Clinoril

There are no adequate studies of sulindac in pregnant women. Therefore, sulindac is not recommended during pregnancy.

It is not known whether sulindac is excreted in breast milk.

The following adverse reactions were reported in clinical trials or have been reported since the drug was marketed. The probability exists of a causal relationship between CLINORIL (sulindac) and these adverse reactions. The adverse reactions which have been observed in clinical trials encompass observations in 1,865 patients, including 232 observed for at least 48 weeks.

Incidence Greater Than 1%

The most frequent types of adverse reactions occurring with CLINORIL (sulindac) are gastrointestinal; these include gastrointestinal pain (10%), dyspepsia***, nausea*** with or without vomiting, diarrhea***, constipation***, flatulence, anorexia and gastrointestinal cramps.

Rash***, pruritus.

Dizziness***, headache***, nervousness.

Tinnitus.

Edema (see WARNINGS).

Incidence Less Than 1 in 100

Gastritis, gastroenteritis or colitis. Peptic ulcer and gastrointestinal bleeding have been reported. GI perforation and intestinal strictures (diaphragms) have been reported rarely.

Liver function abnormalities; jaundice, sometimes with fever; cholestasis; hepatitis; hepatic failure.

There have been rare reports of sulindac metabolites in common bile duct “sludge” and in biliary calculi in patients with symptoms of cholecystitis who underwent a cholecystectomy.

Pancreatitis (see PRECAUTIONS).

Ageusia; glossitis.

Stomatitis, sore or dry mucous membranes, alopecia, photosensitivity.

Erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and exfoliative dermatitis have been reported.

Congestive heart failure, especially in patients with marginal cardiac function; palpitation; hypertension.

Thrombocytopenia; ecchymosis; purpura; leukopenia; agranulocytosis; neutropenia; bone marrow depression, including aplastic anemia; hemolytic anemia; increased prothrombin time in patients on oral anticoagulants (see PRECAUTIONS).

Urine discoloration; dysuria; vaginal bleeding; hematuria; proteinuria; crystalluria; renal impairment, including renal failure; interstitial nephritis; nephrotic syndrome.

Renal calculi containing sulindac metabolites have been observed rarely.

Hyperkalemia.

Muscle weakness.

Depression; psychic disturbances including acute psychosis.

Vertigo; insomnia; somnolence; paresthesia; convulsions; syncope; aseptic meningitis (especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease, see PRECAUTIONS).

Blurred vision; visual disturbances; decreased hearing; metallic or bitter taste.

Epistaxis.

Anaphylaxis; angioneurotic edema; urticaria; bronchial spasm; dyspnea.

A potentially fatal apparent hypersensitivity syndrome has been reported. This syndrome may include constitutional symptoms (fever, chills, diaphoresis, flushing), cutaneous findings (rash or other dermatologic reactions - see above), conjunctivitis, involvement of major organs (changes in liver function including hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated intravascular coagulation, anemia, renal impairment, including renal failure), and other less specific findings (adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain, tachycardia).

A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β-hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, sometimes with fatal outcome (see also PRECAUTIONS, General).

Other reactions have been reported in clinical trials or since the drug was marketed, but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.

Arrhythmia.

Hyperglycemia.

Neuritis.

Disturbances of the retina and its vasculature.

Gynecomastia.

*** Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.

Medication Guide for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

(See the end of this Medication Guide for a list of prescription NSAID medicines.)

What is the most important information I should know about medicines called Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:

• with longer use of NSAID medicines
• in people who have heart disease

NSAID medicines should never be used right before or after a heart surgery called a “coronary artery bypass graft (CABG).”

NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:

• can happen without warning symptoms
• may cause death

The chance of a person getting an ulcer or bleeding increases with:

• taking medicines called “corticosteroids” and “anticoagulants”
• longer use
• smoking
• drinking alcohol
• older age
• having poor health

NSAID medicines should only be used:

• exactly as prescribed
• at the lowest dose possible for your treatment
• for the shortest time needed

What are Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:

• different types of arthritis
• menstrual cramps and other types of short-term pain

Who should not take a Non-Steroidal Anti-Inflammatory Drug (NSAID)?

