CRESTOR (Page 8 of 9)

14.8 Slowing of the Progression of Atherosclerosis

In the Measuring Effects on Intima Media Thickness: an Evaluation Of Rosuvastatin 40 mg (METEOR) study, the effect of therapy with CRESTOR on carotid atherosclerosis was assessed by B-mode ultrasonography in patients with elevated LDL‑C, at low risk (Framingham risk <10% over ten years) for symptomatic coronary artery disease and with subclinical atherosclerosis as evidenced by carotid intimal-medial thickness (cIMT). In this double-blind, placebo-controlled clinical study 984 patients were randomized (of whom 876 were analyzed) in a 5:2 ratio to CRESTOR 40 mg or placebo once daily. Ultrasonograms of the carotid walls were used to determine the annualized rate of change per patient from baseline to two years in mean maximum cIMT of 12 measured segments. The estimated difference in the rate of change in the maximum cIMT analyzed over all 12 carotid artery sites between patients treated with CRESTOR and placebo-treated patients was -0.0145 mm/year (95% CI –0.0196, –0.0093; p< 0.0001).

The annualized rate of change from baseline for the placebo group was +0.0131 mm/year (p< 0.0001). The annualized rate of change from baseline for the group treated with CRESTOR was -0.0014 mm/year (p=0.32).

At an individual patient level in the group treated with CRESTOR, 52.1% of patients demonstrated an absence of disease progression (defined as a negative annualized rate of change), compared to 37.7% of patients in the placebo group.

14.9 Primary Prevention of Cardiovascular Disease

In the J ustification for the U se of Statins in P rimary Prevention: An I ntervention T rial E valuating R osuvastatin (JUPITER) study, the effect of CRESTOR (rosuvastatin calcium) on the occurrence of major cardiovascular (CV) disease events was assessed in 17,802 men (≥50 years) and women (≥60 years) who had no clinically evident cardiovascular disease, LDL‑C levels <130 mg/dL (3.3 mmol/l) and hs‑CRP levels ≥2 mg/L. The study population had an estimated baseline coronary heart disease risk of 11.6% over 10 years based on the Framingham risk criteria and included a high percentage of patients with additional risk factors such as hypertension (58%), low HDL‑C levels (23%), cigarette smoking (16%), or a family history of premature CHD (12%). Study participants had a median baseline LDL‑C of 108 mg/dL and hsCRP of 4.3 mg/L. Study participants were randomly assigned to placebo (n=8901) or rosuvastatin 20 mg once daily (n=8901) and were followed for a mean duration of 2 years. The JUPITER study was stopped early by the Data Safety Monitoring Board due to meeting predefined stopping rules for efficacy in rosuvastatin-treated subjects.

The primary end point was a composite end point consisting of the time-to-first occurrence of any of the following major CV events: CV death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina or an arterial revascularization procedure.

Rosuvastatin significantly reduced the risk of major CV events (252 events in the placebo group vs. 142 events in the rosuvastatin group) with a statistically significant (p< 0.001) relative risk reduction of 44% and absolute risk reduction of 1.2% (see Figure 2). The risk reduction for the primary end point was consistent across the following predefined subgroups: age, sex, race, smoking status, family history of premature CHD, body mass index, LDL‑C, HDL‑C, and hsCRP levels.

Figure 2. Time to First Occurrence of Major Cardiovascular Events in JUPITER

figure two
(click image for full-size original)

The individual components of the primary end point are presented in Figure 3. Rosuvastatin significantly reduced the risk of nonfatal myocardial infarction, nonfatal stroke, and arterial revascularization procedures. There were no significant treatment differences between the rosuvastatin and placebo groups for death due to cardiovascular causes or hospitalizations for unstable angina.

Rosuvastatin significantly reduced the risk of myocardial infarction (6 fatal events and 62 nonfatal events in placebo-treated subjects vs. 9 fatal events and 22 nonfatal events in rosuvastatin-treated subjects) and the risk of stroke (6 fatal events and 58 nonfatal events in placebo-treated subjects vs. 3 fatal events and 30 nonfatal events in rosuvastatin-treated subjects).

In a post-hoc subgroup analysis of JUPITER subjects (n=1405; rosuvastatin=725, placebo=680) with a hsCRP ≥2 mg/L and no other traditional risk factors (smoking, BP ≥140/90 or taking antihypertensives, low HDL‑C) other than age, after adjustment for high HDL‑C, there was no significant treatment benefit with rosuvastatin treatment.

