Diclofenac and Misoprostol

For female patients:

Do not take diclofenac and misoprostol if you are pregnant or plan to become pregnant. If you become pregnant or think you may be pregnant while taking diclofenac and misoprostol, stop taking the medication and call your doctor immediately. Diclofenac and misoprostol may cause miscarriage (pregnancy loss), serious bleeding, or premature birth (baby is born too early) if taken during pregnancy.

Women who can become pregnant generally should not take diclofenac and misoprostol. However, you and your doctor may decide that diclofenac and misoprostol combination is needed to treat your condition. In that case you must:

• agree to use a reliable method of birth control during your treatment;
• have a negative blood test for pregnancy no longer than 2 weeks before you start taking diclofenac and misoprostol;
• begin taking the medication only on the second or third day of the next normal menstrual period.

For all patients:

People who take nonsteroidal anti-inflammatory drugs (NSAIDs) (other than aspirin) such as diclofenac and misoprostol combination 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. Do not use an NSAID such as diclofenac and misoprostol combination if you have recently had a heart attack, unless directed to do so by your doctor. Tell your doctor if you or anyone in your family has or has ever had heart disease, a heart attack, or a stroke, if you smoke, and if you have or have ever had high cholesterol, high blood pressure, 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 will be undergoing a coronary artery bypass graft (CABG; a type of heart surgery), you should not take diclofenac and misoprostol right before or right after the surgery.

NSAIDs such as diclofenac may cause ulcers, bleeding, or holes in the stomach or intestine. Misoprostol is taken in combination with diclofenac to protect the stomach and intestine, but may not prevent all damage to these parts of the body. Problems with the stomach and intestine 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, smoke, or drink large amounts of alcohol while taking diclofenac and misoprostol. Tell your doctor if you take any of the following medications: anticoagulants ('blood thinners') such as warfarin (Jantoven); aspirin; other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn); oral steroids such as dexamethasone, methylprednisolone (Medrol), and prednisone (Rayos); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), fluoxetine (Prozac, in Symbyax), fluvoxamine (Luvox), paroxetine (Paxil, Pexeva), and sertraline (Zoloft); or serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), and venlafaxine (Effexor XR). Tell your doctor if you have any bleeding in your stomach or intestines or if you have any of these symptoms: vomiting a substance that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools. before you begin your treatment with diclofenac and misoprostol. Your doctor will probably tell you not to take diclofenac and misoprostol. Also tell your doctor if you have or have ever had ulcers or a bleeding disorder. If you experience any of the following symptoms, stop taking diclofenac and misoprostol and call your doctor: stomach pain, heartburn, vomiting a substance that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools.

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 diclofenac and misoprostol. 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.

Do not give this medication to anyone else, especially a woman who is or could become pregnant.

Your doctor or pharmacist will give you the manufacturer's patient information sheet for diclofenac and misoprostol and the general Medication Guide for NSAIDs when you begin your treatment 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 (https://www.fda.gov/Drugs/DrugSafety/ucm085729.htm) or the manufacturer's website to obtain the patient information sheet and Medication Guide.

The combination of diclofenac and misoprostol is used to relieve the pain, tenderness, swelling, and stiffness caused by osteoarthritis (arthritis caused by a breakdown of the lining of the joints) and rheumatoid arthritis (arthritis caused by swelling of the lining of the joints) in patients who have a high risk of developing stomach ulcers. Diclofenac is in a class of medications called nonsteroidal anti-inflammatory drugs (NSAIDs). It works by stopping the body's production of a substance that causes pain and inflammation. Misoprostol is in a class of medications called prostaglandins. It prevents ulcers caused by diclofenac by protecting the stomach lining and decreasing stomach acid production.

The combination of diclofenac and misoprostol comes as a tablet to take by mouth. It is usually taken with food two to four times a day. To help you remember to take diclofenac and misoprostol, 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. Take diclofenac and misoprostol combination exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Before taking diclofenac and misoprostol,

• tell your doctor and pharmacist if you are allergic to diclofenac (Cambia, Cataflam, Flector, Licart, Pennsaid, Zipsor), misoprostol (Cytotec), aspirin or other NSAIDs such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn), any other medications, or any of the inactive ingredients in diclofenac and misoprostol tablets. Ask your pharmacist for a list of the inactive ingredients.
• 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 any of the medications listed in the IMPORTANT WARNING section. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• talk to your doctor if you need to take an antacid during your treatment with diclofenac and misoprostol. You should not take antacids that contain magnesium (Mylanta, others).
• tell your doctor if you have or have ever had any of the conditions mentioned in the IMPORTANT WARNING section or inflammatory bowel disease (swelling of the lining of the intestine that may cause painful or bloody diarrhea and cramping); asthma, especially if you also have frequent stuffed or runny nose or nasal polyps (swelling of the lining of the nose); heart failure; liver or kidney disease; or swelling of the hands, feet, ankles, or lower legs.
• tell your doctor if you are breast-feeding.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking diclofenac and misoprostol.

Unless your doctor tells you otherwise, continue your normal diet.

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.

Diclofenac and misoprostol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• gas or bloating
• constipation
• headache

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 or get emergency medical help. Do not take any more diclofenac and misoprostol until you speak to your doctor.

• diarrhea
• unexplained weight gain
• shortness of breath or difficulty breathing
• swelling in the abdomen, ankles, feet, or legs
• unusual tiredness or weakness
• lack of energy
• upset stomach
• loss of appetite
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• flu-like symptoms
• pale skin
• fast heartbeat
• rash or blistering or peeling skin with fever
• hives
• itching
• swelling of the eyes, face, lips, tongue, throat, arms, or hands
• difficulty swallowing
• hoarseness
• unusual vaginal bleeding
• cloudy, discolored, or bloody urine
• back pain
• difficult or painful urination

Diclofenac and misoprostol 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 (https://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

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 (https://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. https://www.upandaway.org

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:

• stomach pain
• nausea
• vomiting
• diarrhea
• confusion
• drowsiness
• low muscle tone
• uncontrollable shaking of a part of the body
• seizures
• shortness of breath
• fever
• fast, pounding, or slow heartbeat

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking diclofenac and misoprostol.

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.

• Arthrotec^® (containing Diclofenac, Misoprostol)