Simvastatin (Cobalt Pharmaceuticals): Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

SIMVASTATIN is the brand name for the substance

• simvastatin, available only on prescription from your doctor.

What the medication is used for:

Your physician has prescribed SIMVASTATIN to lower the levels of cholesterol and fatty substances called triglycerides in your blood and to reduce the health risks associated with Coronary Heart Disease (CHD).

Elevated cholesterol can cause CHD by clogging the blood vessels (atherosclerosis) that carry oxygen and nutrients to the heart.

If you have CHD or other signs of atherosclerosis such as previous stroke, symptoms of peripheral vascular disease, or diabetes (regardless of the amount of cholesterol in your blood), SIMVASTATIN should lessen the risk of heart attack or stroke.

You can also benefit from taking SIMVASTATIN if you have high levels of cholesterol with or without associated high triglycerides (primary hypercholesterolemia, or combined hyperlipidemia) and homozygous familial hypercholesterolemia (high cholesterol inherited from both parents).

As part of your treatment plan to lower cholesterol, and depending on your health and lifestyle, your doctor, nurse or pharmacist may recommend a diet to reduce cholesterol and other measures such as exercise and weight control.

Safety and effectiveness have been studied in 10-17 year old boys and in girls, who had started their menstrual period at least one year before (see Proper Use of this Medication). Simvastatin has not been studied in children under the age of 10 years. For more information, talk to your doctor, nurse or pharmacist.

What it does:

Simvastatin is one of the class of medicines known as HMG-CoA reductase inhibitors. They inhibit, in other words block, an enzyme that is necessary for the body to make cholesterol. In this

way, less cholesterol is produced in the liver. Medicines like this one are prescribed along with, and not as a substitute for, a special diet and other measures. Simvastatin is used to lower the levels of cholesterol [particularly low-density lipoprotein cholesterol (LDL-C)] and fatty substances called triglycerides in your blood.

SIMVASTATIN reduces the amount of cholesterol in your blood. Elevated cholesterol can cause CHD by clogging the blood vessels that carry oxygen and nutrients to the heart.

When it should not be used:

Do not take SIMVASTATIN if you are:

• allergic to simvastatin or any non-medicinal ingredients in the formulation
• diagnosed with active liver disease

• pregnant or breast feeding

• taking any of the following medicines:
• certain antifungal medicines (such as itraconazole, ketoconazole, posaconazole, orvoriconazole)
• HIV protease inhibitors (such as indinavir, nelfinavir, ritonavir, and saquinavir)
• certain hepatitis C virus protease inhibitors (such as boceprevir or telaprevir)
• certain antibiotics (such as erythromycin, clarithromycin, or telithromycin¹)
• antidepressant nefazodone¹
• medicines containing cobicistat
• gemfibrozil (afibric acid medicine for lowering cholesterol)
• cyclosporine
• danazol

Ask your doctor or pharmacist if you are not sure if your medicine is listed above.

What the medicinal ingredient is:

Simvastatin

What the nonmedicinal ingredients are:

Ascorbic acid, magnesium stearate, butylated hydroxyanisole, microcrystalline cellulose, citric acid, pregelatinized starch, talc and lactose monohydrate. Colour coating: Titanium Dioxide, Polydextrose (5 mg, 10 mg, 20 mg, and 80 mg),

Hydroxypropylmethylcellulose, Triacetin, Polyethyleneglycol (5 mg, 10 mg, 20 mg, and 80 mg), Lactose Monohydrate (40 mg), Iron Oxide Yellow (5 mg and 20 mg), Iron Oxide Red (10 mg, 20 mg, and 40 mg), and FD&C Red #40 (80mg).

