Medication Side Effects .info Disclaimer

Crestor

Crestor, aka, Rosuvastatin, is a member of the statin drugs which are used to lower cholesterol. Another member of the statin drug family is Baycol. Baycol was recalled from the market in August, 2001 due to serious, possibly life threatening side effects. Many experts believe that the problems associated with Baycol is a "class" problem that affects all statin drugs. After the FDA issued Crestor Black Box Warnings many experts called for a Crestor recall due to the serious side effects of Crestor. Many lawyers are initiating Crestor lawsuits due to injuries received by crestor users. Crestor side effects include:

• Nausea
• Diarrhea
• Constipation
• Muscle Aching

In addition to the side effects listed above there are two serious side effects such as rhabdomyolysis (which may be fatal) associated with statin medications:

• Rhabdomyolysis. Rhabdomyolysis is the breakdown of muscle fibers resulting in the release of muscle fiber contents into the circulation. Some of these are toxic to the kidney and frequently result in kidney damage. Crestor, Lipitor, Zocor, Mevacor, Pravachol, and Lescol are believed to increase the risk of rhabdomyolysis.
  

• Elevated liver enzymes. Occasionally, statin use causes an increase in liver enzymes. If the increase is only mild, you can continue to take the drug. If the increase is severe, you may need to stop taking it, which usually reverses the problem. Certain other cholesterol-lowering drugs, such as gemfibrozil (Lopid) and niacin, increase the risk of liver problems in people who take statins. Because liver problems may develop without symptoms, people who take statins should have their liver function tested periodically.
  
  
• Statin myopathy. Statins may cause muscle pain and tenderness (statin myopathy). In severe cases, muscle cells can break down (rhabdomyolysis) and release a protein called myoglobin into the bloodstream. Myoglobin can impair kidney function and lead to kidney failure. Certain drugs when taken with statins can increase the risk of rhabdomyolysis. These include gemfibrozil, erythromycin (Erythrocin), anti fungal medications, nefazodone (Serzone), cyclosporine and niacin. If you take statins and have new muscle aching or tenderness, consult with your doctor.

The cholesterol drug Crestor is being relabeled to add a Black Box Warning that starter doses should be reduced in Asian-Americans and some other patients. A clinical trial found that levels of Crestor in Asian patients were double those of Caucasians taking the same dose, increasing the chance of muscle damage.

The new label urges physicians to start Asian patients, those with severe kidney disease and patients taking cyclosporine at the lowest dose level.

Crestor (generic name: rosuvastatin calcium) has been linked to kidney damage and kidney failure. On October 22, 2004, the consumer group Public Citizen said twenty-nine patients who took AstraZeneca's cholesterol drug Crestor have developed kidney damage. Crestor has also been linked to the potentially fatal disease Rhabdomyolysis.

The rate of reported kidney problems is about 75 times higher with Crestor than with all other drugs in the same class combined, consumer group Public Citizen said. According to its analysis, there have been 6.4 reports of acute kidney failure or kidney damage for every 1 million Crestor prescriptions filled.

Crestor has been linked to numerous cases of rhabdomyolysis, a rare muscle destroying disease. Another statin cholesterol drug Baycol was removed from the market.


Crestor Side Effects were Evident Before it was Approved

Crestor was approved by the Food and Drug Administration approval in August 2003, after a delay because of safety concerns. During FDA studies seven cases of the potentially fatal, muscle-destroying condition rhabdomyolysis occurred.

These studies also linked Crestor with cases of kidney abnormalities not seen with other statins. The FDA decided to approve Crestor but at lower dosages. However, records from the FDA and health agencies in Canada and Britain show life-threatening side effects occur even at those lower doses.

Study Finds More Side Effects From Crestor Than Other Statins

The widely used cholesterol-lowering drug Crestor has at least twice the incidence of side effects as other drugs in the statin family. On May 23, 2004 a new study detailed these findings.

The study was based on adverse reactions to statins reported to the Food and Drug Administration by patients and physicians at Tufts-New England Medical Center in Boston.

Most of those reports involved muscle damage, called rhabdomyolysis, and poor functioning of the kidneys.

Crestor prescribing information provided by AstraZeneca:

