Indmethacine - General Information
A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [PubChem]
Pharmacology of Indmethacine
Indmethacine, a nonsteroidal antiinflammatory drug (NSAID) with analgesic and antipyretic properties, is used to treat osteoarthritis and control acute pain.
Indmethacine for patients
Indomethacin, like other drugs of its class, is not free of side effects. The side effects of these drugs can cause discomfort and rarely, there are more serious side effects, such as gastrointestinal bleeding, which may result in hospitalization and even fatal outcomes. NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are often essential agents in the management of arthritis, but they also may be commonly employed for conditions which are less serious. Physicians may wish to discuss with their patients the potential risks and likely benefits of NSAID treatment, particularly when the drugs are used for less serious conditions where treatment without NSAIDs may represent an acceptable alternative to both the patient and physician.
In normal volunteers receiving indomethacin, the administration of diflunisal decreased the renal clearance and significantly increased the plasma levels of indomethacin. In some patients, combined use of INDOCIN and diflunisal has been associated with fatal gastrointestinal hemorrhage. Therefore, diflunisal and INDOCIN should not be used concomitantly.
In a study in normal volunteers, it was found that chronic concurrent administration of 3.6 g of aspirin per day decreases indomethacin blood levels approximately 20%.
The concomitant use of INDOCIN with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy.
Clinical studies have shown that INDOCIN does not influence the hypoprothrombinemia produced by anticoagulants. However, when any additional drug, including INDOCIN, is added to the treatment of patients on anticoagulant therapy, the patients should be observed for alterations of the prothrombin time. In post-marketing experience, bleeding has been reported in patients on concomitant treatment with anticoagulants and INDOCIN. Caution should be exercised when INDOCIN and anticoagulants are administered concomitantly.
When INDOCIN is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased. Therefore, a lower total daily dosage of INDOCIN may produce a satisfactory therapeutic effect. When increases in the dose of INDOCIN are made, they should be made carefully and in small increments.
Caution should be used if INDOCIN is administered simultaneously with methotrexate. INDOCIN has been reported to decrease the tubular secretion of methotrexate and to potentiate its toxicity.
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 carefully monitored.
Capsules INDOCIN 50 mg t.i.d. 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 INDOCIN and lithium are given concomitantly, the patient should be carefully observed for signs of lithium toxicity. (Read circulars for lithium preparations before use of such concomitant therapy.) In addition, the frequency of monitoring serum lithium concentration should be increased at the outset of such combination drug treatment.
INDOCIN given concomitantly with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Therefore, when INDOCIN and digoxin are used concomitantly, serum digoxin levels should be closely monitored.
In some patients, the administration of INDOCIN can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics. Therefore, when INDOCIN and INDOCIN. (Indomethacin) diuretics are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
INDOCIN reduces basal plasma renin activity (PRA), as well as those elevations of PRA induced by furosemide 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 INDOCIN resulted in reversible acute renal failure in two of four healthy volunteers. INDOCIN and triamterene should not be administered together.
INDOCIN and potassium-sparing diuretics each may be associated with increased serum potassium levels. The potential effects of INDOCIN and potassium-sparing diuretics on potassium kinetics and renal function should be considered when these agents are administered concurrently.
Most of the above effects concerning diuretics have been attributed, at least in part, to mechanisms involving inhibition of prostaglandin synthesis by INDOCIN.
Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by non-steroidal antiinflammatory drugs including INDOCIN has been reported. Therefore, when using these blocking agents to treat hypertension, patients should be observed carefully in order to confirm that the desired therapeutic effect has been obtained. INDOCIN can reduce the antihypertensive effects of captopril and losartan.
False-negative results in the dexamethasone suppression test (DST) in patients being treated with INDOCIN have been reported. Thus, results of the DST should be interpreted with caution in these patients.
Indomethacin should not be used in:
- Patients who are hypersensitive to this product.
- Patients in whom acute asthmatic attacks, urticaria, or rhinitis are precipitated by aspirin or other nonsteroidal anti- inflammatory agents.
