ISSUE: An FDA safety review has found no clear evidence of an increased risk of heart attacks, stroke, or other cardiovascular events associated with the use of entacapone for the treatment of Parkinson's disease. As a result, recommendations for using entacapone (Comtan) and a combination of entacapone/carbidopa/levodopa (Stalevo) will remain the same in the drug labels.
FDA alerted patients and health care professionals about a possible increased risk for cardiovascular events and death with a combination of entacapone/carbidopa/levodopa in August 2010. This possible safety issue was observed in a clinical trial called the Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) and in a meta-analysis that combined the cardiovascular-related findings from 15 clinical trials comparing a combination of entacapone/carbidopa/levodopa to carbidopa/levodopa. Carbidopa and levodopa have been used extensively and have not been shown to have an increased cardiovascular risk. FDA was concerned that the entacapone in a combination of entacapone/carbidopa/levodopa was responsible for these cardiovascular risks because the comparison drugs do not contain this ingredient.
To better understand the significance of these findings, FDA required the a combination of entacapone/carbidopa/levodopa manufacturer, Novartis, to study the potential for cardiovascular risk with the entacapone component of the drug. FDA examined the results from this required study and from one additional study and concluded they do not show an increased risk of cardiovascular adverse events with entacapone. The results observed in the original meta-analysis were driven by results of a single study (STRIDE-PD), which was not designed to assess cardiovascular risks. FDA believes that the meta-analysis and STRIDE-PD results are chance findings and do not represent a true increase in risk due to entacapone.
BACKGROUND: Entacapone-containing products, Comtan and a combination of entacapone/carbidopa/levodopa, have been shown to be effective in treating symptoms of Parkinson's disease, such as muscle stiffness, tremors, spasms, and poor muscle control. The combination of entacapone with carbidopa and levodopa in entacapone/carbidopa/levodopa has been shown to reduce end-of-dose 'wearing-off' in patients with Parkinson's disease to a greater degree than with entacapone alone or with the two-drug combination of carbidopa and levodopa.
RECOMMENDATION: Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:
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?
Entacapone is an inhibitor of catechol-O-methyltransferase (COMT). It is used in combination with levodopa and carbidopa (Sinemet) to treat the end-of-dose 'wearing-off' symptoms of Parkinson's disease. Entacapone helps the levodopa and carbidopa work better by allowing more of it to reach the brain, where it has its effects.
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
How should this medicine be used?
Entacapone comes as a tablet to take by mouth. It is taken with every dose of levodopa and carbidopa, up to 8 times a day. Entacapone may be taken with or without food. Read your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take entacapone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Entacapone helps control the symptoms of Parkinson's disease, but it does not cure it. Continue to take entacapone even if you feel well. Do not stop taking entacapone without talking to your doctor. Stopping entacapone suddenly may make your Parkinson's disease worse and could have other dangerous effects. Your doctor probably will decrease your dose gradually if necessary.
What special precautions should I follow?
Before taking entacapone,
- tell your doctor and pharmacist if you are allergic to entacapone or any other drugs.
- tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially ampicillin, apomorphine (Zydis), bitolterol (Tornalate), chloramphenicol (AK-Chlor, Chloromycetin), cholestyramine (Cholybar, Questran, Questran Light, others), medications that cause drowsiness (including medications for anxiety and sleeping pills), dobutamine (Dobutrex), epinephrine (AsthmaHaler, EpiPen Auto-Injector, Primatene Mist, others), erythromycin (E-Base, E.E.S., E-Mycin, others), isoetharine (Arm-a-Med Isoetharine, Beta-2, Bronkometer, others), isoproterenol (Dispos-a-Med Isoproterenol, Isuprel, Medihaler-Iso, others), methyldopa (Aldomet), phenelzine (Nardil), probenecid (Benemid), rifampin (Rifadin, Rimactane), tranylcypromine (Parnate), and vitamins and herbal products.
- tell your doctor if you have or have ever had liver disease or a history of alcoholism.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking entacapone, call your doctor.
- if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking entacapone.
- you should know that this medication may make you drowsy. Do not drive a car or operate heavy machinery until you know how entacapone affects you.
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 your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed dose.
What side effects can this medication cause?
Entacapone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- upset stomach
- movements you cannot control
- stomach pain
If you experience any of the following symptoms, call your doctor immediately:
- difficulty breathing
- high fever
- muscle stiffness
- weakness with or without a fever
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 it at room temperature and away from excess heat and moisture (not in the bathroom).
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.
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
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
What other information should I know?
Keep all appointments with your doctor and the laboratory. You may become dizzy when you get up after sitting or lying down, especially when you begin taking entacapone. To avoid this problem, make sure to get up slowly, especially if you have been sitting or lying down for a long time.
Entacapone may cause your urine to change to a brownish-orange color. This effect is common and is not harmful.
Do not let anyone else take your medicine. 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
- Stalevo® (containing Carbidopa, Entacapone, Levodopa)