Clinoril

Clinoril

sulindac

Manufacturer:

M & H Manufacturing

Distributor:

B L H Trading
/
B L Hua
Full Prescribing Info
Contents
Sulindac.
Action
Clinoril (Sulindac) is a nonsteroidal, antirheumatic agent with anti-inflammatory, analgesic and antipyretic properties.
CLINORIL is a prodrug. Following absorption, sulindac undergoes two major biotransformations: Reversible reduction to the sulfide metabolite and irreversible oxidation to the inactive sulfone metabolite. The sulfide metabolite is a potent inhibitor of prostaglandin synthesis.
CLINORIL usually provides prompt symptomatic relief of inflammation, pain and tenderness, and promotes early restoration of joint mobility. The drug has a prolonged duration of activity, which permits a once- or twice-a-day dosage schedule and may be used for long-term treatment.
Because CLINORIL is excreted in the urine primarily as biologically inactive forms, it may affect renal function less than other non-steroidal anti-inflammatory drugs; however, renal side effects have been reported infrequently with CLINORIL.
Indications/Uses
CLINORIL is indicated for acute or long-term use in the treatment of the following: Osteoarthritis; Rheumatoid arthritis; Ankylosing spondylitis; Juvenile rheumatoid arthritis; Periarticular diseases, such as acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and tenosynovitis; Acute gouty arthritis; Painful low back syndrome (low back pain, commonly referred to as lumbago).
Dosage/Direction for Use
CLINORIL is available for administration as yellow tablets containing 200 mg sulindac.
CLINORIL should be administered once or twice a day. Dosage should be adjusted to the severity of the disease. The usual daily dosage of CLINORIL is 400 mg per day. However, the dosage may be lowered depending on the response. Dosages above 400 mg per day are not recommended.
In acute gouty arthritis, therapy for 7 days is usually adequate.
CLINORIL, when administered orally, should be taken with fluids or food.
In juvenile rheumatoid arthritis, the recommended starting dose for children (two years and older) is 4.5 mg/kg/day in two divided doses with food, and may be increased to 6.0 mg/kg/day in two divided doses if control is not obtained. When control has been achieved, the usual dosage range is 4.5 to 6.0 mg/kg/day in two divided doses. Doses higher than 6.0 mg/kg/day are not recommended.
Overdosage
Cases of overdosage have been reported and rarely, fatalities have occurred. The following signs and symptoms may be observed following overdosage; stupor, coma, diminished urine output and hypotension.
In the event of acute overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage, and the patient carefully observed and given symptomatic and supportive treatment.
Animal studies show that absorption is decreased by the prompt administration of activated charcoal and excretion is enhanced by alkalinization of the urine.
Contraindications
Hypersensitivity to any component of CLINORIL.
CLINORIL should not be used in patients in whom acute asthmatic attacks, urticaria or rhinitis have been precipitated by acetylsalicylic acid or other non-steroidal anti-inflammatory agents.
The drug should not be administered to patients with active gastrointestinal bleeding.
Special Precautions
Platelet Aggregation: CLINORIL is an inhibitor of platelet function, patients who may be adversely affected should be carefully observed when CLINORIL is administered.
Gastrointestinal Effects: CLINORIL should be used with caution in patients having a history of gastrointestinal hemorrhage or ulcers. In patients with an active peptic ulcer, an appropriate therapeutic regimen should be instituted and the physician must weigh the benefits of CLINORIL against possible hazards and carefully monitor the patient's progress.
Hypersensitivity Syndrome: A potentially life-threatening, apparent hypersensitivity syndrome has been reported. In cases where this syndrome is suspected, therapy should be discontinued immediately, and not reinstituted. This syndrome may include constitutional symptoms (fever, chills, diaphoresis, flushing), cutaneous findings (rash or other dermatologic reactions see Side Effects), conjunctivitis involvement of major organs (changes in liver function tests, hepatic failure, jaundice, pancreatitis, pneumonitis with or without pleural effusion, leukopenia, leukocytosis, eosinophilia, disseminated intravascular coagulation, anemia, renal impairment and including renal failure) and other less specific findings (adenitis, arthralgia, arthritis, myalgia, fatigue, malaise, hypotension, chest pain and tachycardia).
