INFORMATION FOR HEALTH PROFESSIONALS
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advised Medsafe that this product has either been discontinued or is no longer
marketed in New Zealand.
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have access to this product information in the interim.
You may be able to find a more current Data Sheet containing the same medicine
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Sulindac USP as:
100mg tablets: Yellow, hexagonal, flat, tablets marked S on one side.
200mg tablets: Yellow, hexagonal, biconvex tablets engraved -N- on one side and 200 on the other.
Sulindac is a non-steroidal, anti-inflammatory indene derivative possessing both analgesic and anti-pyretic activity. Sulindac is inactive, the biological effect being manifested by the sulphide metabolite. The anti-inflammatory effect is manifested via inhibition of prostaglandin synthesis. In clinical studies, a daily dose of sulindac ranging from 200-400mg is similar in effectiveness to 2400-4800mg aspirin.
Sulindac has little CNS effect, uricosuric or diuretic activity or cardiovascular or respiratory effects.
After oral administration approximately 88% is absorbed. In the fasting state peak plasma concentrations are attained in approximately 45 minutes and in about 3 hours when sulindac is administered with food. Peak concentrations of the active sulphide metabolite are attained in approximately one hour in the fasting state and in about four hours after administration of food.
Sulindac is extensively bound to plasma proteins. Elimination occurs by metabolism and excretion via the urine. Two metabolites are produced, the sulphide that is the principal active agent and the sulphone metabolite which is inactive. Approximately 50% of an administered dose is excreted into the urine and approximately 25% in the faeces. Sulindac and its sulphone metabolite (both free and glucuronidated forms) appear in the urine with the suphone metabolite being the major component. The sulphide metabolite appears in the faeces.
The elimination half-life for sulindac is approximately 2.3 hours.
SALDAC (sulindac) is indicated for the relief of signs and symptoms related to osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and acute gouty arthritis.
SALDAC (sulindac) should be administered orally twice a day with food. The maximum recommended dose is 400mg per day.
In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 100mg twice a day. The dosage may be lowered or raised depending on the response.
In acute painful shoulder (acute sub-acromial bursitis/supraspinatus tendinitis) and acute gouty arthritis, the recommended dosage is 200mg twice a day. After a satisfactory response has been achieved, the dosage may be reduced according to the response. In acute painful shoulder, therapy for 7-14 days is usually adequate. In acute gouty arthritis, therapy for 7 days is usually adequate.
The use of SALDAC (sulindac) is contraindicated in patients that have shown hypersensitivity to sulindac.
Patients in whom acute asthmatic attacks have been precipitated by acetylsalicylic acid or other anti-inflammatory agents should not use SALDAC.
SALDAC should not be administered to patients with active peptic ulcers or active inflammatory disease of the gastrointestinal tract. SALDAC is not recommended for use in children. Dose and indications for paediatric patients have not been established.
When SALDAC (sulindac) is administered to patients with a history of upper gastrointestinal disease, it should be used cautiously under close supervision since peptic ulcers and gastrointestinal bleeding have been observed in association with sulindac therapy ( see Adverse Effects ).
Circulating levels of the sulphide and sulphone metabolites may be delayed, elevated and prolonged in patients with poor liver function. Such patients should be closely monitored and may require a reduction of daily dosage.
In rare instances, fever and other evidence of hypersensitivity ( see Adverse Effects ) including abnormalities in one or more liver function tests have occurred during sulindac therapy. Fatalities have occurred in these patients. Within the first one to three months of therapy, hepatitis, jaundice, or both, with or without fever may occur. In some patients, the findings are consistent with those of cholestatic hepatitis. Regular liver function tests should be performed on patients receiving SALDAC.
If patients on sulindac therapy develop unexplained fever, rash or other dermatologic reactions or constitutional symptoms, determinations of liver function should be repeated.
Therapy with SALDAC should be discontinued if fever and other evidence of hypersensitivity, abnormalities in liver function or jaundice occur. Generally, the elevated temperature and abnormalities in liver function caused by sulindac have returned to normal following discontinuation of therapy, however, administration of SALDAC should not be reinstituted in such patients.
Borderline elevations of one or more liver function test results may occur in up to 15% of patients treated with non-steroidal anti-inflammatory agents. Meaningful elevations (3 times the upper limit of normal) of serum ALT or AST concentrations have occurred in less than 1% of patients receiving non-steroidal anti-inflammatory agents in controlled clinical studies. These abnormalities may progress, may remain essentially unchanged or may be transient with continued therapy.
