Diclofenac Misoprostol: Uses, Side Effects and Dosage

ABOUT THIS MEDICATION

What the medication is used for:

Your health care provider has prescribed DICLOFENAC MISOPROSTOL for you for the following:

• short-term and long-term use in the relief of the signs

  and symptoms of rheumatoid arthritis

• short-term and long-term use in the relief of the signs

  and symptoms of osteoarthritis

What it does:

DICLOFENAC MISOPROSTOL contains two different medicines, a nonsteroidal anti-inflammatory drug (NSAID) called diclofenac and a drug that helps to protect the lining of your stomach called misoprostol (because NSAIDs can cause damage to your stomach).

DICLOFENAC MISOPROSTOL (diclofenac plus misprostol), as a nonsteroidal anti-inflammatory drug (NSAID), can reduce the chemicals produced by your body which cause pain and swelling. It helps to relieve joint pain, swelling, and stiffness by reducing the production of certain substances (prostaglandins) and by helping to control inflammation. DICLOFENAC MISOPROSTOL, as a non-steroidal anti-inflammatory drug (NSAID) does NOT cure your illness or prevent it from getting worse but it promotes suppression of the inflammation and the tissue damaging effects resulting from this inflammation. DICLOFENAC MISOPROSTOL can only relieve pain and reduce swelling as long as you continue to take it.

How do NSAIDs cause stomach damage?

Natural prostaglandins play an important role in protecting the stomach by working to keep a thick mucus layer on the inside surface of the stomach. If the lining of the stomach is not protected by a thick layer of mucus, it may be burned by natural stomach acids. NSAIDs lower natural prostaglandins both in the joints and in the stomach. This is good for the joints because it controls pain, swelling and stiffness. Unfortunately, lowering prostaglandins in the stomach can lead to burning stomach pain and the development of tiny holes in the lining of your stomach called “ulcers”.

Oddly enough, some NSAID patients who do develop ulcers never feel any stomach pain. On the other hand, some patients who do feel stomach pain have nothing wrong with them. For this reason people must be very careful when taking NSAIDs.

How does misoprostol protect the stomach?

Misoprostol is a synthetic form of a special kind of prostaglandin that is found in the stomach. Misoprostol replaces the prostaglandins that are lost when taking the NSAID medicine. It protects the thick mucus layer and reduces the acid in your stomach. This can help to protect your stomach from the NSAID.

When it should not be used:

SPECIAL NOTE FOR WOMEN OF CHILDBEARING AGE

Do not take DICLOFENAC MISOPROSTOL if you are pregnant or think you are pregnant. Do not start DICLOFENAC MISOPROSTOL until you have been tested to confirm that you are not pregnant. You should avoid becoming pregnant while you are taking DICLOFENAC MISOPROSTOL and for at least one month (or through one menstrual cycle) after you stop taking it. This means using an effective form of birth control which you should discuss with your doctor. Stop taking DICLOFENAC MISOPROSTOL, and contact your doctor immediately if you do become pregnant during DICLOFENAC MISOPROSTOL therapy.

Misoprostol may cause uterine contractions (contractions of the uterus), premature birth, birth defects and abortion or may otherwise harm the unborn developing baby. Misoprostol has been reported to cause the uterus to tear when given after the eighth week of pregnancy. Tearing of the uterus can result in severe bleeding, hysterectomy, and/or maternal or fetal death. Therefore, if you are pregnant, you must not take this drug.

Abortions caused by misoprostol are likely to be incomplete. An incomplete abortion may result in very serious medical complications, resulting in hospitalization, surgery and possibly infertility, and may result in maternal death.

You should not take DICLOFENAC MISOPROSTOL if you are nursing. The body changes misoprostol to the active form of the drug, misoprostol acid, which could get into the breast milk and cause significant diarrhea in the infant.

DO NOT TAKE DICLOFENAC MISOPROSTOL if you have any of the following medical conditions:

• Heart bypass surgery (planning to have or recently had)
• Severe, uncontrolled heart failure
• Bleeding in the brain or other bleeding disorders
• Current pregnancy or pregnancy cannot be excluded
• Currently breastfeeding (or planning to breastfeed)

• Allergy to ASA (Acetylsalicylic Acid) or other

  NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

• Ulcer (active)
• Bleeding from the stomach or gut (active)

• Inflammatory bowel disease (Crohn’s Disease or

  Ulcerative Colitis)

• Liver disease (active or severe)
• Kidney disease (severe or worsening)
• High potassium in the blood

• Allergy to any other ingredients in DICLOFENAC

  MISOPROSTOL listed in the “nonmedicinal ingredients” section below

Patients who took a drug in the same class as DICLOFENAC MISOPROSTOL after a type of heart surgery [coronary artery bypass grafting (CABG)] were more likely to have heart attacks, strokes, blood clots in the leg(s) or lung(s), and infections or other complications than those who did NOT take that drug.

