Aspen Asia


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Full Prescribing Info
Each capsule contains 25 mg Indomethacin.
Excipients/Inactive Ingredients: Lactose, lecithin, silica-colloidal anhydrous, magnesium stearate, gelatin, titanium dioxide, iron dioxide Yellow CI 77492 and Opacode S-1-8100, HV black printing ink.
ATC Code: M01A B01.
Pharmacology: Pharmacodynamics: Indomethacin 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.
Pharmacokinetics: Absorption: Indomethacin 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 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. Indomethacin is also excreted in milk in small amounts.
Toxicology: Preclinical Safety Data: Carcinogenesis, Mutagenesis, and Impairment of Fertility: There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
Indomethacin 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 Indomethacin is not a simple analgesic, its use should be limited to the above conditions.
Dosage/Direction for Use
The dosage should be carefully adjusted according to the needs of the individual patient.
To reduce the possibility of gastro-intestinal disturbances, Indomethacin 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 50-200 mg daily.
Acute rheumatoid arthritis: Initially 25 mg two or three times a day.
Chronic rheumatic disorders: 25 mg two or three times daily. (If response is inadequate, gradually increase by 25 mg. Adequate response is usually achieved with not more than 150 mg daily, rarely more than 200 mg daily).
Sudden flare up of chronic condition: Increase if necessary, by 25 mg daily until a satisfactory response is obtained, or a dosage of 150-200 mg 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 50 mg two or three times daily, according to severity for 10-14 days. Normally 150 mg daily, rarely 200 mg daily.
Lumbago: 50 mg 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: 50 mg three or four times daily until symptoms subside.
Following orthopaedic procedures: Normally 100-150 mg daily in divided doses until symptoms subside.
Additional considerations: In conditions where patients require a dosage of 150-200 mg a day, it is often possible to reduce this gradually to a maintenance level of 75-100 mg a day. In patients with persistent night pain and/or morning stiffness, a dose of up to 100 mg at bed time may be helpful in affording relief. It is rarely necessary to exceed a dosage of 200 mg 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 (see Precautions).
The following symptoms may be observed following overdosage: Nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. There have been reports of paraesthesias, numbness and convulsions.
No specific information is available on the treatment of overdosage with INDOCID. Treatment is symptomatic and supportive. Therapy with INDOCID should be discontinued and the patient observed closely. If possible, activated charcoal should be given within 1 hour of ingestion, with then correction of dehydration and electrolyte imbalance by established procedures. The patient should be followed for several days because gastrointestinal ulceration and haemorrhage have been reported as adverse reactions of indomethacin. Use of antacids may be helpful.
Contact the Poisons Information Centre for advice on overdose management.
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 Indomethacin or to any of the excipients.
Severe heart failure, hepatic failure and renal failure (see Precautions).
Not to be used in patients who have nasal polyps.
During the last trimester of pregnancy (see Use in Pregnancy & Lactation).
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.
For the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery.
Special Precautions
Carefully consider the potential benefits and risks of INDOCID and other treatment options before deciding to use INDOCID. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.
As advancing years appear to increase the possibility of side effects, INDOCID should be used with greater care in the elderly.
Safe conditions for use in children under two years of age have not been established. Children should be monitored closely and periodic evaluations of liver function should be performed at appropriate intervals. Cases of hepatotoxicity including fatalities have been reported. In rare cases, Indomethacin has been associated with serious liver injury.
Cardiovascular Effects: Cardiovascular Thrombotic Events: Observational studies have shown that non-selective NSAIDs may be associated with an increased risk of serious cardiovascular thrombotic events, including myocardial infarction, stroke, and heart failure, which may increase with duration of use and patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. There is a lack of data from randomized, placebo controlled studies. However, to minimize the potential risk for an adverse cardiovascular event, especially in patients with CV risk factors, the lowest effective dose should be used for the shortest possible duration.
There is no evidence to suggest that concurrent use of aspirin mitigates the increased risk of serious CV events associated with NSAID use. However, the concurrent use of NSAIDs and aspirin does increase the risk of serious GI events.
Hypertension: NSAIDs can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of CV events. Patients taking antihypertensives along with NSAIDs may have impaired anti-hypertensive response and hence NSAIDs, should be administered with caution in patients with hypertension. Furthermore, when given to patients with hypertension, blood pressure should be monitored closely during the initiation of NSAID treatment and at regular intervals thereafter.