Infections: Non-steroidal anti-inflammatory drugs, including CLINORIL may mask the usual signs and symptoms of infection. Therefore, the physician must be continually on the alert for this and should use the drug with extra care in the presence of existing infection.
Ocular Effects: Because of reports of adverse eye findings with agents of this class it is recommended that patients who develop eye complaints during treatment with CLINORIL have ophthalmological evaluations.
Cardiovascular Effects: Peripheral edema has been observed in some patients taking CLINORIL. Therefore, as wilh other drugs in this class, CLINORIL should be used with caution in patients with compromised cardiac function, hypertension, or other conditions predisposed to fluid retention.
Hepatic Effects: In patients with poor liver function, delayed, elevated and prolonged circulating levels of the sulfide and sulfone metabolites may occur. Such patients should be monitored closely; a reduction of daily dosage may be required.
Cases of hepatitis, jaundice, or both, with or without fever, may occur within the first 3 months of therapy. In some patients, the findings are consistent with those of cholestatic hepatitis.
Fever and other evidence of hypersensitivity, including abnormalities in one or more liver function tests and skin reactions, have occurred during therapy with CLINORIL. Fatalities have occurred in some of these patients.
Determinations of liver function should be considered whenever a patient on therapy with CLINORIL develops unexplained fever, rash or other dermatologic reactions or constitutional symptoms. In cases where this syndrome is suspected, therapy should be discontinued immediately and not reinstituted.
The elevated temperature and abnormalities in liver function tests observed with CLINORIL characteristically have reverted to normal after discontinuation of therapy.
Significant (3 times the upper limit of normal) elevations of SGPT (ALAT) or SGOT (ASAT) occurred in controlled clinical trials in less than 1% of patients receiving this therapy. A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver function test has occurred, should be evaluated for evidence of the development of more severe hepatic reactions while on therapy.
Renal Effects: As with other non-steroidal anti-inflammatory drugs, there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome in patients receiving sulindac.
In patients with reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, administration of a non-steroidal antiĀ­-inflammatory agent may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with renal or hepatic dysfunction, diabetes mellitus, advanced age, extracellular volume depletion, congestive heart failure, sepsis, or concomitant use of any nephrotoxic drug. A non-steroidal anti-inflammatory drug should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve. Discontinuation of non-steroidal anti-inflammatory therapy is usually followed by recovery to the pretreatment state.
Since CLINORIL is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored; a lower daily dosage should be used to avoid excessive drug accumulation.
Sulindac metabolites have been reported rarely as the major or a minor component in renal stones in association with other calculus components. CLINORIL should be used with caution in patients with a history of renal lithiasis, and they should be kept well hydrated while receiving CLINORIL.
Use in Pregnancy: CLINORIL should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the fetus. Use of CLINORIL during the third trimester of pregnancy is not recommended.
The known effects of drug of this class on the human fetus during the third trimester of pregnancy include: Constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension; non-closure of the ductus arteriosus postnatally which may be resistant to medical management; myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation and increased risk of necrotizing enterocolitis.
Use in Lactation: It is not known whether sulindac is excreted in human milk. Because other drugs of this class are excreted in human milk, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: The effect of therapy with CLINORIL in children is less than two years of age has not been established, and therapy in this age group is not recommended.
Use In Pregnancy & Lactation
Use in Pregnancy: CLINORIL should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the fetus. Use of CLINORIL during the third trimester of pregnancy is not recommended.