DICLOFENAC MISOPROSTOL should NOT be used in patients under 18 years of age since safety and effectiveness have NOT been established.

DICLOFENAC MISOPROSTOL should NOT be used with other NSAIDs.

What the medicinal ingredients are:

Diclofenac sodium and Misoprostol

What the nonmedicinal ingredients are:

DICLOFENAC MISOPROSTOL 50 mg/200 mcg tablets contain the following nonmedicinal ingredients: Colloidal Silicon Dioxide, Corn Starch, Crospovidone, Hydrogenated Castor Oil, Lactose Monohydrate, Magnesium Stearate, Microcrystalline Cellulose, Povidone K-30, Sodium Hydroxide, Talc, Triethyl Citrate. In addition, the tablet film coating contains: Methacrylic Acid-Ethyl Acrylate, Sodium Lauryl Sulfate, Polysorbate 80.

DICLOFENAC MISOPROSTOL 75 mg/200 mcg tablets contain the following nonmedicinal ingredients: Colloidal Silicon Dioxide, Corn Starch, Crospovidone, Hydrogenated Castor Oil, Lactose Monohydrate, Magnesium Stearate, Microcrystalline Cellulose, Povidone K-30, Sodium Hydroxide, Talc, Triethyl Citrate. In addition, the tablet film coating contains: Methacrylic Acid-Ethyl Acrylate, Sodium Lauryl Sulfate, Polysorbate 80.

What dosage forms it comes in:

DICLOFENAC MISOPROSTOL tablets are formulated as enteric-coated tablets and are available as 50 mg/200 mcg and 75 mg/200 mcg tablets with the following descriptions:

DICLOFENAC MISOPROSTOL 50 mg/200 mcg tablets are white to off-white, round, biconvex tablets, plain on one side and debossed with “0397” on the other side. Each tablet has an enteric-coated core containing 50 mg diclofenac sodium, surrounded by an outer layer containing 200 mcg misoprostol.

DICLOFENAC MISOPROSTOL 75 mg/200 mcg tablets are White to off-white, round, biconvex tablets, plain on one side and debossed with “0398” on the other side. Each tablet has an

enteric-coated core containing 75 mg diclofenac sodium, surrounded by an outer layer containing 200 mcg misoprostol.

WARNINGS AND PRECAUTIONS

If you have, or previously had, any of the following medical conditions, see your health care provider to discuss treatment options other than DICLOFENAC MISOPROSTOL:

• Heart Attack or Angina
• Stroke or Mini-stroke
• Loss of Vision
• Congestive Heart Failure

BEFORE you use DICLOFENAC MISOPROSTOL talk to your doctor or pharmacist if you have any of the following:

• High blood pressure
• High cholesterol
• Diabetes mellitus or on a low sugar diet
• Atherosclerosis
• Poor circulation to your extremities
• Smoker or ex-smoker
• Kidney disease or urine problems
• Previous ulcer or bleeding from the stomach or gut
• Previous bleeding in the brain
• Bleeding problems
• Family history of allergy to NSAIDs, such as acetylsalicylic acid (ASA), celecoxib, diclofenac, diflunisal, etodolac, fenoprofen, fluribiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, mefenamic acid, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, rofecoxib, sulindac, tenoxicam, tiaprofenic acid, tolmetin, or valdecoxib (NOT a complete list)
• Family history of asthma, nasal polyps, long-term swelling of the sinus (chronic sinusitis) or hives
• You are on any special diet, such as low-sodium diet
• You drink alcohol;

DICLOFENAC MISOPROSTOL may cause sensitivity to sunlight.

Fertility may be decreased. The use of DICLOFENAC MISOPROSTOL is not recommended in women who have difficulty conceiving:

WHILE taking DICLOFENAC MISOPROSTOL:

• tell any other doctor, dentist, pharmacist or other health care professional that you consult or see, that you are taking this medication, especially if you are planning to have heart surgery;
• do NOT drink alcoholic beverages while taking this medication because you would be more likely to develop stomach problems;
• some NSAIDs may cause drowsiness or fatigue in some people taking them; be cautious about driving or participating in activities that require alertness if you are drowsy, dizzy or lightheaded after taking this

medication;

• your regular medical checkups are essential.

