INDOMETHACIN

4).

Adults Dysmenorrhoea:

Up to 75 mg a day, starting with onset of cramps or bleeding, and continuing for as long as symptoms usually last. Acute gouty arthritis: 150 mg to 200 mg daily in divided doses until all symptoms and signs subside. Elderly The elderly are at increased risk of the serious consequences of adverse reactions.

If an NSAID is considered necessary, the lowest effective dose should be used and for the shortest possible duration. The patient should be monitored regularly for gastrointestinal bleeding during treatment with indometacin. 3). Chronic conditions In chronic conditions, starting therapy with a low dosage, increasing this gradually as necessary, and continuing a trial of therapy for an adequate period (in some cases, up to one month) will give the best results with a minimum of unwanted reactions.

The recommended oral dosage range is 50 mg to 200 mg daily in divided doses. Method of administration For oral administration. Indometacin Capsules should always be given with food or milk to reduce the chance of gastro-intestinal disturbance.

Blood and lymphatic system disorders:

Blood dyscrasias (such as thrombocytopenia, neutropenia, leukopenia, agranulocytosis, aplastic and haemolytic anaemia), bone marrow depression, petechiae, epistaxis, ecchymosis, purpura and disseminated intravascular coagulation may occur infrequently.

Some patients may develop anaemia secondary to obvious or occult gastro-intestinal bleeding, Appropriate blood determinations are recommended.

Immune and system disorders:

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consist of (a) non-specific allergic reactions and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, rhinitis or (c) assorted skin disorders, including rashes of various types, pruritus, urticaria, purpura, angioedema (swelling of the face, tongue, and inner larynx with constriction of the respiratory passages), and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Metabolism and nutrition disorders:

Hyperglycaemia, hyperkalaemia and glycosuria have been reported rarely.

Nervous system disorders:

Headache and dizziness are common side effects. Starting therapy with a low dose and increasing gradually minimises the incidence of headache. These symptoms frequently disappear on continued therapy or reducing the dosage, but if headache persists despite dosage reduction, indometacin should be withdrawn.

4), depression, vertigo, dizziness, fatigue, dysarthria, coma, cerebral oedema, confusion, nervousness, anxiety and other psychiatric disturbances, depersonalisation, hallucinations, drowsiness, convulsions and aggravation of epilepsy, peripheral neuropathy, paraesthesia, involuntary movements, insomnia and Parkinsonism.

These effects are often transient and abate or disappear upon reducing dosage or stopping treatment. However, occasionally, severe reactions may require stopping therapy.

Eye disorders:

Visual disturbances, blurred vision, optic neuritis and orbital and periorbital pain are seen infrequently. Corneal deposits, retinal or macular disturbances have been reported in some patients with rheumatoid arthritis on prolonged therapy with indometacin, and ophthalmic examinations are desirable in patients given prolonged treatment.

Ear and labyrinth disorders:

Tinnitus or hearing disturbance/auditory defects (rarely deafness) have been reported.

Cardiac disorders:

There have been reports of oedema, hypertension, hypotension, tachycardia, chest pain, arrhythmia, palpitations and cardiac failure. 4).

Vascular disorders:

Flushing has been reported.

Respiratory, thoracic and mediastinal disorders:

Pulmonary eosinophilia. There may be bronchospasm in patients with a previous history of bronchial asthma or other allergic reactions.

Gastro-intestinal disorders:

The most commonly-observed adverse events are gastrointestinal in nature. Nausea, anorexia, vomiting, epigastric discomfort or abdominal pain, dyspepsia, melaena, haematemesis, constipation or diarrhoea all have been reported. 4). Pancreatitis has been reported very rarely.

4). If gastro-intestinal bleeding does occur, treatment with indometacin should be discontinued. Gastro-intestinal disorders which occur can be reduced by giving indometacin with food, milk or antacids.

Hepatobiliary disorders:

Abnormal liver function, cholestasis. Rarely hepatitis and jaundice (associated with some fatalities). Borderline elevations of one or more liver tests may occur, and significant elevations of ALT (SGPT) or AST (SGOT) trials. If abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations such as rash or eosinophilia occur, indometacin should be stopped.

Skin and subcutaneous tissue disorders:

Pruritus, urticaria, angioneurotic oedema, angiitis, photosensitivity, erythema nodosum, rash, exfoliative dermatitis, erythema multiforme, hair loss, sweating and exacerbation of psoriasis have all been reported infrequently. Bullous reactions including Stevens Johnson syndrome and toxic epidermal necrolysis (very rare).

Musculo-skeletal, connective tissue and bone disorders:

Muscle weakness and acceleration of cartilage degeneration.

Renal and urinary disorders:

Elevation of blood urea, haematuria, proteinuria, and renal insufficiency have all been reported. Nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure. In patients with renal, cardiac or hepatic impairment, caution is required since the use of non-steroidal anti-inflammatory drugs may result in deterioration of renal function.

The dose should be kept […]

2, and GI and cardiovascular risks below). 5). 2). 2). Cardiovascular and cerebrovascular effects Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

There are insufficient data to exclude such a risk for indometacin. Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with indometacin after careful consideration.

g. hypertension, hyperlipidaemia, diabetes mellitus and smoking). Cardiovascular, renal and hepatic impairment In patients with reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, the administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure.

Patients at greatest risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics and the elderly, diabetes mellitus, extracellular volume depletion, congestive heart failure, sepsis or concomitant use of any nephrotoxic drug.

Indometacin should be given with caution and renal function should be monitored in these patients. 3 Contraindications). Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state. 8). The dose should be kept as low as possible and renal function should be monitored.

NSAIDs may also cause fluid retention which could further aggravate these conditions. It is reported that a few patients receiving non-steroidal anti-inflammatory drugs manifest borderline elevations in liver function test results. If these persist or worsen, or symptoms of liver disease, a rash or eosinophilia develop, treatment with indometacin should be stopped.

Respiratory disorders Caution is required if administered to patients suffering from or with a previous history of bronchial asthma since NSAIDs have been reported to cause bronchospasm in such patients. Gastrointestinal bleeding, ulceration and perforation GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without warning symptoms or a previous history of serious GI events.

Rarely, intestinal ulceration has been associated with stenosis and obstruction. When GI bleeding or ulceration occurs in patients receiving indometacin, the treatment should be withdrawn. 3), and in the elderly. These patients should commence treatment on the lowest dose available and, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

g. 5). 8). Gastro-intestinal disorders that occur can be reduced by taking indometacin with food or milk. They usually disappear on reducing the dosage; if not, the risks of continuing therapy should be weighed against the possible benefits.

If gastro-intestinal bleeding or ulceration does occur, indometacin should immediately be discontinued. 5). 8). Impaired female fertility The use of indometacin may impair female fertility and is not recommended in women attempting to conceive.

In women who have difficulties conceiving or who are undergoing investigation of infertility, […]

1). • NSAIDS are contraindicated in patients with angioneurotic oedema. g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin or other non-steroidal anti-inflammatory drugs. • 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 NSAID therapy. 4). • Patients with nasal polyps. 6). • Safety in children has not been established. • Patients with coagulation defects.