"The U.S. Food and Drug Administration today approved the first generic versions of Celebrex (celecoxib) capsules, a treatment for rheumatoid arthritis, osteoarthritis, short-term (acute) pain, and other conditions.
Teva Pharmaceutical Indus"...
(Generic versions may still be available.)
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- Cardiovascular Thrombotic Events [see WARNINGS AND PRECAUTIONS]
- GI Bleeding, Ulceration and Perforation [see WARNINGS AND PRECAUTIONS]
- Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
- Hypertension [see WARNINGS AND PRECAUTIONS]
- Heart Failure and Edema [see WARNINGS AND PRECAUTIONS]
- Renal Toxicity and Hyperkalemia [see WARNINGS AND PRECAUTIONS]
- Anaphylactic Reactions [see WARNINGS AND PRECAUTIONS]
- Serious Skin Reactions [see WARNINGS AND PRECAUTIONS]
- Hematologic Toxicity [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In a gastroscopic study in 45 healthy subjects, the number of gastric mucosal abnormalities was significantly higher in the group receiving INDOCIN Capsules than in the group taking INDOCIN Suppositories or placebo.
In a double-blind comparative clinical study involving 175 patients with rheumatoid arthritis, however, the incidence of upper gastrointestinal adverse effects with INDOCIN Suppositories or Capsules was comparable. The incidence of lower gastrointestinal adverse effects was greater in the suppository group.
The adverse reactions for INDOCIN Capsules 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 INDOCIN Capsules may also occur with use of the suspension.
Table 1 : Summary of Adverse Reactions for INDOCIN
|Incidence greater than 1 %||Incidence less than 1%|
|nausea* with or without vomiting
dyspepsia* (including indigestion, heartburn and epigastric pain)
abdominal distress or pain
bloating (includes distension)
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 preexisting sigmoid lesions (diverticulum, carcinoma, etc.)
development of ulcerative colitis and regional ileitis
toxic hepatitis and jaundice (some fatal cases have been reported) intestinal strictures (diaphragms)
|CENTRAL NERVOUS SYSTEM|
depression and fatigue (including malaise and listlessness)
|anxiety (includes nervousness)
involuntary muscle movements
psychic disturbances including psychotic episodes
mental confusion drowsiness
aggravation of epilepsy and parkinsonism
|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
|congestive heart failure
flushing or sweating
|none||pruritus rash; urticaria petechiae or ecchymosis||exfoliative dermatitis
loss of hair
toxic epidermal necrolysis
|None||leukopenia bone marrow depression anemia secondary to obvious or occult gastrointestinal bleeding||aplastic anemia
disseminated intravascular coagulation
acute respiratory distress
rapid fall in blood pressure resembling a shock-like state
|BUN elevation renal insufficiency, including renal failure|
|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:
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 Aβ hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome
Read the Indocin (indomethacin) Side Effects Center for a complete guide to possible side effects
See Table 2 for clinically significant drug interactions with indomethacin.
Table 2 : Clinically Significant Drug Interactions
|Drugs That Interfere with Hemostasis|
|Intervention:||Monitor patients with concomitant use of INDOCIN with anticoagulants (e.g., warfarin), antiplatelet agents (e.g., aspirin), selective serotonin reuptake inhibitors (SSRIs), and serotonin norepinephrine reuptake inhibitors (SNRIs) for signs of bleeding [see WARNINGS AND PRECAUTIONS].|
|Clinical Impact:||Controlled clinical studies showed that the concomitant use of NSAIDs and analgesic doses of aspirin does not produce any greater therapeutic effect than the use of NSAIDs alone. In a clinical study, the concomitant use of an INDOCIN and aspirin was associated with a significantly increased incidence of GI adverse reactions as compared to use of the INDOCIN alone [see WARNINGS AND PRECAUTIONS].|
|Intervention:||Concomitant use of INDOCIN and analgesic doses of aspirin is not generally recommended because of the increased risk of bleeding [see WARNINGS AND PRECAUTIONS]. INDOCIN is not a substitute for low dose aspirin for cardiovascular protection.|
|ACE Inhibitors, Angiotensin Receptor Blockers, and Beta-Blockers|
|Clinical Impact:||Clinical studies, as well as post-marketing observations, showed that NSAIDs reduced the natriuretic effect of loop diuretics (e.g., furosemide) and thiazide diuretics in some patients. This effect has been attributed to the NSAID inhibition of renal prostaglandin synthesis. 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.