Patients who experience signs and/or symptoms suggestive of liver dysfunction or an abnormal liver function test result while receiving sulindac should be evaluated for evidence of the development of a severe hepatic reaction. Although such reactions are rare, sulindac should be discontinued if abnormal liver function test results persist or worsen, if clinical signs and symptoms consistent with liver disease develop or if systemic manifestations occur (e.g. eosinophilia or rash).
SALDAC (sulindac) is an inhibitor of platelet function, which has less effect on platelet function and bleeding time than acetylsalicylic acid. Patients who may be adversely affected by this action should be carefully observed when SALDAC is administered.
There have been several reported cases of pancreatitis in patients receiving sulindac and if this occurs, SALDAC treatment should be discontinued and should not be reinstituted.
It is recommended that patients who develop eye complaints during treatment with SALDAC have ophthalmologic examinations due to reports of adverse eye findings with non-steroidal anti-inflammatory agents.
Sulindac is eliminated primarily by the kidneys, therefore patients with significantly impaired renal function should be closely monitored. A reduction of daily dosage may be anticipated to avoid excessive medicine accumulation.
Since there have been reports of renal adverse experiences with sulindac, caution should be exercised when administering the medicine to patients with conditions associated with increased risk of the effects of non-steroidal anti-inflammatory agents on renal function. SALDAC should therefore be used with caution in the presence of renal impairment, in elderly patients, and in those with conditions such as extracellular volume depletion, congestive heart failure, sepsis and systemic lupus erythematosus.
Concomitant use of any nephrotoxic agent should be avoided. Recovery of renal function to pretreatment levels usually occurs following discontinuance of non-steroidal anti-inflammatory agent therapy.
Caution should be exercised when SALDAC is used in patients with compromised cardiac function, hypertension, or other conditions predisposing to fluid retention since peripheral, cardiac and non-cardiac oedema have been observed in some patients taking sulindac.
If a reduction in dosage or withdrawal of corticosteroid is considered in patients on concomitant therapy with corticosteroids, then it is generally necessary to reduce the corticosteroid dosage gradually over several months in order to avoid an exacerbation of disease or signs and symptoms of adrenal insufficiency. Generally, it is not recommended that abrupt withdrawal of chronic corticosteroid treatment occur even when patients have had a serious complication of chronic corticosteroid therapy.
Patients should be aware that because of the medicine's anti-inflammatory and analgesic activity, SALDAC may mask the usual signs of infection.
The safety of sulindac has not been established in pregnant women and therefore the use of SALDAC (sulindac) is not recommended during pregnancy.
Although it is not known whether sulindac is secreted in human milk, nursing should not be undertaken while a patient is on SALDAC since it is known that sulindac is secreted in the milk of lactating rats.
Multi-clinic, multi-investigator clinical trials involving 24,000 general practice patients with rheumatoid arthritis, osteoarthritis or ankylosing spondylitis treated with sulindac indicated the following adverse reactions and their approximate incidence (%). Additional adverse reactions were reported in additional clinical trials.
Gastrointestinal: Gastrointestinal pain was the most common adverse reaction reported (7.2%). Other gastrointestinal disturbances included nausea, with or without vomiting (6.5%), constipation (3.0%), diarrhoea (1.5%), dyspepsia, flatulence, anorexia and gastrointestinal cramps. The following adverse reactions had a frequency of less than 1%, gastritis or gastroenteritis, peptic ulcer, gastrointestinal bleeding, pancreatitis and gastrointestinal perforation, which has been reported rarely.
Hepatobiliary: Hepatobiliary effects were reported by less than 1% of the patients and included liver function abnormalities, jaundice, sometimes with fever, cholestasis and hepatitis.
Central Nervous System: Central nervous system effects reported included dizziness (2.7%), drowsiness (2.1%), headache (1.7%), nervousness and tinnitus. CNS side effects reported less frequently (< 1%) included vertigo, somnolence, insomnia, sweating, asthenia and blurred vision.
Dermatologic: Rash (3%) and pruritis were the most frequently reported dermatologic side effects, stomatitis, sore or dry mucous membranes, erythema multiforme, toxic epidermal necrolysis and Stevens-Johnson syndrome were reported less frequently.
Cardiovascular: Congestive heart failure in patients with marginal cardiac function and palpitations are two cardiovascular side effects reported less frequently (< 1%).
