AUDIENCE: Consumer, Patient, Health Professional, Pharmacy
ISSUE: FDA is warning that use of NSAIDs around 20 weeks or later in pregnancy may cause rare but serious kidney problems in an unborn baby. This can lead to low levels of amniotic fluid surrounding the baby and possible complications.
For prescription NSAIDs, FDA is requiring changes to the prescribing information to describe the risk of kidney problems in unborn babies that result in low amniotic fluid.
For over-the-counter (OTC) NSAIDs intended for use in adults, FDA will also update the Drug Facts labels, available at: http://bit.ly/2Uadlbz. These labels already warn to avoid using NSAIDs during the last 3 months of pregnancy because the medicines may cause problems in the unborn child or complications during delivery. The Drug Facts labels already advise pregnant and breastfeeding women to ask a health care professional before using these medicines.
- are a class of medicines available by prescription and OTC. They are some of the most commonly used medicines for pain and fever.
- are used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.
- work by blocking the production of certain chemicals in the body that cause inflammation.
- are available alone and combined with other medicines. Examples of NSAIDs include aspirin, ibuprofen, naproxen, diclofenac, and celecoxib.
Common side effects of NSAIDs include: stomach pain, constipation, diarrhea, gas, heartburn, nausea, vomiting, and dizziness.
- If you are pregnant, do not use NSAIDs at 20 weeks or later in pregnancy unless specifically advised to do so by your health care professional because these medicines may cause problems in your unborn baby.
- Many OTC medicines contain NSAIDs, including those used for pain, colds, flu, and insomnia, so it is important to read the Drug Facts labels, available at: http://bit.ly/2Uadlbz, to find out if the medicines contain NSAIDs.
- Talk to your health care professional or pharmacist if you have questions or concerns about NSAIDs or which medicines contain them.
- Other medicines, such as acetaminophen, are available to treat pain and fever during pregnancy. Talk to your pharmacist or health care professional for help deciding which might be best.
Health Care Professionals
- FDA recommends that health care professionals should limit prescribing NSAIDs between 20 to 30 weeks of pregnancy and avoid prescribing them after 30 weeks of pregnancy. If NSAID treatment is determined necessary, limit use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours and discontinue the NSAID if oligohydramnios is found. FDA is warning that use of NSAIDs around 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment.
- These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.
- Oligohydramnios is often, but not always, reversible with treatment discontinuation.
- Complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.
- If NSAID treatment is deemed necessary between 20 to 30 weeks of pregnancy, limit use to the lowest effective dose and shortest duration possible. As currently described in the NSAID labels, avoid prescribing NSAIDs at 30 weeks and later in pregnancy because of the additional risk of premature closure of the fetal ductus arteriosus.
- The above recommendations do not apply to low-dose 81 mg aspirin prescribed for certain conditions in pregnancy.
- Consider ultrasound monitoring of amniotic fluid if NSAID treatment extends beyond 48 hours. Discontinue the NSAID if oligohydramnios occurs and follow up according to clinical practice.
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 moderate to moderately severe pain and should not be used for longer than 5 days in a row, for mild pain, or for pain from chronic (long-term) conditions. You may be given ketorolac to take by mouth or as an injection before you begin using ketorolac nasal spray. You must stop using nasal ketorolac on the fifth day after you receive your first dose of ketorolac in any form. Talk to your doctor if you still have pain after 5 days of treatment with ketorolac.
Ketorolac nasal spray should not be used to relieve pain in children 17 years of age or younger.
People who use 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 use these medications. These events may happen without warning and may cause death. This risk may be higher for people who use 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, numbness or weakness in one part or side of the body, trouble seeing in one or both eyes, trouble walking or loss of balance or coordination, severe headache with no known cause, or slurred speech.
If you will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not use 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 than 65 years of age, have poor health, drink alcohol, or smoke while using 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); or selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft). Do not take aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn) or any other forms of ketorolac while you are using ketorolac nasal spray. 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 using 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 an increased risk of bleeding. It may take longer than usual for you to stop bleeding if you are cut or injured. Tell your doctor if you have or have ever had a bleeding disorder, or bleeding in your brain. Your doctor will probably tell you not to use ketorolac nasal spray. Call your doctor if you have bleeding that is unusual or if you fall and get hurt, especially if you hit your head.