DESCRIPTION
CRESTOR® (rosuvastatin calcium) is a synthetic lipid-lowering
agent. Rosuvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-
coenzyme A (HMG-CoA) reductase. This enzyme catalyzes
the conversion of HMG-CoA to mevalonate, an early and
rate-limiting step in cholesterol biosynthesis.
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. The empirical formula
for rosuvastatin calcium is (C22H27FN3O6S)2Ca. Its molecular
weight is 1001.14. Its structural formula is:
Rosuvastatin calcium is a white amorphous powder that is
sparingly soluble in water and methanol, and slightly soluble in
ethanol. Rosuvastatin is a hydrophilic compound with a partition
coefficient (octanol/water) of 0.13 at pH of 7.0.
CRESTOR Tablets for oral administration contain 5, 10, 20, or
40 mg of rosuvastatin and the following inactive ingredients:
microcrystalline cellulose NF, lactose monohydrate NF, tribasic
calcium phosphate NF, crospovidone NF, magnesium stearate NF,
hypromellose NF, triacetin NF, titanium dioxide USP, yellow ferric
oxide, and red ferric oxide NF.
CLINICAL PHARMACOLOGY
General: In the bloodstream, cholesterol and triglycerides (TG)
circulate as part of lipoprotein complexes. With ultracentrifugation,
these complexes separate into very-low-density lipoprotein
(VLDL), intermediate-density lipoprotein (IDL), and low-density
lipoprotein (LDL) fractions that contain apolipoprotein B-100
(ApoB-100) and high-density lipoprotein (HDL) fractions.
Cholesterol and TG synthesized in the liver are incorporated into
VLDL and secreted into the circulation for delivery to peripheral
tissues. TG are removed by the action of lipases, and in a series of
steps, the modified VLDL is transformed first into IDL and then
into cholesterol-rich LDL. IDL and LDL are removed from the
circulation mainly by high affinity ApoB/E receptors, which are
expressed to the greatest extent on liver cells. HDL is hypothesized
to participate in the reverse transport of cholesterol from
tissues back to the liver.
Epidemiologic, experimental, and clinical studies have established
that high LDL cholesterol (LDL-C), low HDL cholesterol
(HDL-C), and high plasma TG promote human atherosclerosis
and are risk factors for developing cardiovascular disease. In
contrast, higher levels of HDL-C are associated with decreased
cardiovascular risk.
Like LDL, cholesterol-enriched triglyceride-rich lipoproteins,
including VLDL, IDL, and remnants, can also promote atherosclerosis.
Elevated plasma triglycerides are frequently found with low
HDL-C levels and small LDL particles, as well as in association
with non-lipid metabolic risk factors for coronary heart disease
(CHD). As such, total plasma TG has not consistently been shown
to be an independent risk factor for CHD. Furthermore, the independent
effect of raising HDL or lowering TG on the risk of
coronary and cardiovascular morbidity and mortality has not been
determined.
Mechanism of Action: Rosuvastatin is a selective and competitive
inhibitor of HMG-CoA reductase, the rate-limiting enzyme that
converts 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate,
a precursor of cholesterol. In vivostudies in animals, and in vitro
studies in cultured animal and human cells have shown rosuvastatin
to have a high uptake into, and selectivity for, action in the
liver, the target organ for cholesterol lowering. In in vivo and
in vitrostudies, rosuvastatin produces its lipid-modifying effects
in two ways. First, it increases the number of hepatic LDL receptors
on the cell-surface to enhance uptake and catabolism of LDL.
Second, rosuvastatin inhibits hepatic synthesis of VLDL, which
reduces the total number of VLDL and LDL particles.
Rosuvastatin reduces total cholesterol (total-C), LDL-C, ApoB,
and nonHDL-C (total cholesterol minus HDL-C) in patients with
homozygous and heterozygous familial hypercholesterolemia
(FH), nonfamilial forms of hypercholesterolemia, and mixed
dyslipidemia. Rosuvastatin also reduces TG and produces
increases in HDL-C. Rosuvastatin reduces total-C, LDL-C, VLDLcholesterol
(VLDL-C), ApoB, nonHDL-C and TG, and increases
HDL-C in patients with isolated hypertriglyceridemia. The effect of
rosuvastatin on cardiovascular morbidity and mortality has not
been determined.
Pharmacokinetics and Drug Metabolism
Absorption: In clinical pharmacology studies in man, peak plasma
concentrations of rosuvastatin were reached 3 to 5 hours
following oral dosing. Both peak concentration (Cmax) and area
under the plasma concentration-time curve (AUC) increased in
approximate proportion to rosuvastatin dose. The absolute
bioavailability of rosuvastatin is approximately 20%.
Administration of rosuvastatin with food decreased the rate of
drug absorption by 20% as assessed by Cmax, but there was no
effect on the extent of absorption as assessed by AUC.
Plasma concentrations of rosuvastatin do not differ following
evening or morning drug administration.
Significant LDL-C reductions are seen when rosuvastatin is given
with or without food, and regardless of the time of day of drug
administration.
Distribution: 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.
Metabolism: 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 rosuvastatin. Overall, greater than 90% of
active plasma HMG-CoA reductase inhibitory activity is accounted
for by rosuvastatin.
Excretion: Following oral administration, rosuvastatin and its
metabolites are primarily excreted in the feces (90%). The elimination
half-life (t1/2) of rosuvastatin is approximately 19 hours.
After an intravenous dose, approximately 28% of total body
clearance was via the renal route, and 72% by the hepatic route.
Special Populations
Race: A population pharmacokinetic analysis revealed no clinically
relevant differences in pharmacokinetics among Caucasian,
Hispanic, 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 Cmax) in Asian subjects when compared
with a Caucasian control group. (See WARNINGS, Myopathy/
Rhabdomyolysis, PRECAUTIONS, General and DOSAGE AND
ADMINISTRATION.)
Gender: There were no differences in plasma concentrations of
rosuvastatin between men and women.
Geriatric: There were no differences in plasma concentrations of
rosuvastatin between the nonelderly and elderly populations (age
≥65 years).
Pediatric: In a pharmacokinetic study, 18 patients (9 boys and
9 girls) 10 to 17 years of age with heterozygous FH received