• do not give DICLOFENAC MISOPROSTOL to

  anyone else. It has been prescribed for your specific condition. DICLOFENAC MISOPROSTOL may not be the correct treatment for another person, and would be dangerous if the other person were pregnant.

• Fertility may be decreased. The use of DICLOFENAC

  MISOPROSTOL is not recommended in women trying to get pregnant. In women who have difficulty conceiving, stopping DICLOFENAC MISOPROSTOL should be considered.

INTERACTIONS WITH THIS MEDICATION

Talk to your health care provider and pharmacist if you are taking any other medication (prescription or non-prescription) such as any of the following (NOT a complete list):

• Acetylsalicylic Acid (ASA) or other NSAIDs (e.g.

  ASA, celecoxib, diclofenac, ibuprofen, indomethacin, ketorolac, meloxicam, naproxen)

• Antacids

• Antidepressants

  • Selective Serotonin Reuptake Inhibitors (SSRIs)

    (e.g. citalopram, fluoxetine, paroxetine, sertraline)

• Blood pressure medications

  • ACE (Angiotensin converting enzyme) inhibitors

    (e.g. enalapril, lisinopril, perindopril, ramipril)

  • ARBs (angiotensin II receptor blockers) (e.g.

    candesartan, irbesartan, losartan, valsartan)

• Blood thinners (e.g. warfarin, ASA, clopidogrel)

• Corticosteroids (including glucocorticoids) (e.g.

  prednisone)

• Cyclosporin
• Digoxin
• Diuretics (e.g. furosemide, hydrochlorothiazide)
• Lithium
• Methotrexate
• Oral contraceptives
• Oral hypoglycemics (diabetes medications)
• Phenytoin (a medicine used to treat seizures)
• Tacrolimus
• Sulfinpyrazone (a medicine used to treat gout)

• Voriconazole (a medicine used to treat fungal

  infections)

Do not take ASA (acetylsalicylic acid), ASA-containing compounds, ibuprofen or other drugs used to relieve symptoms of arthritis while taking DICLOFENAC MISOPROSTOL unless directed to do so by your physician.

Your health care provider may prescribe low dose ASA (acetylsalicylic acid) as a blood thinner to reduce your risk of having a heart attack or stroke while you are taking DICLOFENAC MISOPROSTOL. Take only the amount of ASA prescribed by your healthcare provider. You are more

likely to upset or damage your stomach if you take both DICLOFENAC MISOPROSTOL and ASA than if you took DICLOFENAC MISOPROSTOL alone.

Do not take antacids that contain magnesium (because they can cause diarrhea) while you are taking DICLOFENAC MISOPROSTOL. Ask your pharmacist to help you select a suitable brand.

Stomach problems may be more likely to occur if you drink alcoholic beverages. Therefore, do not drink alcoholic beverages while taking this medication.

PROPER USE OF THIS MEDICATION

Usual dose for Patients 18 Years of Age and Older:

*If your symptoms are not adequately controlled, you should contact your doctor, who may increase the total daily dose to a maximum of 150 mg (50 mg three times a day or 75 mg twice a day) for a short period of time and with close monitoring. If you are older than 65 years, have liver problems, kidney problems, or heart problems; the maximum total dose per day is 100 mg of diclofenac (50 mg twice a day).

DICLOFENAC MISOPROSTOL should be swallowed whole.

To lessen stomach upset, take DICLOFENAC MISOPROSTOL immediately after a meal or with food or milk. Also, you should remain standing or sitting upright (i.e. do not lie down) for about 15-30 minutes after taking the medicine. This helps to prevent irritation that may lead to trouble swallowing.

Take DICLOFENAC MISOPROSTOL only as directed by your health care provider. Do NOT take more of it, do NOT take it more often and do NOT take it for a longer period of time than your healthcare provider ordered. If possible, you should take the lowest dose of this medication for the shortest time period. Taking too much DICLOFENAC MISOPROSTOL may increase the chance of unwanted and sometimes dangerous side effects, especially if you are an elderly patient, have other disease or take other medications.

If you will be using DICLOFENAC MISOPROSTOL for more than 7 days, see your healthcare provider regularly to discuss whether this medicine is working for your and if it is causing you any unwanted effects. Be sure to take DICLOFENAC MISOPROSTOL regularly as prescribed. In some types of arthritis, up to two weeks may pass before you feel the full effects of this medicine. During treatment, your doctor may decide to adjust the dosage according to your response to the medication.

