Pronunciation:

dye-KLOE-fen-ak SOE-dee-um, mye-soe-PROST-ol

Brand Names:

• Arthrotec

Dosage Forms:

• Tablet, Enteric Coated

Warnings:

Uterine Rupture, Abortion, Premature Birth, and Birth DefectsAdministration of misoprostol, a component of diclofenac sodium/misoprostol, to pregnant women can cause uterine rupture, abortion, premature birth, or birth defects. Uterine rupture has occurred when misoprostol was administered in pregnant women to induce labor or an abortion. Diclofenac sodium/misoprostol is contraindicated in pregnancy and not recommended in women of childbearing potential. Patients must be advised of the abortifacient property and warned not to give the drug to others. If diclofenac sodium/misoprostol is prescribed, verify the pregnancy status of females of reproductive potential prior to initiation of treatment and advise them to use effective contraception during treatment.Cardiovascular Thrombotic EventsNSAIDs cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Diclofenac sodium/misoprostol is contraindicated in the setting of CABG surgery.Gastrointestinal Bleeding, Ulceration, and PerforationNSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events .

Classifications:

Therapeutic—

Analgesic

Pharmacologic—

Diclofenac

Chemical—

Diclofenac

Uses of This Medicine:

Diclofenac and misoprostol combination is used to relieve the symptoms of arthritis (eg, osteoarthritis or rheumatoid arthritis) in patients who may develop stomach or duodenal ulcers from taking nonsteroidal anti-inflammatory drugs (NSAIDs).

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) used to relieve symptoms of arthritis such as inflammation, swelling, stiffness, and joint pain. Misoprostol is used to decrease the risk of having stomach and bowel ulcers.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of diclofenac and misoprostol combination in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of diclofenac and misoprostol combination in the elderly. However, elderly patients may be more sensitive to the effects of diclofenac and misoprostol combination than younger adults, and are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Acenocoumarol
• Amiloride
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Bemetizide
• Bemiparin
• Bendroflumethiazide
• Benzthiazide
• Betrixaban
• Bivalirudin
• Budesonide
• Bumetanide
• Cangrelor
• Capecitabine
• Ceritinib
• Certoparin
• Chlorothiazide
• Chlorthalidone
• Cilostazol
• Citalopram
• Clomipramine
• Clopamide
• Clopidogrel
• Cyclopenthiazide
• Cyclosporine
• Cyclothiazide
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Deferiprone
• Deflazacort
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexketoprofen
• Diazoxide
• Dibenzepin
• Diflunisal
• Digoxin
• Dipyridamole
• Dipyrone
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Emtricitabine
• Enoxaparin
• Eplerenone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Etozolin
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Feverfew
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Furosemide
• Ginkgo
• Gossypol
• Heparin
• Hydrochlorothiazide
• Hydrocortisone
• Hydroflumethiazide
• Ibuprofen
• Iloprost
• Imipramine
• Indapamide
• Inotersen
• Ketoprofen
• Lepirudin
• Levoketoconazole
• Levomilnacipran
• Lithium
• Lofepramine
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Magnesium Salicylate
• Mavacamten
• Meadowsweet
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Melphalan
• Mesalamine
• Methotrexate
• Methyclothiazide
• Methylprednisolone
• Metolazone
• Milnacipran
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Olsalazine
• Opipramol
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Parnaparin
• Paroxetine
• Pemetrexed
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Phenyl Salicylate
• Piketoprofen
• Piretanide
• Piroxicam
• Polythiazide
• Potassium Citrate
• Prasugrel
• Prednisolone
• Prednisone
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Quinethazone
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylamide
• Salicylic Acid
• Salsalate
• Selexipag
• Sertraline
• Sibutramine
• Sodium Salicylate
• Sparsentan
• Spironolactone
• Sulfasalazine
• Sulfinpyrazone
• Sulindac
• Sulodexide
• Tacrolimus
• Tenofovir Alafenamide
• Tenofovir Disoproxil Fumarate
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Trazodone
• Treprostinil
• Triamterene
• Trichlormethiazide
• Trimipramine
• Trolamine Salicylate
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Xipamide

