4 CONTRAINDICATIONS

4.1 Active liver disease, which may include unexplained persistent

elevations in hepatic transaminase levels

4.2 Hypersensitivity to any component of this medication

4.3 Pregnancy

Women who are pregnant or may become pregnant. Atorvastatin may cause fetal harm when administered to a pregnant woman. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Atherosclerosis is a chronic process and discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of atorvastatin use during pregnancy; however in rare reports, congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, atorvastatin revealed no evidence of teratogenicity. ATORVASTATIN 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, atorvastatin should be discontinued immediately and the patient apprised of the potential hazard to the fetus [see Use in Specific Populations (8.1)].

4.4 Nursing mothers

It is not known whether atorvastatin is excreted into human milk; however a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require atorvastatin treatment should not breastfeed their infants [see Use in Specific Populations (8.3)].

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category X

Atorvastatin calcium is contraindicated in women who are or may become pregnant. Serum cholesterol and triglycerides increase during normal pregnancy. Lipid lowering drugs offer no benefit during pregnancy because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy.

There are no adequate and well-controlled studies of atorvastatin use during pregnancy. There have been rare reports of congenital anomalies following intrauterine exposure to statins. In a review of about 100 prospectively followed pregnancies in women exposed to other statins, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed the rate expected in the general population. However, this study was only able to exclude a three-to-four-fold increased risk of congenital anomalies over background incidence. In 89% of these cases, drug treatment started before pregnancy and stopped during the first trimester when pregnancy was identified.

Atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. Atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. These doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure based on surface area (mg/m2) [see Contraindications, Pregnancy (4.3)].

In a study in rats given 20, 100, or 225 mg/kg/day, from gestation day 7 through to lactation day 21 (weaning), there was decreased pup survival at birth, neonate, weaning, and maturity in pups of mothers dosed with 225 mg/kg/day. Body weight was decreased on days 4 and 21 in pups of mothers dosed at 100 mg/kg/day; pup body weight was decreased at birth and at days 4, 21, and 91 at 225 mg/kg/day. Pup development was delayed (rotorod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). These doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human AUC at 80 mg/day.

Statins may cause fetal harm when administered to a pregnant woman. Atorvastatin calcium should be administered to women of childbearing potential only when such patients are highly unlikely to conceive and have been informed of the potential hazards. If the woman becomes pregnant while taking atorvastatin calcium, it should be discontinued immediately and the patient advised again as to the potential hazards to the fetus and the lack of known clinical benefit with continued use during pregnancy.

8.3 Nursing Mothers

It is not known whether atorvastatin is excreted in human milk, but a small amount of another drug in this class does pass into breast milk. Nursing rat pups had plasma and liver drug levels of 50% and 40%, respectively, of that in their mother’s milk. Animal breast milk drug levels may not accurately reflect human breast milk levels. Because another drug in this class passes into human milk and because statins have a potential to cause serious adverse reactions in nursing infants, women requiring atorvastatin treatment should be advised not to nurse their infants [see Contraindications (4)].

8.4 Pediatric Use

Safety and effectiveness in patients 10 to 17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial of 6 months’ duration in adolescent boys and postmenarchal girls. Patients treated with atorvastatin calcium had an adverse experience profile generally similar to that of patients treated with placebo. The most common adverse experiences observed in both groups, regardless of causality assessment, were infections.**Doses greater than 20 mg have not been studied in this patient population.**In this limited controlled study, there was no significant effect on growth or sexual maturation in boys or on menstrual cycle length in girls [see Clinical Studies (14.6); Adverse Reactions, Pediatric Patients (ages 10 to 17 years) (6.3); and Dosage and Administration, Heterozygous Familial Hypercholesterolemia in Pediatric Patients (10 to 17 years of age) (2.2)]. Adolescent females should be counseled on appropriate contraceptive methods while on atorvastatin therapy [see Contraindications, Pregnancy (4.3) and Use in Specific Populations, Pregnancy (8.1)]. Atorvastatin has not been studied in controlled clinical trials involving pre-pubertal patients or patients younger than 10 years of age.

Clinical efficacy with doses up to 80 mg/day for 1 year have been evaluated in an uncontrolled study of patients with homozygous FH including 8 pediatric patients [see Clinical Studies, Homozygous Familial Hypercholesterolemia (14.5)].

8.5 Geriatric Use

Of the 39,828 patients who received atorvastatin calcium in clinical studies, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older adults cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, atorvastatin calcium should be prescribed with caution in the elderly.

8.6 Hepatic Impairment

Atorvastatin calcium is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels [see Contraindications (4) and Pharmacokinetics (12.3)].

10 OVERDOSAGE

There is no specific treatment for atorvastatin overdosage. In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. Due to extensive drug binding to plasma proteins, hemodialysis is not expected to significantly enhance atorvastatin clearance.

15 REFERENCES

1National Cholesterol Education Program (NCEP): Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents, Pediatrics. 89(3):495-501. 1992.

16 HOW SUPPLIED/STORAGE AND HANDLING

Atorvastatin calcium tablets are supplied as white, oval, biconvex film-coated tablets of atorvastatin calcium containing 10, 20, 40 and 80 mg atorvastatin.