What dosage forms it comes in:

Tablet 5 mg (cream shield-shaped), 10 mg (pink shield-shaped), 20 mg (tan shield-shaped), 40 mg (pink shield-shaped) and 80 mg (pink capsule-shaped)

WARNINGS AND PRECAUTIONS

Before taking SIMVASTATIN, tell your doctor, nurse or pharmacist if you:

• are pregnant, intend to become pregnant, are breast-

  feeding or intend to breast-feed

• have thyroid problems

• regularly drink three or more alcoholic drinks daily

• are taking any other cholesterol lowering medication

  such as fibrates (gemfibrozil, fenofibrate), niacin or ezetimibe

• are taking any other medications, including prescription,

  nonprescription and natural health products as drug interactions are possible

• have a family history of muscular disorders

• had any past problems with the muscles (pain,

  tenderness), after using an HMG-CoA reductase inhibitor (“statin”) such as atorvastatin (Lipitor*), fluvastatin (Lescol*), lovastatin , pravastatin (Pravachol*), or rosuvastatin (Crestor*), or have developed an allergy or intolerance to them

• have kidney or liver problems

• have diabetes. Slightly increased blood sugar can occur

  when you take SIMVASTATIN Discuss with your doctor, nurse or pharmacist your risk of developing diabetes

• have undergone surgery or other tissue injury
• do excessive physical exercise

• are of childbearing age. Cholesterol compounds are

  essential elements for the development of a fetus. Cholesterol-lowering drugs can harm the fetus. If you are of childbearing age, discuss with your doctor, nurse or pharmacist the potential hazards to the fetus and the importance of birth control methods.

• become pregnant. SIMVASTATIN should not be used

  by pregnant women. If you become pregnant, discontinue use immediately and discuss with your doctor, nurse or pharmacist.

• are Asian.

When starting or increasing the dose of SIMVASTATIN or at any time, if you experience any unexplained muscle pain, tenderness or weakness, you must report promptly to your doctor.

Be sure to tell your doctor you are taking SIMVASTATIN before undergoing any major elective surgery or if you have any other new major medical issues.

INTERACTIONS WITH THIS MEDICATION

You should tell your doctor, nurse or pharmacist about all drugs that you are using or plan to use, including those obtained without a prescription, while taking SIMVASTATIN. You should also tell any doctor who is prescribing a new medication for you that you are taking SIMVASTATIN.

Because taking SIMVASTATIN with any of the following drugs or substances can increase the risk of muscle problems (see Side Effects of this medicine - and what you should do), it is particularly important to tell your doctor, nurse or pharmacist if you are taking:

• antifungal agents (such as itraconazole, ketoconazole, posaconazole, or voriconazole)
• HIV protease inhibitors (such as indinavir, nelfinavir, ritonavir, and saquinavir)
• boceprevir or telaprevir (drugs used to treat hepatitis C virus infection)

• the antibiotics (erythromycin, clarithromycin,

  telithromycin¹, and fusidic acid (intravenous¹ or oral¹)

• the antidepressant nefazodone¹
• medicines containing cobicistat
• cyclosporine (immunosuppressant)
• danazol

• fibrates/fibric acid derivatives (bezafibrate and

  gemfibrozil) (drugs to treat lipid problems)

• amiodarone (a drug used to treat an irregular heartbeat)
• verapamil or diltiazem or amlodipine (drugs used to treat high blood pressure, angina, or other heart conditions)
• lomitapide (a drug used to treat a serious and rare genetic cholesterol condition)

• grapefruit juice (which should be avoided while taking

  SIMVASTATIN).

It is also important to tell your doctor, nurse or pharmacist if you are taking corticosteroids, anticoagulants (drug that prevents blood clots, such as warfarin), colchicine (a medicine used for gout), digoxin (a drug used to treat heart problems), niacin or fenofibrate, another fibric acid derivative. Also tell your doctor if you are taking niacin or a niacin-containing product and are Chinese.

Some of these have already been listed in the above section “When it should not be used”.

PROPER USE OF THIS MEDICATION

Usual Dose:

• Take your medication exactly as your doctor, nurse or pharmacist instructed. Do not change the dose unless directed by your doctor. It is usually recommended as a single dose with the evening meal. Because of the increased risk of muscle problems taking 80 mg each day is only recommended for patients who have been taking this amount for a long time with no muscle problems or for patients at high risk of heart disease problems who have problems taking other statins. It is important to continue taking the tablets as instructed. Do not alter the dosage or stop taking the medicine without consulting your doctor, nurse or pharmacist.
• For children (10-17 years old), the recommended usual starting dose is 10 mg a day in the evening. The maximum recommended dose is 40 mg a day.
• Carefully follow any measures that your doctor, nurse or pharmacist has recommended for diet, exercise or weight control.