single and multiple oral doses of rosuvastatin. Both Cmax and AUC
of rosuvastatin were similar to values observed in adult subjects
administered the same doses.
Renal Insufficiency: Mild to moderate renal impairment (creatinine
clearance ≥ 30 mL/min/1.73m2) had no influence on plasma
concentrations of rosuvastatin when oral doses of 20 mg rosuvastatin
were administered for 14 days. However, plasma
concentrations of rosuvastatin increased to a clinically significant
extent (about 3-fold) in patients with severe renal impairment
(CLcr < 30 mL/min/1.73m2) compared with healthy subjects
(CLcr > 80 mL/min/1.73m2) (see PRECAUTIONS, General).
Hemodialysis: Steady-state plasma concentrations of rosuvastatin
in patients on chronic hemodialysis were approximately
50% greater compared with healthy volunteer subjects with
normal renal function.
Hepatic Insufficiency: In patients with chronic alcohol liver
disease, plasma concentrations of rosuvastatin were modestly
increased. In patients with Child-Pugh A disease, Cmax and AUC
were increased by 60% and 5%, respectively, as compared with
patients with normal liver function. In patients with Child-Pugh B
disease, Cmax and AUC were increased 100% and 21%, respectively,
compared with patients with normal liver function (see
CONTRAINDICATIONS and WARNINGS, Liver Enzymes).
Drug-Drug Interactions
Cytochrome P450 3A4: In vitro and in vivo data indicate that
rosuvastatin clearance is not dependent on metabolism by
cytochrome P450 3A4 to a clinically significant extent. This has
been confirmed in studies with known cytochrome P450 3A4
inhibitors (ketoconazole, erythromycin, itraconazole).
Ketoconazole: Coadministration of ketoconazole (200 mg twice
daily for 7 days) with rosuvastatin (80 mg) resulted in no change
in plasma concentrations of rosuvastatin.
Erythromycin: Coadministration of erythromycin (500 mg four
times daily for 7 days) with rosuvastatin (80 mg) decreased AUC
and Cmax of rosuvastatin by 20% and 31%, respectively. These
reductions are not considered clinically significant.
Itraconazole: Itraconazole (200 mg once daily for 5 days)
resulted in a 39% and 28% increase in AUC of rosuvastatin after
10 mg and 80 mg dosing, respectively. These increases are not
considered clinically significant.
Fluconazole: Coadministration of fluconazole (200 mg once daily
for 11 days) with rosuvastatin (80 mg) resulted in a 14% increase
in AUC of rosuvastatin. This increase is not considered clinically
significant.
Cyclosporine: Coadministration of cyclosporine with rosuvastatin
resulted in no significant changes in cyclosporine plasma concentrations.
However, Cmax and AUC of rosuvastatin increased
11- and 7-fold, respectively, compared with historical data in
healthy subjects. These increases are considered to be
clinically significant (see PRECAUTIONS, Drug Interactions,
WARNINGS, Myopathy/Rhabdomyolysis, and DOSAGE AND
ADMINISTRATION).
Warfarin: Coadministration of warfarin (25 mg) with rosuvastatin
(40 mg) did not change warfarin plasma concentrations but
increased the International Normalized Ratio (INR) (see PRECAUTIONS,
Drug Interactions).
Digoxin: Coadministration of digoxin (0.5 mg) with rosuvastatin
(40 mg) resulted in no change to digoxin plasma concentrations.
Fenofibrate: Coadministration of fenofibrate (67 mg three times
daily) with rosuvastatin (10 mg) resulted in no significant
changes in plasma concentrations of rosuvastatin or fenofibrate
(see PRECAUTIONS, Drug Interactions, and WARNINGS,
Myopathy/Rhabdomyolysis).
Gemfibrozil: Coadministration of gemfibrozil (600 mg twice daily
for 7 days) with rosuvastatin (80 mg) resulted in a 90% and 120%
increase for AUC and Cmax of rosuvastatin, respectively.
This increase is considered to be clinically significant (see
PRECAUTIONS, Drug Interactions, WARNINGS, Myopathy/
Rhabdomyolysis, DOSAGE AND ADMINISTRATION).
Antacid: Coadministration of an antacid (aluminum and magnesium
hydroxide combination) with rosuvastatin (40 mg)
resulted in a decrease in plasma concentrations of rosuvastatin by
54%. However, when the antacid was given 2 hours after
rosuvastatin, there were no clinically significant changes in
plasma concentrations of rosuvastatin (see PRECAUTIONS,
Information for Patients).
Oral contraceptives: Coadministration of oral contraceptives
(ethinyl estradiol and norgestrel) with rosuvastatin resulted in an
increase in plasma concentrations of ethinyl estradiol and
norgestrel by 26% and 34%, respectively.
CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets
Ca2+
F
OH OH O
O
SO2Me
N
N
N
2
Clinical Studies
Hypercholesterolemia (Heterozygous Familial
and Nonfamilial) and Mixed Dyslipidemia
(Fredrickson Type IIa and IIb)
CRESTOR reduces total-C, LDL-C, ApoB, nonHDL-C, and TG, and
increases HDL-C, in patients with hypercholesterolemia and
mixed dyslipidemia. Therapeutic response is seen within 1 week,
and maximum response is usually achieved within 4 weeks and
maintained during long-term therapy.
CRESTOR is effective in a wide variety of adult patient populations
with hypercholesterolemia, with and without hypertriglyceridemia,
regardless of race, gender, or age and in special
populations such as diabetics or patients with heterozygous FH.
Experience in pediatric patients has been limited to patients with
homozygous FH.
Dose-Ranging Study: In a multicenter, double-blind, placebocontrolled,
dose-ranging study in patients with hypercholesterolemia,
CRESTOR given as a single daily dose for
6 weeks significantly reduced total-C, LDL-C, nonHDL-C, and
ApoB, across the dose range (Table 1).
Table 1. Dose-Response in Patients
With Primary Hypercholesterolemia
(Adjusted Mean % Change From Baseline at Week 6)
Dose N Total-C LDL-C NonHDL-C ApoB TG HDL-C
Placebo 13 -5 -7 -7 -3 -3 3
5 17 -33 -45 -44 -38 -35 13
10 17 -36 -52 -48 -42 -10 14
20 17 -40 -55 -51 -46 -23 8
40 18 -46 -63 -60 -54 -28 10
Active-Controlled Study: CRESTOR was compared with the
HMG-CoA reductase inhibitors atorvastatin, simvastatin, and
pravastatin in a multicenter, open-label, dose-ranging study of
2,240 patients with Type IIa and IIb hypercholesterolemia. After
randomization, patients were treated for 6 weeks with a single
daily dose of either CRESTOR, atorvastatin, simvastatin, or
pravastatin (Figure 1 and Table 2).
Figure 1. Percent LDL-C Change by Dose of
CRESTOR, Atorvastatin, Simvastatin, and Pravastatin
at Week 6 in Patients With Type IIa/IIb Dyslipidemia
