 12 days Digoxin 0.5 mg single dose 1.0 1.0 40 mg QD for 28 days Oral Contraceptive (ethinyl estradiol 0.035 mg & norgestrel 0.180, 0.215 and 0.250 mg) QD for 21 Days EE 1.3 NG 1.3 EE 1.3 NG 1.2 EE = ethinyl estradiol, NG = norgestrel, QD= Once daily 12.5 Pharmacogenomics Disposition of rosuvastatin, involves OATP1B1 and other transporter proteins.

Higher plasma concentrations of rosuvastatin have been reported in very small groups of patients (n=3 to 5) who have two reduced function alleles of the gene that encodes OATP1B1 ( SLCO1B1 521T > C).

The frequency of this genotype (i.e., SLCO1B1 521 C/C) is generally lower than 5% in most racial/ethnic groups.

The impact of this polymorphism on efficacy and/or safety of rosuvastatin has not been clearly established.

Mechanism of action

Rosuvastatin is a selective and competitive inhibitor of HMG Co-A reductase, an enzyme responsible for controlling the transformation of 3-hydroxy-3-methylglutaryl coenzyme A into mevalonate, a precursor of cholesterol.

The main site of action for rosuvastatin is the liver, the target organ for cholesterol lowering.

Rosuvastatin increases the number of

LDL receptors ( Low-Density Lipoprotein) on the hepatocyte surface, increasing the uptake of LDL cholesterol, and strengthening its catabolism and inhibiting hepatic synthesis of VLDL (Very Low-Density Lipoprotein), thereby reducing the number of VLDL and LDL particles.

• Transaminases (increase) (Rare)
• Proteinuria KPC (increase)
• Urticaria (Uncommon)
• Rash (Uncommon)
• Pruritus (Uncommon)
• Stevens-Johnson Syndrome Asthenia (Common)
• Edema Sexual disorder
• Gynecomastia (Very rare)
• Thrombocytopenia (Rare)
• Hepatitis (Very rare)
• Ictery (Very rare)
• Acute hepatitis Hypersensitivity (Rare)
• Lupic syndrome (Rare)
• Angioedema DRESS syndrome
• Non-insulin-dependent diabetes (Common)
• Feeling dizzy (Common)
• Depression Nightmare
• Sleep disorder Insomnia Abdominal pain (Common)
• Nausea (Common)
• Constipation (Common)
• Pancreatitis (Rare)
• Diarrhoea Muscle pain (Common)
• Myopathy (Rare)
• Muscle loss (Rare)
• Rhabdomyolysis (Rare)
• Joint pain (Very rare)
• Tendinopathy Strand cut Immune-mediated necrotic myopathy
• Myositis Headache (Common)
• Memory loss (Very rare)
• Polyneuropathy (Very rare)
• Myasthenia
• Myasthenia eye Peripheral neuropathy Interstitial pneumopathy (Exceptional)
• Cough
• Dyspnoea Haematuria (Very rare)
• Renal disorder Acute renal impairment.

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 or a medical toxicologist for additional overdosage management recommendations.

Rosuvastatin tablets is contraindicated in the following conditions: Acute liver failure or decompensated cirrhosis.

Hypersensitivity to rosuvastatin or any excipients in rosuvastatin tablets.

Hypersensitivity reactions including rash, pruritus, urticaria, and angioedema have been reported with rosuvastatin.

Acute liver failure or decompensated cirrhosis.

Take orally with or without food, at any time of day. Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating rosuvastatin tablets, and adjust dosage if necessary.

Recommended dosage range is to 40 mg once daily.

Recommended dosage range is to 10 mg once daily for patients aged to less than 10 years of age, and to 20 mg once daily for patients aged 10 years and older.

Recommended dosage is 20 mg once daily for patients aged 7 years and older.

Initiate at 5 mg once daily.

Consider risks and benefits of treatment if not adequately controlled at doses up to 20 mg once daily.

Impairment (not on hemodialysis) : Initiate at 5 mg once daily; do not exceed 10 mg once daily.

See full prescribing information for rosuvastatin tablets dosage and administration modifications due to drug interactions. 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.