Congestive Heart Failure, Fluid Retention and Oedema: Congestive heart failure, fluid retention and peripheral oedema have been observed in some patients taking INDOCID. Therefore, as with other non-steroidal anti-inflammatory drugs, INDOCID should be used with caution in patients with cardiac dysfunction, hypertension, or other conditions predisposing to fluid retention.
Serious Gastrointestinal Effects: All NSAIDs can cause gastrointestinal discomfort and serious, potentially fatal gastrointestinal effects such as ulcers, bleeding and perforation, which may increase with dose or duration of use, but can occur at any time without warning. Upper GI ulcers, gross bleeding or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3-6 months and in about 2-4% of patients treated for one year. These trends continue with longer duration of use, increasing the likelihood of developing a serious GI event at some time during the course of therapy. However, even short time therapy is not without risk.
Caution is advised in patients with risk factors for gastrointestinal events who may be at greater risk of developing serious gastrointestinal events, e.g. the elderly, those with a history of serious GI events, smoking and alcoholism. When gastrointestinal bleeding or ulcerations occur in patients receiving NSAIDs, the drug should be withdrawn immediately. Doctors should warn patients about the signs and symptoms of serious gastrointestinal toxicity.
The concurrent use of aspirin and NSAIDs also increases the risk of serious gastrointestinal adverse events.
Because of the occurrence and at times severity of gastrointestinal reactions the risks of continuing therapy with INDOCID in the face of such symptoms must be weighed against the possible benefits to the individual patient.
Gastrointestinal bleeding without obvious ulcer formation and perforation of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) have occurred. Increased abdominal pain in ulcerative colitis patients or the development of ulcerative and regional ileitis have been reported to occur rarely.
Renal Effects: Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Advanced Renal Disease: No information is available from controlled clinical studies regarding the use of INDOCID in patients with advanced renal disease. Therefore, treatment with INDOCID is not recommended in these patients with advanced renal disease. If therapy must be initiated, close monitoring of the patient's renal function is advisable
Platelet Aggregation: INDOCID, like other non-steroidal anti-inflammatory agents, can inhibit platelet aggregation. This effect is of shorter duration than that seen with acetylsalicylic acid and usually disappears within 24 hours after discontinuation of INDOCID. INDOCID has been shown to prolong bleeding time (but within the normal range) in normal subjects. Because this effect may be exaggerated in patients with underlying haemostatic defects, INDOCID should be used with caution in persons with coagulation defects.
Anticoagulants: Concurrent use of NSAIDs and warfarin has been associated with severe, sometimes fatal, haemorrhage, especially in the elderly. The exact mechanism is unknown, but may involve enhanced bleeding from NSAID-induced gastrointestinal ulceration, or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs. INDOCID should be used in combination with warfarin only if absolutely necessary, and patients taking this combination should be closely monitored. In post marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and INDOCID. Caution should be exercised when INDOCID and anticoagulants are administered concomitantly. Adjustment of dosage for oral anticoagulants may be required.
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.
Use In Pregnancy & Lactation
Use in Pregnancy: Congenital abnormalities have been reported in association with NSAID administration in man; however, these are low in frequency and do not appear to follow any discernible pattern. In view of the known effects of NSAIDs on the foetal cardiovascular system (risk of closure of the ductus arteriosus), use in the last trimester of pregnancy is contraindicated. The onset of labour may be delayed and the duration increased with an increased bleeding tendency in both mother and child (see Contraindications). NSAIDs should not be used during the first two trimesters of pregnancy or labour unless the potential benefit to the patients outweighs the potential risk to the foetus.
Use in Lactation: In limited studies so far available, NSAIDs can appear in breast milk in very low concentrations. NSAIDs should, if possible, be avoided when breastfeeding. See Precautions, regarding female fertility.
Adverse Reactions
Central Nervous System: Central nervous system adverse effects are headache, dizziness, light-headedness, depression, vertigo and fatigue (including malaise and listlessness). Reactions reported infrequently include mental confusion, anxiety, syncope, drowsiness, convulsions, coma, peripheral neuropathy, muscle weakness, involuntary muscle movements, insomnia, psychic disturbances such as depersonalisation, psychotic episodes and rarely, paraesthesias, dysarthria, aggravation of epilepsy and parkinsonism. These are often transient and disappear frequently with continued treatment or with a reduction of dosage. However, the severity of these may, on occasion, require stopping therapy.