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Atenolol
• Azilsartan
• Azilsartan Medoxomil
• Benazepril
• Betaxolol
• Bisoprolol
• Candesartan
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cholestyramine
• Ciprofloxacin
• Colestipol
• Enalapril
• Enalaprilat
• Eprosartan
• Esmolol
• Fosinopril
• Irbesartan
• Labetalol
• Levobunolol
• Lisinopril
• Losartan
• Metipranolol
• Metoprolol
• Moexipril
• Nadolol
• Nebivolol
• Olmesartan
• Oxprenolol
• Penbutolol
• Perindopril
• Phenylbutazone
• Pindolol
• Propranolol
• Quinapril
• Ramipril
• Sotalol
• Spirapril
• Telmisartan
• Timolol
• Trandolapril
• Valsartan

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Asthma or
• Bleeding problems or
• Congestive heart failure or
• Edema (fluid retention or body swelling) or
• Heart attack, recent or history of or
• Heart or blood vessel disease or
• Hypertension (high blood pressure) or
• Inflammatory bowel disease or
• Kidney disease or
• Liver disease (eg, hepatitis) or
• Porphyria (blood disorder) or
• Stomach or bowel ulcers or bleeding, history of or
• Stroke, history of or
• Systemic lupus erythematosus (SLE)—Use with caution. May make these conditions worse.

• Aspirin-sensitive asthma or
• Aspirin (or other NSAIDs) sensitivity, history of or
• Kidney disease, severe or
• Stomach or bowel bleeding, active—Should not be used in patients with these conditions.

• Coagulopathy (bleeding problem) or
• Liver disease, advanced—Use with caution. May increase risk for stomach or bowel bleeding.

• Dehydration or
• Hypovolemia (low blood volume)—Use with caution. Must be corrected first before using this medicine.

• Heart surgery (eg, coronary artery bypass graft [CABG])—Should not be used to relieve pain right before or after the surgery.

Proper Use of This Medicine:

For safe and effective use of this medicine, do not take more of it, do not take it more often, and do not take it for a longer time than ordered by your doctor. Taking too much of this medicine may increase the chance of unwanted effects. Do not change the dose or stop using this medicine without checking first with your doctor.

This medicine should come with a Medication Guide or a patient information leaflet. Read and follow these instructions carefully. Ask your doctor if you have any questions.

Do not take diclofenac and misoprostol combination with magnesium-containing antacids. Antacids may be taken with diclofenac and misoprostol combination, if needed, to help relieve stomach pain, unless otherwise directed by your doctor. However, do not take magnesium-containing antacids, since they may cause diarrhea or worsen the diarrhea that is sometimes caused by this medicine.

Do not give this medicine to another person.

Take this medicine with food to prevent diarrhea and stomach upset.

Swallow the tablets whole. Do not chew, crush, or dissolve it.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For osteoarthritis:
    • Adults—One tablet of Arthrotec® 50 3 times a day. Your doctor may adjust your dose as needed and tolerated. Some patients who cannot tolerate the usual dose can be given Arthrotec® 75 2 times a day or Arthrotec® 50 2 times a day. Each Arthrotec® 50 contains 50 milligrams (mg) diclofenac sodium and 200 micrograms (mcg) misoprostol, while Arthrotec® 75 contains 75 mg diclofenac sodium and 200 mcg misoprostol.
    • Children—Use and dose must be determined by your doctor.
  • For rheumatoid arthritis:
    • Adults—One tablet of Arthrotec 50 3 or 4 times a day. Your doctor may adjust your dose as needed and tolerated. Some patients who cannot tolerate the usual dose can be given Arthrotec® 75 2 times a day or Arthrotec® 50 2 times a day. Each Arthrotec® 50 contains 50 milligrams (mg) diclofenac sodium and 200 micrograms (mcg) misoprostol, while Arthrotec® 75 contains 75 mg diclofenac sodium and 200 mcg misoprostol.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using This Medicine:

