INDOCIN®
(indomethacin) Capsules, Suppositories
Cardiovascular Risk
Gastrointestinal Risk
INDOCIN* is supplied in three dosage forms. Capsules INDOCIN for oral administration contain either 25 mg or 50 mg of indomethacin and the following inactive ingredients: colloidal silicon dioxide, FD&C Blue 1, FD&C Red 3, gelatin, lactose, lecithin, magnesium stearate, and titanium dioxide. Suspension INDOCIN for oral use contains 25 mg of indomethacin per 5 mL, alcohol 1%, and sorbic acid 0.1% added as a preservative and the following inactive ingredients: antifoam AF emulsion, flavors, purified water, sodium hydroxide or hydrochloric acid to adjust pH, sorbitol solution, and tragacanth. Suppositories INDOCIN for rectal use contain 50 mg of indomethacin and the following inactive ingredients: butylated hydroxyanisole, butylated hydroxytoluene, edetic acid, glycerin, polyethylene glycol 3350, polyethylene glycol 8000 and sodium chloride. Indomethacin is a non-steroidal anti-inflammatory indole derivative designated chemically as 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid. Indomethacin is practically insoluble in water and sparingly soluble in alcohol. It has a pKa of 4.5 and is stable in neutral or slightly acidic media and decomposes in strong alkali. The suspension has a pH of 4.0-5.0. The structural formula is:
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Last updated on RxList: 7/11/2007
Carefully consider the potential benefits and risks of INDOCIN and other treatment options before deciding to use INDOCIN. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
Indomethacin has been found effective in active stages of the following:
Carefully consider the potential benefits and risks of INDOCIN and other treatment options before deciding to use INDOCIN. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
After observing the response to initial therapy with INDOCIN, the dose and frequency should be adjusted to suit an individual patient's needs.
INDOCIN is available as 25 and 50 mg Capsules INDOCIN, Oral Suspension INDOCIN, containing 25 mg of indomethacin per 5 mL, and 50 mg Suppositories INDOCIN for rectal use.
Adverse reactions appear to correlate with the size of the dose of INDOCIN in most patients but not all. Therefore, every effort should be made to determine the smallest effective dosage for the individual patient.
INDOCIN ordinarily should not be prescribed for pediatric patients 14 years of age and under (see PRECAUTIONS, Pediatric Use).
Dosage Recommendations for Active Stages of the Following:
1. Moderate to severe rheumatoid arthritis including acute flares of chronic
disease; moderate to severe ankylosing spondylitis; and moderate to severe osteoarthritis.
Suggested Dosage:
Capsules INDOCIN 25 mg b.i.d. or t.i.d. If this is well tolerated, increase
the daily dosage by 25 or by 50 mg, if required by continuing symptoms, at weekly
intervals until a satisfactory response is obtained or until a total daily dose
of 150-200 mg is reached. DOSES ABOVE THIS AMOUNT GENERALLY DO NOT INCREASE
THE EFFECTIVENESS OF THE DRUG.
In patients who have persistent night pain and/or morning stiffness, the giving of a large portion, up to a maximum of 100 mg, of the total daily dose at bedtime, either orally or by rectal suppositories, may be helpful in affording relief. The total daily dose should not exceed 200 mg. In acute flares of chronic rheumatoid arthritis, it may be necessary to increase the dosage by 25 mg or, if required, by 50 mg daily.
If minor adverse effects develop as the dosage is increased, reduce the dosage rapidly to a tolerated dose and OBSERVE THE PATIENT CLOSELY.
If severe adverse reactions occur, STOP THE DRUG. After the acute phase of the disease is under control, an attempt to reduce the daily dose should be made repeatedly until the patient is receiving the smallest effective dose or the drug is discontinued.
Careful instructions to, and observations of, the individual patient are essential to the prevention of serious, irreversible, including fatal, adverse reactions.
As advancing years appear to increase the possibility of adverse reactions, INDOCIN should be used with greater care in the elderly (see PRECAUTIONS, Geriatric Use).
2. Acute painful shoulder (bursitis and/or tendinitis).
Initial Dose:
75-150 mg daily in 3 or 4 divided doses.
The drug should be discontinued after the signs and symptoms of inflammation
have been controlled for several days. The usual course of therapy is 7-14 days.
3. Acute gouty arthritis.
Suggested Dosage:
Capsules INDOCIN 50 mg t.i.d. until pain is tolerable. The dose should then
be rapidly reduced to complete cessation of the drug. Definite relief of pain
has been reported within 2 to 4 hours. Tenderness and heat usually subside in
24 to 36 hours, and swelling gradually disappears in 3 to 5 days.