Figure 3. Major CV Events by Treatment Group in JUPITER

figure three
(click image for full-size original)

At one year, rosuvastatin increased HDL‑C and reduced LDL‑C, hsCRP, total cholesterol and serum triglyceride levels (p< 0.001 for all versus placebo).

HOW SUPPLIED

Product: 68151-4634

NDC: 68151-4634-9 1 TABLET, FILM COATED in a PACKAGE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Patients should be instructed not to take 2 doses of CRESTOR within 12 hours of each other.

Skeletal Muscle Effects

Patients should be advised to report promptly unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing CRESTOR.

Concomitant Use of Antacids

When taking CRESTOR with an aluminum and magnesium hydroxide combination antacid, the antacid should be taken at least 2 hours after CRESTOR administration.

Embryofetal Toxicity

Advise females of reproductive potential of the risk to a fetus, to use effective contraception during treatment, and to inform their healthcare provider of a known or suspected pregnancy [see Contraindications (4) and Use in Specific Populations (8.1, 8.3)].

Lactation

Advise women not to breastfeed during treatment with CRESTOR [see Contraindications (4) and Use in Specific Populations (8.2)].

Liver Enzymes

It is recommended that liver enzyme tests be performed before the initiation of CRESTOR and if signs or symptoms of liver injury occur. All patients treated with CRESTOR should be advised to promptly report any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.

CRESTOR is a trademark of the AstraZeneca group of companies.

© AstraZeneca 2015, 2016

Licensed from SHIONOGI & CO., LTD., Osaka, Japan

Distributed by:

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

ASTRAZENECA

Rev. May 2016

PATIENT INFORMATION

CRESTOR® (Kres-tor)

rosuvastatin calcium

Tablets

Read this Patient Information carefully before you start taking CRESTOR and each time you get a refill. If you have any questions about CRESTOR, ask your doctor. Only your doctor can determine if CRESTOR is right for you.

What is CRESTOR?

CRESTOR is a prescription medicine that contains a cholesterol-lowering medicine called rosuvastatin calcium. Most of the cholesterol in your blood is made in the liver. CRESTOR works by reducing cholesterol in two ways: CRESTOR blocks an enzyme in the liver causing the liver to make less cholesterol, and CRESTOR increases the uptake and breakdown by the liver of cholesterol already in the blood.

CRESTOR is used along with diet to:

lower the level of your “bad” cholesterol (LDL)
increase the level of your “good” cholesterol (HDL)
lower the level of fat in your blood (triglycerides)
slow the buildup of fatty deposits (plaque) in the walls of blood vessels

CRESTOR is used to treat:

adults who cannot control their cholesterol levels by diet and exercise alone
children 8 to 17 years of age with heterozygous familial hypercholesterolemia (an inherited condition that causes high levels of LDL)
children 7 to 17 years of age with homozygous familial hypercholesterolemia (an inherited condition that causes high levels of LDL).

CRESTOR is not approved for use in children with heterozygous familial hypercholesterolemia younger than 8 years of age or for use in children with homozygous familial hypercholesterolemia younger than 7 years of age.

CRESTOR is used to reduce the risk of heart attacks and strokes in men 50 years of age and older and women 60 years of age and older who do not have known heart disease but do have certain additional risk factors.

It is not known if CRESTOR is safe and effective in people who have Fredrickson Type I and V dyslipidemias.

Who should not take CRESTOR?

Do not take CRESTOR if you:

are allergic to rosuvastatin calcium or any of the ingredients in CRESTOR. See the end of this leaflet for a complete list of ingredients in CRESTOR.
have liver problems.
are pregnant or think you may be pregnant, or are planning to become pregnant. CRESTOR may harm your unborn baby. If you become pregnant, stop taking CRESTOR and call your doctor right away. If you are not planning to become pregnant you should use effective birth control (contraception) while you are taking CRESTOR.
are breastfeeding. Medicines like CRESTOR can pass into your breast milk and may harm your baby.

What should I tell my doctor before and while taking CRESTOR?

Tell your doctor if you:

have unexplained muscle aches or weakness
have or have had kidney problems
have or have had liver problems
drink more than 2 glasses of alcohol daily
have thyroid problems
are 65 years of age or older
are of Asian descent
are pregnant or think you may be pregnant, or are planning to become pregnant
are breastfeeding

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Talk to your doctor before you start taking any new medicines.