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant, especially during the later part of pregnancy can cause miscarriage, premature birth, very serious birth defects, or tearing of the uterus. If you are a woman who can bear children, your doctor may give you a pregnancy test within 2 weeks before you start using this medicine to make sure you are not pregnant. Use an effective form of birth control to keep from getting pregnant while you are using this medicine and after the last dose. The most effective forms of birth control are hormone birth control pills, patches, shots, vaginal rings, or implants, an IUD, or a vasectomy (for men). One of these forms of birth control should be combined with a condom, a diaphragm, or a cervical cap. You must have a negative pregnancy test before you will be allowed to take this medicine. If you think you have become pregnant while using this medicine, tell your doctor right away.

This medicine may increase your risk of having blood clots, heart attack, or stroke. This is more likely in people who already have heart or blood vessel disease. People who use this medicine for a long time might also have a higher risk. Check with your doctor right away if you have swelling and pain in your arms, legs, or stomach, chest pain, trouble breathing, loss of sensation, confusion, or problems with muscle control or speech.

This medicine may cause bleeding, perforation, or ulcers in your stomach or bowels. These problems can happen without warning signs and are more likely to occur if you have had a stomach ulcer, if you smoke or drink alcohol regularly, are over 60 years of age, in poor health, or using certain medicines (eg, steroid medicine, blood thinner).

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Your blood pressure might get too high while you are using this medicine. This may cause headaches, dizziness, or blurred vision. You might need to measure your blood pressure at home. If you think your blood pressure is too high, call your doctor right away.

This medicine may cause a serious type of allergic reaction called anaphylaxis, which can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing or swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

Serious skin reactions including Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) can occur during treatment with this medicine. Check with your doctor right away if you have blistering, peeling, or loosening of the skin, chest pain, chills, cough, diarrhea, fever, itching, joint or muscle pain, painful or difficult urination, red skin lesions, sore throat, sores ulcers, white spots in the mouth or on the lips, swollen glands, unusual bleeding or bruising, or unusual tiredness or weakness. .

Check with your doctor right away if you have bloody urine, a decrease in frequency or amount of urine, an increase in blood pressure, increased thirst, loss of appetite, lower back or side pain, nausea, swelling of the face, fingers, or lower legs, trouble breathing, unusual tiredness or weakness, vomiting, or weight gain. These could be symptoms of a serious kidney problem.

Hyperkalemia (high potassium in the blood) may occur while you are using this medicine. Check with your doctor right away if you have stomach pain, confusion, difficulty with breathing, irregular heartbeat, nausea or vomiting, nervousness, numbness or tingling in the hands, feet, or lips, or weakness or heaviness of the legs.

This medicine can cause worsening of your heart failure. Check with your doctor right away if you have chest pain, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, tightness in the chest, trouble breathing, or weight gain.

This medicine may cause diarrhea in some people. The diarrhea will usually disappear within a few days as your body adjusts to the medicine. However, check with your doctor right away if the diarrhea is severe or does not stop after a week.

Stomach problems may be more likely to occur if you drink alcoholic beverages while being treated with this medicine. Therefore, do not regularly drink alcoholic beverages while taking this medicine, unless otherwise directed by your doctor.