No. 3316 - Capsules INDOCIN, 25 mg are opaque blue and white capsules, coded
INDOCIN and MSD 25. They are supplied as follows:
NDC 0006-0025-68 bottles of 100
NDC 0006-0025-82 bottles of 1000.
No. 3317 - Capsules INDOCIN, 50 mg are opaque blue and white capsules, coded
INDOCIN and MSD 50. They are supplied as follows:
NDC 0006-0050-68 bottles of 100.
No. 3376 - Oral Suspension INDOCIN, 25 mg per 5 mL, is an off-white suspension
with a pineapple coconut mint flavor. It is supplied as follows:
NDC 0006-3376-66 in bottles of 237 mL.
No. 3354 - Suppositories INDOCIN, 50 mg each, are white, opaque, rectal suppositories
and are supplied as follows:
NDC 0006-0150-30, boxes of 30.
Store Oral Suspension INDOCIN below 30°C (86°F). Avoid temperatures above 50°C (122°F). Protect from freezing.
Store Suppositories INDOCIN below 30°C (86°F). Avoid transient temperatures above 40°C (104°F).
Suppositories INDOCIN® are distributed by: MERCK & CO., INC., Whitehouse
Station, N J 08889, USA
Manufactured by: MERCK SHARP & DOHME., (Italia) S.p.A. 27100 = Pavia, Italy
Capsules and Oral Suspension INDOCIN® are distributed and manufactured by:
MERCK & CO., INC., Whitehouse Station, N J 08889, USA
FDA rev date: 1/30/2007
Last updated on RxList: 7/11/2007
In a gastroscopic study in 45 healthy subjects, the number of gastric mucosal abnormalities was significantly higher in the group receiving Capsules INDOCIN than in the group taking Suppositories INDOCIN or placebo.
In a double-blind comparative clinical study involving 175 patients with rheumatoid arthritis, however, the incidence of upper gastrointestinal adverse effects with Suppositories or Capsules INDOCIN was comparable. The incidence of lower gastrointestinal adverse effects was greater in the suppository group.
The adverse reactions for Capsules INDOCIN listed in the following table have been arranged into two groups: (1) incidence greater than 1%; and (2) incidence less than 1%. The incidence for group (1) was obtained from 33 double-blind controlled clinical trials reported in the literature (1,092 patients). The incidence for group (2) was based on reports in clinical trials, in the literature, and on voluntary reports since marketing. The probability of a causal relationship exists between INDOCIN and these adverse reactions, some of which have been reported only rarely.
The adverse reactions reported with Capsules INDOCIN may occur with use of the suppositories. In addition, rectal irritation and tenesmus have been reported in patients who have received the suppositories.
The adverse reactions reported with Capsules INDOCIN may also occur with use of the suspension.
| Incidence greater than 1% | Incidence less than 1% | |
| GASTROINTESTINAL | ||
| nausea** with or without vomiting dyspepsia** (including indigestion, heartburn and epigastric pain) diarrhea abdominal distress or pain constipation |
anorexia bloating (includesdistension) flatulence peptic ulcer gastroenteritis rectal bleeding proctitis single or multiple ulcerations, including perforation and hemorrhage of the esophagus,stomach, duodenum or small and large intestines intestinal ulceration associated with stenosis and obstruction |
gastrointestinal bleeding without obvious ulcer formation and perforation
of pre-existing sigmoid lesions (diverticulum, carcinoma, etc.) development
of ulcerative colitis and regional ileitis ulcerative stomatitis toxic hepatitis and jaundice (some fatal cases have been reported) intestinal strictures (diaphragms) |
| CENTRAL NERVOUS SYSTEM | ||
| headache (11.7%) dizziness** vertigo somnolence depression and fatigue (including malaise and listlessness) |
anxiety (includes nervousness) muscle weakness involuntary muscle movements insomnia muzziness psychic disturbances including psychoticepisodes mental confusion drowsiness |
light-headedness syncope paresthesia aggravation of epilepsy and parkinsonism depersonalization coma peripheral neuropathy convulsion dysarthria |
| SPECIAL SENSES | ||
| tinnitus | ocular - corneal deposits and retinal disturbances, including those of the macula, have been reported in some patients on prolonged therapy with INDOCIN | blurred vision diplopia hearing disturbances, deafness |
| CARDIOVASCULAR | ||
| none | hypertension hypotension tachycardia chest pain |
congestive heart failure arrhythmia; palpitations |
| METABOLIC | ||
| none | edema weight gain fluid retention flushing or sweating |
hyperglycemia glycosuria hyperkalemia |
| INTEGUMENTARY | ||
| none | pruritus rash; urticaria petechiae or ecchymosis |
exfoliative dermatitis erythema nodosum loss of hair Stevens-Johnson syndrome erythema multiforme toxic epidermal necrolysis |
| HEMATOLOGIC | ||
| none | leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding |
aplastic anemia hemolytic anemia agranulocytosis thrombocytopenic purpura disseminated intravascular coagulation |
| HYPERSENSITIVITY | ||
| none | acute anaphylaxis acute respiratory distress rapid fall in blood pressure resembling a shock-like state angioedema |
dyspnea asthma purpura angiitis pulmonary edema fever |
| GENITOURINARY | ||
