Indocin

Dosage Forms And Strengths

INDOCIN (indomethacin) Oral Suspension 25 mg per 5 mL, is an off-white suspension with a pineapple coconut mint flavor.

Storage And Handling

INDOCIN (indomethacin) Oral Suspension, 25 mg per 5 mL, is an off-white suspension with a pineapple coconut mint flavor. It is supplied as follows:

NDC 42211-101-11 in bottles of 237 mL

Store below 30°C (86°F). Avoid temperatures above 50°C (122°F). Do not freeze.

Manufactured by: Patheon Inc. 111 Consumers Dr. Whitby ON L1N 5Z5 Canada. Distributed by: Iroko Pharmaceuticals, LLC, One Kew Place150 Rouse Boulevard, Philadelphia, PA 19112. Revised: May 2016

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 Capsules

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 Aβ hemolytic streptococcus, has been described in persons treated with nonsteroidal anti-inflammatory agents, including indomethacin, sometimes with fatal outcome

Mechanism Of Action

Indomethacin has analgesic, anti-inflammatory, and antipyretic properties.

The mechanism of action of INDOCIN, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).

Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Indomethacin concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Pharmacokinetics

Following single oral doses of INDOCIN Capsules 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 INDOCIN Capsules are virtually 100% bioavailable, with 90% of the dose absorbed within 4 hours. A single 50 mg dose of INDOCIN Oral Suspension was found to be bioequivalent to a 50 mg INDOCIN Capsule when each was administered with food. With a typical therapeutic regimen of 25 or 50 mg three times a day, the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.

Indomethacin is highly bound to protein in plasma (about 99%) over the expected range of therapeutic plasma concentrations. Indomethacin has been found to cross the blood-brain barrier and the placenta, and appears in breast milk.

Metabolism

Indomethacin exists in the plasma as the parent drug and its desmethyl, desbenzoyl, anddesmethyldesbenzoyl metabolites, all in the unconjugated form. Appreciable formation of glucuronide conjugates of each metabolite and of indomethacin are formed.

Excretion

Indomethacin is eliminated via renal excretion, metabolism, and biliary excretion. Indomethacin undergoes appreciable enterohepatic circulation. About 60% of an oral dose is recovered in urine as drug and metabolites (26% as indomethacin and its glucuronide), and 33% is recovered in feces (1.5% as indomethacin). The mean half-life of indomethacin is estimated to be about 4.5 hours.

Specific Populations

Pediatric: The pharmacokinetics of INDOCIN has not been investigated in pediatric patients.

Race: Pharmacokinetic differences due to race have not been identified.

Hepatic Impairment: The pharmacokinetics of INDOCIN has not been investigated in patients with hepatic impairment.

Renal Impairment: The pharmacokinetics of INDOCIN has not been investigated in patients with renal impairment [see WARNINGS AND PRECAUTIONS].

Drug Interaction Studies

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% [see DRUG INTERACTIONS].

When NSAIDs were administered with aspirin, the protein binding of NSAIDs were reduced, although the clearance of free NSAID was not altered. The clinical significance of this interaction is not known. See Table 2 for clinically significant drug interactions of NSAIDs with aspirin [see DRUG INTERACTIONS].

In normal volunteers receiving indomethacin, the administration of diflunisal decreased the renal clearance and significantly increased the plasma levels of indomethacin [see DRUG INTERACTIONS].

Clinical Studies

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.

Indocin is part of the drug class:

• Acetic acid derivatives and related substances

Before taking indomethacin, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to indomethacni or to any of its ingredients
• are allergic to aspirin or other NSAIDs
• have liver disease
• have kidney disease
• experience seizures
• have mental illness or depression
• have Parkinson’s disease
• have frequent stuffed or runny nose or nasal polyps
• have inflammation of the rectum, if using suppositories
• are pregnant or breastfeeding

Indomethacin may not be the safest medication choice in people who are 65 years or older. Talk to your doctor about the risks of taking indomethacin if you are over the age of 65.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take indomethacin exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The indomethacin dose your doctor recommends will be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

Oral:

The recommended dose range of oral indomethacin for the treatment of moderate to severe rheumatoid arthritis is 25 to 50 mg two or three times a day.