**10 mg tablets:**Atorvastatin calcium tablets, 10 mg, are available for oral administration as white, oval, biconvex film-coated tablets, engraved “APO” on one side, “A10” on the other side.

Bottles of 30 (NDC 60505-2578-3)

Bottles of 90 (NDC 60505-2578-9)

Bottles of 500 (NDC 60505-2578-5)

Bottles of 1,000 (NDC 60505-2578-8)

Bottles of 5,000 (NDC60505-2578-7)

Blister of 100 (NDC 60505-2578-0)

**20 mg tablets:**Atorvastatin calcium tablets, 20 mg, are available for oral administration as white, oval, biconvex film-coated tablets, engraved “APO” on one side, “ATV20” on the other side.

Bottles of 30 (NDC 60505-2579-3)

Bottles of 90 (NDC 60505-2579-9)

Bottles of 500 (NDC 60505-2579-5)

Bottles of 1,000 (NDC 60505-2579-8)

Bottles of 5,000 (NDC 60505-2579-7)

Blister of 100 (NDC 60505-2579-0)

**40 mg tablets:**Atorvastatin calcium tablets, 40 mg, are available for oral administration as white, oval, biconvex film-coated tablets, engraved “APO” on one side, “ATV40” on the other side.

Bottles of 30 (NDC 60505-2580-3)

Bottles of 90 (NDC 60505-2580-9)

Bottles of 500 (NDC 60505-2580-5)

Bottles of 1,000 (NDC 60505-2580-8)

Bottles of 4,000 (NDC 60505-2580-7)

Blister of 100 (NDC 60505-2580-0)

**80 mg tablets:**Atorvastatin calcium tablets, 80 mg, are available for oral administration as white, oval, biconvex film-coated tablets, engraved “APO” on one side, “ATV80” on the other side.

Bottles of 30 (NDC 60505-2671-3)

Bottles of 90 (NDC 60505-2671-9)

Bottles of 500 (NDC60505-2671-5)

Bottles of 1,000 (NDC 60505-2671-8)

Bottles of 2,500 (NDC 60505-2671-7)

Blister of 100 (NDC 60505-2672-0)

StorageStore at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Dispense in a tight container [see USP].

PATIENT INFORMATION

Atorvastatin Calcium Tablets

Read the Patient Information that comes with atorvastatin calcium tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or treatment.

If you have any questions about atorvastatin calcium tablets, ask your doctor or pharmacist.

What are atorvastatin calcium tablets?

Atorvastatin calcium tablets are a prescription medicine that lowers cholesterol in your blood. It lowers the LDL-C ("bad" cholesterol) and triglycerides in your blood. It can raise your HDL-C ("good" cholesterol) as well. Atorvastatin calcium tablets are for adults and children over 10 whose cholesterol does not come down enough with exercise and a low-fat diet alone.

Atorvastatin calcium tablets can lower the risk for heart attack, stroke, certain types of heart surgery, and chest pain in patients who have heart disease or risk factors for heart disease such as:

•

age, smoking, high blood pressure, low HDL-C, heart disease in the family. 

Atorvastatin calcium tablets can lower the risk for heart attack or stroke in patients with diabetes and risk factors such as:

•

eye problems, kidney problems, smoking, or high blood pressure. 

Atorvastatin calcium tablets start to work in about 2 weeks.

What is Cholesterol?

Cholesterol and triglycerides are fats that are made in your body. They are also found in foods. You need some cholesterol for good health, but too much is not good for you. Cholesterol and triglycerides can clog your blood vessels. It is especially important to lower your cholesterol if you have heart disease, smoke, have diabetes or high blood pressure, are older, or if heart disease starts early in your family.

Who Should Not Take Atorvastatin Calcium Tablets?

Do not take atorvastatin calcium tablets if you:

•

are pregnant or think you may be pregnant, or are planning to become pregnant. Atorvastatin calcium tablets may harm your unborn baby. If you get pregnant, stop taking atorvastatin calcium tablets and call your doctor right away. 

•

are breast feeding. Atorvastatin calcium tablets can pass into your breast milk and may harm your baby. 

•

have liver problems.

•

are allergic to atorvastatin calcium tablets or any of its ingredients. The active ingredient is atorvastatin. See the end of this leaflet for a complete list of ingredients in atorvastatin calcium tablets. 

Atorvastatin calcium tablets have not been studied in children under 10 years of age.

Before You Start Atorvastatin Calcium Tablets

Tell your doctor if you:

•

have muscle aches or weakness

•

drink more than 2 glasses of alcohol daily

•

have diabetes

•

have a thyroid problem 

•

have kidney problems 

Some medicines should not be taken with atorvastatin calcium tablets. Tell your doctor about all the medicines you take, including prescription and non- prescription medicines, vitamins, and herbal supplements. Atorvastatin calcium tablets and certain other medicines can interact causing serious side effects. Especially tell your doctor if you take medicines for:

•

your immune system

•

cholesterol

•

infections 

•

birth control

•

heart failure

•

HIV or AIDS 

Know all the medicines you take. Keep a list of them with you to show your doctor and pharmacist.