| none | hematuria vaginal bleeding proteinuria nephrotic syndrome interstitial nephritis |
BUN elevation renal insufficiency, including renal failure |
| MISCELLANEOUS | ||
| none | epistaxis breast changes, including enlargement and tenderness, or gynecomastia |
|
| ** Reactions occurring in 3% to 9% of patients treated with INDOCIN. (Those reactions occurring in less than 3% of the patients are unmarked.) | ||
Causal relationship unknown: Other reactions have been reported but occurred under circumstances where a causal relationship could not be established. However, in these rarely reported events, the possibility cannot be excluded. Therefore, these observations are being listed to serve as alerting information to physicians:
Cardiovascular: Thrombophlebitis
Hematologic: Although there have been several reports of leukemia, the supporting information is weak
Genitourinary: Urinary frequency.
A rare occurrence of fulminant necrotizing fasciitis, particularly in association with Group A β hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome (see also PRECAUTIONS, General).
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors and angiotensin II antagonists. INDOCIN can reduce the antihypertensive effects of captopril and losartan. These interactions should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors or angiotensin II antagonists. In some patients with compromised renal function, the co-administration of an NSAID and an ACE-inhibitor or an angiotensin II antagonist may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible.
When INDOCIN is administered with aspirin, its protein binding is reduced, although the clearance of free INDOCIN is not altered. The clinical significance of this interaction is not known.
The use of INDOCIN in conjunction with aspirin or other salicylates is not recommended. Controlled clinical studies have shown that the combined use of INDOCIN and aspirin does not produce any greater therapeutic effect than the use of INDOCIN alone. In a clinical study of the combined use of INDOCIN and aspirin, 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 g of aspirin per day decreases indomethacin blood levels approximately 20%.
Blunting of the antihypertensive effect of beta-adrenoceptor blocking agents by non-steroidal anti-inflammatory 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.
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.
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.
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. This response has been attributed to inhibition of renal prostaglandin synthesis.
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.
During concomitant therapy with NSAIDs, the patient should be observed closely for signs of renal failure (see WARNINGS, Renal Effects), as well as to assure diuretic efficacy.
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 NSAIDs 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.
NSAIDs have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. This may indicate that they could enhance the toxicity of methotrexate. Caution should be used when NSAIDs are administered concomitantly with methotrexate.
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. The effects of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have a risk of serious GI bleeding higher than users of either drug alone.
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.
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.
Last updated on RxList: 7/11/2007
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk. To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. Physicians and patients should remain alert for the development of such events, even in the absence of previous CV symptoms. Patients should be informed about the signs and/or symptoms of serious CV events and the steps to take if they occur.
There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use. The concurrent use of aspirin and an NSAID does increase the risk of serious GI events (see GI WARNINGS).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).
NSAIDs, including INDOCIN, 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 thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs. NSAIDs, including INDOCIN, should be used with caution in patients with hypertension. Blood pressure (BP) should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.
Fluid retention and edema have been observed in some patients taking NSAIDs. INDOCIN should be used with caution in patients with fluid retention or heart failure.
In a study of patients with severe heart failure and hyponatremia, INDOCIN was associated with significant deterioration of circulatory hemodynamics, presumably due to inhibition of prostaglandin dependent compensatory mechanisms.
NSAIDs, including INDOCIN, can cause serious gastrointestinal (GI) adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. Only one in five patients, who develop a serious upper GI adverse event on NSAID therapy is symptomatic. 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-term therapy is not without risk.