This medicine may cause a delay in ovulation for women and may affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

Taking nonsteroidal anti-inflammatory drugs (eg, acetaminophen, aspirin or other salicylates, or ketorolac, Toradol®) together with this medicine on a regular basis may increase the chance of unwanted effects. The risk will depend on how much of each medicine you take everyday, and on how long you take these medicines together. If your doctor directs you to take these medicines together on a regular basis, follow his or her directions carefully. However, do not take acetaminophen or aspirin or other salicylates together with this medicine for more than a few days, and do not take any ketorolac (eg, Toradol®) while you are taking this medicine, unless your doctor has directed you to do so and is following your progress.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or non-prescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Stomach pain

Less common

Black, tarry stools

bladder pain

bloody or cloudy urine

burning feeling in the chest or stomach

burning while urinating

chest pain, discomfort, or tightness

chills

cough

deep or fast breathing with dizziness

difficult, burning, or painful urination

difficulty swallowing

dizziness

double vision

feeling of constant movement of self or surroundings

fever

frequent urge to urinate

heartburn

increased sensitivity of the skin to sunlight

increased volume of pale, dilute urine

indigestion

itching, skin rash

lightheadedness

longer or heavier menstrual periods

lower back or side pain

nosebleed

numbness of the feet, hands, and around the mouth

pain or burning in the throat

pain with swallowing

redness or other discoloration of the skin

seeing double

sensation of spinning

severe sunburn

sores, ulcers, or white spots on the lips or in the mouth

sore throat

stomach upset or tenderness

swollen glands

unusual bleeding or bruising

unusual tiredness or weakness

vaginal bleeding

vomiting with or without blood

Incidence not known

Ankle, knee, or great toe joint pain

anxiety

black, tarry stools

bleeding gums

blindness

blistering, peeling, or loosening of the skin

bloating or swelling of the face, arms, hands, lower legs, or feet

bluish color of the skin

blurred vision

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

burning, dry, or itching eyes

cloudy or dark urine

decreased frequency or amount of urine

decreased vision

diarrhea

difficulty in speaking

dilated neck veins

discharge, excessive tearing

dizziness, fainting, or lightheadedness when getting up suddenly from a lying or sitting position

drowsiness

excessive muscle tone

eye pain

fainting

fast, irregular, pounding, or racing heartbeat or pulse

general feeling of illness

headache, severe and throbbing

hoarseness

inability to move the arms, legs, or facial muscles

inability to speak

increased sensitivity to pain or touch

increased thirst

irregular, fast or slow, or shallow breathing

joint pain, stiffness, or swelling

large, hive-like swelling on the pain, face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals

light-colored stools

lightheadedness

loss of appetite

loss of consciousness

muscle stiffness, tension, or tightness

nausea

nervousness

night blindness

pain or discomfort in the arms, jaw, back, or neck

pains in the stomach, side, or abdomen, possibly radiating to the back

pain, warmth, or burning in the fingers, toes, and legs

pale or blue lips, fingernails, or skin pale skin

pinpoint red spots on the skin

pounding in the ears

problems with vision or hearing

rapid weight gain

red skin lesions, often with a purple center

redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

redness or soreness of the skin

seizures

severe stomach cramping

slow heartbeat

slow speech

sneezing

sores, welts, or blisters

stiff neck or back

tremor

trouble breathing

unusual bleeding or bruising

unusual weight gain or loss

upper right stomach pain

uterine cramping and bleeding

vomiting of material that looks like coffee grounds, severe and continuing

yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Belching

excess air or gas in the stomach or bowels

full feeling

passing gas

Less common

Breast pain

change in or loss of taste

confusion about identity, place, and time

constipation

continuing ringing or buzzing or other unexplained noise in the ears

decreased concentration

depression

difficulty in moving

dry mouth

frequent urge to defecate

increased clear or white vaginal discharge

irritability

itching of the vagina or genital area

lack or loss of strength

loss or thinning of hair

pain during sexual intercourse

seeing, hearing, or feeling things that are not there

straining while passing stool

thick, white vaginal discharge with no odor or with a mild odor

trouble sleeping

Incidence not known

Blemishes on the skin

decreased interest in sexual intercourse

inability to have or keep an erection

loss in sexual ability, desire, drive, or performance

pimples

sleepiness or unusual drowsiness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.