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INDOCIN* (Indomethacin) cannot be considered a simple analgesic and should not be used in conditions other than those recommended under INDICATIONS.
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, 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-1 H -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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*Registered trademark of MERCK & CO., INC.
INDOCIN is a non-steroidal drug with anti-inflammatory, 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.
Indomethacin has been reported to diminish basal and CO 2 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 .
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.
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.
Indomethacin has been found effective in active stages of the following:
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.
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. Furthermore, in one of these clinical studies, the incidence of gastrointestinal side effects was significantly increased with combined therapy (see DRUG INTERACTIONS ).
INDOCIN 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 non-steroidal anti-inflammatory agents.
Suppositories INDOCIN are contraindicated in patients with a history of proctitis or recent rectal bleeding.
General:
Because of the variability of the potential of INDOCIN to cause adverse reactions in the individual patient, the following are strongly recommended:
Gastrointestinal Effects:
Single or multiple ulcerations, including perforation and hemorrhage of the esophagus, stomach, duodenum or small and large intestine, have been reported to occur with INDOCIN. Fatalities have been reported in some instances. Rarely, 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.
Because of the occurrence, and at times severity, of gastrointestinal reactions to INDOCIN, the prescribing physician must be continuously alert for any sign or symptom signaling a possible gastrointestinal reaction. The risks of continuing therapy with INDOCIN in the face of such symptoms must be weighed against the possible benefits to the individual patient.
INDOCIN should not be given to patients with active gastrointestinal lesions or with a history of recurrent gastrointestinal lesions except under circumstances which warrant the very high risk and where patients can be monitored very closely.
The gastrointestinal effects may be reduced by giving Capsules INDOCIN immediately after meals, with food, or with antacids.
Risk of GI Ulcerations, Bleeding and Perforation with NSAID Therapy
Serious gastrointestinal toxicity such as bleeding, ulceration, and perforation, can occur at any time, with or without warning symptoms, in patients treated chronically with NSAID therapy. Although minor upper gastrointestinal problems, such as dyspepsia, are common, usually developing early in therapy, physicians should remain alert for ulceration and bleeding in patients treated chronically with NSAIDs even in the absence of previous GI tract symptoms. In patients observed in clinical trials of several months to two years duration, symptomatic upper GI ulcers, gross bleeding or perforation appear to occur in approximately 1% of patients treated for 3-6 months, and in about 2-4% of patients treated for one year. Physicians should inform patients about the signs and/or symptoms of serious GI toxicity and what steps to take if they occur.
Studies to date have not identified any subset of patients not at risk of developing peptic ulceration and bleeding. Except for a prior history of serious GI events and other risk factors known to be associated with peptic ulcer disease, such as alcoholism, smoking, etc., no risk factors (e.g., age, sex) have been associated with increased risk. Elderly or debilitated patients seem to tolerate ulceration or bleeding less well than other individuals and most spontaneous reports of fatal GI events are in this population. Studies to date are inconclusive concerning the relative risk of various NSAIDs in causing such reactions. High doses of any NSAID probably carry a greater risk of these reactions, although controlled clinical trials showing this do not exist in most cases. In considering the use of relatively large doses (within the recommended dosage range), sufficient benefit should be anticipated to offset the potential increased risk of GI toxicity.
Renal Effects:
As with other non-steroidal anti-inflammatory drugs, long term administration of indomethacin to animals has resulted in renal papillary necrosis and other abnormal renal pathology. In humans, there have been reports of acute interstitial nephritis with hematuria, proteinuria, and occasionally nephrotic syndrome.
A second form of renal toxicity has been seen in patients with prerenal and renal conditions leading to a reduction in renal blood flow or blood volume, where the renal prostaglandins have a supportive role in the maintenance of renal perfusion. In these patients administration of an NSAID may cause a dose dependent reduction in prostaglandin formation and may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with conditions such as renal or hepatic dysfunction, diabetes mellitus, advanced age, extracellular volume depletion from any cause, congestive heart failure, septicemia, pyelonephritis, or concomitant use of any nephrotoxic drug. INDOCIN or other NSAIDs should be given with caution and renal function should be monitored in any patient who may have reduced renal reserve. Discontinuation of NSAID therapy is typically followed by recovery to the pretreatment state.