Rarely, in patients taking INDOCIN, intestinal ulceration has been associated with stenosis and obstruction. 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 colitis and regional ileitis have been reported to occur rarely.
NSAIDs should be prescribed with extreme caution in those with prior history of ulcer disease or gastrointestinal bleeding. Patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use NSAIDs have a greater than 10-fold increased risk for developing a GI bleed compared to patients with neither of these risk factors. Other factors that increase the risk for GI bleeding in patients treated with NSAIDs include concomitant use of oral corticosteroids or anticoagulants, longer duration of NSAID therapy, smoking, use of alcohol, older age, and poor general health status. Most spontaneous reports of fatal GI events are in elderly or debilitated patients and therefore, special care should be taken in treating this population.
To minimize the potential risk for an adverse GI event in patients treated with an NSAID, the lowest effective dose should be used for the shortest possible duration. Patients and physicians should remain alert for signs and symptoms of GI ulceration and bleeding during NSAID therapy and promptly initiate additional evaluation and treatment if a serious GI adverse event is suspected. This should include discontinuation of the NSAID until a serious GI adverse event is ruled out. For high risk patients, alternate therapies that do not involve NSAIDs should be considered.
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 nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate over 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, patients with volume depletion, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.
Increases in serum potassium concentration, including hyperkalemia, have been reported with use of INDOCIN, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state (see PRECAUTIONS, DRUG INTERACTIONS).
No information is available from controlled clinical studies regarding the use of INDOCIN in patients with advanced renal disease. Therefore, treatment with INDOCIN is not recommended in these patients with advanced renal disease. If INDOCIN therapy must be initiated, close monitoring of the patient's renal function is advisable.
As with other NSAIDs, anaphylactic/anaphylactoid reactions may occur in patients without known prior exposure to INDOCIN. INDOCIN should not be given to patients with the aspirin triad. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS - Preexisting Asthma). Emergency help should be sought in cases where an anaphylactic/anaphylactoid reaction occurs.
NSAIDs, including INDOCIN, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
In late pregnancy, as with other NSAIDs, INDOCIN should be avoided because it may cause premature closure of the ductus arteriosus.
Corneal deposits and retinal disturbances, including those of the macula, have been observed in some patients who had received prolonged therapy with INDOCIN. The prescribing physician should be alert to the possible association between the changes noted and INDOCIN. It is advisable to discontinue therapy if such changes are observed. Blurred vision may be a significant symptom and warrants a thorough ophthalmological examination. Since these changes may be asymptomatic, ophthalmologic examination at periodic intervals is desirable in patients where therapy is prolonged.
INDOCIN may aggravate depression or other psychiatric disturbances, epilepsy, and parkinsonism, and should be used with considerable caution in patients with these conditions. If severe CNS adverse reactions develop, INDOCIN should be discontinued.
INDOCIN may cause drowsiness; therefore, patients should be cautioned about engaging in activities requiring mental alertness and motor coordination, such as driving a car. INDOCIN may also cause headache. Headache which persists despite dosage reduction requires cessation of therapy with INDOCIN.
INDOCIN cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.
The pharmacological activity of INDOCIN in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including INDOCIN. These laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. Notable elevations of ALT or AST (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with NSAIDs. In addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported.
A patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with INDOCIN. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), INDOCIN should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including INDOCIN. This may be due to fluid retention, occult or gross GI blood loss, or an incompletely described effect upon erythropoiesis. Patients on long-term treatment with NSAIDs, including INDOCIN, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia.
NSAIDs inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. Unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. Patients receiving INDOCIN who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
Patients with asthma may have aspirin-sensitive asthma. The use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. Since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, INDOCIN should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
Patients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.
Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, INDOCIN should be discontinued.
In an 81-week chronic oral toxicity study in the rat at doses up to 1 mg/kg/day, indomethacin had no tumorigenic effect.
Indomethacin produced no neoplastic or hyperplastic changes related to treatment in carcinogenic studies in the rat (dosing period 73-110 weeks) and the mouse (dosing period 62-88 weeks) at doses up to 1.5 mg/kg/day.
Indomethacin did not have any mutagenic effect in in vitro bacterial tests (Ames test and E. coli with or without metabolic activation) and a series of in vivo tests including the host-mediated assay, sex-linked recessive lethals in Drosophila, and the micronucleus test in mice.
Indomethacin at dosage levels up to 0.5 mg/kg/day had no effect on fertility in mice in a two generation reproduction study or a two litter reproduction study in rats.