Both INDOCIN and potassium-sparing diuretics may be associated with increased serum potassium levels. The potential effects of INDOCIN and potassium-sparing diuretics on potassium levels and renal function should be considered when these agents are administered concurrently.
|Intervention:||Indomethacin and triamterene should not be administered together. During concomitant use of INDOCIN with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects. Be aware that indomethacin and potassium-sparing diuretics may both be associated with increased serum potassium levels [see WARNINGS AND PRECAUTIONS].|
|Clinical Impact:||The concomitant use of INDOCIN with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin.|
|Intervention:||During concomitant use of INDOCIN and digoxin, monitor serum digoxin levels.|
|Clinical Impact:||NSAIDs have produced elevations in plasma lithium levels and reductions in renal lithium clearance. The mean minimum lithium concentration increased 15%, and the renal clearance decreased by approximately 20%. This effect has been attributed to NSAID inhibition of renal prostaglandin synthesis.|
|Intervention:||During concomitant use of INDOCIN and lithium, monitor patients for signs of lithium toxicity.|
|Clinical Impact:||Concomitant use of NSAIDs and methotrexate may increase the risk for methotrexate toxicity (e.g., neutropenia, thrombocytopenia, renal dysfunction).|
|Intervention:||During concomitant use of INDOCIN and methotrexate, monitor patients for methotrexate toxicity.|
|Clinical Impact:||Concomitant use of INDOCIN and cyclosporine may increase cyclosporine's nephrotoxicity.|
|Intervention:||During concomitant use of INDOCIN and cyclosporine, monitor patients for signs of worsening renal function.|
|NSAIDs and Salicylates|
|Clinical Impact:||Concomitant use of indomethacin with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [see WARNINGS AND PRECAUTIONS]. Combined use with diflunisal may be particularly hazardous because diflunisal causes significantly higher plasma levels of indomethacin [ see CLINICAL PHARMACOLOGY]. In some patients, combined use of indomethacin and diflunisal has been associated with fatal gastrointestinal hemorrhage.|
|Intervention:||The concomitant use of indomethacin with other NSAIDs or salicylates, especially diflunisal, is not recommended.|
|Clinical Impact:||Concomitant use of INDOCIN and pemetrexed may increase the risk of pemetrexed-associated myelosuppression, renal, and GI toxicity (see the pemetrexed prescribing information).|
|Intervention:||During concomitant use of INDOCIN and pemetrexed, in patients with renal impairment whose creatinine clearance ranges from 45 to 79 mL/min, monitor for myelosuppression, renal and GI toxicity. NSAIDs with short elimination half-lives (e.g., diclofenac, indomethacin) should be avoided for a period of two days before, the day of, and two days following administration of pemetrexed. In the absence of data regarding potential interaction between pemetrexed and NSAIDs with longer half-lives (e.g., meloxicam, nabumetone), patients taking these NSAIDs should interrupt dosing for at least five days before, the day of, and two days following pemetrexed administration.|
|Clinical Impact:||When indomethacin is given to patients receiving probenecid, the plasma levels of indomethacin are likely to be increased.|
|Intervention:||During the concomitant use of INDOCIN and probenecid, a lower total daily dosage of indomethacin may produce a satisfactory therapeutic effect. When increases in the dose of indomethacin are made, they should be made carefully and in small increments.|
Effects On Laboratory Tests
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.
False-negative results in the dexamethasone suppression test (DST) in patients being treated with indomethacin have been reported. Thus, results of the DST should be interpreted with caution in these patients.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 11/28/2016
Additional Indocin Information
Indocin - User Reviews
Indocin User Reviews
Now you can gain knowledge and insight about a drug treatment with Patient Discussions.
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options