Indometacin 25mg Capsules
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Indometacin Capsules 25mg
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 25mg Indometacin Ph.Eur
Also contains Lactose Ph. Eur- 60.000 mg For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
A hard white capsule printed with ‘BL 25’ containing a white powder.
4. CLINICAL PARTICULARS
4.1. Therapeutic Indications
Indometacin is a non-steroidal analgesic and anti-inflammatory agent indicated for the following conditions:
• Active stages of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, acute musculoskeletal disorders, degenerative joint disease of the hip, low back pain and acute gout and lumbago.
• Periarticular disorders such as bursitis, tendinitis, synovitis, tenosynovitis and capsulitis.
• It is also indicated for pain, inflammation and oedema following orthopaedic procedures and pain and associated symptoms of primary dysmenorrhoea.
Since indometacin is not a simple analgesic, its use should be limited to the above conditions.
4.2. Posology and Method of Administration
The dosage of Indometacin should be adjusted to suit the individual needs of the patient.
In chronic conditions, starting with a low dose and increasing 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 while minimising unwanted reactions. Indometacin should be taken with food, milk or an antacid in order to minimise gastro-intestinal disturbances.
Adults: The recommended oral dosage range is 50-200mg daily in divided doses.
Acute rheumatic disorders: 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.
Dysmenorrhoea: Up to 75mg daily, starting with onset of symptoms and continuing for as long as they usually last.
Children: Safety and dosage has not been established.
Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).
Method of Administration
For oral administration
To be taken preferably with or after food
4.3. Contra-indications
• Hypersensitivity to Indometacin or to any of the excipients.
• Active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proved ulceration or bleeding)
• NSAIDs are contraindicated in patients who have previously shown hypersensitivity reactions (e.g. asthma, rhinitis, angioneurotic oedema or urticaria) in response to ibuprofen, aspirin, or other non-steroidal antiinflammatory drugs.
• Severe heart failure, hepatic failure and renal failure (see section 4.4).
• Third trimester of pregnancy (see section 4.6).
• History of gastrointestinal bleeding or perforation, related to previous NSAIDs therapy.
• Nasal polyps associated with angioneurotic oedema.
• Safety in children has not been established
4.4. Special Warnings and Precautions for Use
• Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).
• The use of indomethacin with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors, should be avoided (see section 4.5)
• Elderly
• The elderly have an increased frequency of adverse reactions to NSAIDS especially gastro intestinal bleeding and perforation which may be fatal (see section 4.2)
• Particular care should be taken with older patients who are more susceptible to side-effects from Indomethacin (see section 4.2)
• 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. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, and smoking).
• 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.
• 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 greater risk of this reaction are those with impaired renal function, liver dysfunction, cardiac impairment, those taking diuretics, 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 (see also section 4.3). Discontinuation of NSAID therapy is usually followed by recovery to the pre-treatment state.
• In patients with renal, cardiac, hepatic impairment, hypertension, heart failure or conditions predisposing to fluid retention caution is required since the use of NSAIDs may result in deterioration of renal function. The dose should be
kept as low as possible and renal function should be monitored. NSAIDs may also cause fluid retention which may further aggravate these conditions.
• Headache, dizziness and light-headedness may occur with Indometacin and are usually minimised by starting therapy with a low dosage and increasing it gradually. Symptoms often disappear with continued therapy or by reducing the dosage, but if headache persists, Indometacin should be withdrawn.
• Acute interstitial nephritis with haematuria, proteinuria and occasionally nephrotic syndrome has been reported in patients receiving long-term therapy with indometacin.Discontinuation of Indometacin will usually result in return of renal function to the pre-treatment state. Elevations of plasma potassium concentration, including hyperkalaemia have been reported, even in some patients without renal impairment. Patients with significantly impaired renal function should be closely monitored and lower dosages used, in order to avoid excessive accumulation of drug and metabolites.
• Borderline elevations of certain liver function tests may occur with Indometacin administration. Significant elevation of ALT (SGPT) or AST (SGOT) has been seen in less than 1% of patients receiving Indometacin in controlled clinical trials. Larger doses, particularly when used in children, have been associated with reports of hepatitis. False negative test results have been reported in the dexamethasone suppression test (DST) in patients receiving the drug.
• 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.
• 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 (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and section 4.5).
• 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 (see section 4.5).
• When GI bleeding or ulceration occurs in patients receiving indometacin, the treatment should be withdrawn.
• 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 (see section 4.8).
• 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.