Teratogenic studies were conducted in mice and rats at dosages of 0.5, 1.0, 2.0, and 4.0 mg/kg/day. Except for retarded fetal ossification at 4 mg/kg/day considered secondary to the decreased average fetal weights, no increase in fetal malformations was observed as compared with control groups. Other studies in mice reported in the literature using higher doses (5 to 15 mg/kg/day) have described maternal toxicity and death, increased fetal resorptions, and fetal malformations. Comparable studies in rodents using high doses of aspirin have shown similar maternal and fetal effects. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women.
INDOCIN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.
The known effects of indomethacin and other drugs of this class on the human fetus during the third trimester of pregnancy include: constriction of the ductus arteriosus prenatally, tricuspid incompetence, and pulmonary hypertension; non-closure of the ductus arteriosus postnatally which may be resistant to medical management; myocardial degenerative changes, platelet dysfunction with resultant bleeding, intracranial bleeding, renal dysfunction or failure, renal injury/dysgenesis which may result in prolonged or permanent renal failure, oligohydramnios, gastrointestinal bleeding or perforation, and increased risk of necrotizing enterocolitis.
In rats and mice, 4.0 mg/kg/day given during the last three days of gestation caused a decrease in maternal weight gain and some maternal and fetal deaths. An increased incidence of neuronal necrosis in the diencephalon in the live-born fetuses was observed. At 2.0 mg/kg/day, no increase in neuronal necrosis was observed as compared to the control groups. Administration of 0.5 or 4.0 mg/kg/day during the first three days of life did not cause an increase in neuronal necrosis at either dose level.
In rat studies with NSAIDs, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. The effects of INDOCIN on labor and delivery in pregnant women are unknown.
INDOCIN is excreted in the milk of lactating mothers. INDOCIN is not recommended for use in nursing mothers.
Safety and effectiveness in pediatric patients 14 years of age and younger has not been established.
INDOCIN should not be prescribed for pediatric patients 14 years of age and younger unless toxicity or lack of efficacy associated with other drugs warrants the risk.
In experience with more than 900 pediatric patients reported in the literature or to the manufacturer who were treated with Capsules INDOCIN, side effects in pediatric patients were comparable to those reported in adults. Experience in pediatric patients has been confined to the use of Capsules INDOCIN.
If a decision is made to use indomethacin for pediatric patients two years of age or older, such patients should be monitored closely and periodic assessment of liver function is recommended. There have been cases of hepatotoxicity reported in pediatric patients with juvenile rheumatoid arthritis, including fatalities. If indomethacin treatment is instituted, a suggested starting dose is 1-2 mg/kg/day given in divided doses. Maximum daily dosage should not exceed 3 mg/kg/day or 150-200 mg/day, whichever is less. Limited data are available to support the use of a maximum daily dosage of 4 mg/kg/day or 150-200 mg/day, whichever is less. As symptoms subside, the total daily dosage should be reduced to the lowest level required to control symptoms, or the drug should be discontinued.
As with any NSAID, caution should be exercised in treating the elderly (65 years and older) since advancing age appears to increase the possibility of adverse reactions (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation and DOSAGE AND ADMINISTRATION). Elderly patients seem to tolerate ulceration or bleeding less well than other individuals and many spontaneous reports of fatal GI events are in this population (see WARNINGS, Gastrointestinal Effects - Risk of Ulceration, Bleeding, and Perforation).
Indomethacin may cause confusion or, rarely, psychosis (see ADVERSE REACTIONS); physicians should remain alert to the possibility of such adverse effects in the elderly.
This drug is known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function (see WARNINGS, Renal Effects).
Last updated on RxList: 7/11/2007
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.
Treatment is symptomatic and supportive. The stomach should be emptied as quickly as possible if the ingestion is recent. If vomiting has not occurred spontaneously, the patient should be induced to vomit with syrup of ipecac. If the patient is unable to vomit, gastric lavage should be performed. Once the stomach has been emptied, 25 or 50 g of activated charcoal may be given. Depending on the condition of the patient, close medical observation and nursing care may be required. The patient should be followed for several days because gastrointestinal ulceration and hemorrhage have been reported as adverse reactions of indomethacin. Use of antacids may be helpful.
The oral LD50 of indomethacin in mice and rats (based on 14 day mortality response) was 50 and 12 mg/kg, respectively.
INDOCIN is contraindicated in patients with known hypersensitivity to indomethacin or the excipients (see DESCRIPTION).
