Sulindac

Sulindac Structure: in Kenya

SULINDAC MODE OF ACTION

Sulindac is a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic activities in animal models. The mechanism of action, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.

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INDICATIONS:

Sulindac is a non-steroidal anti-inflammatory drug with analgesic and antipyretic activity and is indicated in rheumatoid arthritis, osteoarthritis, acute gouty arthritis, ankylosing spondylitis and musculoskeletal and periarticular disorders such as tendinitis, tenosynovitis and bursitis.

DOSAGE AND ADMINISTRATION:

Sulindac should be administered orally twice a day with food. The maximum dosage is 400 mg per day. Dosages above 400 mg per day are not recommended.

In osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, the recommended starting dosage is 150 mg twice a day. The dosage may be lowered or raised depending on the response.

A prompt response (within one week) can be expected in about one-half of patients with osteoarthritis, ankylosing spondylitis, and rheumatoid arthritis. Others may require longer to respond.

In acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis) and acute gouty arthritis, the recommended dosage is 200 mg 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 to 14 days is usually adequate. In acute gouty arthritis, therapy for 7 days is usually adequate.

CONTRAINDICATIONS:

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. NSAIDS are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

Severe hepatic, renal and cardiac failure.

During the last trimester of pregnancy .

Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

Use with concomitant NSAIDs including cyclooxygenase 2 specific inhibitors .

ADVERSE REACTIONS:

Gastrointestinal: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in older people, may occur Nausea, vomiting, anorexia, diarrhoea, flatulence, constipation, gastrointestinal cramps, dyspepsia, abdominal pain, melaena, haematemesis, pancreatitis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease  have been reported following administration. Less frequently, gastritis and gastroenteritis have been observed. Pancreatitis has been reported very rarely.

Hypersensitivity: Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (hypersensitivity vasculitis) (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm, dyspnoea or epistaxis or (c) assorted skin disorders, including rashes of various types, sore or dry mucous membranes, pruritus, urticaria, purpura, angiodema, alopecia and, more rarely exfoliative and bullous dermatoses (including toxic epidermal necrolysis, erythema multiforme and Stevens-Johnson syndrome).

Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Less frequently, congestive heart failure, especially in patients with marginal cardiac function, palpitation, hypertension and arrhythmia have been reported with sulindac. Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) ).

Other adverse events reported less commonly include:

Genito-urinary: urine discoloration, vaginal bleeding, haematuria, proteinuria, crystalluria, gynaecomastia

Renal: Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure.

Hepatic: Abnormal liver function, hepatitis, cholestasis and jaundice.

Neurological and special senses: Visual disturbance including blurred vision, optic neuritis, decreased hearing, metallic or bitter taste, headaches, paraesthesia, reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus, mixed connective tissue disease), with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation , depression, nervousness, confusion, hallucinations, convulsions, syncope, psychic disturbances including acute psychosis, tinnitus, vertigo, somnolence, insomnia, sweating, asthenia, dizziness, malaise, fatigue and drowsiness.

Haematological: Thrombocytopenia, neutropenia, agranulocytosis, leucopenia, bone marrow depression including aplastic anaemia, haemolytic anaemia, increased prothrombin time in patients on oral anticoagulants

Metabolic: hyperkalaemia, hyperglycaemia

Dermatological: photosensitivity, ecchymosis, purpura.

DRUG INTERACTIONS:

Other analgesics including cyclooxygenase-2 selective inhibitors: Avoid concomitant use of two or more NSAIDs (including aspirin) as this may increase the risk of adverse effects .

Anti-hypertensives: May be a reduced anti-hypertensive effect.

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of NSAIDs.

Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside levels.

Lithium: Decreased elimination of lithium.

Methotrexate: Decreased elimination of methotrexate.

Ciclosporin: Increased risk of nephrotoxicity. Renal function should be carefully monitored.

Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration as NSAIDs can reduce the effect of mifepristone.

Corticosteroids: Increased risk of GI ulceration or bleeding .

Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin . Patients should be carefully monitored to ascertain that no change in their anticoagulant dosage is necessary.

Quinolone antibiotics: Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): Increased risk of gastrointestinal bleeding .

Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.

Probenecid: Use of probenecid with sulindac leads to increased levels in plasma of sulindac and the inactive sulphone metabolite.

Diflunisal: Concurrent administration with diflunisal may lead to a reduction in plasma level of the active metabolite of sulindac.

Dimethyl sulfoxide: Concurrent use of dimethyl sulfoxide and sulindac is not recommended since this has been shown to lead to both a reduction in plasma levels of the active sulphide metabolite and to causing peripheral neuropathy.

Zidovudine: Increased risk of haematological toxicity when NSAIDs are given with zidovudine. There is evidence of an increased risk of haemarthroses and haematoma in HIV(+) haemophiliacs receiving concurrent treatment with zidovudine and ibuprofen.


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