INDOMETHACIN

The dosage of indometacin should be carefully adjusted to suit the need of the individual patient. In order to reduce the possibility of gastrointestinal disturbances, indometacin capsule should always be taken with food, milk or antacid and in chronic conditions start the therapy with a low dosage, increasing as required and continuing a trail of therapy for an adequate period (in some cases up to one month), will give the best results with a minimum of unwanted reactions.

Adult dosage :

The recommended oral dosage range is 50-200mg daily in divided doses.

Acute rheumatoid arthritis:

Initially 25mg two or three times a day. Chronic rheumatic disorders: 25mg two or three times daily. (If response is inadequate, gradually increase by 25mg. Adequate response is usually achieved with not more than 150mg daily, rarely more than 200mg daily).

Sudden flare up of chronic condition:

Increase if necessary, by 25mg daily until a satisfactory response is obtained, or a dosage of 150-200mg daily is reached. (If this causes any adverse effects, it should be reduced to a tolerable level for two or three days, then carefully increased, as tolerated).

Acute musculoskeletal disorders:

Initially 50mg two or three times daily, according to severity for 10-14 days. Normally 150mg daily, rarely 200mg daily. Lumbago: 50mg two or three times daily, according to severity. Duration of treatment is not normally more than five days, but may be continued for up to 10 days.

Gouty arthiritis:

Acute attack: 50mg three or four times daily until symptoms subside.

Following orthopaedic procedures:

Normally 100-150mg daily in divided doses until symptoms subside.

Additional considerations:

In conditions where patients require a dosage of 150- 200mg a day, it is often possible to reduce this gradually to a maintenance level of 75-100mg a day. In patients with persistent night pain and/or morning stiffness, a dose of up to 100mg at bed time may be helpful in affording relief.

It is rarely necessary to exceed a dosage of 200mg a day. Dosage in dysmenorrhoea : up to 75mg a day, starting with the onset of cramps or bleeding, and continuing for as the symptoms last.

Children :

Paediatric dosage is not established.

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 GI bleeding during NSAID therapy.

4) Method of Administration; For oral administration. To be taken preferably with or after food.

Blood and lymphatic disorders:

Infrequently, blood dyscrasias may occur including leucopenia, neutropenia, petechiae or ecchymosis, purpura, apalastic or haemolytic anaemia, agranulocytosis, bone-marrow depression, disseminated intra-vascular coagulation, and particularly thrombocytopenia.

Because some patients may develop anaemia secondary to obvious or occult gastro-intestinal bleeding, appropriate blood determinations are recommended. Epistaxis has been reported rarely.

Hypersensitivity :

Hypersensitivity reactions have been reported following treatment with NSAIDs. These may consists of (a) non specific allergic reaction and anaphylaxis (b) respiratory tract reactivity comprising asthma, aggravated asthma, bronchospasm or dyspnoea, or (c) assorted skin disorders including rashes of various types, pruritus, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Metabolism and nutrition disorders:

Hyperglycaemia, glycosuria, hyperkalaemia, sweating has been reported rarely.

Nervous system disorders :

Visual disturbances, headaches, paraesthesia, dizziness and lightheadedness 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, confusion, vertigo, malaise, fatigue, dysarthria, syncope, coma, cerebral oedema, nervousness, mental confusion, anxiety and other psychiatric disturbances, muscle weakness, involuntary muscle movements, depersonalisation, hallucinations, drowsiness, convulsions and aggravation of epilepsy and parkinsonism, peripheral neuropathy, involuntary movements and insomnia.

These effects are often transient and abate or disappear frequently on reduced or stopping treatment. However, the severity of these may, on occasion, require cessation of therapy.

Eye disorders :

Infrequently blurred vision, diplopia, optic neuritis and orbital and peri-orbital pain. Corneal deposits and retinal or macular disturbances have been reported in patients with rheumatoid arthritis on prolonged therapy; but similar changes may be expected in such patients who have not received indometacin.

Ophthalmic examinations are desirable in patients given prolonged treatment.

Ear and labyrinth disorders :

Tinnitus, hearing disturbance (rarely deafness).

Cardiac disorders:

Oedema has been reported in association with NSAID treatment. Other adverse events reported less commonly include increased blood pressure, tachycardia, chest pain, arrhythmia, palpitation, hypotension, congestive heart failure (all infrequent).

Vascular disorders :

Flushing has been reported rarely Respiratory, thoracic and mediastinal disorders : Pulmonary eosinophilia. Bronchospasm may be precipitated in patient suffering from or with a history of bronchial asthma or allergic disease.