INDOCIN should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic/anaphylactoid reactions to NSAIDs have been reported in such patients (see WARNINGS - Anaphylactic/Anaphylactoid Reactions, and PRECAUTIONS - Preexisting Asthma).
INDOCIN is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
Suppositories INDOCIN are contraindicated in patients with a history of proctitis or recent rectal bleeding.
Last updated on RxList: 7/11/2007
INDOCIN is a non-steroidal anti-inflammatory drug (NSAID) that exhibits antipyretic and analgesic properties. Its mode of action, like that of other anti-inflammatory drugs, is not known. However, its therapeutic action is not due to pituitary-adrenal stimulation.
INDOCIN is a potent inhibitor of prostaglandin synthesis in vitro. Concentrations are reached during therapy which have been demonstrated to have an effect in vivo as well. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Moreover, prostaglandins are known to be among the mediators of inflammation. Since indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.
INDOCIN has been shown to be an effective anti-inflammatory agent, appropriate for long-term use in rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.
INDOCIN affords relief of symptoms; it does not alter the progressive course of the underlying disease.
INDOCIN suppresses inflammation in rheumatoid arthritis as demonstrated by relief of pain, and reduction of fever, swelling and tenderness. Improvement in patients treated with INDOCIN for rheumatoid arthritis has been demonstrated by a reduction in joint swelling, average number of joints involved, and morning stiffness; by increased mobility as demonstrated by a decrease in walking time; and by improved functional capability as demonstrated by an increase in grip strength. INDOCIN may enable the reduction of steroid dosage in patients receiving steroids for the more severe forms of rheumatoid arthritis. In such instances the steroid dosage should be reduced slowly and the patients followed very closely for any possible adverse effects.
Indomethacin has been reported to diminish basal and CO2 stimulated cerebral blood flow in healthy volunteers following acute oral and intravenous administration. In one study after one week of treatment with orally administered indomethacin, this effect on basal cerebral blood flow had disappeared. The clinical significance of this effect has not been established.
Capsules INDOCIN have been found effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis - see INDICATIONS AND USAGE.
Following single oral doses of Capsules INDOCIN 25 mg or 50 mg, indomethacin is readily absorbed, attaining peak plasma concentrations of about 1 and 2 mcg/mL, respectively, at about 2 hours. Orally administered Capsules INDOCIN are virtually 100% bioavailable, with 90% of the dose absorbed within 4 hours. A single 50 mg dose of Oral Suspension INDOCIN was found to be bioequivalent to a 50 mg INDOCIN capsule when each was administered with food.
Indomethacin is eliminated via renal excretion, metabolism, and biliary excretion. Indomethacin undergoes appreciable enterohepatic circulation. The mean half-life of indomethacin is estimated to be about 4.5 hours. With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.
The rate of absorption is more rapid from the rectal suppository than from Capsules INDOCIN. Ordinarily, therefore, the total amount absorbed from the suppository would be expected to be at least equivalent to the capsule. In controlled clinical trials, however, the amount of indomethacin absorbed was found to be somewhat less (80-90%) than that absorbed from Capsules INDOCIN. This is probably because some subjects did not retain the material from the suppository for the one hour necessary to assure complete absorption. Since the suppository dissolves rather quickly rather than melting slowly, it is seldom recovered in recognizable form if the patient retains the suppository for more than a few minutes.
Indomethacin exists in the plasma as the parent drug and its desmethyl, desbenzoyl, and desmethyl-desbenzoyl metabolites, all in the unconjugated form. About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent is recovered in feces (1.5 percent as indomethacin).
About 99% of indomethacin is bound to protein in plasma over the expected range of therapeutic plasma concentrations. Indomethacin has been found to cross the blood-brain barrier and the placenta.
Last updated on RxList: 7/11/2007
Medication Guide
for
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
(See the end of this Medication Guide for a list of prescription NSAID medicines.)
NSAID medicines may increase the chance of a heart attack or stroke that can lead to death. This chance increases:
NSAID medicines should never be used right before or after a heart surgery called a "coronary artery bypass graft (CABG)."
NSAID medicines can cause ulcers and bleeding in the stomach and intestines at any time during treatment. Ulcers and bleeding:
The chance of a person getting an ulcer or bleeding increases with:
NSAID medicines should only be used:
NSAID medicines are used to treat pain and redness, swelling, and heat (inflammation) from medical conditions such as:
Serious side effects include:
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Other side effects include:
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These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.