• Gastro-intestinal disorders which occur can be reduced by giving indomethacin with food, milk or antacids.
• 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 (see section 4.8).
• 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 (see section 4.8). 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 should be discontinued at the first appearance of skin rash, mucosal lesions, or any of other sign of hypersensitivity.
• 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, withdrawal of Indometacin should be considered.
• Others:
• Indometacin may aggravate impaired renal functions, bleeding disorders psychiatric disorders, epilepsy, parkinsonism and should therefore be used with caution in such cases.
• Indomethacin may mask the signs and symptoms of infectious disease and this should be borne in mind in order to avoid delay in starting treatment for infections. Indometacin should be used with caution in patients with an existing, albeit controlled infection. Caution is advised with concomitant use of live vaccines.
• Indometacin should be used with caution in patients with coagulation defects as it can inhibit platelet aggregation. This effect may be exaggerated in
patients with underlying haemostatic defects. This effect usually disappears within 24 hours of discontinuing indometacin.
• Patients should be carefully observed to detect any unusual manifestations of drug sensitivity.
• 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. Eye changes may occur in patients with rheumatoid arthritis which may be related to the underlying disease or to therapy. Therefore, in patients receiving Indometacin for chronic rheumatoid arthritis, periodic ophthalmological examinations are recommended. If eye changes are noted, Indometacin should be discontinued.
• 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.
Important information regarding the Ingredients of Indomethacin Capsules
Patients with rare hereditary problems of galactose intolerance, the Lapp
lactase
deficiency or glucose-galactose malabsorption should not take this medicine
4.5. Interactions with other Medicaments and other forms of Interaction
• 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 (see section 4.4).
• Salicylates: Use of Indometacin with aspirin or other salicylates is not recommended because there is no enhancement of therapeutic effect while the incidence of gastro-intestinal side-effects is increased. Moreover, coadministration of aspirin may decrease the blood concentration of indomethacin.
• 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. Skin reactions and neurotoxicity have been reported with ciprofloxacin.
• Anti-coagulants: NSAIDs may enhance the effects of anti-coagulants, such as warfarin (see section 4.4). ). Indometacin is highly protein-bound and should be used with caution in combination with other highly protein-bound drugs such as oral anticoagulants, hydantoins, sulphonylureas and some sulphonamides. Interactions have been reported with these agents and other non-steroidal anti-inflammatory drugs.
• Antidepressants (SSRIs): Increased risk of gastrointestinal bleeding.(see section 4.4)
• Antidiabetics: the effect of sulphonylureas may be increased by NSAIDs. Isolated case of metabolic acidosis with metformin.
• Anti-hypertensives: Reduced antihypertensive effect. Indometacin may acutely reduce the antihypertensive effect of beta-blockers due partly to indometacin’s inhibition of prostaglandin synthesis. Patients receiving dual therapy should have the antihypertensive effect of their therapy reassessed. Therefore, caution should be exercised when considering the addition of indometacin to the regimen of a patient taking any of the following antihypertensive agents: alpha-adrenergic blocking agents, ACE inhibitors,
beta-adrenergic blocking agents, angiotensin-2-receptor antagonists, hydralazine or nifedipine. Hyperkalaemia has also been reported when NSAIDs are taken with ACE inhibitors. Indometacin may antagonise the effects of antihypertensive agents and may increase the risk of renal impairment associated with the use of ACE inhibitors
• Antiepileptics: Effect of phenytoin possibly increased by NSAIDs.
• Anti-platelet agents: Increased risk of gastrointestinal bleeding (see section 4.4) Increased risk of bleeding with clopidogrel. Indometacin can inhibit platelet aggregation an effect which disappears within 24 hours of discontinuation; the bleeding time may be prolonged and this effect may be exaggerated in patients with an underlying haemostatic defect.
• Antipsychotics: Increased drowsiness with indometacin and haloperidol.
• Antivirals: Pharmacokinetic changes have been recorded with zalcitabine/indometacin. 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. Risk of indometacin toxicity with ritonavir, avoid concomitant use.
• Benzodiazepines: Increased risk of dizziness with diazepam and indometacin.
• Cardiac glycosides: NSAIDs may exacerbate cardiac failure, reduce GFR and increase plasma glycoside concentration.
• Ciclosporin: Increased risk of nephrotoxicity. Administration of NSAIDs concomitantly with ciclosporin has been associated with an increase in ciclosporin-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking ciclosporin, and renal function should be monitored carefully.