- Suppositories INDOCIN are contraindicated in patients with a history of proctitis or recent rectal bleeding.
Additional information about Indmethacine
Indmethacine Indication: For moderate to severe rheumatoid arthritis including acute flares of chronic disease, ankylosing spondylitis, osteoarthritis, acute painful shoulder (bursitis and/or tendinitis) and acute gouty arthritis.
Mechanism Of Action: Antiinflammatory effects of Indmethacine are believed to be due to inhibition of cylooxygenase in platelets which leads to the blockage of prostaglandin synthesis. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.
Drug Interactions: Acebutolol Risk of inhibition of renal prostaglandins
Atenolol Risk of inhibition of renal prostaglandins
Betaxolol Risk of inhibition of renal prostaglandins
Bevantolol Risk of inhibition of renal prostaglandins
Bisoprolol Risk of inhibition of renal prostaglandins
Carteolol Risk of inhibition of renal prostaglandins
Carvedilol Risk of inhibition of renal prostaglandins
Methotrexate The NSAID increases the effect and toxicity of methotrexate
Diflunisal Diflunisal increases the effect and toxicity of indomethacin
Esmolol Risk of inhibition of renal prostaglandins
Labetalol Risk of inhibition of renal prostaglandins
Metoprolol Risk of inhibition of renal prostaglandins
Nadolol Risk of inhibition of renal prostaglandins
Losartan Indmethacine decreases the effect of losartan
Lithium The NSAID increases serum levels of lithium
Oxprenolol Risk of inhibition of renal prostaglandins
Penbutolol Risk of inhibition of renal prostaglandins
Pindolol Risk of inhibition of renal prostaglandins
Practolol Risk of inhibition of renal prostaglandins
Probenecid Probenecid increases the effect/toxicity of indomethacin
Sotalol Risk of inhibition of renal prostaglandins
Propranolol Risk of inhibition of renal prostaglandins
Timolol Risk of inhibition of renal prostaglandins
Warfarin The NSAID increases the anticoagulant effect
Acenocoumarol The NSAID increases the anticoagulant effect
Dicumarol The NSAID increases the anticoagulant effect
Anisindione The NSAID increases the anticoagulant effect
Torasemide The NSAID decreases the diuretic and antihypertensive effects of the loop diuretic
Bumetanide The NSAID decreases the diuretic and antihypertensive effects of the loop diuretic
Furosemide The NSAID decreases the diuretic and antihypertensive effects of the loop diuretic
Ethacrynic acid The NSAID decreases the diuretic and antihypertensive effects of the loop diuretic
Cyclosporine Monitor for nephrotoxicity
Alendronate Increased risk of gastric toxicity
Triamterene Risk of acute renal impairment with this combination
Food Interactions: Avoid alcohol.
Take with food or antacids to reduce irritation.
Generic Name: Indomethacin
Synonyms: IMN; Indomethacinum; Indomethacine; Indometacyna; Indometacine; Indomethancin; Indomethazine; Indomethine; Indometicina
Drug Category: Tocolytic Agents; Cardiovascular Agents; Anti-inflammatory Agents; Nonsteroidal Antiinflammatory Agents (NSAIDs)
Drug Type: Small Molecule; Approved; Investigational
Absorption: Bioavailability is approximately 100% following oral administration and 80–90% following rectal administration.
Toxicity (Overdose): The following symptoms may be observed following overdosage: nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. There have been reports of paresthesias, numbness, and convulsions. The oral LD50 of indomethacin in mice and rats (based on 14 day mortality response) was 50 and 12 mg/kg, respectively.
Protein Binding: 97%
Half Life: 4.5 hours
Dosage Forms of Indmethacine: Powder, for solution Intravenous
Chemical IUPAC Name: 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]acetic acid
Chemical Formula: C19H16ClNO4
Indomethacin on Wikipedia: https://en.wikipedia.org/wiki/Indomethacin
Organisms Affected: Humans and other mammals