AUDIENCE: Patient, Health Professional, OBGYN, Cardiology, Endocrinology, Pharmacy
ISSUE: The FDA is requesting revisions to the information about use in pregnancy in the prescribing information of the entire class of statin medicines. These changes include removing the contraindication against using these medicines in all pregnant patients. A contraindication is FDA's strongest warning and is only added when a medicine should not be used because the risk clearly outweighs any possible benefit. Because the benefits of statins may include prevention of serious or potentially fatal events in a small group of very high-risk pregnant patients, contraindicating these drugs in all pregnant women is not appropriate.
FDA expects removing the contraindication will enable health care professionals and patients to make individual decisions about benefit and risk, especially for those at very high risk of heart attack or stroke. This includes patients with homozygous familial hypercholesterolemia and those who have previously had a heart attack or stroke.
BACKGROUND: Statins are a class of prescription medicines that have been used for decades to lower low-density lipoprotein (LDL-C or "bad") cholesterol in the blood. Medicines in the statin class include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.
- Patients: Patients taking statins should notify their health care professionals if they become pregnant or suspect they are pregnant. Your health care professional will be able to advise whether you should stop taking the medicine during pregnancy and whether you may stop your statin temporarily while breastfeeding. Patients who are at high risk of heart attack or stroke who require statins after giving birth should not breastfeed and should use alternatives such as infant formula.
- Health Care Professionals: Health care professionals should discontinue statin therapy in most pregnant patients, or they can consider the ongoing therapeutic needs of the individual patient, particularly those at very high risk for cardiovascular events during pregnancy. Because of the chronic nature of cardiovascular disease, treatment of hyperlipidemia is not generally necessary during pregnancy. Discuss with patients whether they may discontinue statins temporarily while breastfeeding. Advise those who require a statin because of their cardiovascular risk that breastfeeding is not recommended because the medicine may pass into breast milk
The FDA hopes the revised language in the prescribing information will help reassure health care professionals that statins are safe to prescribe in patients who can become pregnant, and help them reassure patients with unintended statin exposure in early pregnancy or before pregnancy is recognized that the medicine is unlikely to harm the unborn baby.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Why is this medication prescribed?
Simvastatin is used together with diet, weight-loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Simvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol (''bad cholesterol'') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol (''good cholesterol'') in the blood. Simvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Simvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.
Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.
How should this medicine be used?
Simvastatin comes as a tablet and as a suspension to take by mouth. The tablets are usually taken once a day in the evening. The suspension is usually taken once a day in the evening on an empty stomach. Take simvastatin at around the same time every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take simvastatin exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Shake suspension well for at least 20 seconds before each use.
If you will be taking the simvastatin suspension, do not use a household teaspoon to measure your dose. Household teaspoons are not accurate measuring devices, and you may receive too much medication or not enough medication if you measure your dose with a household teaspoon. Instead, use a properly marked measuring device such as a medicine spoon or oral syringe. Ask your doctor or pharmacist if you need help getting or using a measuring device.
Your doctor may start you on a low dose of simvastatin and gradually increase your dose, not more than once every 4 weeks.
Continue to take simvastatin even if you feel well. Do not stop taking simvastatin without talking to your doctor.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before taking simvastatin,
- tell your doctor and pharmacist if you are allergic to simvastatin, any other medications, or any of the ingredients in simvastatin tablets or oral suspension. Ask your doctor or pharmacist for a list of the ingredients.
- tell your doctor if you are taking antifungal medications such as itraconazole (Sporanox), ketoconazole (Nizoral), posaconazole (Noxafil) and voriconazole (Vfend); clarithromycin (Biaxin, in Prevpac); cobicistat-containing medications (Stribild); cyclosporine (Gengraf, Neoral, Sandimmune); danazol; erythromycin (E.E.S., E-Mycin, Erythrocin); gemfibrozil (Lopid); HIV protease inhibitors such as atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), saquinavir (Invirase), and tipranavir (Aptivus); nefazodone; telaprevir (Incivek); and telithromycin (Ketek). Your doctor will probably tell you not to take simvastatin if you are taking these medications.
- tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amiodarone (Cordarone, Pacerone); amlodipine (Norvasc, in Caduet, in Lotrel); anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven); colchicine (Colcrys); digoxin (Digitek, Lanoxicaps, Lanoxin); diltiazem (Cardizem, Dilacor, Tiazac); dronedarone (Multaq); other cholesterol-lowering medications such as fenofibrate (Tricor), lomitapide (Juxtapid), and niacin (nicotinic acid, Niacor, Niaspan); ranolazine (Ranexa); and verapamil (Calan, Covera, Isoptin, Verelan). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Other medications may also interact with simvastatin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have liver disease. Your doctor will order blood tests to see how well your liver is working even if you do not think you have liver disease. Your doctor will probably tell you not to take simvastatin if you have liver disease or if the tests show that you may be developing liver disease.
- tell your doctor if you drink more than two alcoholic beverages per day, if you are 65 years of age or older, or if you are Asian, especially if you are Chinese. Also tell your doctor if you have or have ever had an underactive thyroid gland, diabetes, seizures, muscle aches or weakness, low blood pressure, or kidney disease.
- tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant during your treatment with simvastatin. Talk to your doctor about birth control methods that will work for you. If you become pregnant while taking simvastatin, stop taking simvastatin and call your doctor immediately. Simvastatin can harm the fetus.
- tell your doctor if you are breastfeeding. You should not breastfeed while you are taking simvastatin.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking simvastatin. If you are hospitalized due to serious injury or infection, tell the doctor who treats you that you are taking simvastatin.
- ask your doctor about the safe use of alcoholic beverages while you are taking simvastatin. Alcohol can increase the risk of serious side effects.
What special dietary instructions should I follow?
Eat a low-fat, low-cholesterol diet. Be sure to follow all exercise and dietary recommendations made by your doctor or dietitian. You can also visit the National Cholesterol Education Program (NCEP) website for additional dietary information at http://www.nhlbi.nih.gov/health/public/heart/chol/chol_tlc.pdf.
Avoid drinking grapefruit juice while taking simvastatin.
What should I do if I forget a dose?
Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue the regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Simvastatin may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- stomach pain
- memory loss or forgetfulness
- itchy or red skin
Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or get emergency medical help.
- muscle pain, tenderness, or weakness with or without fever or lack of energy
- dark red urine
- decreased urination
- lack of energy, tiredness, or weakness
- loss of appetite
- pain in the upper right part of the stomach
- yellowing of the skin or eyes
- dark colored urine
- fever or chills
- swelling of the face, throat, tongue, lips, eyes, hands, feet, ankles, or lower legs
- difficulty breathing or swallowing
- joint pain
- sensitivity to light
This medication may cause other side effects. Call your doctor if you have any unusual problems while you are taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
What should I know about storage and disposal of this medication?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the tablets at room temperature and away from excess heat and moisture (not in the bathroom). Store the suspension at room temperature. Do not freeze or refrigerate the suspension. Be sure to use the suspension within 30 days of opening the bottle and discard any remaining medication after 30 days.
It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org
Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.
In case of emergency/overdose
In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests during your treatment, especially if you develop symptoms of liver damage.
Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking simvastatin.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Brand names of combination products
- Juvisync® (containing Simvastatin, Sitagliptin)¶
- Simcor® (containing Niacin, Simvastatin)
- Vytorin® (containing Ezetimibe, Simvastatin)
¶ This branded product is no longer on the market. Generic alternatives may be available.