The recommended dose range of oral indomethacin for the treatment of shoulder bursitis and/or tendonitis is 75 to 150 mg daily divided into three or four doses. Therapy is usually continued for 7 to 14 days.

The recommended dose range of oral indomethacin for the treatment of acute gouty arthritis is 50 mg three times a day.

Topical:

The recommended dose range of indomethacin suppository for the treatment of moderate to severe rheumatoid arthritis is 25 to 50 mg two or three times a day.

The recommended dose range of indomethacin suppository for the treatment of shoulder bursitis and/or tendonitis is 75 to 150 mg daily divided into three or four doses. Therapy is usually continued for 7 to 14 days.

The recommended dose range of indomethacin suppository for the treatment of acute gouty arthritis is 50 mg three times a day.

Injectable:

The recommended dose range of indomethacin injection for the treatment of a patent ductus arteriosus 0.1 to 0.25 mg/kg, depending on the age of the newborn infant. Typically, only one course of therapy is required.

Taking an NSAID can increase your risk of life-threatening heart or circulation problems, including heart attack or stroke. This risk will increase the longer you use an NSAID. Do not use this medicine just before or after having heart bypass surgery (also called coronary artery bypass graft, or CABG).

NSAIDs can also increase your risk of serious effects on the stomach or intestines, including bleeding or perforation (forming of a hole). These conditions can be fatal and gastrointestinal effects can occur without warning at any time while you are taking an NSAID. Older adults may have an even greater risk of these serious gastrointestinal side effects.

Do not use this medication if you are allergic to indomethacin, or if you have a history of allergic reaction to aspirin or other NSAIDs.

Before taking indomethacin tell your doctor if you are allergic to any drugs, or if you have:

• a history of heart attack, stroke, or blood clot;
• heart disease, congestive heart failure, high blood pressure;
• a history of stomach ulcers or bleeding;
• liver or kidney disease,
• a seizure disorder such as epilepsy;
• asthma;
• polyps in your nose;
• a bleeding or blood clotting disorder; or
• if you smoke.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take indomethacin.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Taking indomethacin during the last 3 months of pregnancy may harm the unborn baby. Do not take indomethacin during pregnancy unless your doctor has told you to.

Indomethacin passes into breast milk and may affect a nursing baby. Do not take indomethacin without first talking to your doctor if you are breast-feeding a baby.

Do not give this medicine to a child younger than 14 years old without the advice of a doctor.

Indomethacin can increase your risk of fatal heart attack or stroke, especially if you use it long term or take high doses, or if you have heart disease. Do not use this medicine just before or after heart bypass surgery (coronary artery bypass graft, or CABG).

Indomethacin may also cause stomach or intestinal bleeding, which can be fatal. These conditions can occur without warning while you are using indomethacin, especially in older adults.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose symptoms may include vomiting, severe headache, dizziness, confusion, numbness, tingling, or seizure (convulsions).

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of indomethacin capsules, suspension, and suppositories in children younger than 14 years of age. Safety and efficacy have not been established.

Appropriate studies have not been performed on the relationship of age to the effects of Tivorbex® capsules in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of indomethacin in the elderly. However, elderly patients may be more sensitive to the effects of indomethacin than younger adults, and are more likely to have unwanted side effects (eg, confusion, psychosis) and age-related kidney or stomach problems, which may require caution and an adjustment in the dose for patients receiving indomethacin.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Ketorolac