Gastrointestinal disorders:

The most commonly-observed adverse events are gastrointestinal in nature. Anorexia, epigastric discomfort,ulceration at any point in the gastro-intestinal tract (even with resultant stenosis and obstruction), bleeding (even without obvious ulceration or from a diverticulum) and perforation of preexisting sigmoid lesions (such as diverticulum or carcinoma), increased abdominal pain or exacerbation of the condition in patients with ulcerative colitis or Crohns disease (or the development of this condition), intestinal strictures and regional ileitis have been rarely reported.

Occasionally severe reactions stopping therapy, ulceration of the oesophagus, stomach or duodenum, sometimes with haemorrhage and perforation; gastro-intestinal tract bleeding. Rarely intestinal ulceration followed by stensis and obstruction has been reported.

4 Special warnings and precautions for use). 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.

4) have been reported following administration. Less frequently, gastric has been observed. Pancreatitis has been reported very rarely.

Hepatobiliary disorders :

Cholestasis, borderline elevations of one or more liver tests may occur, and significant elevations of ALT (SGPT) or AST (SGOT) have been seen in less than 1% of patients receiving therapy with NSAIDs in controlled clinical 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. Abnormal liver function, hepatitis and jaundice are infrequent.

Skin and subcutaneous tissue disorders :

Pruritus, urticaria, angioneurotic oedema angitis, erythema nod sum, skin rash, photosensitivity, exfoliative dermatitis. Bullous reactions including Steven Johnson syndrome, erythema multiform, toxic epidermal necrolysis, loss of hair, rapid fall in blood pressure resembling a shock like state, acute respiratory distress including sudden dyspnoea, asthma and pulmonary oedema (all infrequent).

Musculoskeletal and connective tissue disorders :

Muscle weakness and acceleration of cartilage degeneration.

Renal and urinary disorders :

Blood urea elevation, haematuria, nephrotoxicity […]

2, and GI and cardiovascular risks below). 5) Cardiovascular and cerebrovascular effects Clinical trail 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, smoking). Indometacin should be used with caution in patients with psychiatric disorders, epilepsy, or Parkinsonism, as it may tend to aggravate these disorders. Gastro-intestinal disorders may be minimised by giving indometacin with food, milk or with an antacid.

If gastro-intestinal bleeding occurs, indometacin should be immediately discontinued. Indometacin may mask the signs and symptoms of infection, so antibiotic therapy should be initiated promptly if an infection occurs during therapy with indometacin.

It should be used cautiously in patients with existing but controlled infection. Caution is advised with concomitant use of live vaccines. In patients with rheumatoid arthiris, eye changes may occur which may be related to the underlying disease or to the therapy.

Therefore, in chronic rheumatoid disease, opthalmological examination at periodic intervals are recommended. Therapy should be discontinued if eye changes are observed for any unwanted effects on peripheral blood (anaemia), liver function or gastro-intestinal tract.

Cardiovascular, Renal and Hepatic Impairment:

The administration of NSAIDs may cause a dose dependent reduction in prostaglandin formation and precipitate renal failure. Patients at great risk of this reaction are those with impaired renal function, cardiac impairment, liver dysfunction, those taking diuretics, the elderly, diabetes mellitus, extracellular volume depletion, congestive heart failure, sepsis, or concomitant use of any nephrotoxic drug.

3-Contraindication) Caution in patient with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy. Acute interstitial nephritis with haematuria, and occasionally nephritic syndrome has been reported in patients receiving long term administration of indometacin.

In patients, with a reduced renal blood flow where renal prostaglandins play a major role in maintaining renal perfusion, administration of a NSAID may precipitate overt renal decompensation. Indometacin should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve, a lower daily dosage should be used to avoid excessive drug accumulation.

Discontinuation of indometacin is usually followed by recovery to the pre-treatment state. Increase in plasma potassium concentration, including hyperkalaemia, have been reported, even in some patients without renal impairment (attributed to hyporenin- anaemic hypo aldosteronism state).

2- Posology and administration) 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 precipitate bronchospasm in such patients.

Caution is advised in patients with pre-existing sigmoid lesions (such as diverticulum or carcinoma) (or the development of these conditions) as indometacin can aggravate these conditions.

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. 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. g. 5). Patients with a history of GI toxicity, particular when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

5). 8 – Undersirable effects) Indometacin can inhibit platelet aggregation. The […]

• Active peptic ulcer; a recurrent history of gastro-intestinal lesions; in patients who have nasal polyps associated with angioneurotic oedema. • Safety for use in children has not been established. 1). g. asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.

4-special warnings and precautions for use). 6-Pregnancy and lactation) • Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding). • History of upper gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.

• Use with concomitant NSAIDs including cyclo oxygenase 2 specific inhibitors (See section