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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.
Central Nervous System
Incidence Less Than 1 in 100
Thrombocytopenia; ecchymosis; purpura; leukopenia; agranulocytosis; neutropenia; bone marrow depression, including aplastic anemia; hemolytic anemia; increased prothrombin time in patients on oral anticoagulants (see PRECAUTIONS).
Renal calculi containing sulindac metabolites have been observed rarely.
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.
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.
Disturbances of the retina and its vasculature.
*** Incidence between 3% and 9%. Those reactions occurring in 1% to 3% of patients are not marked with an asterisk.
Read the Clinoril (sulindac) Side Effects Center for a complete guide to possible side effects
ACE-Inhibitors and Angiotensin II Antagonists
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. These interactions should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors or angiotensin II antagonists. In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, the co-administration of an NSAID and an ACE-inhibitor or an angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore, the combination should be administered with caution in patients with compromised renal function.
Acetaminophen had no effect on the plasma levels of sulindac or its sulfide metabolite.
The concomitant administration of aspirin with sulindac significantly depressed the plasma levels of the active sulfide metabolite. A double-blind study compared the safety and efficacy of CLINORIL (sulindac) 300 or 400 mg daily given alone or with aspirin 2.4 g/day for the treatment of osteoarthritis. The addition of aspirin did not alter the types of clinical or laboratory adverse experiences for CLINORIL (sulindac) ; however, the combination showed an increase in the incidence of gastrointestinal adverse experiences. Since the addition of aspirin did not have a favorable effect on the therapeutic response to CLINORIL (sulindac) , the combination is not recommended.
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 carefully monitored.
The concomitant administration of CLINORIL (sulindac) and diflunisal in normal volunteers resulted in lowering of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.
Clinical studies, as well as post marketing observations, have shown that CLINORIL (sulindac) can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
DMSO should not be used with sulindac. Concomitant administration has been reported to reduce the plasma levels of the active sulfide metabolite and potentially reduce efficacy. In addition, this combination has been reported to cause peripheral neuropathy.
NSAIDs have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. The mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. These effects have been attributed to inhibition of renal prostaglandin synthesis by the NSAID. Thus, when NSAIDs and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity.
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
The concomitant use of CLINORIL (sulindac) with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Although sulindac and its sulfide metabolite are highly bound to protein, studies in which CLINORIL (sulindac) was given at a dose of 400 mg daily have shown no clinically significant interaction with oral anticoagulants. However, patients should be monitored carefully until it is certain that no change in their anticoagulant dosage is required. Special attention should be paid to patients taking higher doses than those recommended and to patients with renal impairment or other metabolic defects that might increase sulindac blood levels. The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
Oral hypoglycemic agents
Although sulindac and its sulfide metabolite are highly bound to protein, studies in which CLINORIL (sulindac) was given at a dose of 400 mg daily, have shown no clinically significant interaction with oral hypoglycemic agents. However, patients should be monitored carefully until it is certain that no change in their hypoglycemic dosage is required. Special attention should be paid to patients taking higher doses than those recommended and to patients with renal impairment or other metabolic defects that might increase sulindac blood levels.
Probenecid given concomitantly with sulindac had only a slight effect on plasma sulfide levels, while plasma levels of sulindac and sulfone were increased. Sulindac was shown to produce a modest reduction in the uricosuric action of probenecid, which probably is not significant under most circumstances.
Propoxyphene hydrochloride had no effect on the plasma levels of sulindac or its sulfide metabolite.
Read the Clinoril Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 7/1/2010
This monograph has been modified to include the generic and brand name in many instances.
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