NSAID medicines that need a prescription
| Generic Name | Tradename |
| Celecoxib | Celebrex |
| Diclofenac | Cataflam, Voltaren, Arthrotec (combined with misoprostol) |
| Diflunisal | Dolobid |
| Etodolac | Lodine, Lodine XL |
| Fenoprofen | Nalfon, Nalfon 200 |
| Flurbiprofen | Ansaid |
| Ibuprofen | Motrin, Tab-Profen, Vicoprofen* (combined with hydrocodone), Combunox (combined with oxycodone) |
| Indomethacin | Indocin, Indocin SR, Indo-Lemmon, Indomethegan |
| Ketoprofen | Oruvail |
| Ketorolac | Toradol |
| Mefenamic Acid | Ponstel |
| Meloxicam | Mobic |
| Nabumetone | Relafen |
| Naproxen | Naprosyn, Anaprox, Anaprox DS, EC-Naprosyn, Naprelan, Naprapac (copackaged with lansoprazole) |
| Oxaprozin | Daypro |
| Piroxicam | Feldene |
| Sulindac | Clinoril |
| Tolmetin | Tolectin, Tolectin DS, Tolectin 600 |
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Last updated on RxList: 7/11/2007
IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.
INDOMETHACIN - ORAL
(in-doh-METH-uh-sin)
COMMON BRAND NAME(S): Indocin
WARNING: This drug may infrequently cause serious (rarely fatal) bleeding from the stomach or intestines. This side effect can occur without warning at any time during treatment with indomethacin. The elderly are at increased risk for serious stomach/intestinal bleeding.
Drugs related to indomethacin have rarely caused blood clots to form, resulting in serious (possibly fatal) heart attacks and strokes. This medication might also rarely cause similar problems. The risk of these serious side effects may increase if you have heart disease and with longer use of this medication. Talk to your doctor or pharmacist about the benefits and risks of treatment, as well as other possible medication choices.
Stop taking indomethacin and seek immediate medical attention if you notice any of the following rare but very serious side effects: black stools, persistent stomach/abdominal pain, vomit that looks like coffee grounds, chest pain, shortness of breath, weakness on one side of the body, sudden vision changes, slurred speech.
This medication should not be used right before or after heart bypass surgery.
USES: Indomethacin is used to relieve pain, swelling, and joint stiffness caused by arthritis, gout, bursitis, and tendonitis. Reducing these symptoms helps you do more of your normal daily activities. This medication is known as a nonsteroidal anti-inflammatory drug (NSAID).
OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.
This medication may also be used to relieve pain caused by inflammation of the pouch surrounding the heart and other conditions as prescribed by your doctor.
HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using indomethacin and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.
Take this medication by mouth with a full glass of water (8 ounces or 240 milliliters) unless your doctor directs you otherwise. Do not lie down for at least 30 minutes after taking this drug. Take this medication either with food, right after meals, or with antacids to prevent stomach upset.
Dosage is based on your medical condition and response to therapy. In adults, do not use more than 200 milligrams per day. In children, dosage is also based on weight. The maximum dose for children is 4 milligrams per kilogram a day or 150 to 200 milligrams a day, whichever is less. To minimize side effect risks (e.g., stomach bleeding), use this medication at the lowest effective dose for the shortest possible length of time. Do not increase your dose or use it more often than prescribed. For ongoing conditions such as arthritis, continue using it as directed by your doctor. Discuss the risks and benefits with your doctor or pharmacist.
In certain conditions (e.g., arthritis), it may take up to 4 weeks of regular use before the full benefits of this drug take effect.
If you are taking this drug on an "as needed" basis (not on a regular schedule), remember that pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has significantly worsened, the medicine may not work as well.
Inform your doctor if your condition worsens.
Upset stomach, heartburn, headache, tiredness, drowsiness, or dizziness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Tell your doctor immediately if any of these unlikely but serious side effects occur: stomach pain, swelling of the hands/feet, sudden/unexplained weight gain, vision changes, hearing changes (e.g., ringing in the ears), mental/mood changes (e.g., confusion, hallucinations), fast/pounding heartbeat, persistent/severe headache, fainting, muscle weakness, uncontrollable movements, difficult/painful swallowing.
Tell your doctor immediately if any of these rare but very serious side effects occur: change in the amount of urine, easy bruising/bleeding, signs of infection (e.g., fever, persistent sore throat), unexplained stiff neck, seizures.