Do not take an NSAID medicine:

• if you had an asthma attack, hives, or other allergic reaction with aspirin or any other NSAID medicine
• for pain right before or after heart bypass surgery

Tell your healthcare provider:

• about all of your medical conditions.
• about all of the medicines you take. NSAIDs and some other medicines can interact with each other and cause serious side effects. Keep a list of your medicines to show to your healthcare provider and pharmacist.
• if you are pregnant. NSAID medicines should not be used by pregnant women late in their pregnancy.
• if you are breastfeeding. Talk to your doctor.

What are the possible side effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

Get emergency help right away if you have any of the following symptoms:

Stop your NSAID medicine and call your healthcare provider right away if you have any of the following symptoms:

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

• Aspirin is an NSAID medicine but it does not increase the chance of a heart attack. Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can also cause ulcers in the stomach and intestines.
• Some of these NSAID medicines are sold in lower doses without a prescription (over-the­counter). Talk to your healthcare provider before using over-the-counter NSAIDs for more than 10 days.

NSAID medicines that need a prescription

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

This Medication Guide has been approved by the U.S. Food and Drug Administration.

* Vicoprofen contains the same dose of ibuprofen as over-the-counter (OTC) NSAIDs, and is usually used for less than 10 days to treat pain. The OTC NSAID label warns that long term continuous use may increase the risk of heart attack or stroke.

Serious side effects have been reported with Clinoril including:

• Cardiovascular thrombotic events. Clinoril can increase your risk of cardiovascular and heart diseases such as strokes and myocardial infarctions, which can lead to death. Tell your doctor if you have a history of heart disease.
• Gastrointestinal effects. Clinoril can cause digestive tract problems such as ulcers, bleeding, inflammation, and perforations (small holes). Tell your doctor if you have a history of digestive problems, or if you smoke or frequently drink alcohol. Alert your doctor if you take anticoagulants (blood-thinners) or corticosteroids such as prednisone.
• Hepatic events. Clinoril c­­an cause damage to the liver and increase liver tests. Tell your doctor if you have a history of liver disease.
• Hypertension. Clinoril may raise your blood pressure. Tell your doctor if you have a history of high blood pressure or take ACE inhibitors (such as lisinopril and enalapril) or diuretics (water pills).
• Congestive heart failure and edema. Clinoril can increase the chance of congestive heart failure, fluid retention, and weight gain.
• Renal effects. Kidney damage can result from the use of Clinoril. Tell your doctor if you have a history of kidney disease or take ACE inhibitors (such as lisinopril and enalapril) or diuretics (water pills).
• Hypersensitivity reaction. An allergic reaction to Clinoril can occur. Symptoms of a hypersensitivity reaction include:
  • hives
  • rash
  • difficulty breathing or swallowing
  • itching
  • swelling
• Adverse skin reactions. Clinoril can lead to dangerous skin reactions. Symptoms of a skin reaction include:
  • rash
  • red, itchy, or scaly skin
  • blisters
  • fever
• Pregnancy. Clinoril should not be taken past the 30th week of pregnancy.

Clinoril can cause dizziness. Do not drive or operate heavy machinery until you know how Clinoril affects you.

Do not take Clinoril if you:

• are allergic to Clinoril 
• will have or have recently had coronary (heart) surgery

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Clinoril, there are no specific foods that you must exclude from your diet when receiving Clinoril.

Before taking Clinoril tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• have a history of heart, liver, or kidney disease
• have a history of gastrointestinal (digestive) problems
• have hypertension, or high blood pressure
• have a history of asthma
• have diabetes
• take ACE inhibitors such as lisinopril (Prinivil) and enalapril (Vasotec)
• take aspirin (Ecotrin) and other non-steroidal anti-inflammatory drugs (NSAIDs)
• take diuretics, or water pills, such as thiazides (hydrochlorothiazide) and furosemide (Lasix)
• are allergic to Clinoril 
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Sulindac can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Even people without heart disease or risk factors could have a stroke or heart attack while taking this medicine.