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. 2.2 Recommended Dosage in Adult Patients The dosage range for rosuvastatin tablets is 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.

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. 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.

There are no dosage adjustment recommendations for patients with mild and moderate renal impairment. 2.6 Dosage 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.

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.

Do not exceed 10 mg once daily.

Do not exceed 20 mg once daily.

Avoid concomitant use.

If used concomitantly, initiate at 5 mg once daily and do not exceed 10 mg once daily.

If used concomitantly, initiate at 5 mg once daily and do not exceed 20 mg once daily.

Sofbuvir/velpatasvir/voxilaprevir Ledipasvir/sofosbuvir Concomitant use not recommended. o Simeprevir o Dasabuvir/ombitasvir/paritaprevir/ritonavir o Elbasvir/Grazoprevir o Sofosbuvir/Velpatasvir o Glecaprevir/Pibrentasvir o Atazanavir/Ritonavir o Lopinavir/Ritonavir Initiate at 5 mg once daily.

Do not exceed 5 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.

Rosuvastatin tablets are supplied as

Strength How Supplied NDC Tablet Description 5 mg bottles of 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 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 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 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.

Store at controlled room temperature, 20ºC to 25ºC (68ºF to 77ºF); excursions permitted between 15°C and 30°C (59°F and 86°F) .

Protect from moisture.

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.

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.

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.

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 to 4% and to 20%, respectively.

Medicaid cohort linkage study of 1,152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders.

• including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use.

• using propensity score‑based methods.

The relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus.

There were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders.

In the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified.

Study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births.

In female rats given and 50 mg/kg/day before mating and continuing through to gestation day 7 resulted in decreased fetal body weight (female pups) and delayed ossification at 50 mg/kg/day (10 times the human exposure at the MRHD dose of 40 mg/day based on AUC).

In pregnant rats given and 50 mg/kg/day of rosuvastatin from gestation day 7 through lactation day 21 (weaning), decreased pup survival occurred at 50 mg/kg/day (dose equivalent to 12 times the MRHD of 40 mg/day based body surface area).

In pregnant rabbits given 0.3, 1, and 3 mg/kg/day of rosuvastatin from gestation day to day 18, decreased fetal viability and maternal mortality was observed at 3 mg/kg/day (dose equivalent to the MRHD of 40 mg/day based on body surface area).

Rosuvastatin crosses the placenta in rats and rabbits and is found in fetal tissue and amniotic fluid at 3% and 20%, respectively, of the maternal plasma concentration following a single 25 mg/kg oral gavage dose on gestation day in rats.

In rabbits, fetal tissue distribution was 25% of maternal plasma concentration after a single oral gavage dose of 1 mg/kg on gestation day 18.

The safety and effectiveness of rosuvastatin as an adjunct to diet to reduce LDL-C have been established in pediatric patients 8 years of age and older with HeFH.

Use of rosuvastatin for this indication is based on one 12-week controlled trial with a 40-week open-label extension period in 176 pediatric patients 10 years of age and older with HeFH and one 2-year open-label, uncontrolled trial in 175 pediatric patients 8 years of age and older with HeFH.

In the 1-year trial with a 12-week controlled phase, there was no detectable effect of rosuvastatin on growth, weight, BMI (body mass index), or sexual maturation in patients aged to 17 years.

The safety and effectiveness of rosuvastatin as an adjunct to other LDL-C-lowering therapies to reduce LDL-C have been established pediatric patients 7 years of age and older with HoFH.

Use of rosuvastatin for this indication is based on a randomized, placebo-controlled, cross-over study in 14 pediatric patients 7 years of age and older with HoFH.

The safety and effectiveness of rosuvastatin have not been established in pediatric patients younger than 8 years of age with HeFH, younger than 7 years of age with HoFH, or in pediatric patients with other types of hyperlipidemia (other than HeFH or HoFH).

Of the 10,275 patients in clinical studies with rosuvastatin, 3,159 (31%) were 65 years and older, and 698 (6.8%) were 75 years and older.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Advanced age (≥65 years) is a risk factor for rosuvastatin-associated myopathy and rhabdomyolysis.

Dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy.

Monitor geriatric patients receiving rosuvastatin for the increased risk of myopathy.