Haematologic: Haematologic effects with an incidence of less than 1% included, thrombocytopenia, ecchymosis, purpura, leukopenia and increased prothrombin time in patients on oral anticoagulants (see Warnings and Precautions ).
Miscellaneous: Oedema has been reported in some patients ( see Warnings and Precautions ). Hypersensitivity reactions including anaphylaxis and angio-neurotic oedema have been reported (< 1%).
A potentially fatal apparent hypersensitivity syndrome has been reported in a few patients which has consisted of some or all of the following findings: fever, chills, skin rash or other dermatologic reactions, changes in liver function, jaundice, pneumonitis, leukopenia, eosinophilia and renal impairment.
Other adverse experiences have been reported in patients receiving sulindac and, although a causal relationship has not been established, the possibility cannot be excluded and the serious nature of some of these reactions requires that patients be monitored carefully by their physicians.
| Cardiovascular: | hypertension. |
|---|---|
| Haematologic: | bone marrow depression, including aplastic anaemia and haemolytic anaemia. |
| Nervous system: | paresthesias, neuritis. |
| Special senses: | transient visual disturbances, decreased hearing. |
| Respiratory: | epistaxis. |
| Psychiatric: | depression, psychic disturbances including acute psychosis. |
| Genitourinary: | vaginal bleeding, haematuria, renal impairment, interstitial nephritis, nephrotic syndrome. |
Studies in which sulindac was given at a dose of 400mg daily, have shown no clinically significant interaction with oral anticoagulants or oral hypoglycaemic agents although sulindac and its sulphide metabolite are highly bound to protein. Patients should be monitored carefully until it is certain that no change in their anticoagulant or hypoglycaemic dosage is required while receiving SALDAC treatment. Patients taking higher doses than those recommended and patients with renal impairment or other metabolic defects that might increase sulindac blood levels should receive special attention.
Administration of acetylsalicylic acid concomitantly with sulindac is reported to significantly depress the plasma levels of the active sulphide metabolite. The safety and efficacy of sulindac, 300mg daily, given alone or with acetylsalicylic acid, 1.5g/day for the treatment of chronic rheumatic diseases was compared. The combination of sulindac and acetylsalicylic acid is not recommended since it showed no favourable effect on therapeutic response. It has also been reported that the types of clinical or laboratory adverse experiences for sulindac are not altered by the addition of acetylsalicylic acid, however, the combination shows an increase in the incidence of gastrointestinal adverse reactions.
Concomitant administration of probenecid with sulindac increased plasma levels of sulindac and sulphone while having only a slight effect on plasma sulphide levels. Sulindac produced a modest reduction in the uricosuric action of probenecid which, under most circumstances, is not significant.
Concurrent use of sulindac with antihypertensives or diuretics may decrease the diuretic, natriuretic and antihypertensive effects of diuretics such as furosemide. Concurrent use may also increase the risk of renal failure.
Propoxyphene hydrochloride and paracetamol (acetaminophen) are reported to have no effect on the plasma levels of sulindac or its sulphide metabolite.
It has been reported that no significant difference in absorption, as measured by the urinary recovery of sulindac occurred when sulindac was administered alone or with an antacid.
There have been reports of cases of overdosage and rarely deaths have occurred. Following overdosage, the following signs and symptoms may be observed: stupor, coma, diminished urine output and hypotension.
In acute sulindac overdosage, the stomach should be emptied immediately by emesis or by gastric lavage. Supportive and symptomatic treatment should be initiated and patients should be carefully monitored.
Animal studies have shown that absorption of sulindac from the G.I. tract is decreased by prompt administration of activated charcoal and elimination is enhanced by alkalinisation of the urine.
Store below 30°C. Protect from light and moisture.
Prescription Medicine.
Bottles of 100 tablets.
Sulindac is (Z)-5-fluoro-2-methyl-1-[[p-(methylsulphinyl) phenyl] methylene]-1H-in-dene-3-acetic acid. Its molecular formula and weight are C20H17FO3S and 356.4 respectively. Sulindac is a yellow compound. It is a weak organic acid practically insoluble in water below pH 4.5, but soluble as the sodium salt or in buffers of pH 6 or higher.
Douglas Pharmaceuticals Ltd
P O Box 45-027
AUCKLAND 8
Ph: (09) 835- 0660
Fax: (09) 835-0665
13 September 1999