Gastrointestinal: Gastrointestinal reactions which occur most frequently are nausea, anorexia, vomiting, epigastric distress, abdominal pain, constipation, and diarrhoea. Others which may develop are ulceration - single or multiple - of oesophagus, stomach, duodenum or small or large intestine, including perforation and haemorrhage with a few fatalities having been reported; gastrointestinal tract bleeding without obvious ulcer formation; and increased abdominal pain when used in patients with pre-existing ulcerative colitis. Rarely, intestinal strictures (diaphragms) and intestinal ulceration followed by stenosis and obstruction has been reported. Reactions which occur infrequently are stomatitis; gastritis, flatulence; bleeding from the sigmoid colon - occult or from a diverticulum; and perforation of pre-existing sigmoid lesions (diverticula, carcinoma). Other gastrointestinal side effects which may or may not be caused by indomethacin include ulcerative colitis and regional ileitis.
Studies in man with radioactive chromate tagged red blood cells indicate that the highest recommended oral dosage of indomethacin (50 mg, 4 times a day) produces less faecal blood loss than average doses of acetylsalicylic acid (600 mg, 4 times a day).
Hepatic: Hepatic reactions reported on rare occasions are jaundice and hepatitis and some fatal cases have been reported.
Cardiovascular-Renal: Cardiovascular-renal reactions which may occur infrequently include oedema, elevation of blood pressure, tachycardia, chest pain, arrhythmia, palpitations, hypotension, congestive heart failure, BUN elevation, and haematuria.
Hypersensitivity: Hypersensitivity reactions reported infrequently are pruritus, urticaria, angiitis, erythema nodosum, skin rashes, exfoliative dermatitis, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, loss of hair, acute respiratory distress, a rapid fall in blood pressure resembling a shock-life state, acute anaphylaxis, angioneurotic oedema, sudden dyspnoea, asthma and pulmonary oedema.
Haematological: Haematological reactions which may develop infrequently in conjunction with indomethacin therapy are leucopenia, petechiae or ecchymosis, purpura, aplastic and haemolytic anaemia and thrombocytopenia and disseminated intravascular coagulation. Rarely, agranulocytosis and bone marrow depression have been reported, but a definite relationship to indomethacin has not been established. Some patients may manifest anaemia secondary to obvious or occult gastrointestinal bleeding. Therefore, appropriate blood determinations are recommended.
Eye: Blurred vision, diplopia and orbital and periorbital pain may occur infrequently. Corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients with rheumatoid arthritis on prolonged therapy with INDOCID. Similar eye changes have been observed in some patients with this disease who have not received INDOCID.
Ear: Tinnitus, hearing disturbances, and deafness rarely, have been reported to occur.
Genitourinary: Reported rarely: Proteinuria, nephrotic syndrome, interstitial nephritis and renal insufficiency, including renal failure.
Miscellaneous: Miscellaneous adverse reactions reported rarely include vaginal bleeding, hyperglycaemia and glycosuria, hyperkalaemia, flushing and sweating, epistaxis, ulcerative stomatitis and breast changes, including enlargement and tenderness, or gynaecomastia.
Adverse effect-causal relationship unknown: The following additional adverse effects have been reported; however a causal relationship to therapy with INDOCID has not been established: Cardiovascular: Thrombophlebitis.
Haematologic: Although there have been several reports of leukaemia, the supporting information is weak.
Genitourinary: Urinary frequency.
Miscellaneous: Rare occurrences of fulminant necrotizing fasciitis, particular in association with Group A β-haemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, sometimes with fatal outcome (see also Precautions).
Drug Interactions
Acetylsalicylic acid: The use of INDOCID in conjunction with acetylsalicylic acid or other salicylates is not recommended. Controlled clinical studies have shown that the combined use of INDOCID and acetylsalicylic acid does not produce any greater therapeutic effect than the use of INDOCID alone. Furthermore, in one of these clinical studies, the incidence of gastrointestinal side effects was significantly increased with combined therapy. In a study in normal volunteers, it was found that chronic concurrent administration of 3.6 gm of acetylsalicylic acid per day decreases indomethacin blood levels approximately 20%.
Diflunisal: The combined use of INDOCID and diflunisal has been associated with fatal gastrointestinal hemorrhage. The coadministration of diflunisal and INDOCID results in an increase of about 30-35% in indomethacin plasma levels and a concomitant decrease in renal clearance of indomethacin and its conjugate. Therefore, INDOCID and diflunisal should not be used concomitantly.
