a) Symptoms:
Symptoms include headache, nausea, vomiting, epigastric pain, gastrointestinal bleeding, rarely diarrhoea, disorientation, excitation, coma, drowsiness, dizziness, tinnitus, fainting, occasionally convulsions. In cases of significant poisoning acute renal failure and liver damage are possible.
b) Therapeutic measure
Patients should be treated symptomatically as required. Within one hour of ingestion of a potentially toxic amount, activated charcoal should be considered. Alternatively, in adults, gastric lavage should be considered within one hour of ingestion of a potentially life-threatening overdose. Good urine output should be ensured. Renal and liver function should be closely monitored. Patients should be observed for at least four hours after ingestion of potentially toxic amounts. Frequent or prolonged convulsions should be treated with intravenous diazepam. Other measures may be indicated by the patient's clinical condition.
- NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (eg asthma, rhinitis, angioedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal anti-inflammatory drugs.
- Hypersensitivity to Indometacin Sopharma or to any of the excipients.
- Severe heart failure, hepatic failure and renal failure.
- Not to be used in patients who have nasal polyps
- During the last trimester of pregnancy.
- Safety in children has not been established.
- 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.
None known.
- Blood and lymphatic disorders: blood dyscrasias (such as thrombocytopenia,
neutropenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia), bone marrow depression, petechiae, ecchymoses, purpura, and disseminated intravascular coagulation may occur infrequently. As some patients manifest 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 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, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
- Metabolic and nutrition disorders: Hyperglycaemia, glycosuria, hyperkalaemia has been reported rarely.
- Nervous system disorders: Visual disturbances, optic neuritis, tinnitus, headache, 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 Sopharma should be withdrawn. Other CNS effects include reports of aseptic meningitis (especially in patients with existing autoimmune disorders, such as systemic lupus erythematosus or mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation , depression, vertigo, fatigue, malaise, dysarthria, syncope, coma, cerebral oedema, nervousness, confusion, anxiety and other psychiatric disturbances, depersonalisation, hallucinations, drowsiness, convulsions and aggravation of epilepsy and parkinsonism, peripheral neuropathy, paraesthesia, involuntary movements and insomnia. These effects are often transient and abate or disappear on reduced or stopping treatment. However, the severity of these may, on occasion, require cessation of therapy.
- Eye disorders: blurred vision, diplopia, optic neuritis and orbital and peri-orbital pain are seen infrequently. Corneal deposits and retinal or macular disturbances have been reported in some patients with rheumatoid arthritis on prolonged therapy with Indometacin Sopharma. Ophthalmic examinations are desirable in patients given prolonged treatment.
- Ear and labyrinth disorders: tinnitus or hearing disturbances (rarely deafness) have been reported.
- Cardiac disorders: There have been reports of hypotension, tachycardia, chest pain, arrhythmia, palpitations.
- Cardiovascular and cerebrovascular:
Oedema hypertension and cardiac failure have been reported in association with NSAID treatment.
- Vascular disorders: flushing has been reported rarely.
- Respiratory, thoracic and mediastinal disorders: pulmonary eosinophilia. There may be bronchospasm in patients with a history of bronchial asthma or other 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. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur. If gastro-intestinal bleeding does occur treatment with Indometacin Sopharma should be discontinued. Gastro-intestinal disorders which occur can be reduced by giving Indometacin Sopharma with food, milk or antacids. Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease have been reported following administration. Less frequently, gastritis has been observed. Pancreatitis has been reported very rarely.
- Hepato-biliary 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 Sopharma should be stopped. Abnormal liver function, hepatitis and jaundice.
- Skin and subcutaneous tissue disorders: pruritus, urticaria, angioneurotic oedema, angiitis, erythema nodosum, rash, photosensitivity, exfoliative dermatitis, bullous reactions including Stevens Johnson syndrome and Toxic Epidermal Necrolysis (very rare). Photosensitivity, erythema multiforme, hair loss, sweating and exacerbation of psoriasis.
- Musculo-skeletal, connective tissue and bone disorders: muscle weakness and acceleration of cartilage degeneration.
- Renal and urinary disorders: haematuria, nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure, renal insufficiency, proteinuria have all been reported. 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 as low as possible and renal function should be monitored.
- Reproductive system and breast disorders: vaginal bleeding, breast changes (enlargement, tenderness, gynaecomastia)
- Clinical trial and epidemiological data suggest that the 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).