This drug may rarely cause serious (possibly fatal) liver disease. If you notice any of the following rare but very serious side effects, stop taking indomethacin and tell your doctor immediately: yellowing eyes/skin, dark urine, unusual/extreme tiredness, severe stomach/abdominal pain, persistent nausea/vomiting.
A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking indomethacin, tell your doctor or pharmacist if you are allergic to it; or to aspirin or other NSAIDs (e.g., ibuprofen, naproxen, celecoxib); or if you have any other allergies.
This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: aspirin-sensitive asthma (a history of worsening breathing with runny/stuffy nose after taking aspirin or other NSAIDs), severe kidney disease, recent heart bypass surgery (CABG).
Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, poorly controlled diabetes, stomach/intestine/esophagus problems (e.g., bleeding, ulcers), heart disease (e.g., congestive heart failure, history of heart attack), blood disorders (e.g., anemia), bleeding or clotting problems, high blood pressure, swelling (edema, fluid retention), a severe loss of body water (dehydration), stroke, mental/mood conditions (e.g., depression, psychoses), seizures, Parkinson's disease, high level of potassium in the blood, asthma, growths in the nose (nasal polyps).
Before having surgery, tell your doctor or dentist that you are using this medication.
This drug may make you dizzy or drowsy; use caution engaging in activities requiring alertness such as driving or using machinery.
This medicine may cause stomach bleeding. Daily use of alcohol and tobacco may increase your risk for stomach bleeding, especially when combined with this medicine. Limit alcohol and stop smoking. Consult your doctor or pharmacist for more information.
This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths, and sunlamps. Use a sunscreen and wear protective clothing when outdoors.
The elderly may be more sensitive to the side effects of this drug, especially stomach/intestinal bleeding, kidney effects, and mental/mood changes.
Children may be more sensitive to the side effects of this drug, especially serious liver problems. Caution is advised when this drug is used in children. Discuss the risks and benefits of treatment with your doctor.
This medication should be used only when clearly needed during the first 6 months of pregnancy. It is not recommended for use during the last 3 months of pregnancy due to possible harm to the unborn baby and interference with normal labor/delivery. Discuss the risks and benefits with your doctor.
This drug passes into breast milk. Therefore, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.
This drug should not be used with the following medications because very serious interactions may occur: cidofovir, other NSAIDs (e.g., diflunisal, ketorolac), high doses of aspirin and related drugs (salicylates), a certain "water pill" (a diuretic called triamterene).
If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting indomethacin.
Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: anti-platelet drugs (e.g., cilostazol, clopidogrel), oral bisphosphonates (e.g., alendronate), "blood thinners" (e.g., enoxaparin, heparin, warfarin), corticosteroids (e.g., prednisone), cyclosporine, desmopressin, digoxin, high blood pressure drugs (including ACE inhibitors such as captopril, angiotensin receptor blockers such as losartan, and beta-blockers such as metoprolol), lithium, methotrexate, pemetrexed, potassium supplements, probenecid, SSRI antidepressants (e.g., fluoxetine, sertraline), other "water pills" (diuretics such as furosemide, hydrochlorothiazide, spironolactone).
Check all prescription and nonprescription medicine labels carefully for other pain/fever drugs (NSAIDs such as aspirin, celecoxib, ibuprofen). These drugs are similar to this medication, so taking one of these drugs while also taking this medication may increase your risk of side effects. However, if your doctor has prescribed low doses of aspirin to prevent heart attack or stroke (usually at dosages of 81-325 milligrams a day), you should continue to take the aspirin. Daily use of NSAIDs (e.g., ibuprofen) may decrease aspirin's ability to prevent heart attack/stroke. Consult your doctor or pharmacist for more details and to discuss other possible treatments (e.g., acetaminophen) for your pain/fever.
This medication can affect the results of certain lab tests. Make sure laboratory personnel and your doctors know you use this drug.
This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include severe stomach pain, vomit that looks like coffee grounds, extreme drowsiness, slow or shallow breathing, confusion, seizures.
NOTES: Do not share this medication with others.
Laboratory and/or medical tests (e.g., complete blood count, liver and kidney function tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.
Non-drug treatment for arthritis that is approved by your doctor (e.g., weight loss if needed, strengthening and conditioning exercises) may help improve your flexibility, range of motion, and joint function. Consult your doctor for specific instructions.
MISSED DOSE: If you are prescribed this drug on a regular schedule (not just "as needed") and you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.
STORAGE: Store at room temperature between 59-86 degrees F (15-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.
Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.
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