How Should I Take Atorvastatin Calcium Tablets?

•

Take atorvastatin calcium tablets exactly as prescribed by your doctor. Do not change your dose or stop atorvastatin calcium tablets without talking to your doctor. Your doctor may do blood tests to check your cholesterol levels during your treatment with atorvastatin calcium tablets. Your dose of atorvastatin calcium tablets may be changed based on these blood test results. 

•

Take atorvastatin calcium tablets each day at any time of day at about the same time each day. Atorvastatin calcium tablets can be taken with or without food. Don't break atorvastatin calcium tablets before taking. 

•

Your doctor should start you on a low-fat diet before giving you atorvastatin calcium tablets. Stay on this low-fat diet when you take atorvastatin calcium tablets. 

•

If you miss a dose of atorvastatin calcium tablets, take it as soon as you remember. Do not take atorvastatin calcium tablets if it has been more than 12 hours since you missed your last dose. Wait and take the next dose at your regular time. Do not take 2 doses of atorvastatin calcium tablets at the same time. 

•

If you take too much atorvastatin calcium tablets or overdose, call your doctor or Poison Control Center right away. Or go to the nearest emergency room. 

What Should I Avoid While Taking Atorvastatin Calcium Tablets?

•

Talk to your doctor before you start any new medicines. This includes prescription and nonprescription medicines, vitamins, and herbal supplements. Atorvastatin calcium tablets and certain other medicines can interact causing serious side effects. 

•

Do not get pregnant. If you get pregnant, stop taking atorvastatin calcium tablets right away and call your doctor. 

What are the Possible Side Effects of Atorvastatin Calcium Tablets?

Atorvastatin calcium tablets can cause serious side effects. These side effects have happened only to a small number of people. Your doctor can monitor you for them. These side effects usually go away if your dose is lowered or atorvastatin calcium tablets are stopped. These serious side effects include:

•

**Muscle problems.**Atorvastatin calcium tablets can cause serious muscle problems that can lead to kidney problems, including kidney failure. You have a higher chance for muscle problems if you are taking certain other medicines with atorvastatin calcium tablets.

•

**Liver problems.**Your doctor should do blood tests to check your liver before you start taking atorvastatin calcium tablets and if you have symptoms of liver problems while you take atorvastatin calcium tablets. Call your doctor right away if you have the following symptoms of liver problems:

•

feel tired or weak 

•

loss of appetite 

•

upper belly pain 

•

dark amber colored urine 

•

yellowing of your skin or the whites of your eyes 

Call your doctor right away if you have:

•

muscle problems like weakness, tenderness, or pain that happen without a good reason, especially if you also have a fever or feel more tired than usual. This may be an early sign of a rare muscle problem. 

•

muscle problems that do not go away even after your doctor has advised you to stop taking atorvastatin calcium tablets. Your doctor may do further tests to diagnose the cause of your muscle problems. 

•

allergic reactions including swelling of the face, lips, tongue, and/or throat that may cause difficulty in breathing or swallowing which may require treatment right away.

•

nausea and vomiting.

•

passing brown or dark-colored urine.

•

you feel more tired than usual 

•

your skin and whites of your eyes get yellow.

•

stomach pain.

•

allergic skin reactions. 

In clinical studies, patients reported the following common side effects while taking atorvastatin calcium tablets: diarrhea, upset stomach, muscle and joint pain, and alterations in some laboratory blood tests.

The following additional side effects have been reported with atorvastatin calcium tablets: tiredness, tendon problems, memory loss and confusion.

Talk to your doctor or pharmacist if you have side effects that bother you or that will not go away.

These are not all the side effects of atorvastatin calcium tablets. Ask your doctor or pharmacist for a complete list.****

How do I store Atorvastatin Calcium Tablets

•

Store atorvastatin calcium tablets at room temperature, 68 to 77°F (20 to 25°C).

•

Do not keep medicine that is out of date or that you no longer need.

•

**Keep atorvastatin calcium tablets and all medicines out of the reach of children.**Be sure that if you throw medicine away, it is out of the reach of children. 

General Information About Atorvastatin Calcium Tablets

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use atorvastatin calcium tablets for a condition for which it was not prescribed. Do not give atorvastatin calcium tablets to other people, even if they have the same problem you have. It may harm them.

This leaflet summarizes the most important information about atorvastatin calcium tablets. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about atorvastatin calcium tablets that is written for health professionals.

What are the Ingredients in Atorvastatin Calcium Tablets?

**Active Ingredient:**atorvastatin calcium

Inactive Ingredients:calcium acetate, croscarmellose sodium, sodium carbonate, microcrystalline cellulose, magnesium stearate (vegetable source), colloidal silicon dioxide, hypromellose, hydroxypropyl cellulose, polyethylene glycol and titanium dioxide.

Manufactured By: Manufactured For:

Apotex Inc. Apotex Corp.

Toronto, ON Weston, Florida

Canada, M9L 1T9 33326

Revised: June 2013

Rev. 6