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Indometacin Sopharma has non-steroidal analgesic and anti-inflammatory properties.
It is indicated for the following conditions:
- active stages of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, degenerative joint disease of the hip, acute musculoskeletal disorders, gout and lumbago.
- inflammation, pain and oedema following orthopaedic procedures.
- treatment of pain and associated symptoms of primary dysmenorrhoea.
Since Indometacin Sopharma is not a simple analgesic, its use should be limited to the above conditions.
ATC CODE: M01A B01
Indometacin Sopharma is a non-steroidal anti-inflammatory agent with analgesic and antipytretic properties.
The analgesic properties have been attributed to both central and peripheral effect, which are distinct from its anti-inflammatory activity.
Absorption: Indometacin Sopharma is readily absorbed from the gastrointestinal tract; peak plasma concentrations are reached in about 0.5-2 hours after a dose.
Distribution: More than 90% is bound to plasma proteins. It is distributed into synovial fluid, CNS and placenta. Low concentrations have been found in breast mik.
Metabolism: It is metabolised in the liver primarily by demethylation and deacetylation, it also undergoes glucuronidation and enterohepatic circulation. Half-life is between 3 - 11 hours.
Elimination: Mainly excreted in the urine, approximately 60%, the pH of the urine can affect this amount. Lesser amounts in the faeces. Indometacin Sopharma is also excreted in milk in small amounts.
- The use of Indometacin Sopharma capsules with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors, should be avoided
- 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).).
Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.
- Elderly:
The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal.
- 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 Sopharma 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 previous history of serious GI events.
When GI bleeding or ulceration occurs in patients receiving Indometacin Sopharma, the treatment should be withdrawn.
The risk of GI bleeding, ulceration or perforation is higher with increasing
NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation , and in the elderly.).
Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.
Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin.
NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as these conditions may be exacerbated.
- SLE and mixed connective tissue disease:
In patients with systemic lupus erythematosus (SLE) and mixed connective tissue disorders there may be an increased risk of aseptic meningitis.
- Impaired female fertility:
The use of Indometacin Sopharma 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, withdrawal of Indometacin Sopharma should be considered.
- Indometacin Sopharma should be used with caution in patients with coagulation defects as Indometacin Sopharma can inhibit platelet aggregation. This effect may be exaggerated in patients with underlying haemostatic defects. Inhibition of platelet aggregation usually disappears within 24 hours of discontinuing Indometacin Sopharma.
- Caution is required in post-operative patients as bleeding time is prolonged (but within normal range) in normal adults.
- During prolonged therapy, periodic ophthalmic examinations are recommended, as corneal deposits and retinal disturbances have been reported. In patients with rheumatoid arthritis, eye changes may occur which may be related to the underlying disease or to the therapy.
Therefore, in chronic rheumatoid disease, ophthalmological examinations are periodic intervals are recommended. Therapy should be discontinued if eye changes are observed.
- Patients should be periodically observed to allow early detection of any unwanted effects on peripheral blood (anaemia), liver function , or gastrointestinal tract especially during prolonged therapy.
- Medication Overuse Headache (MOH):
After long term treatment with analgesics, headache may develop or aggravate. Headache caused by overuse of analgesics (MOH - medication-overuse headache) should be suspected in patients who have frequent or daily headaches despite (or because of) regular use of analgesics. Patients with medication overuse headache should not be treated by increasing the dose. In such cases the use of analgesics should be discontinued in consultation with a doctor.
- Avoid concomitant use of two or more NSAIDs.
- Dermatological:
Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs. Patients appear to be at highest risk for these reactions early in the course of therapy: the onset of the reaction occurring in the majority of cases within the first month of treatment. Indometacin Sopharma capsules should be discontinued at the first appearance of skin rash, mucosal lesions, and any other sign of hypersensitivity.
- Increases in plasma potassium concentration, including hyperkalaemia have been reported, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninaemic-hypoaldosteronism state.
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery.
Posology
The dosage should be carefully adjusted according to the needs of the individual patient.
To reduce the possibility of gastro-intestinal disturbances, Indometacin Sopharma capsules should always be taken with food, milk or an antacid and in chronic conditions start the therapy with a low dosage, increasing as required.
Adults: The recommended oral dosage range is 50-200mg daily.
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.
Gout: 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.
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.
Children: Safety for use in children has not been established.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms.
Method of Administration
For oral administration.
To be taken preferably with or after food.
Not applicable.
Administrative data