Other NSAIDS: The concomitant use of INDOCID with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Probenecid: When INDOCID is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased. Therefore, a lower total daily dosage of INDOCID may produce a satisfactory therapeutic effect. When increases in the dose of INDOCID are made under these circumstances they should be made cautiously and in small increments.
Methotrexate: Caution should be used if INDOCID is administered simultaneously with methotrexate. INDOCID has been reported to decrease the tubular secretion of methotrexate and to potentiate toxicity.
Cyclosporine: Administration of non-steroidal anti-inflammatory drugs concomitantly with cyclosporine has been associated with an increase in cyclosporine-induced toxicity, possibly due to decreased synthesis of renal prostacyclin. NSAIDs should be used with caution in patients taking cyclosporine, and renal function should be monitored carefully.
Lithium: Indomethacin 50 mg given three times a day produced a clinically relevant elevation of plasma lithium and reduction in renal lithium clearance in psychiatric patients and normal subjects with steady state plasma lithium concentrations. This effect has been attributed to inhibition of prostaglandin synthesis. As a consequence, when indomethacin and lithium are given concomitantly, the patient should be observed carefully for signs of lithium toxicity. (Read circulars for lithium preparations before use of such concomitant therapy). In addition, the frequency of monitoring serum lithium concentrations should be increased at the outset of such combination drug treatment.
Diuretics: In some patients, the administration of INDOCID can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCID and diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
INDOCID reduces basal plasma renin activity (PRA) as well as those elevations of PRA induced by frusemide administration, or salt or volume depletion. These facts should be considered when evaluating plasma renin activity in hypertensive patients.
It has been reported that the addition of triamterene to a maintenance schedule of INDOCID resulted in reversible acute renal failure in two of four healthy volunteers. INDOCID and triamterene should not be administered together.
INDOCID and potassium-sparing diuretics each may be associated with increased serum potassium levels. The potential effects of INDOCID and potassium-sparing diuretics on potassium kinetics and renal function should be considered when these agents are administered concurrently.
Most of the previously mentioned effects concerning diuretics have been attributed, at least in part, to mechanisms involving inhibition of prostaglandin synthesis by INDOCID.
Antihypertensive medications: Co-administration of INDOCID and some antihypertensive agents has resulted in an attenuation of the latter's hypotensive effect acutely, due at least in part to indomethacin's inhibition of prostaglandin synthesis. The prescriber should, therefore, exercise caution when considering the addition of INDOCID to the regimen of a patient taking one of the following antihypertensive agents: An alpha-adrenergic blocking agent (such as prazosin), an angiotensin converting enzyme inhibitor (such as captopril or lisinopril), a beta-adrenergic blocking agent, a diuretic (see diuretic), hydralazine, or losartan (an angiotensin II receptor antagonist).
In some patients, the administration of INDOCID can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCID and diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
In some patients with compromised renal function (e.g., elderly patients or patients who are volume-depleted, including those on diuretic therapy) who are being treated with non-steroidal anti-inflammatory drugs, including selective cyclooxygenase-2 inhibitors, the co-administration of angiotensin II receptor antagonists or ACE inhibitors may result in further deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Therefore, the combination should be administered with caution in patients with compromised renal function.
Beta-Adrenergic Receptor Blocking Agents: A decrease in the anti-hypertensive effect of beta-adrenergic receptor blocking agents by non-steroidal anti-inflammatory drugs including indomethacin has been reported. Therefore, when using a beta-blocking agent to treat hypertension, patients should be observed carefully in order to confirm that the desired therapeutic effect has been obtained.
Digoxin: INDOCID given concomitantly with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Therefore, when INDOCID and digoxin are used concomitantly, serum digoxin levels should be closely monitored.
Phenylpropanolamine: Hypertensive crises have been reported due to oral phenylpropanolamine alone and rarely to phenylpropanolamine given with INDOCID. This additive effect is probably due at least in part to indomethacin's inhibition of prostaglandin synthesis. Caution should be exercised when INDOCID and phenylpropanolamine are administered concomitantly.
Caution For Usage
Incompatibilities: Not applicable.
Special precautions for disposal and other handling: No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Store below 25°C in a dry place. Protect from light.
Shelf life: 2 years.
ATC Classification
M01AB01 - indometacin ; Belongs to the class of acetic acid derivatives and related substances of non-steroidal antiinflammatory and antirheumatic products.
Cap 25 mg (ivory hard gelatin) x 50's.
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