Increases in serum potassium concentration, including hyperkalemia, have been reported, 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 ).
Since INDOCIN is eliminated primarily by the kidneys, patients with significantly impaired renal function should be closely monitored; a lower daily dosage should be anticipated to avoid excessive drug accumulation.
Ocular Effects:
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.
Central Nervous System Effects:
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.
Use in Pregnancy and the Neonatal Period
INDOCIN is not recommended for use in pregnant women, since safety for use has not been established. 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.
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.
As with other non-steroidal anti-inflammatory agents which inhibit prostaglandin synthesis, indomethacin has been found to delay parturition in rats.
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.
Use in Nursing Mothers
INDOCIN is excreted in the milk of lactating mothers. INDOCIN is not recommended for use in nursing mothers.
General
Non-steroidal anti-inflammatory drugs, including INDOCIN, may mask the usual signs and symptoms of infection. Therefore, the physician must be continually on the alert for this and should use the drug with extra care in the presence of existing infection.
Fluid retention and peripheral edema have been observed in some patients taking INDOCIN. Therefore, as with other non-steroidal anti-inflammatory drugs, INDOCIN should be used with caution in patients with cardiac dysfunction, hypertension, or other conditions predisposing to fluid retention.
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.
INDOCIN, like other non-steroidal anti-inflammatory agents, can inhibit platelet aggregation. This effect is of shorter duration than that seen with aspirin and usually disappears within 24 hours after discontinuation of INDOCIN. INDOCIN 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 hemostatic defects, INDOCIN should be used with caution in persons with coagulation defects.
As with other non-steroidal anti-inflammatory drugs, borderline elevations of one or more liver tests may occur in up to 15% of patients. These abnormalities may progress, may remain essentially unchanged, or may be transient with continued therapy. The SGPT (ALT) test is probably the most sensitive indicator of liver dysfunction. Meaningful (3 times the upper limit of normal) elevations of SGPT or SGOT (AST) occurred in controlled clinical trials in less than 1% of patients. 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 more severe hepatic reaction while on therapy with INDOCIN. Severe hepatic reactions, including jaundice and cases of fatal hepatitis, have been reported with INDOCIN as with other non-steroidal anti-inflammatory drugs. Although such reactions are rare, if abnormal liver tests persist or worsen, if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), INDOCIN should be discontinued.
Information for Patients
INDOCIN, 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 (Non-steroidal 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 (see , PRECAUTIONS and ADVERSE REACTIONS ) 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.
Laboratory Tests
Because serious GI tract ulceration and bleeding can occur without warning symptoms, physicians should follow chronically treated patients for the signs and symptoms of ulceration and bleeding and should inform them of the importance of this follow-up (see , Risk of GI Ulcerations, Bleeding and Perforation with NSAID Therapy ).
Carcinogenesis, Mutagenesis, Impairment of Fertility
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.
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.
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 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 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 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. There are reports that INDOCIN can reduce the antihypertensive effect of captopril in some patients.
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.
Pediatric Use
Effectiveness in pediatric patients 14 years of age and younger has not been established (see ).
Geriatric Use
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 , General ; 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 , Risk of GI Ulcerations, Bleeding and Perforation with NSAID Therapy ).
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 , Renal Effects ).
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.
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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 (beta)-hemolytic streptococcus, has been described in persons treated with non-steroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome (see also PRECAUTIONS , General ).
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 LD 50 of indomethacin in mice and rats (based on 14 day mortality response) was 50 and 12 mg/kg, respectively.
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.
Always give Capsules INDOCIN or Oral Suspension INDOCIN with food, immediately after meals, or with antacids to reduce gastric irritation.
Pediatric Use
INDOCIN ordinarily should not be prescribed for pediatric patients 14 years of age and under (see ).
Adult Use
Dosage Recommendations for Active Stages of the Following:
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 SHARP & DOHME, Division of Merck & Co., INC.
Manufactured by:
MERCK SHARP & DOHME
(Italia) S.p.A.
27100--Pavia, Italy
Capsules and Oral Suspension INDOCIN® are distributed and manufactured by:
MERCK SHARP & DOHME, Division of Merck & Co., INC.
7873327 Issued October 1999
COPYRIGHT © MERCK & CO., INC., 1988
All rights reserved
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