Sulindac

Uses

Sulindac is used for the symptomatic treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, periarticular inflammatory disorders, acute painful shoulder (acute subacromial bursitis/ supraspinatus tendinitis), acute gouty arthritis.

Sulindac is also used to associated treatment for these conditions: Ankylosing Spondylitis (AS), Colorectal Polyps, Gouty Arthritis, Osteoarthritis (OA), Rheumatoid Arthritis, Tendonitis exacerbated, Acute Subacromial bursitis, Acute supraspinatus tendinitis

How Sulindac works

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.

Dosage

Sulindac dosage

The usual dosage is 100 mg to 200 mg twice a day, although dosages should be optimized for each individual. The maximal daily dose is 400 mg. Therapy for seven days in acute gouty arthritis and for seven to fourteen days in acute painful shoulder is usually sufficient. After a satisfactory response has been achieved, the dosage may be reduced according to the response. Sulindac should be taken with food

Side Effects

Gastrointestinal side effects are the most common and consist of abdominal pain, nausea and constipation. Gastrointestinal ulceration and bleeding may also occur. The most frequently reported central nervous system side effects are drowsiness, dizziness, headache and nervousness. Other adverse effects include depression, tinnitus, confusion, light-headedness, insomnia, psychiatric disturbances, syncope, convulsions, coma, peripheral neuropathy, blurred vision and other ocular effects, oedema and mass gain, hypertension, hematuria, skin rashes, pruritus, urticaria, stomatitis, alopecia and hypersensitivity reactions. A hypersensitivity syndrome consisting of fever and chills, skin rashes or other cutaneous manifestations, hepatotoxicity, renal toxicity (including renal failure), leukopenia, thrombocytopenia, eosinophilia, inflammed glands or lymph nodes, and arthralgia have been reported. Leucopenia, purpura, thrombocytopenia, aplastic anaemia, haemolytic anaemia, agranulocytosis, epitaxis, hyperglycaemia, hyperkalaemia and vaginal bleeding have been reported. There have also been reports of hepatitis and jaundice or renal failure.

Toxicity

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.

Precaution

Patients intolerant of one of the non-steroidal anti-inflammatory analgesics, including Aspirin, may be intolerant of Sulindac.

Interaction

Sulindac and its sulphide metabolite are highly protein bound. Patients should be monitored carefully until it is certain that no change in their anticoagulant or hypoglycaemic dosage is required. Aspirin has been shown to decrease the bioavailability of the active sulfide metabolite of Sulindac. The combination showed an increase in the incidence of gastrointestinal side-effects, without providing additional symptomatic relief, and is therefore not recommended. Prolonged concurrent use of Paracetamol with Sulindac may increase the risk of adverse renal effects. It is recommended that patients be under close medical supervision while receiving such combined therapy. Probenecid may increase the plasma concentration of Sulindac and its sulfone metabolite, and slightly decrease the plasma concentration of the active sulfide metabolite.

Food Interaction

• Avoid alcohol. Ingesting alcohol may increase the risk of gastrointestinal bleeding.
• Take with food.

Sulindac Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss.

The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

Sulindac Hypertension interaction

[Major] Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure.

Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

[Moderate] Nonsteroidal anti-inflammatory drugs (NSAIDs), including topicals, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events.

NSAIDs should be used with caution in patients with hypertension.

Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the course of therapy.

Sulindac Drug Interaction

Moderate: aspirin, duloxetine, omega-3 polyunsaturated fatty acids, metoprololUnknown: aripiprazole, cyclobenzaprine, lamotrigine, atorvastatin, pregabalin, esomeprazole, acetaminophen / hydrocodone, hydroxychloroquine, montelukast, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, ergocalciferol, cholecalciferol, cetirizine

Sulindac Disease Interaction

Major: asthma, fluid retention, GI toxicity, rash, renal toxicities, thrombosisModerate: anemia, heart failure, hepatotoxicity, hyperkalemia, hypertension, platelet aggregation inhibition, nephrolithiasis

Elimination Route

Approximately 90% absorbed in humans following oral administration.

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.

Clearance

• Renal cl=68.12 +/- 27.56 mL/min [NORMAL (19-41 yrs)]

Elimination Route

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.

Pregnancy & Breastfeeding use

Use in pregnancy: Sulindac should be used during the first two trimesters of pregnancy only if the potential benefit justifies the potential risk to the foetus. Use of Sulindac during the third trimester of pregnancy is not recommended.

Use in lactation: It is not known whether Sulindac is excreted in human milk. So a decision should be made whether to discontinue nursing or discontinue the medicine taking into account the importance of the medicine to the mother.

Contraindication

Patients known to be allergic to Sulindac and those in whom acute asthmatic attacks, urticaria or rhinitis have been precipitated by Aspirin or other non-steroidal anti-inflammatory agents. Sulindac is also contraindicated in patients with a history of active gastro-intestinal bleeding or peptic ulceration. It should not be given to children, pregnant or lactating women.

Special Warning

Patient with renal impairment: Sulindac should be administered with caution to patients with impaired renal function and to those with bleeding disorders, epilepsy, parkinsonism or psychiatric disorders.

Patient with hepatic impairment: In the presence of liver function impairment the half life of Sulindac is prolonged and a reduction of daily dosage may be required.

Acute Overdose

Reported symptoms have generally reflected the gastro-intestinal, renal and central nervous system toxicities of Sulindac. Treatment is symptomatic and supportive.

Storage Condition

Store in a cool and dry place protected from light. Keep out of reach of children.

Innovators Monograph

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