Do not use this medicine just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Sulindac may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using sulindac, especially in older adults.

You should not use sulindac if you are allergic to it, or if you have ever had an asthma attack or severe allergic reaction after taking aspirin or an NSAID.

To make sure sulindac is safe for you, tell your doctor if you have:

• heart disease, high blood pressure, high cholesterol, diabetes, or if you smoke;

• a history of heart attack, stroke, or blood clot;

• a history of stomach ulcers or bleeding;

• kidney disease or a history of kidney stones;

• liver disease;

• a pancreas disorder;

• asthma;

• fluid retention; or

• a connective tissue disease such as Marfan syndrome, Sjogren's syndrome, or lupus.

Taking sulindac during the last 3 months of pregnancy may harm the unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using sulindac.

It is not known whether sulindac passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Sulindac is not approved for use by anyone younger than 18 years old.

Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger amounts or for longer than recommended. Use the lowest dose that is effective in treating your condition.

Take sulindac with food.

If you use this medicine long-term, you may need frequent medical tests.

Store at room temperature away from moisture and heat. Keep the bottle tightly closed when not in use.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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:

• Acid or sour stomach
• belching
• constipation
• headache
• heartburn
• nausea or vomiting
• skin rash
• stomach pain

• Excess air or gas in the stomach or intestines
• itching skin
• passing gas
• stomach cramps
• swelling
• weight loss

• Back or leg pains
• bleeding gums
• blistering, peeling, or loosening of the skin
• bloating
• bloody or black, tarry stools
• bloody or cloudy urine
• blurred or loss of vision
• burning feeling in the chest or stomach
• burning while urinating
• chest pain
• chills
• clay-colored stools
• confusion
• cough or hoarseness
• cracks in the skin
• dark urine
• decreased urine output
• diarrhea
• difficult or labored breathing
• difficult or painful urination
• difficulty with swallowing
• dilated neck veins
• discoloration of urine
• disturbed color perception
• dizziness
• double vision
• extreme fatigue
• eye pain
• fainting
• feeling of warmth
• fever
• flu-like symptoms
• general body swelling
• general feeling of discomfort or illness
• groin pain
• halos around lights
• hives
• increased sensitivity of the skin to sunlight
• increased sweating
• increased thirst
• indigestion
• irregular breathing
• joint or muscle pain
• large, flat, blue, or purplish patches in the skin
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• loss of appetite
• loss of heat from the body
• lower back or side pain
• muscle aches, pains, or weakness
• nervousness
• night blindness
• noisy breathing
• nosebleeds
• numbness or tingling in the hands, feet, or lips
• overbright appearance of lights
• painful or difficult urination
• pains in the stomach, side, or abdomen, possibly radiating to the back
• pale skin
• persistent bleeding or oozing from puncture sites, mouth, or nose
• pinpoint red or purple spots on the skin
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• redness of the face, neck, arms and occasionally, upper chest
• redness or other discoloration of the skin
• redness, swelling, or soreness of the tongue
• scaly skin
• seizures
• severe or continuing stomach pain
• severe sunburn
• shortness of breath
• slow or fast, irregular, pounding, or racing heartbeat or pulse
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stiff neck or back
• stomach upset
• swelling of the face, fingers, feet, or lower legs
• swelling or inflammation of the mouth
• swollen or painful glands
• tenderness in the stomach area
• tightness in the chest
• troubled breathing
• tunnel vision
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• upper right abdominal pain
• vomiting of blood or material that looks like coffee grounds
• watery or bloody diarrhea
• weakness or heaviness of the legs
• weight gain
• wheezing
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Change in consciousness
• decreased awareness or responsiveness
• loss of consciousness
• severe sleepiness

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:

• Continuing ringing or buzzing or other unexplained noise in the ears
• hearing loss

• Burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• burning, dry, or itching eyes
• decreased hearing
• difficulty with moving
• discharge, excessive tearing
• discouragement
• false sense of well-being
• feeling of constant movement of self or surroundings
• feeling sad or empty
• hair loss or thinning of the hair
• hallucinations
• irritability
• loss of interest or pleasure
• metallic or bitter taste
• mood swings
• muscle cramping or stiffness
• personality changes
• redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• restlessness
• sensation of spinning
• sleepiness or unusual drowsiness
• sleeplessness
• sore or dry mucous membranes
• swelling or redness in the joints
• trouble with concentrating
• trouble with sleeping
• unable to sleep
• vaginal bleeding

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.

The following adverse reactions were reported in clinical trials or have been reported since the drug was marketed. The probability exists of a causal relationship between Clinoril and these adverse reactions. The adverse reactions which have been observed in clinical trials encompass observations in 1,865 patients, including 232 observed for at least 48 weeks.

Incidence Greater Than 1%

Gastrointestinal

The most frequent types of adverse reactions occurring with Clinoril are gastrointestinal; these include gastrointestinal pain (10%), dyspepsia3, nausea3 with or without vomiting, diarrhea3, constipation3, flatulence, anorexia and gastrointestinal cramps.

Dermatologic

Rash3, pruritus.

Central Nervous System

Dizziness3, headache3, nervousness.

Special Senses

Tinnitus.

Miscellaneous

Edema (see WARNINGS).

Incidence Less Than 1 in 100

Gastrointestinal

Gastritis, gastroenteritis or colitis. Peptic ulcer and gastrointestinal bleeding have been reported. GI perforation and intestinal strictures (diaphragms) have been reported rarely.

Liver function abnormalities; jaundice, sometimes with fever; cholestasis; hepatitis; hepatic failure.

There have been rare reports of sulindac metabolites in common bile duct "sludge" and in biliary calculi in patients with symptoms of cholecystitis who underwent a cholecystectomy.

Pancreatitis (see PRECAUTIONS).

Ageusia; glossitis.

Dermatologic

Stomatitis, sore or dry mucous membranes, alopecia, photosensitivity.

Erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and exfoliative dermatitis have been reported.

Cardiovascular

Congestive heart failure, especially in patients with marginal cardiac function; palpitation; hypertension.

Hematologic

Thrombocytopenia; ecchymosis; purpura; leukopenia; agranulocytosis; neutropenia; bone marrow depression, including aplastic anemia; hemolytic anemia; increased prothrombin time in patients on oral anticoagulants (see PRECAUTIONS).

Genitourinary

Urine discoloration; dysuria; vaginal bleeding; hematuria; proteinuria; crystalluria; renal impairment, including renal failure; interstitial nephritis; nephrotic syndrome.

Renal calculi containing sulindac metabolites have been observed rarely.

Metabolic

Hyperkalemia.

Musculoskeletal

Muscle weakness.

Psychiatric

Depression; psychic disturbances including acute psychosis.

Nervous System

Vertigo; insomnia; somnolence; paresthesia; convulsions; syncope; aseptic meningitis (especially in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease, see PRECAUTIONS).

Special Senses

Blurred vision; visual disturbances; decreased hearing; metallic or bitter taste.

Respiratory

Epistaxis.

Hypersensitivity Reactions

Anaphylaxis; angioneurotic edema; urticaria; bronchial spasm; dyspnea.

Hypersensitivity vasculitis.

A potentially fatal apparent hypersensitivity syndrome has been reported. This syndrome may include constitutional symptoms (fever, chills, diaphoresis, flushing), cutaneous findings (rash or other dermatologic reactions  see above), conjunctivitis, involvement of major organs (changes in liver function including hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated intravascular coagulation, anemia, renal impairment, including renal failure), and other less specific findings (adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain, tachycardia).