• Corticosteroids: Increased risk of gastrointestinal ulceration or bleeding (see section 4.4). If the patient is receiving corticosteroids concomitantly, a reduction in dosage of these may be possible but should only be effected slowly under supervision.
• Cytotoxics Caution should be employed in use with cyclophosphamide as acute water intoxication has been reported.
• Desmopressin: Indometacin enhances effects of desmopressin.
• Diflunisal: Avoid concomitant use. Co-administration of diflunisal with indometacin increases the plasma level of indometacin by approximately one third with a concomitant decrease in renal clearance. Fatal gastrointestinal haemorrhage has occurred.
• Diuretics: NSAIDS may reduce the effectiveness of all types of diuretics. Indometacin may reduce the diuretic and antihypertensive effect of thiazides and furosemide in some patients. Indometacin may cause blocking of the furosemide -induced increase in plasma renin activity. Diuretics can increase the risk of nephrotoxicity of NSAIDs.
• Lithium: Decreased elimination of lithium which may increase risk of toxicity of this drug. Indometacin is an inhibitor of prostaglandin synthesis and therefore the following drug interactions may occur; indometacin may raise plasma lithium levels and reduce lithium clearance in subjects with steady state plasma lithium concentrations. At the onset of such combined therapy, plasma lithium concentration should be monitored more frequently.
• Mifepristone: NSAIDs should not be used for 8-12 days after mifepristone administration, as NSAIDs can reduce the effect of mifepristone.
• Muromonab-CD3: Significant rise in incidence of psychosis and encephalopathy in patients receiving both these drugs.
• Muscle Relaxants: Increased risk of baclofen toxicity due to reduced rate of excretion.
• Pentoxifylline: Possible increased risk of bleeding when taken with NSAIDs.
• Penicillamine: Possible increased risk of nephrotoxicity when NSAIDs given with penicillamine.
• Methotrexate: Decreased elimination of methotrexate which may increase risk of toxicity of this drug. Simultaneous use should be undertaken with caution.
• Probenecid: Probenecid delays excretion of indometacin, with resultant increase in plasma levels of indometacin. When increases in the dose of indometacin are made under these circumstances, they should be made cautiously and in small increments.
• Tacrolimus: Possible increased risk of nephrotoxicity when NSAIDs are given with tacrolimus.
• Tiludronic acid: The bioavailability of tiludronic acid is increased by indometacin. Bisphosphonates bioavailability increased by indometacin.
• Triamterene: Indometacin and triamterene should not be administered together since reversible renal failure may be induced.
• Vasodilators: Possible increased risk of bleeding with NSATDS.
• Laboratory tests: False-negative results in the dexamethasone suppression test (DST) in patients being treated with indometacin have been reported. Thus, results of this test should be used with caution in these patients.
4.6. Fertility, Pregnancy and Lactation Pregnancy:
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5 %. The risk is believed to increase with dose and duration of therapy. In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre-and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period. During the first and second trimester of pregnancy, Indometacin should not be given unless clearly necessary. If Indometacin is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
- renal dysfunction, which may progress to renal failure with oligo-hydroamniosis;
the mother and the neonate, at the end of pregnancy, to:
- possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
- inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, Indometacin is contraindicated during the third trimester of pregnancy.
Lactation:
In the limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. However, convulsions were reported in an infant whose mother received 200mg of indometacin a day. NSAIDs should, if possible, be avoided when breastfeeding.
See section 4.4 Special warnings and precautions for use, regarding female fertility.
4.7. Effects on Ability to Drive and Use Machines
Undesirable effects such as dizziness, drowsiness, fatigue and visual disturbances are possible after taking NSAIDs. If affected, patients should not drive or operate machinery
4.8. Undesirable Effects
• Blood and lymphatic disorders: Disseminated intravascular coagulation and particularly Thrombocytopenia, neutropenia, agranulocytosis, and blood dyscrasias may occur infrequently including leucopenia aplastic anaemia and haemolytic anaemia, petechiae or ecchymosis, purpura and bone marrow depression. Epistaxis has been reported rarely.
• Appropriate blood determinations are recommended since some patients may develop anaemia secondary to obvious or occult gastro-intestinal bleeding.
• 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, pruritis, urticaria, purpura, angiodema and, more rarely exfoliative and bullous dermatoses (including epidermal necrolysis, erythema multiforme).
• Metabolic and nutrition disorders: Hyperglycaemia, glycosuria, hyperkalaemia has been reported rarely.