This medication has been prescribed specifically for you. Do NOT give it to anyone else. It may harm them, even if their symptoms seem to be similar to yours.

DICLOFENAC MISOPROSTOL is NOT recommended for use in patients under 18 years of age since safety and effectiveness have NOT been established.

Missed Dose:

If you miss a dose of DICLOFENAC MISOPROSTOL, take the next dose at the regular time. It is important that DICLOFENAC MISOPROSTOL be taken as prescribed. Try to remember to take DICLOFENAC MISOPROSTOL at the appropriate time. Having a regular routine associated with taking your medicine will help.

Do not take a double dose.

Overdose:

Symptoms of overdose may include stomach pain, confusion, drowsiness, low muscle tone, shaking hands that you cannot control, seizures, shortness of breath, diarrhea, fever, rapid or pounding heartbeat, slow heartbeat, dizziness or fainting

Seek immediate medical attention if you think that you or anyone else may have taken too much DICLOFENAC MISOPROSTOL. Do this even if there are no signs of discomfort or poisoning.

For management of a suspected drug overdose, contact your regional Poison Control Centre.

SIDE EFFECTS AND WHAT TO DO ABOUT THEM

DICLOFENAC MISOPROSTOL may cause some undesirable reactions especially when used for a long time or in large doses. When these side effects occur, you may require medical attention. Report all symptoms or side effects to your health care provider.

DICLOFENAC MISOPROSTOL may cause you to become drowsy or tired. Be careful about driving or participating in activities that require you to be alert. If you become drowsy, dizzy or light-headed after DICLOFENAC MISOPROSTOL, do NOT drive or operate machinery.

DICLOFENAC MISOPROSTOL may cause you to become more sensitive to sunlight. Any exposure to sunlight or sunlamps may cause sunburn, skin blisters, skin rash, redness, itching or discolouration, or vision changes. If you have reaction from the sun, check with your health care provider.

Check with your healthcare provider IMMEDIATELY if you develop chills, fever, muscle aches or pains, or other flu-like symptoms, especially if they occur before or together with a skin rash. These symptoms may be the first signs of a SERIOUS ALLERGIC REACTION to this medication.

If you are not getting any relief of your arthritis or if any

problems develop, check with your doctor.

Elderly, frail, or debilitated patients often seem to experience more frequent or more severe side effects.

Stomach upset is one of the common problems with NSAIDs. If stomach upset (indigestion, nausea, vomiting, stomach pain or diarrhea) occurs and continues, contact your doctor.

Because misoprostol increases mucus production some patients experience diarrhea. Keep taking your DICLOFENAC MISOPROSTOL. It is just a sign that the drug is working. Usually the diarrhea goes away in two to three days. If it is not gone after a week, check with your doctor.

While your body gets used to misoprostol you may feel a crampy pain in your stomach. Like the diarrhea it usually goes away in a few days. If it doesn’t, check with your doctor.

This is not a complete list of side effects. For any unexpected effects while taking DICLOFENAC MISOPROSTOL, contact your doctor or pharmacist.

HOW TO STORE IT

Store at room temperature (15-30EC). Protect from heat and humidity.

Do NOT keep outdated medicine or medicine no longer needed. Any outdated or unused medicine should be returned to your pharmacist.

Keep out of the reach of children.

REPORTING SUSPECTED SIDE EFFECTS

You can report any suspected adverse reactions associated with the use of health products to the Canada Vigilance Program by one of the following 3 ways:

---------------------------------------------------------------------------- $ Report online at www.healthcanada.gc.ca/medeffect $ Call toll-free at 1-866-234-2345

$ Complete a Canada Vigilance Reporting Form and:

• Fax toll-free to 1-866-678-6789, or

• Mail to: Canada Vigilance Program Health Canada

  Postal Locator 0701E

  Ottawa, ON K1A 0K9

Postage paid labels, Canada Vigilance Reporting Form and the adverse reaction reporting guidelines are available on the MedEffect^™ Canada Web site at www.healthcanada.gc.ca/medeffect.

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MORE INFORMATION

This document plus the full product monograph, prepared for health professionals can be found by contacting the sponsor, Abri Pharmaceuticals Inc., at 1-866-254-6111

Abri Pharmaceuticals Inc.

6500 Kitimat Road

Mississauga, ON

Canada, L5N 2B8

Date revised: April 18, 2013