Box plots are a representation of the 25th, 50th, and 75th percentile values, with
whiskers representing the 10th and 90th percentile values.
Mean baseline LDL-C: 189 mg/dL.
Table 2. Percent Change in LDL-C From Baseline to Week 6
(LS means §) by Treatment Group
(sample sizes ranging from 156-167 patients per group)
Treatment Daily Dose
Treatment 10 mg 20 mg 40 mg 80 mg
CRESTOR -46* -52† -55‡ —
Atorvastatin -37 -43 -48 -51
Pravastatin -20 -24 -30 —
Simvastatin -28 -35 -39 -46
* CRESTOR 10 mg reduced LDL-C significantly more than atorvastatin 10 mg;
pravastatin 10 mg, 20 mg, and 40 mg; simvastatin 10 mg, 20 mg, and 40 mg.
(p<0.002)
† CRESTOR 20 mg reduced LDL-C significantly more than atorvastatin 20 mg
and 40 mg; pravastatin 20 mg and 40 mg; simvastatin 20 mg, 40 mg, and
80 mg. (p<0.002)
‡ CRESTOR 40 mg reduced LDL-C significantly more than atorvastatin 40 mg;
pravastatin 40 mg; simvastatin 40 mg and 80 mg (p<0.002)
§ Corresponding standard errors are approximately 1.00
Heterozygous Familial Hypercholesterolemia
In a study of patients with heterozygous FH (baseline mean LDL
of 291), patients were randomized to CRESTOR 20 mg or
atorvastatin 20 mg. The dose was increased by 6-week intervals.
Significant LDL-C reductions from baseline were seen at each
dose in both treatment groups (Table 3).
Table 3. Mean LDL-C Percentage Change From Baseline
CRESTOR Atorvastatin
(n=435) (n=187)
LS Mean* (95% CI) LS Mean (95% CI)
Week 6 20 mg -47% (-49%, -46%) -38% (-40%, -36%)
Week 12 40 mg -55% (-57%, -54%) -47% (-49%, -45%)
Week 18 80 mg NA -52% (-54%, -50%)
* LS Means are least square means adjusted for baseline LDL.
Hypertriglyceridemia
(Fredrickson Type IIb & IV)
In a double-blind, placebo-controlled dose-response study in
patients with baseline TG levels from 273 to 817 mg/dL,
CRESTOR given as a single daily dose (5 to 40 mg) over 6 weeks
significantly reduced serum TG levels (Table 4).
Table 4. Dose-Response in Patients With Primary
Hypertriglyceridemia Over 6 Weeks Dosing
Median (Min, Max) Percent Change From Baseline
CRESTOR CRESTOR CRESTOR CRESTOR
Dose Placebo 5 mg 10 mg 20 mg 40 mg
N = 26 N = 25 N = 23 N = 27 N = 25
Triglycerides 1 (-40, 72) -21 (-58, 38) -37 (-65, 5) -37 (-72, 11) -43 (-80, -7)
NonHDL-C 2 (-13, 19) -29 (-43, -8) -49 (-59, -20) -43 (-74, -12) -51 (-62, -6)
VLDL-C 2 (-36, 53) -25 (-62, 49) -48 (-72, 14) -49 (-83, 20) -56 (-83, 10)
Total-C 1 (-13, 17) -24 (-40, -4) -40 (-51, -14) -34 (-61, -11) -40 (-51, -4)
LDL-C 5 (-30, 52) -28 (-71, 2) -45 (-59, 7) -31 (-66, 34) -43 (-61, -3)
HDL-C -3 (-25, 18) 3 (-38, 33) 8 (-8, 24) 22 (-5, 50) 17 (-14, 63)
Homozygous Familial Hypercholesterolemia
In an open-label, forced-titration study, homozygous FH patients
(n=40, 8-63 years) were evaluated for their response to CRESTOR
20 to 40 mg titrated at a 6-week interval. In the overall population,
the mean LDL-C reduction from baseline was 22%. About one-third
of the patients benefited from increasing their dose from 20 mg to
40 mg with further LDL lowering of greater than 6%. In the 27
patients with at least a 15% reduction in LDL-C, the mean LDL-C
reduction was 30% (median 28% reduction). Among 13 patients
with an LDL-C reduction of <15%, 3 had no change or an increase
in LDL-C. Reductions in LDL-C of 15% or greater were observed
in 3 of 5 patients with known receptor negative status.
INDICATIONS AND USAGE
CRESTOR is indicated:
1. as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB,
nonHDL-C, and TG levels and to increase HDL-C in patients
with primary hypercholesterolemia (heterozygous familial
and nonfamilial) and mixed dyslipidemia (Fredrickson Type IIa
and IIb);
2. as an adjunct to diet for the treatment of patients with elevated
serum TG levels (Fredrickson Type IV);
3. to reduce LDL-C, total-C, and ApoB in patients with homozygous
familial hypercholesterolemia as an adjunct to other
lipid-lowering treatments (e.g., LDL apheresis) or if such treatments
are unavailable.
According to NCEP-ATP III guidelines, therapy with lipid-altering
agents should be a component of multiple-risk-factor intervention
in individuals at increased risk for coronary heart disease due to
hypercholesterolemia. The two major modalities of LDL-lowering
therapy are therapeutic lifestyle changes (TLC) and drug therapy.
The TLC Diet stresses reductions in saturated fat and cholesterol
intake. Table 5 defines LDL-C goals and cutpoints for initiation of
TLC and for drug consideration.
Table 5. NCEP Treatment Guidelines:
LDL-C Goals and Cutpoints for Therapeutic Lifestyle Changes
and Drug Therapy in Different Risk Categories
LDL level at which to LDL level at which
Risk Category LDL Goal initiate TLC to consider drug
therapy
CHDa or
CHD Risk Equivalent <100 mg/dL ≥100 mg/dL ≥130 mg/dL
(10-year risk >20%) (100-129 mg/dL:
drug optional)b
2+ Risk Factors <130 mg/dL ≥130 mg/dL ≥130 mg/dL
(10-year risk ≤20%) 10-year risk 10-20%
≥160 mg/dL
10-year risk <10%
0-1 Risk Factorc <160 mg/dL ≥160 mg/dL ≥190 mg/dL
(160-189 mg/dL)
(LDL-lowering
drug optional)
a CHD = coronary heart disease.
b Some authorities recommend use of LDL-lowering drugs in this category if an
LDL-C <100 mg/dL cannot be achieved by TLC. Others prefer use of drugs that
primarily modify triglycerides and HDL-C, e.g., nicotinic acid or fibrate. Clinical
judgment also may call for deferring drug therapy in this subcategory.
c Almost all people with 0-1 risk factor have 10-year risk<10%; thus, 10-year
risk assessment in people with 0-1 risk factor is not necessary.
After the LDL-C goal has been achieved, if the TG is still
≥ 200 mg/dL, nonHDL-C (total-C minus HDL-C) becomes a
secondary target of therapy. NonHDL-C goals are set 30 mg/dL
higher than LDL-C goals for each risk category.
At the time of hospitalization for a coronary event, consideration
can be given to initiating drug therapy at discharge if the LDL-C
is ≥ 130 mg/dL (see NCEP Treatment Guidelines, above).
Patients >20 years of age should be screened for elevated cholesterol
levels every 5 years.
Prior to initiating therapy with CRESTOR, secondary causes for
hypercholesterolemia (e.g., poorly-controlled diabetes mellitus,
hypothyroidism, nephrotic syndrome, dyslipoproteinemias,
obstructive liver disease, other drug therapy, and alcoholism)
should be excluded, and a lipid profile performed to measure
total-C, LDL-C, HDL-C, and TG. For patients with TG <400 mg/dL
(<4.5 mmol/L), LDL-C can be estimated using the following
