Brands, Medical Use, Clinical Data
Drug Category
- Anti-Inflammatory Agents, Non-Steroidal
- Antineoplastic Agents
- Cyclooxygenase Inhibitors
Dosage Forms
- 150 and 200 mg tablets for oral administration
Brands / Synonyms
Clinoril; Clinoril
; Sulindac
Indications
For acute or long-term use in the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis. ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.
Pharmacology
Sulindac is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.
Mechanism of Action
Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both cylooxygenase-1 (COX-1) and cylooxygenase-2 (COX-2) which leads to the inhibition of prostaglandin synthesis, and results in the inhibition of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Absorption
Approximately 90% absorbed in man following oral administration.
Toxicity
Acute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdosage have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdosage: stupor, coma, diminished urine output and hypotension.
Biotrnasformation / Drug Metabolism
Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Available evidence indicates that the biological activity resides with the sulfide metabolite.
Contraindications
CLINORIL should not be used in:
Patients who are hypersensitive to this product.
Patients in whom acute asthmatic attacks, urticaria, or rhinitis are precipitated by aspirin or other
non-steroidal anti-inflammatory agents.
Drug Interactions
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.
Although sulindac and its sulfide metabolite are highly bound to 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. 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 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 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; 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, the combination is not recommended.
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.
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 to potentiate its
toxicity.
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 and diflunisal in normal volunteers resulted in lowering
of the plasma levels of the active sulindac sulfide metabolite by approximately one-third.
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.
Neither propoxyphene hydrochloride nor acetaminophen had any effect on the plasma levels of sulindac
or its sulfide metabolite.
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