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AUDIENCE: Health Professional, Consumer
ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: http://www.fda.gov/Drugs/DrugSafety/ucm451800.htm for a list of non-aspirin nonsteroidal anti-inflammatory drug products.
Prescription NSAID labels will be revised to reflect the following information:
The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.
The risk appears greater at higher doses.
It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.
NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.
In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.
Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.
There is an increased risk of heart failure with NSAID use.
BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.
RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety .
Ketorolac is used for the short-term relief of moderately severe pain and should not be used for longer than 5 days, for mild pain, or for pain from chronic (long-term) conditions. You will receive your first doses of ketorolac by intravenous (into a vein) or intramuscular (into a muscle) injection in a hospital or medical office. After that, your doctor may choose to continue your treatment with oral ketorolac. You must stop taking oral ketorolac on the fifth day after you received your first ketorolac injection. Talk to your doctor if you still have pain after 5 days or if your pain is not controlled with this medication. Ketorolac may cause serious side effects, especially when taken improperly. Take ketorolac exactly as directed. Do not take more of it or take it more often than prescribed by your doctor.
People who take nonsteroidal anti-inflammatory drugs (NSAIDs) (other than aspirin) such as ketorolac may have a higher risk of having a heart attack or a stroke than people who do not take these medications. These events may happen without warning and may cause death. This risk may be higher for people who take NSAIDs for a long time. Tell your doctor if you or anyone in your family has or has ever had heart disease, a heart attack, or a stroke or 'ministroke;' if you smoke; and if you have or have ever had high cholesterol, high blood pressure, bleeding or clotting problems, or diabetes. Get emergency medical help right away if you experience any of the following symptoms: chest pain, shortness of breath, weakness in one part or side of the body, or slurred speech.
If you are having surgery, including dental surgery, tell the doctor or dentist that you are taking ketorolac. If you will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not take ketorolac right before or right after the surgery.
NSAIDs such as ketorolac may cause ulcers, bleeding, or holes in the stomach or intestine. These problems may develop at any time during treatment, may happen without warning symptoms, and may cause death. The risk may be higher for people who take NSAIDs for a long time, are older in age, have poor health, or drink large amounts of alcohol while taking ketorolac. Tell your doctor if you take any of the following medications: anticoagulants ('blood thinners') such as warfarin (Coumadin); aspirin; or oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone). Do not take aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn) while you are taking ketorolac. Also tell your doctor if you have or have ever had ulcers or bleeding in your stomach or intestines. If you experience any of the following symptoms, stop taking ketorolac and call your doctor: stomach pain, heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.
Ketorolac may cause kidney failure. Tell your doctor if you have kidney or liver disease, if you have had severe vomiting or diarrhea or think you may be dehydrated, and if you are taking angiotensin-converting enzyme (ACE) inhibitors such as benazepril (Lotensin), captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik); or diuretics ('water pills'). If you experience any of the following symptoms, stop taking ketorolac and call your doctor: swelling of the hands, arms, feet, ankles, or lower legs; unexplained weight gain; confusion; or seizures.
Some people have severe allergic reactions to ketorolac. Tell your doctor if you are allergic to ketorolac, aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn), or any other medications. Also tell your doctor if you have or have ever had asthma, especially if you also have frequent stuffed or runny nose or nasal polyps (swelling of the lining of the nose). If you experience any of the following symptoms, stop taking ketorolac and call your doctor right away: rash; hives; itching; swelling of the eyes, face, throat, tongue, arms, hands, ankles, or lower legs; difficulty breathing or swallowing; or hoarseness.
Do not breastfeed while you are taking ketorolac.
Keep all appointments with your doctor and the laboratory. Your doctor will monitor your symptoms carefully and will probably order certain tests to check your body's response to ketorolac. Be sure to tell your doctor how you are feeling so that your doctor can prescribe the right amount of medication to treat your condition with the lowest risk of serious side effects.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with ketorolac and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website (http://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) to obtain the Medication Guide.
WHY is this medicine prescribed?
Ketorolac is used to relieve moderately severe pain, usually after surgery. Ketorolac is in a class of medications called NSAIDs. It works by stopping the body's production of a substance that causes pain, fever, and inflammation.
HOW should this medicine be used?
Ketorolac comes as a tablet to take by mouth. It is usually taken every 4 to 6 hours on a schedule or as needed for pain. If you are taking ketorolac on a schedule, take it at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand.
Are there OTHER USES for this medicine?
This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
What SPECIAL PRECAUTIONS should I follow?
Before taking ketorolac,
- do not take ketorolac if you are taking probenecid.
- 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 the medications listed in the IMPORTANT WARNING section and any of the following: antidepressants; medications for anxiety or mental illness; medications for seizures such as carbamazepine (Tegretol) or phenytoin (Dilantin); methotrexate (Rheumatrex); sedatives; sleeping pills; and tranquilizers. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
- tell your doctor if you have or have ever had the conditions mentioned in the IMPORTANT WARNING section or swelling of the hands, feet, ankles, or lower legs.
- tell your doctor if you are pregnant, especially if you are in the last few months of your pregnancy, or you plan to become pregnant. If you become pregnant while taking ketorolac, call your doctor.
- talk to your doctor about the risks and benefits of taking ketorolac if you are 65 years of age or older. Older adults should not usually take ketorolac because it is not as safe as other medications that can be used to treat the same condition.
- you should know that this medication may make you drowsy or dizzy. Do not drive a car or operate machinery until you know how this medication affects you.
- talk to your doctor about the safe use of alcohol while taking this medication. Alcohol can make the side effects of ketorolac worse.
What SPECIAL DIETARY instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What should I do IF I FORGET to take a dose?
If your doctor has told you to take ketorolac regularly, 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 medicine cause?
Ketorolac may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- sores in the mouth
Some side effects can be serious. If you experience any of the following symptoms, or those mentioned in the IMPORTANT WARNING section, call your doctor immediately. Do not take any more ketorolac until you speak to your doctor.
- yellowing of the skin or eyes
- excessive tiredness
- unusual bleeding or bruising
- lack of energy
- loss of appetite
- pain in the upper right part of the stomach
- flu-like symptoms
- pale skin
- fast heartbeat
- cloudy, discolored, or bloody urine
- back pain
- difficult or painful urination
Ketorolac may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
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). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
What should I do in case of 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.
Symptoms of overdose may include the following:
- stomach pain
- bloody, black, or tarry stools
- vomit that is bloody or looks like coffee grounds
- slowed breathing or fast, shallow breathing
- coma (loss of consciousness for a period of time)
What OTHER INFORMATION should I know?
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.
- Also available generically