AUDIENCE: Rheumatology, Internal Medicine, Patient
ISSUE: FDA is alerting the public that preliminary results from a safety clinical trial show an increased risk of heart-related death with febuxostat (Uloric) compared to another gout medicine called allopurinol. FDA required the febuxostat drug manufacturer, Takeda Pharmaceuticals, to conduct this safety study when the medicine was approved in 2009. Once the final results from the manufacturer are received, FDA will conduct a comprehensive review and will update the public with any new information.
The febuxostat drug labels already carry a Warning and Precaution about cardiovascular events because the clinical trials conducted before approval showed a higher rate of heart-related problems in patients treated with febuxostat compared to allopurinol. These problems included heart attacks, strokes, and heart-related deaths. As a result, FDA required an additional safety clinical trial after the drug was approved and on the market to better understand these differences, and that trial was finished recently.
The safety trial was conducted in over 6,000 patients with gout treated with either febuxostat or allopurinol. The primary outcome was a combination of heart-related death, non-deadly heart attack, non-deadly stroke, and a condition of inadequate blood supply to the heart requiring urgent surgery. The preliminary results show that overall, febuxostat did not increase the risk of these combined events compared to allopurinol. However, when the outcomes were evaluated separately, febuxostat showed an increased risk of heart-related deaths and death from all causes.
BACKGROUND: Febuxostat is FDA-approved to treat a type of arthritis called gout in adults. Gout happens when a naturally occurring substance in the body called uric acid builds up and causes sudden attacks of redness, swelling, and pain in one or more joints. Febuxostat works by lowering uric acid levels in the blood.
RECOMMENDATION: Health care professionals should consider this safety information when deciding whether to prescribe or continue patients on febuxostat. Patients should talk to your health care professionals if you have any questions or concerns. Do not stop taking your medicine without first consulting with your health care professional.
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?
Febuxostat is used to treat gout. Gout is a type of arthritis in which uric acid, a naturally occurring substance in the body, builds up in the joints and causes sudden attacks of redness, swelling, pain, and heat in one or more joints. Febuxostat is in a class of medications called xanthine oxidase inhibitors. It works by decreasing the amount of uric acid that is made in the body. Febuxostat is used to prevent gout attacks, but not to treat them once they occur.
How should this medicine be used?
Febuxostat comes as a tablet to take by mouth. It is usually taken once a day with or without food. Take febuxostat 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 febuxostat exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Your doctor may increase your dose of febuxostat after 2 weeks if a laboratory test shows that you still have too much uric acid in your blood.
It may take several months before febuxostat begins to prevent gout attacks. Febuxostat may increase the number of gout attacks during the first few months of your treatment. Your doctor may prescribe another medication such as colchicine or a nonsteroidal anti-inflammatory drug (NSAID) to prevent gout attacks during the first 6 months of your treatment. Continue to take febuxostat even if you have gout attacks during your early treatment.
Febuxostat controls gout but does not cure it. Continue to take febuxostat even if you feel well. Do not stop taking febuxostat without talking to your doctor.
Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.
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 febuxostat,
- tell your doctor and pharmacist if you are allergic to febuxostat, any other medications, or any of the ingredients in febuxostat. Ask your pharmacist for a list of the ingredients.
- tell your doctor if you are taking azathioprine (Azasan, Imuran), mercaptopurine (Purinethol), or theophylline (Elixophyllin, Theo-24, Uniphyl, others). Your doctor will probably tell you not to take febuxostat if you are taking one or more of these medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention cancer chemotherapy medications. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor if you have or have ever had chest pain; an organ transplant; cancer; a stroke; Lesch-Nyhan syndrome (an inherited disease that causes high levels of uric acid in the blood, joint pain, and problems with motion and behavior); or heart, kidney, or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking febuxostat, call your doctor.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
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 your regular dosing schedule. Do not take a double dose to make up for a missed one.
What side effects can this medication cause?
Febuxostat may cause side effects. Tell your doctor if either of these symptoms is severe or does not go away:
- joint pain
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- chest pain
- shortness of breath
- slow or difficult speech
- dizziness or faintness
- weakness or numbness of an arm or leg
Febuxostat may cause you to have high levels of liver enzymes in your blood. This may be a sign of liver damage. Your doctor will monitor you carefully during your treatment.
Febuxostat may cause other side effects. Call your doctor if you have any unusual problems while 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 it at room temperature, away from light, 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 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 will order certain lab tests to check your body's response to febuxostat.
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.