¹ not Marketed in Canada

• When taking SIMVASTATIN, you should avoid

  consuming grapefruit juice.

• When taking SIMVASTATIN concurrently with

  cholestyramine or any other resin, an interval of at least two hours should be maintained between the two drugs.

• Keep your appointments regularly with your doctor,

  nurse or pharmacist so that your blood can be tested and your progress checked at proper intervals.

• Avoid drinking large quantities of alcohol.

• Do not start taking any other medicines unless you

  have discussed the matter with your doctor, nurse or pharmacist.

• Let your doctor, nurse or pharmacist know if you suffer a

  severe injury, or severe infection.

• If you have to undergo any kind of surgery, tell your

  doctor, nurse or pharmacist about the planned surgery; and also inform the doctor in charge that you are taking this medicine.

Overdose:

In case of drug overdose, contact a health care practitioner, hospital emergency department or regional Poison Control Centre immediately, even if there are no symptoms.

Missed Dose:

If you miss taking a tablet at its usual time, take it as soon as possible. But, if it is too close to the time of your next dose: take only the prescribed dose at the appointed time. Do not take a double dose.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

Along with its intended action, any medication may cause unwanted effects.

The following side effects that may occur, generally do not require medical attention, and may come and go during treatment. If any of the following persist or become troublesome, do check with your doctor, nurse or pharmacist:

Constipation, diarrhea, gas, stomach upset, nausea Pain in the abdomen

Headache

Skin rash

Poor memory

Memory loss

Confusion

Trouble sleeping

Depression

Erectile dysfunction

Breathing problems including persistent cough and/or shortness of breath or fever.

Possible side effects reported with other statins: Sleep disturbances, including nightmares.

Side effects such as myalgia (muscle pain), myopathy (muscle disease with aching or weakness [that in very rare cases may not go away after stopping SIMVASTATIN]), rhabdomyolysis (a muscle wasting disease or muscle breakdown), associated tenderness and rare cases of muscle breakdown resulting in kidney damage that can lead to death have been reported with other drugs of this class, known as HMG-CoA reductase inhibitors (“statins”), including SIMVASTATIN. This risk of muscle breakdown is greater for patients taking higher doses of SIMVASTATIN, particularly the 80 mg dose. This risk of muscle breakdown is greater for older patients (65 years of age and older), female patients, patients with abnormal kidney function and patients with thyroid problems.

See your doctor regularly to check your cholesterol level and to check for side effects. Your doctor should do blood tests to check your liver before you start taking SIMVASTATIN and if you have any symptoms of liver problems while you take SIMVASTATIN.

SIMVASTATIN can cause abnormal blood test results. Your doctor will decide when to perform blood tests and will interpret the results.

This is not a complete list of side effects. For any unexpected effects while taking SIMVASTATIN, contact your doctor, nurse or pharmacist.

HOW TO STORE IT

Store your tablets at room temperature (15°C - 30°C), in the original package, away from heat and direct light, and out of damp places, such as the bathroom or kitchen.

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

Do not use outdated medicine.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

• Report online at www.healthcanada.gc.ca/medeffect
• Call toll-free at 1-866-234-2345

• Complete a Canada Vigilance Reporting Form and

  • Fax toll-free to 1-866-678-6789, or

  • Mail to: Canada Vigilance Program

    Health Canada

    Postal Locator 0701E Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^™ Canada Web site at www.healthcanada.gc.ca/medeffect.

MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be obtained by contacting Cobalt Pharmaceuticals Inc., at: 1-866-254-6111.

Cobalt Pharmaceuticals Inc.

6733 Mississauga Road, Suite 400

Mississauga, Ontario

L5N 6J5

Last revised: May 12, 2015.