Sulindac

356.41100

356.41

250-893-8

757344

DTXSID4023624

M - Musculo-skeletal system

2930909090

73.58000

5.23120

Yellow solid.

1.38 g/cm3

183 °C

581.6ºC at 760 mmHg

305.6ºC

1.672

Soluble in water, methanol, ethanol.

Keep tightly closed.

4.7

192.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|191.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

III

6.1(b)

UN 3249

3

R22

NK8226000

Xn

Stable at normal temperatures and pressures.

Missing Phrase - N15.00950417-P261-P280-P284-P304 + P340-P342 + P311

H301-H317-H334-H361

|Danger|H301 (98.68%): Toxic if swallowed [Danger Acute toxicity, oral]|P201, P202, P260, P261, P264, P270, P272, P280, P281, P285, P301+P310, P302+P352, P304+P341, P305+P351+P338, P308+P313, P314, P321, P330, P333+P313, P337+P313, P342+P311, P363, P405, and P501|Aggregated GHS information provided by 77 companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Acute oral toxicity (LD50) in rats is 264 mg/kg. Cases of overdose have been reported and rarely, deaths have occurred. The following signs and symptoms may be observed following overdose: stupor, coma, diminished urine output and hypotension.

Chronic therapy with sulindac is associated with a low rate of serum aminotransferase elevations, which are rarely severe and usually self-limited. Clinically apparent acute liver injury from sulindac is well known, but rare (~5 cases in 100,000 prescriptions and ~0.1% of users). Sulindac hepatotoxicity typically presents with fever, rash, nausea and vomiting and abdominal pain arising within a few days or weeks of starting the medication and followed shortly thereafter by jaundice. Occasionally, the onset may be delayed, particularly if therapy is intermittent. The clinical pattern suggests an allergic hepatitis and is somewhat similar to the hepatotoxicity of the sulfonamides. The pattern of serum enzyme elevations is usually hepatocellular or mixed at the onset, but may then become cholestatic. However, recovery is usually rapid once sulindac is stopped. Histology is consistent with an allergic hepatitis with spotty necrosis and marked inflammatory cell infiltration with prominence of eosinophils. In many instances, the features of hypersensitivity (such as facial swelling, desquamating rash, pharyngitis, stomatitis, lymphadenopathy, and hypotension) overshadow the liver injury and are more commonly the cause of death. Sulindac can also cause acute liver injury with a more delayed latency with few or no features of hypersensitivity. These cases are usually cholestatic and can be prolonged and lead to vanishing bile duct syndrome.

At 1 mcg/ml concentrations, approximately 93% sulindac and 98% of its sulfide metabolite are bound to human serum albumin.

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.|FDA Label|Treatment of Familial Adenomatous Polyposis

Sulindac is a commonly used nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and used predominantly to treat chronic arthritis. Sulindac is a rare, but well established cause of idiosyncratic, clinically apparent drug induced liver disease.

Nonsteroidal Antiinflammatory Drugs

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

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)|Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)|Compounds or agents that combine with cyclooxygenase (PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES) and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of eicosanoids, prostaglandins, and thromboxanes. (See all compounds classified as Cyclooxygenase Inhibitors.)

Approximately 90% absorbed in humans following oral administration.|Sulindac is excreted in rat milk; concentrations in milk were 10 to 20% of those levels in plasma. It is not known if sulindac is excreted in human milk. Approximately 50% of the administered dose of sulindac is excreted in the urine with the conjugated sulfone metabolite accounting for the major portion. Hepatic metabolism is an important elimination pathway.|Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]

Undergoes two major biotransformations: reversible reduction to the sulfide metabolite, and irreversible oxidation to the sulfone metabolite. Sulindac and its sulfide and sulfone metabolites undergo extensive enterohepatic circulation. Available evidence indicates that the biological activity resides with the sulfide metabolite. Side chain hydroxylation and hydration of the double bond also occur.

The mean half-life of sulindac is 7.8 hours while the mean half-life of the sulfide metabolite is 16.4 hours.

Sulindac's exact mechanism of action is unknown. Its antiinflammatory effects are believed to be due to inhibition of both COX-1 and COX-2 which leads to 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.

Aclin

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