Taking CRESTOR with certain other medicines may affect each other causing side effects. CRESTOR may affect the way other medicines work, and other medicines may affect how CRESTOR works.

Especially tell your doctor if you take:

cyclosporine (a medicine for your immune system)
gemfibrozil (a fibric acid medicine for lowering cholesterol)
anti‑viral medicines including HIV or hepatitis C protease inhibitors (such as lopinavir, ritonavir, fosamprenavir, tipranavir, atazanavir, or simeprevir)
certain anti-fungal medicines (such as itraconazole, ketoconazole and fluconazole)
coumarin anticoagulants (medicines that prevent blood clots, such as warfarin)
niacin or nicotinic acid
fibric acid derivatives (such as fenofibrate)
colchicine (a medicine used to treat gout)

Ask your doctor or pharmacist for a list of these medicines if you are not sure.

Know all of the medicines you take. Keep a list of them to show your doctor and pharmacist when you get new medicine.

How should I take CRESTOR?

Take CRESTOR exactly as your doctor tells you to take it.
Take CRESTOR, by mouth, 1 time each day. Swallow the tablet whole.
CRESTOR can be taken at any time of day, with or without food.
Do not change your dose or stop CRESTOR without talking to your doctor, even if you are feeling well.
Your doctor may do blood tests to check your cholesterol levels before and during your treatment with CRESTOR. Your doctor may change your dose of CRESTOR if needed.
Your doctor may start you on a cholesterol lowering diet before giving you CRESTOR. Stay on this diet when you take CRESTOR.
Wait at least 2 hours after taking CRESTOR to take an antacid that contains a combination of aluminum and magnesium hydroxide.
If you miss a dose of CRESTOR, take it as soon as you remember. However, do not take 2 doses of CRESTOR within 12 hours of each other.
If you take too much CRESTOR or overdose, call your doctor or go to the nearest hospital emergency room right away.

What are the Possible Side Effects of CRESTOR?

CRESTOR may cause serious side effects, including:

Muscle pain, tenderness and weakness (myopathy). Muscle problems, including muscle breakdown, can be serious in some people and rarely cause kidney damage that can lead to death. Tell your doctor right away if:
o
you have unexplained muscle pain, tenderness, or weakness, especially if you have a fever or feel more tired than usual, while you take CRESTOR.
o
you have muscle problems that do not go away even after your doctor has told you to stop taking CRESTOR. Your doctor may do further tests to diagnose the cause of your muscle problems.
Your chances of getting muscle problems are higher if you:
o
are taking certain other medicines while you take CRESTOR
o
are 65 years of age or older
o
have thyroid problems (hypothyroidism) that are not controlled
o
have kidney problems
o
are taking higher doses of CRESTOR
Liver problems. Your doctor should do blood tests to check your liver before you start taking CRESTOR and if you have symptoms of liver problems while you take CRESTOR. Call your doctor right away if you have any of the following symptoms of liver problems:
o
feel unusually tired or weak
o
loss of appetite
o
upper belly pain
o
dark urine
o
yellowing of your skin or the whites of your eyes

The most common side effects may include: headache, muscle aches and pains, abdominal pain, weakness, and nausea.

Additional side effects that have been reported with CRESTOR include memory loss and confusion.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of CRESTOR. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store CRESTOR?

Store CRESTOR at room temperature, between 68°F to 77°F (20°C to 25°C) and in a dry place.
Safely throw away medicine that is out of date or no longer needed.

Keep CRESTOR and all medicines out of the reach of children.

What are the Ingredients in CRESTOR?

Active Ingredient: rosuvastatin as rosuvastatin calcium

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.

General Information about the safe and effective use of CRESTOR

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use CRESTOR for a condition for which it was not prescribed. Do not give CRESTOR to other people, even if they have the same medical condition you have. It may harm them.

You can ask your pharmacist or doctor for information about CRESTOR that is written for health professionals.

CRESTOR is a trademark of the AstraZeneca group of companies.

© AstraZeneca 2015, 2016

Licensed from SHIONOGI & CO., LTD., Osaka, Japan

Distributed by:

AstraZeneca Pharmaceuticals LP

Wilmington, DE 19850

For more information, go to the CRESTOR website at www.crestor.com or call 1-800-CRESTOR.

This Patient Information has been approved by the U.S. Food and Drug Administration Revised 5/16

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