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); angiotensin II receptor blockers such as azilsartan (Edarbi), candesartan(Atacand), eprosartan (Teveten), irbesartan (Avapro, in Avalide), losartan (Cozaar, in Hyzaar), olmesartan (Benicar, in Azor), telmisartan (Micardis), and valsartan (Diovan, in Exforge); or diuretics ('water pills'). If you experience any of the following symptoms, stop using ketorolac and call your doctor: swelling of the hands, arms, feet, ankles, or lower legs; unexplained weight gain; decreased urination, confusion; or seizures.
Keep all appointments with your doctor. 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. 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) to obtain the Medication Guide.
Talk to your doctor about the risks of using ketorolac nasal spray.
Why is this medication prescribed?
Ketorolac nasal spray is used for the short-term relief of moderate to moderately severe pain. 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?
Nasal ketorolac comes as a liquid to spray in the nose. It is usually used once every 6 to 8 hours as needed to control pain for up to 5 days. Use ketorolac nasal spray exactly as directed. Do not use more or less of it or use it more often than prescribed by your doctor.
Ketorolac nasal spray comes in bottles that each contain a one-day supply of medication. Do not use any single bottle of ketorolac nasal spray for more than one day. Dispose of the bottle within 24 hours of using the first dose, even if the bottle still contains some medication. You will receive enough bottles of medication so that you have a new bottle to use for each day of treatment.
Before you use ketorolac nasal spray for the first time, read the written instructions that come with the medication. Be sure that you understand how to prepare the bottle before the first use and how to use the spray. Ask your doctor or pharmacist if you have any questions about how to use this medication.
Ketorolac nasal spray is only for use in the nose. Be careful not to get the medication in your eyes. If you do get ketorolac nasal spray in your eye, wash out the eye with water or sterile saline solution and call your doctor if irritation lasts longer than an hour.
You may have an uncomfortable feeling in your throat after you use ketorolac nasal spray. If this happens, drink a sip of water.
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 using ketorolac nasal spray,
- Tell your doctor if you are allergic to ketorolac, aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn), any other medications, or ethylendiamine tetraacetic acid (EDTA; an ingredient found in some foods and medications), or any of the other ingredients in ketorolac nasal spray. Ask your pharmacist for a list of the ingredients.
- tell your doctor if you are taking pentoxifylline (Pentoxil, Trental) or probenecid. Your doctor will probably tell you not to use ketorolac nasal spray if you are taking 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 the medications listed in the IMPORTANT WARNING section and any of the following: alprazolam (Niravam, Xanax);carbamazepine (Epitol, Tegretol); lithium (Eskalith, Lithobid);methotrexate (Rheumatrex, Trexall); phenytoin (Dilantin, Phenytek);or thiothixene (Navane). 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 the conditions listed in the IMPORTANT WARNING section or asthma, especially if you also have frequent stuffed or runny nose or nasal polyps (swelling of the lining of the nose), inflammatory bowel disease such as Crohn's disease (a condition in which the body attacks the lining of the digestive tract, causing pain, diarrhea, weight loss, and fever) or ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum).
- 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. Ketorolac may cause serious harm to the fetus when taken in the last few months of pregnancy. If you become pregnant while using ketorolac nasal spray, call your doctor.
- Do not breastfeed during your treatment with ketorolac nasal spray.
- If you are having surgery, including dental surgery, tell the doctor or dentist that you are using ketorolac nasal spray.
What special dietary instructions should I follow?
Make sure you drink plenty of fluids while using ketorolac nasal spray.
Unless your doctor tells you otherwise, continue your normal diet.
What should I do if I forget a dose?
This medication is usually used as needed. If your doctor has told you to use ketorolac nasal spray regularly, use 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 use a double dose to make up for a missed one.
What side effects can this medication cause?
Ketorolac nasal spray may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- pain, discomfort, or irritation in your nose
- increased tears
- irritation in your throat
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- difficulty breathing or swallowing
- extreme tiredness
- lack of energy
- loss of appetite
- pain in the upper right part of the stomach
- yellowing of the eyes or skin
- flu-like symptoms
- blistering or peeling skin
- slow heartbeat
Ketorolac nasal spray may cause other side effects. Call your doctor if you have any unusual problems while using 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 and away from direct sunlight, 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.
Symptoms of overdose may include the following:
- stomach pain
- decreased urination
- bloody, black, or tarry stools
- vomit that is bloody or looks like coffee grounds
- slowed breathing
- coma (loss of consciousness for a period of time)
What other information should I know?
Keep all appointments with your doctor.
Do not let anyone else use your medication. This prescription is not refillable. If you continue to have pain after you finish using ketorolac nasal spray, call your doctor.
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.