Clinoril

Clinoril - General Information

Clinoril is a non-steroidal anti-inflammatory drug of the arylalkanoic acid class that is marketed in the U.S. by Merck as Clinoril. Like other NSAIDs, it is useful in the treatment of acute or chronic inflammatory conditions. Clinoril is a prodrug, derived from sulfinylindene that is converted in the body to an active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class. The exact mechanism of its NSAID properties is unknown, but it is thought to act on enzymes COX-1 and COX-2, inhibiting prostaglandin synthesis.

Pharmacology of Clinoril

Clinoril is a non-steroidal anti-inflammatory indene derivative, also possessing analgesic and antipyretic activities.

Clinoril for patients

Sulindac, like other drugs of its class, is not free of side effects. The side effects of these drugs can cause discomfort and, rarely, there are more serious side effects such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes.

NSAIDs (Non-steroidal Anti-inflammatory Drugs) are often essential agents in the management of arthritis, but they also may be commonly employed for conditions which are less serious.

Physicians may wish to discuss with their patients the potential risks and likely benefits of NSAID treatment, particularly when the drugs are used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.

Clinoril 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.

Clinoril 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.

Additional information about Clinoril

Clinoril Indication: 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.
Mechanism Of Action: Clinoril'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.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Sulindac
Synonyms: Not Available
Drug Category: Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Agents; Cyclooxygenase Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Sulindac: Clinoril;
Absorption: Approximately 90% absorbed in man following oral administration.
Toxicity (Overdose): 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.
Protein Binding: Not Available
Biotransformation: 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.
Half Life: The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.
Dosage Forms of Clinoril: Tablet Oral
Chemical IUPAC Name: 2-[6-fluoro-2-methyl-3-[(4-methylsulfinylphenyl)methylidene]inden-1-yl]acetic acid
Chemical Formula: C20H17FO3S
Sulindac on Wikipedia: https://en.wikipedia.org/wiki/Sulindac
Organisms Affected: Humans and other mammals