equation: LDL-C = total-C – (0.20 x [TG] + HDL-C). For TG
levels >400 mg/dL (>4.5 mmol/L), this equation is less
accurate and LDL-C concentrations should be determined by
ultracentrifugation.
CRESTOR has not been studied in Fredrickson Type I, III, and
V dyslipidemias.
CONTRAINDICATIONS
CRESTOR is contraindicated in patients with a known hypersensitivity
to any component of this product.
Rosuvastatin is contraindicated in patients with active liver
disease or with unexplained persistent elevations of serum
transaminases (see WARNINGS, Liver Enzymes).
Pregnancy and Lactation
Atherosclerosis is a chronic process and discontinuation of lipidlowering
drugs during pregnancy should have little impact on the
outcome of long-term therapy of primary hypercholesterolemia.
Cholesterol and other products of cholesterol biosynthesis are
essential components for fetal development (including synthesis
of steroids and cell membranes). Since HMG-CoA reductase
inhibitors decrease cholesterol synthesis and possibly the
synthesis of other biologically active substances derived from
cholesterol, they may cause fetal harm when administered to
pregnant women. Therefore, HMG-CoA reductase inhibitors
are contraindicated during pregnancy and in nursing mothers.
ROSUVASTATIN SHOULD BE ADMINISTERED TO WOMEN OF
CHILDBEARING AGE ONLY WHEN SUCH PATIENTS ARE HIGHLY
UNLIKELY TO CONCEIVE AND HAVE BEEN INFORMED OF THE
POTENTIAL HAZARDS. If the patient becomes pregnant while
taking this drug, therapy should be discontinued immediately and
the patient apprised of the potential hazard to the fetus.
CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets
-75%
-60%
-30%
-45%
-15%
0%
10 dose (mg) =
Percent change from
baseline in LDL-C
CRESTOR Atorvastatin Pravastatin Simvastatin
10 20 40 10 20 40 80 20 40 80 10 20 40
WARNINGS
Liver Enzymes
HMG-CoA reductase inhibitors, like some other lipid-lowering
therapies, have been associated with biochemical abnormalities
of liver function. The incidence of persistent elevations (>3 times
the upper limit of normal [ULN] occurring on 2 or more consecutive
occasions) in serum transaminases in fixed dose studies was
0.4, 0, 0, and 0.1% in patients who received rosuvastatin 5, 10,
20, and 40 mg, respectively. In most cases, the elevations were
transient and resolved or improved on continued therapy or after
a brief interruption in therapy. There were two cases of jaundice,
for which a relationship to rosuvastatin therapy could not be
determined, which resolved after discontinuation of therapy.
There were no cases of liver failure or irreversible liver disease in
these trials.
It is recommended that liver function tests be performed before
and at 12 weeks following both the initiation of therapy and any
elevation of dose, and periodically (e.g., semiannually) thereafter.
Liver enzyme changes generally occur in the first 3 months
of treatment with rosuvastatin. Patients who develop increased
transaminase levels should be monitored until the abnormalities
have resolved. Should an increase in ALT or AST of >3 times
ULN persist, reduction of dose or withdrawal of rosuvastatin is
recommended.
Rosuvastatin should be used with caution in patients who
consume substantial quantities of alcohol and/or have a history of
liver disease (see CLINICAL PHARMACOLOGY, Special
Populations, Hepatic Insufficiency). Active liver disease or unexplained
persistent transaminase elevations are contraindications
to the use of rosuvastatin (see CONTRAINDICATIONS).
Myopathy/Rhabdomyolysis
Rare cases of rhabdomyolysis with acute renal failure
secondary to myoglobinuria have been reported with rosuvastatin
and with other drugs in this class.
Uncomplicated myalgia has been reported in rosuvastatin-treated
patients (see ADVERSE REACTIONS). Creatine kinase (CK) elevations
(>10 times upper limit of normal) occurred in 0.2% to 0.4%
of patients taking rosuvastatin at doses of up to 40 mg in clinical
studies. Treatment-related myopathy, defined as muscle aches or
muscle weakness in conjunction with increases in CK values
>10 times upper limit of normal, was reported in up to 0.1% of
patients taking rosuvastatin doses of up to 40 mg in clinical
studies. In clinical trials, the incidence of myopathy and rhabdomyolysis
increased at doses of rosuvastatin above the
recommended dosage range (5 to 40 mg). In postmarketing
experience, effects on skeletal muscle, e.g. uncomplicated
myalgia, myopathy and, rarely, rhabdomyolysis have been
reported in patients treated with HMG-CoA reductase inhibitors
including rosuvastatin. As with other HMG-CoA reductase
inhibitors, reports of rhabdomyolysis with rosuvastatin are rare,
but higher at the highest marketed dose (40 mg). Factors that
may predispose patients to myopathy with HMG-CoA reductase
inhibitors include advanced age (≥65 years), hypothyroidism, and
renal insufficiency.
Consequently:
1. Rosuvastatin should be prescribed with caution in patients with
predisposing factors for myopathy, such as, renal impairment
(see DOSAGE AND ADMINISTRATION), advanced age, and
inadequately treated hypothyroidism.
2. Patients should be advised to promptly report unexplained
muscle pain, tenderness, or weakness, particularly if accompanied
by malaise or fever. Rosuvastatin therapy should be
discontinued if markedly elevated CK levels occur or myopathy
is diagnosed or suspected.
3. The 40 mg dose of rosuvastatin is reserved only for those
patients who have not achieved their LDL-C goal utilizing the
20 mg dose of rosuvastatin once daily (see DOSAGE AND
ADMINISTRATION).
4. The risk of myopathy during treatment with rosuvastatin may
be increased with concurrent administration of other
lipid-lowering therapies or cyclosporine, (see CLINICAL PHARMACOLOGY,
Drug Interactions, PRECAUTIONS, Drug
Interactions, and DOSAGE AND ADMINISTRATION). The
benefit of further alterations in lipid levels by the combined
use of rosuvastatin with fibrates or niacin should be carefully
weighed against the potential risks of this combination.
Combination therapy with rosuvastatin and gemfibrozil
should generally be avoided. (See DOSAGE AND ADMINISTRATION
and PRECAUTIONS, Drug Interactions).
5. The risk of myopathy during treatment with rosuvastatin may
be increased in circumstances which increase rosuvastatin
drug levels (see CLINICAL PHARMACOLOGY, Special
Populations, Race and Renal Insufficiency, and PRECAUTIONS,
General).
6. Rosuvastatin therapy should also be temporarily withheld in