• Nervous system disorders: Visual disturbances, optic neuritis, tinnitus, headache, dizziness and light headedness 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. Other CNS effects include reports of aseptic meningitis (especially in patients with existing auto-immune disorders, such as systemic lupus erythematosus or mixed connective tissue disease) with symptoms such as stiff neck, headache, nausea, vomiting, fever or disorientation (see section 4.4), 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 pains are seen infrequently. Comeal deposits and retinal or macular disturbances have been reported in some patients with rheumatoid arthritis on prolonged therapy with indometacin. Ophthalmic examinations are desirable in patients given prolonged treatment.
• Ear and labyrinth disorders: tinnitus or hearing disturbances (rarely deafness) have been reported.
• Cardiovascular and cerebrovascular: Oedema, hypertension, hypotension, tachycardia, chest pain, arrhythmia, palpitations 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: The most commonly-observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn’s disease epigastric distress, ulceration of the oesophagus, anorexia, (see section 4.4) have been reported following administration. Infrequently, perforation of pre-existing sigmoid lesions, bleeding from the sigmoid colon, and regional ileitis has occurred. Rarely, intestinal ulceration followed by stenosis and obstruction has been reported. Pancreatitis has been reported very rarely.
• 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 pre-existing sigmoid lesions (such as diverticulum or carcinoma) have occurred; and increased abdominal pain or exacerbation of the condition in patients with Crohn’s disease(or the development of this condition) have been rarely reported. 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.
• Hepatic: 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) 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. Rarely hepatitis and jaundice (associated with some fatalities).
• Dermatological: Bullous reactions including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis (very rare), Photosensitivity, urticaria, pruritus, angiitis, angioneurotic oedema, erythema nodosum, skin rash and exfoliative dermatitis, alopecia, sweating, exacerbation of psoriaris, acute anaphylaxis, rapid fall in blood pressure resembling a shock-like state and acute respiratory distress including sudden dyspnoea, asthma and pulmonary oedema.
• Musculo-skeletal, connective tissue and bone disorders: muscle weakness and acceleration of cartilage degeneration.
• Renal and urinary disorders: Nephrotoxicity in various forms, including interstitial nephritis, nephritic syndrome, haematuria, proteinuria, renal insufficiency or 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 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 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) (see section 4.4).
4.9. Overdose
a) Symptoms:
Symptoms 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:
Treatment: 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
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Anti-inflammatory and anti-rheumatic products
ATC CODE: M01A B01
Indometacin is a non-steroidal anti-inflammatory agent with analgesic and antipyretic properties.
The analgesic properties have been attributed to both central and peripheral effect, which are distinct from its anti-inflammatory activity. It inhibits the activity of the enzyme cyclo-oxygenase which results in decreased formation of the precursors of prostaglandins and thromboxane from arachidonic acid. While resultant decreased in synthesis and activity of prostaglandins may be responsible for many of the effects of indometacin, other actions may also contribute to its therapeutic effects.
Pharmacokinetic Properties
5.2.
Absorption: Indometacin is readily absorbed from the gastro-intestinal 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 milk.
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 is also excreted in milk in small amount.
5.3. Preclinical safety data
There are no preclinical data of relevance to the prescriber which are additional to that already included.
6. PHARMACEUTICAL PARTICULARS
6.1. List of Excipients
Specially dried maize starch
Lactose
Explotab
Magnesium stearate
Capsule Dry Gel No.3 WH/WH 3.325
Colourant composition:
Cap: titanium dioxide E171 Body: titanium dioxide E171
6.2. Incompatibilities
None known.
6.3. Shelf Life
36 months.
6.4. Special Precautions for Storage
Store below 25°C.
Protect from light.
6.5 Nature and contents of container
An amber glass bottle with a tin-plate screw cap fitted with a waxed aluminium faced pulpboard liner.
Pack size: 250, 500 capsules
Or
Blister packs comprising of 250 micron PVC and 20 micron clear Aluminium foil
Pack sizes: 28 capsules
(Not all pack sizes may be marketed)
6.6. Instruction for Use/Handling
None stated.
7. MARKETING AUTHORISATION HOLDER
Bristol Laboratories Ltd Unit 3, Canalside,
Northbridge Rd Berkhamsted Herts HP41EG
United Kingdom
8. MARKETING AUTHORIZATION NUMBER
PL 17907/0173
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
16th February 2005
10 DATE OF REVISION OF THE TEXT
24/02/2012