The known effects of drug of this class on the human fetus during the third trimester of pregnancy include: Constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension; non-closure of the ductus arteriosus postnatally which may be resistant to medical management; myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation and increased risk of necrotizing enterocolitis.
Use in Lactation: It is not known whether sulindac is excreted in human milk. Because other drugs of this class are excreted in human milk, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Side Effects
CLINORIL is generally well tolerated. Those side effects experienced are usually mild and may often respond to a reduction in dosage.
The following side effects were reported in clinical trials or have been reported since the drug was marketed: Side Effects Reported Frequently: Gastrointestinal: The most frequent types of side effects occurring with CLINORIL are gastrointestinal; these include gastrointestinal pain, dyspepsia, nausea with or without vomiting, diarrhea, constipation, flatulence, anorexia and gastrointestinal cramps.
Dermatologic: Rash, pruritus.
Central Nervous System: Dizziness, headache, nervousness.
Special Senses: Tinnitus.
Miscellaneous: Edema.
Side Effects Reported Less Frequently: The probability exists of a causal relationship between CLINORIL and these side effects: Gastrointestinal: Stomatitis, gastritis or gastroenteritis. Peptic ulcer, colitis, gastrointestinal bleeding and GI perforations have been reported rarely. Fatalities have occurred. Liver function test abnormalities, jaundice sometimes with fever, cholestasis, hepatitis, hepatic failure, pancreatitis, ageusia, glossitis and intestinal strictures (diaphragms).
It has also been reported that a probable sulindac metabolite has been found in biliary sludge in patients with symptoms of cholecystitis who underwent a cholecystectomy.
Dermatologic: Sore or dry mucous membranes, alopecia, photosensitivity, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis.
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.
Genitourinary: Urine discoloration, dysuria, vaginal bleeding, hematuria, proteinuria, crystalluria, renal impairment including renal failure, interstitial nephritis, nephrotic syndrome.
Nervous System: Vertigo, somnolence, insomnia, sweating, asthenia, paresthesias, convulsions, syncope, depression, psychic disturbances including acute psychosis, aseptic meningitis.
Metabolic: Hyperkalemia.
Musculoskeletal: Muscle weakness.
Special Senses: Visual disturbances (including blurred vision), decreased hearing, metallic or bitter taste.
Respiratory: Epistaxis.
Hypersensitivity Reactions: Anaphylaxis and angioneurotic edema. Bronchial spasm, dyspnea, hypersensitivity vasculitis, hypersensitivity syndrome (see Precautions).
Drug Interactions
Dimethyl Sulfoxide: DMSO (dimethyl sulfoxide) should not be used with sulindac. Concomitant administration has been reported to reduce the plasma levels of the active sulfide metabolite and may potentially reduce efficacy. In addition, this combination has been reported to cause peripheral neuropathy.
Methotrexate: Caution should be used if CLINORIL is administered concomitantly with methotrexate. Non-steroidal anti-inflammatory drugs have been reported to decrease the tubular secretion of methotrexate and potentiate the toxicity.
Cyclosporine: Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine and renal function should be monitored carefully.
Acetylsalicylic Acid: The concomitant administration of acetylsalicylic acid with sulindac in normal volunteers significantly depressed the plasma levels of the active sulfide metabolite. In a clinical study, the combination showed an increase in the incidence of gastrointestinal side effects. Since the addition of acetylsalicylic acid did not have a favorable effect on the therapeutic response to CLINORIL, the combination is not recommended.
Other NSAIDS: The concomitant use of CLINORIL with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Oral anticoagulants and hypoglycemic agents: Although sulindac and the sulfide metabolite are highly bound protein, studies, in which CLINORIL was given at a dose of 400 mg daily, have shown no clinically significant interaction with oral anticoagulants or oral hypoglycemic agents. However, patients should be monitored carefully until it is certain that no change in their anticoagulant or hypoglycemic dosage is required.
Diflunisal: The concomitant administration of CLINORIL and diflunisal in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.
Storage
Store below 30°C.
Protect from sunlight and excessive heat.
ATC Classification
M01AB02 - sulindac ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.
Presentation/Packing
Tab 200 mg (yellow) x 10 x 10's.
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