any patient with an acute, serious condition suggestive of
myopathy or predisposing to the development of renal failure
secondary to rhabdomyolysis (e.g., sepsis, hypotension,
dehydration, major surgery, trauma, severe metabolic,
endocrine, and electrolyte disorders, or uncontrolled
seizures).
PRECAUTIONS
General
Before instituting therapy with rosuvastatin, an attempt should be
made to control hypercholesterolemia with appropriate diet and
exercise, weight reduction in obese patients, and treatment of
underlying medical problems (see INDICATIONS AND USAGE).
Administration of rosuvastatin 20 mg to patients with severe renal
impairment (CLcr <30 mL/min/1.73 m2) resulted in a 3-fold
increase in plasma concentrations of rosuvastatin compared with
healthy volunteers (see WARNINGS, Myopathy/Rhabdomyolysis
and DOSAGE AND ADMINISTRATION).
The result of a large pharmacokinetic study conducted in the US
demonstrated an approximate 2-fold elevation in median
exposure in Asian subjects (having either Filipino, Chinese,
Japanese, Korean, Vietnamese or Asian-Indian origin) compared
with a Caucasian control group. This increase should be
considered when making rosuvastatin dosing decisions for
Asian patients. (See WARNINGS, Myopathy/Rhabdomyolysis;
CLINICAL PHARMACOLOGY, Special Populations, Race, and
DOSAGE AND ADMINISTRATION.)
Information for Patients
Patients should be advised to report promptly unexplained
muscle pain, tenderness, or weakness, particularly if accompanied
by malaise or fever.
When taking rosuvastatin with an aluminum and magnesium
hydroxide combination antacid, the antacid should be taken at
least 2 hours after rosuvastatin administration (see CLINICAL
PHARMACOLOGY, Drug Interactions).
Laboratory Tests
In the rosuvastatin clinical trial program, dipstick-positive
proteinuria and microscopic hematuria were observed among
rosuvastatin-treated patients, predominantly in patients dosed
above the recommended dose range (i.e., 80 mg). However, this
finding was more frequent in patients taking rosuvastatin 40 mg,
when compared to lower doses of rosuvastatin or comparator
statins, though it was generally transient and was not associated
with worsening renal function. Although the clinical significance
of this finding is unknown, a dose reduction should be considered
for patients on rosuvastatin 40 mg therapy with unexplained
persistent proteinuria during routine urinalysis testing.
Drug Interactions
Cyclosporine: When rosuvastatin 10 mg was coadministered
with cyclosporine in cardiac transplant patients, rosuvastatin
mean Cmax and mean AUC were increased 11-fold and
7-fold, respectively, compared with healthy volunteers. These
increases are considered to be clinically significant and require
special consideration in the dosing of rosuvastatin to patients
taking concomitant cyclosporine (see WARNINGS, Myopathy/
Rhabdomyolysis, and DOSAGE AND ADMINISTRATION).
Warfarin: Coadministration of rosuvastatin to patients on stable
warfarin therapy resulted in clinically significant rises in INR (>4,
baseline 2-3). In patients taking coumarin anticoagulants and
rosuvastatin concomitantly, INR should be determined before
starting rosuvastatin and frequently enough during early therapy
to ensure that no significant alteration of INR occurs. Once a
stable INR time has been documented, INR can be monitored at
the intervals usually recommended for patients on coumarin anticoagulants.
If the dose of rosuvastatin is changed, the same
procedure should be repeated. Rosuvastatin therapy has not been
associated with bleeding or with changes in INR in patients not
taking anticoagulants.
Gemfibrozil: Coadministration of a single rosuvastatin dose to
healthy volunteers on gemfibrozil (600 mg twice daily) resulted in
a 2.2- and 1.9-fold, respectively, increase in mean Cmax and mean
AUC of rosuvastatin (see DOSAGE AND ADMINISTRATION).
Endocrine Function
Although clinical studies have shown that rosuvastatin alone does
not reduce basal plasma cortisol concentration or impair adrenal
reserve, caution should be exercised if any HMG-CoA reductase
inhibitor or other agent used to lower cholesterol levels is administered
concomitantly with drugs that may decrease the levels or
activity of endogenous steroid hormones such as ketoconazole,
spironolactone, and cimetidine.
CNS Toxicity
CNS vascular lesions, characterized by perivascular hemorrhages,
edema, and mononuclear cell infiltration of perivascular
spaces, have been observed in dogs treated with several other
members of this drug class. A chemically similar drug in this
class produced dose-dependent optic nerve degeneration
(Wallerian degeneration of retinogeniculate fibers) in dogs, at a
dose that produced plasma drug levels about 30 times higher
than the mean drug level in humans taking the highest recommended
dose. Edema, hemorrhage, and partial necrosis in the
interstitium of the choroid plexus was observed in a female dog
sacrificed moribund at day 24 at 90 mg/kg/day by oral gavage
(systemic exposures 100 times the human exposure at 40 mg/day
based on AUC comparisons). Corneal opacity was seen in dogs
treated for 52 weeks at 6 mg/kg/day by oral gavage (systemic
exposures 20 times the human exposure at 40 mg/day based on
AUC comparisons). Cataracts were seen in dogs treated for
12 weeks by oral gavage at 30 mg/kg/day (systemic exposures
60 times the human exposure at 40 mg/day based on AUC
comparisons). Retinal dysplasia and retinal loss were seen in
dogs treated for 4 weeks by oral gavage at 90 mg/kg/day
(systemic exposures 100 times the human exposure at 40 mg/day
based on AUC). Doses ≤30 mg/kg/day (systemic exposures
≤60 times the human exposure at 40 mg/day based on AUC
comparisons) following treatment up to one year, did not reveal
retinal findings.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 104-week carcinogenicity study in rats at dose levels of 2, 20,
60, or 80 mg/kg/day by oral gavage, the incidence of uterine
stromal polyps was significantly increased in females at
80 mg/kg/day at systemic exposure 20 times the human exposure
at 40 mg/day based on AUC. Increased incidence of polyps was
not seen at lower doses.
In a 107-week carcinogenicity study in mice given 10, 60,
200 mg/kg/day by oral gavage, an increased incidence of hepatocellular
adenoma/carcinoma was observed at 200 mg/kg/day at
systemic exposures 20 times human exposure at 40 mg/day
