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: Web Sitefor 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: Web Siteand Web Site.
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 ( Web Site) to obtain the Medication Guide.