Causal Relationship Unknown

A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β-hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, sometimes with fatal outcome (see also PRECAUTIONS, General).

Other reactions have been reported in clinical trials or since the drug was marketed, but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, that possibility cannot be excluded. Therefore, these observations are listed to serve as alerting information to physicians.

Cardiovascular

Arrhythmia.

Metabolic

Hyperglycemia.

Nervous System

Neuritis.

Special Senses

Disturbances of the retina and its vasculature.

Miscellaneous

Gynecomastia.

Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.

Applies to sulindac: compounding powder, oral tablet

General

The most frequently reported adverse effects were gastrointestinal (GI) in nature and included GI pain, dyspepsia, nausea with or without vomiting, diarrhea, constipation, flatulence, and GI cramps.[Ref]

Gastrointestinal

Common (1% to 10%): Gastrointestinal (GI) pain, dyspepsia, nausea, vomiting, diarrhea, constipation, flatulence, anorexia, GI cramps
Frequency not reported: Gastritis, gastroenteritis, colitis, peptic ulcer, GI bleeding, GI perforation, intestinal strictures, pancreatitis, glossitis, stomatitis, hematemesis, melena[Ref]

Nervous system

Common (1% to 10%): Dizziness, headache
Frequency not reported: Ageusia, paresthesia, somnolence, convulsions, syncope, neuritis, drowsiness[Ref]

Other

Common (1% to 10%): Tinnitus, edema
Frequency not reported: Sore/dry mucous membranes, vertigo, insomnia, aseptic meningitis, hearing decreased, metallic/bitter taste, asthenia, malaise, fatigue[Ref]

Psychiatric

Common (1% to 10%): Nervousness
Frequency not reported: Depression, psychic disturbances, acute psychosis, hallucinations, confusion[Ref]

Dermatologic

Common (1% to 10%): Rash, pruritus
Frequency not reported: Alopecia, photosensitivity, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, ecchymosis, purpura, urticaria, angioneurotic edema, fulminant necrotizing fasciitis, sweating[Ref]

Hematologic

Frequency not reported: Thrombocytopenia, leukopenia, agranulocytosis, neutropenia, bone marrow depression, aplastic anemia, hemolytic anemia, prothrombin time increased[Ref]

Cardiovascular

Frequency not reported: Congestive heart failure, palpitation, hypertension, arrhythmia[Ref]

Hypersensitivity

Frequency not reported: Anaphylaxis, hypersensitivity vasculitis[Ref]

A potentially fatal apparent hypersensitivity reaction has been reported. Signs and symptoms of such reaction include constitutional symptoms (e.g., fever, chills, diaphoresis, and flushing), cutaneous reactions (e.g., rash or other dermatologic reactions), conjunctivitis, involvement of major organs (e.g., changes in liver function including hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated intravascular coagulation, anemia, renal impairment, including renal failure), and other less specific findings (e.g., adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain, and tachycardia).[Ref]

Hepatic

Rare cases of metabolites of this drug being found in common bile duct "sludge" and biliary calculi have been reported in patients with symptoms of cholecystitis who underwent a cholecystectomy.[Ref]

Frequency not reported: Jaundice, cholestasis, hepatitis, hepatic failure, liver function abnormalities[Ref]

Renal

Frequency not reported: Renal impairment, renal failure, interstitial nephritis, nephrotic syndrome, renal calculi[Ref]

Metabolic

Frequency not reported: Hyperkalemia, hyperglycemia[Ref]

Musculoskeletal

Frequency not reported: Muscle weakness[Ref]

Genitourinary

Frequency not reported: Urine discoloration, dysuria, vaginal bleeding, hematuria, proteinuria, crystalluria[Ref]

Ocular

Frequency not reported: Blurred vision, visual disturbances, disturbance of retina and its vasculature[Ref]

Respiratory

Frequency not reported: Epistaxis, bronchial spasm, dyspnea[Ref]

Endocrine

Frequency not reported: Gynecomastia[Ref]

Some side effects of Clinoril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.