based on AUC. An increased incidence of hepatocellular tumors
was not seen at lower doses.
Rosuvastatin was not mutagenic or clastogenic with or without
metabolic activation in the Ames test with Salmonella
typhimurium and Escherichia coli, the mouse lymphoma assay,
and the chromosomal aberration assay in Chinese hamster
lung cells. Rosuvastatin was negative in the in vivo mouse
micronucleus test.
In rat fertility studies with oral gavage doses of 5, 15,
50 mg/kg/day, males were treated for 9 weeks prior to and
throughout mating and females were treated 2 weeks prior to
mating and throughout mating until gestation day 7. No adverse
effect on fertility was observed at 50 mg/kg/day (systemic exposures
up to 10 times human exposure at 40 mg/day based on AUC
comparisons). In testicles of dogs treated with rosuvastatin at
30 mg/kg/day for one month, spermatidic giant cells were seen.
Spermatidic giant cells were observed in monkeys after 6-month
treatment at 30 mg/kg/day in addition to vacuolation of seminiferous
tubular epithelium. Exposures in the dog were
20 times and in the monkey 10 times human exposure at
40 mg/day based on body surface area comparisons. Similar
findings have been seen with other drugs in this class.
Pregnancy
Pregnancy Category X
See CONTRAINDICATIONS.
Rosuvastatin may cause fetal harm when administered to a pregnant
woman. Rosuvastatin is contraindicated in women who are
or may become pregnant. Safety in pregnant women has not been
established. There are no adequate and well-controlled studies of
rosuvastatin in pregnant women. Rosuvastatin crosses the
placenta 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 16
in rats. A higher fetal tissue distribution (25% maternal plasma
concentration) was observed in rabbits after a single oral gavage
CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets
dose of 1 mg/kg on gestation day 18. If this drug is administered
to a woman with reproductive potential, the patient should be
apprised of the potential hazard to a fetus.
In female rats given oral gavage doses of 5, 15, 50 mg/kg/day
rosuvastatin before mating and continuing through day 7 postcoitus
results in decreased fetal body weight (female pups)
and delayed ossification at the high dose (systemic exposures
10 times human exposure at 40 mg/day based on AUC
comparisons).
In pregnant rats given oral gavage doses of 2, 10, 50 mg/kg/day
from gestation day 7 through lactation day 21 (weaning),
decreased pup survival occurred in groups given 50 mg/kg/day,
systemic exposures ≥12 times human exposure at 40 mg/day
based on body surface area comparisons.
In pregnant rabbits given oral gavage doses of 0.3, 1, 3 mg/kg/day
from gestation day 6 to lactation day 18 (weaning), exposures
equivalent to human exposure at 40 mg/day based on body
surface area comparisons, decreased fetal viability and maternal
mortality was observed.
Rosuvastatin was not teratogenic in rats at ≤25 mg/kg/day or in
rabbits ≤3 mg/kg/day (systemic exposures equivalent to human
exposure at 40 mg/day based on AUC or body surface comparison,
respectively).
Nursing Mothers
It is not known whether rosuvastatin is excreted in human milk.
Studies in lactating rats have demonstrated that rosuvastatin is
secreted into breast milk at levels 3 times higher than that
obtained in the plasma following oral gavage dosing. Because
many drugs are excreted in human milk and because of the potential
for serious adverse reactions in nursing infants from
rosuvastatin, a decision should be made whether to discontinue
nursing or administration of rosuvastatin taking into account the
importance of the drug to the lactating woman.
Pediatric Use
The safety and effectiveness in pediatric patients have not been
established. Treatment experience with rosuvastatin in a pediatric
population is limited to 8 patients with homozygous FH. None of
these patients was below 8 years of age.
Geriatric Use
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. The overall frequency of adverse events and types of
adverse events were similar in patients above and below 65 years
of age. (See WARNINGS, Myopathy/Rhabdomyolysis.)
The efficacy of rosuvastatin in the geriatric population (≥65 years
of age) was comparable to the efficacy observed in the
non-elderly.
ADVERSE REACTIONS
Rosuvastatin is generally well tolerated. Adverse reactions
have usually been mild and transient. In clinical studies of
10,275 patients, 3.7% were discontinued due to adverse
experiences attributable to rosuvastatin. The most frequent
adverse events thought to be related to rosuvastatin were
myalgia, constipation, asthenia, abdominal pain, and nausea.
Clinical Adverse Experiences
Adverse experiences, regardless of causality assessment,
reported in ≥2% of patients in placebo-controlled clinical studies
of rosuvastatin are shown in Table 6; discontinuations due to
adverse events in these studies of up to 12 weeks duration
occurred in 3% of patients on rosuvastatin and 5% on placebo.
Table 6. Adverse Events in Placebo-Controlled Studies
Rosuvastatin Placebo
Adverse event N=744 N=382
Pharyngitis 9.0 7.6
Headache 5.5 5.0
Diarrhea 3.4 2.9
Dyspepsia 3.4 3.1
Nausea 3.4 3.1
Myalgia 2.8 1.3
Asthenia 2.7 2.6
Back pain 2.6 2.4
Flu syndrome 2.3 1.8
Urinary tract infection 2.3 1.6
Rhinitis 2.2 2.1
Sinusitis 2.0 1.8
In addition, the following adverse events were reported, regardless
of causality assessment, in ≥1% of 10,275 patients treated
with rosuvastatin in clinical studies. The events in italicsoccurred
in ≥2% of these patients.
Body as a Whole: Abdominal pain, accidental injury, chest pain,
infection, pain,pelvic pain, and neck pain.
Cardiovascular System: Hypertension, angina pectoris, vasodilatation,
and palpitation.
Digestive System: Constipation, gastroenteritis, vomiting,
flatulence, periodontal abscess, and gastritis.
Endocrine: Diabetes mellitus.
Hemic and Lymphatic System: Anemia and ecchymosis.
Metabolic and Nutritional Disorders: Peripheral edema.
Musculoskeletal System: Arthritis, arthralgia, and pathological
fracture.
Nervous System: Dizziness, insomnia, hypertonia, paresthesia,
depression,anxiety, vertigo, and neuralgia.
Respiratory System: Bronchitis, cough increased, dyspnea,
pneumonia, and asthma.
Skin and Appendages: Rashand pruritus.
Laboratory Abnormalities: In the rosuvastatin clinical trial
program, dipstick-positive proteinuria and microscopic hematuria
were observed among rosuvastatin-treated patients, predominantly
in patients dosed above the recommended dose range
(i.e., 80 mg). However, this finding was more frequent in patients
taking rosuvastatin 40 mg, when compared to lower doses of
rosuvastatin or comparator statins, though it was generally transient
and was not associated with worsening renal function. (See
PRECAUTIONS, Laboratory Tests.)
Other abnormal laboratory values reported were elevated creatine
phosphokinase, transaminases, hyperglycemia, glutamyl
transpeptidase, alkaline phosphatase, bilirubin, and thyroid
function abnormalities.
Other adverse events reported less frequently than 1% in the
rosuvastatin clinical study program, regardless of causality
assessment, included arrhythmia, hepatitis, hypersensitivity
reactions (i.e., face edema, thrombocytopenia, leukopenia,
vesiculobullous rash, urticaria, and angioedema), kidney failure,
syncope, myasthenia, myositis, pancreatitis, photosensitivity
reaction, myopathy, and rhabdomyolysis.
Postmarketing Experience
In addition to the events reported above, as with other drugs
in this class, the following event has been reported during postmarketing
experience with CRESTOR, regardless of causality
assessment: very rare cases of jaundice.
OVERDOSAGE
There is no specific treatment in the event of overdose. In the
event of overdose, the patient should be treated symptomatically
and supportive measures instituted as required. Hemodialysis
does not significantly enhance clearance of rosuvastatin.
DOSAGE AND ADMINISTRATION
The patient should be placed on a standard cholesterol-lowering
diet before receiving CRESTOR and should continue on this diet
during treatment. CRESTOR can be administered as a single dose
at any time of day, with or without food.
Hypercholesterolemia (Heterozygous Familial
and Nonfamilial) and Mixed Dyslipidemia
(Fredrickson Type IIa and IIb)
The dose range for CRESTOR is 5 to 40 mg once daily. Therapy
with CRESTOR should be individualized according to goal of
therapy and response. The usual recommended starting dose of
CRESTOR is 10 mg once daily. However, initiation of therapy with
5 mg once daily should be considered for patients requiring
less aggressive LDL-C reductions, who have predisposing factors
for myopathy, and as noted below for special populations such
as patients taking cyclosporine, Asian patients, and patients
with severe renal insufficiency (see CLINICAL PHARMACOLOGY,
Race, and Renal Insufficiency, and Drug Interactions). For
patients with marked with marked hypercholesterolemia
(LDL-C >190 mg/dL) and aggressive lipid targets, a 20-mg
starting dose may be considered. After initiation and/or upon
titration of CRESTOR, lipid levels should be analyzed within 2 to
4 weeks and dosage adjusted accordingly.
The 40-mg dose of CRESTOR is reserved only for those patients
who have not achieved their LDL-C goal utilizing the 20 mg
dose of CRESTOR once daily (see WARNINGS, Myopathy/
Rhabdomyolysis). When initiating statin therapy or switching
from another statin therapy, the appropriate CRESTOR starting
dose should first be utilized, and only then titrated according to
the patient’s individualized goal of therapy.
Homozygous Familial Hypercholesterolemia
The recommended starting dose of CRESTOR is 20 mg once daily
in patients with homozygous FH. The maximum recommended
daily dose is 40 mg. CRESTOR should be used in these patients
as an adjunct to other lipid-lowering treatments (e.g., LDL
apheresis) or if such treatments are unavailable. Response to
therapy should be estimated from pre-apheresis LDL-C levels.
Dosage in Asian Patients
Initiation of CRESTOR therapy with 5 mg once daily should be
considered for Asian patients. The potential for increased
systemic exposures relative to Caucasians is relevant when
considering escalation of dose in cases where hypercholesterolemia
is not adequately controlled at doses of 5, 10, or 20 mg
once daily. (See WARNINGS, Myopathy/Rhabdomyolysis,
CLINICAL PHARMACOLOGY, Special Populations, Race, and
PRECAUTIONS, General).
Dosage in Patients Taking Cyclosporine
In patients taking cyclosporine, therapy should be limited to
CRESTOR 5 mg once daily (see WARNINGS, Myopathy/
Rhabdomyolysis, and PRECAUTIONS, Drug Interactions).
Concomitant Lipid-Lowering Therapy
The effect of CRESTOR on LDL-C and total-C may be enhanced
when used in combination with a bile acid binding resin. If
CRESTOR is used in combination with gemfibrozil, the dose
of CRESTOR should be limited to 10 mg once daily (see WARNINGS,
Myopathy/Rhabdomyolysis, and PRECAUTIONS, Drug
Interactions).
Dosage in Patients With Renal Insufficiency
No modification of dosage is necessary for patients with mild to
moderate renal insufficiency. For patients with severe renal
impairment (CLcr <30 mL/min/1.73 m2) not on hemodialysis,
dosing of CRESTOR should be started at 5 mg once daily and not
to exceed 10 mg once daily (see PRECAUTIONS, General, and
CLINICAL PHARMACOLOGY, Special Populations, Renal
Insufficiency).
HOW SUPPLIED
CRESTOR® (rosuvastatin calcium) Tablets are supplied as:
5 mg tablets: Yellow, round, biconvex, coated tablets identified as
“CRESTOR” and “5” debossed on one side and plain on the other
side of the tablet.
(NDC 0310-0755-90) bottles of 90
10 mg tablets: Pink, round, biconvex, coated tablets identified as
“CRESTOR” and “10” debossed on one side and plain on the
other side of the tablet.
(NDC 0310-0751-90) bottles of 90
(NDC 0310-0751-39) unit dose packages of 100
20 mg tablets: Pink, round, biconvex, coated tablets identified as
“CRESTOR” and “20” debossed on one side and plain on the
other side of the tablet.
(NDC 0310-0752-90) bottles of 90
(NDC 0310-0752-39) unit dose packages of 100
40 mg tablets: Pink, oval, biconvex, coated tablets identified as
“CRESTOR” debossed on one side and “40” debossed on the
other side of the tablet.
(NDC 0310-0754-30) bottles of 30
(NDC 0310-0754-39) unit dose packages of 100
Storage
Store at controlled room temperature, 20-25°C (68-77°F) [see
USP]. Protect from moisture.
Rx only
CRESTOR is a trademark of the AstraZeneca group of companies
©AstraZeneca 2005
Licensed from SHIONOGI & CO., LTD., Osaka, Japan
Manufactured for:
AstraZeneca Pharmaceuticals LP
Wilmington, DE 19850
By: IPR Pharmaceuticals, Inc.
Carolina, PR 00984
PCC 630301
30043-00 31028-00
Rev 03/05 227422
CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets CRESTOR® (rosuvastatin calcium) Tablets