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Amiloride
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Balsalazide
• Bemiparin
• Bendroflumethiazide
• Benzthiazide
• Betamethasone
• Betrixaban
• Bismuth Subsalicylate
• Bivalirudin
• Bromfenac
• Budesonide
• Bufexamac
• Bumetanide
• Cangrelor
• Celecoxib
• Certoparin
• Chlorothiazide
• Chlorthalidone
• Choline Magnesium Trisalicylate
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopamide
• Clopidogrel
• Cortisone
• Cyclopenthiazide
• Cyclosporine
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Deflazacort
• Desipramine
• Desirudin
• Desmopressin
• Desvenlafaxine
• Dexamethasone
• Dexibuprofen
• Dexketoprofen
• Diazoxide
• Dibenzepin
• Diflunisal
• Digoxin
• Dipyridamole
• Dipyrone
• Dothiepin
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Enoxaparin
• Eplerenone
• Epoprostenol
• Eptifibatide
• Escitalopram
• Ethacrynic Acid
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Feverfew
• Floctafenine
• Flufenamic Acid
• Fluocortolone
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Furosemide
• Ginkgo
• Gossypol
• Heparin
• Hydrochlorothiazide
• Hydrocortisone
• Hydroflumethiazide
• Ibuprofen
• Iloprost
• Imipramine
• Indapamide
• Ketoprofen
• Lepirudin
• Levomilnacipran
• Lithium
• Lofepramine
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Magnesium Salicylate
• Meadowsweet
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Mesalamine
• Methotrexate
• Methyclothiazide
• Methylprednisolone
• Metolazone
• Milnacipran
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Olsalazine
• Opipramol
• Oxaprozin
• Oxyphenbutazone
• Paramethasone
• Parecoxib
• Parnaparin
• Paroxetine
• Pemetrexed
• Pentosan Polysulfate Sodium
• Pentoxifylline
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Phenyl Salicylate
• Piketoprofen
• Piroxicam
• Polythiazide
• Potassium
• Pralatrexate
• Prasugrel
• Prednisolone
• Prednisone
• Probenecid
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Protriptyline
• Reboxetine
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylamide
• Salicylic Acid
• Salsalate
• Sertraline
• Sibutramine
• Sodium Salicylate
• Spironolactone
• Sulfasalazine
• Sulindac
• Tacrolimus
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticagrelor
• Ticlopidine
• Tinzaparin
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Torsemide
• Treprostinil
• Triamterene
• Trichlormethiazide
• Trimipramine
• Trolamine Salicylate
• Valdecoxib
• Vasopressin
• Venlafaxine
• Vilazodone
• Vorapaxar
• Vortioxetine
• Warfarin
• Xipamide

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Alacepril
• Atenolol
• Azilsartan
• Azilsartan Medoxomil
• Benazepril
• Betaxolol
• Bisoprolol
• Candesartan
• Captopril
• Carteolol
• Carvedilol
• Celiprolol
• Cilazapril
• Delapril
• Enalapril
• Enalaprilat
• Eprosartan
• Esmolol
• Fosinopril
• Gentamicin
• Imidapril
• Irbesartan
• Labetalol
• Levobunolol
• Lisinopril
• Losartan
• Metipranolol
• Metoprolol
• Moexipril
• Nadolol
• Nebivolol
• Olmesartan
• Oxprenolol
• Penbutolol
• Pentopril
• Perindopril
• Pindolol
• Practolol
• Propranolol
• Quinapril
• Ramipril
• Sotalol
• Spirapril
• Telmisartan
• Temocapril
• Timolol
• Trandolapril
• Valsartan
• Zofenopril

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Bleeding problems or
• Blood clots or
• Dehydration or
• Depression or other mental changes or
• Edema (fluid retention or body swelling) or
• Heart attack, recent or
• Heart disease (eg, congestive heart failure) or
• Hypertension (high blood pressure) or
• Hyperkalemia (high potassium levels in the blood) or
• Kidney disease or
• Liver disease (eg, hepatitis), history of or
• Parkinson's disease or
• Seizures or epilepsy, history of or
• Stomach or intestinal ulcers or bleeding, history of or
• Stroke, history of—Use with caution. May make these conditions worse.

• Aspirin-sensitive asthma, history of or
• Aspirin sensitivity, history of—Should not be used in patients with these conditions.

• Heart surgery (eg, coronary artery bypass graft [CABG] surgery)—Should not be used to relieve pain right before or after the surgery.

Applies to indomethacin: compounding powder, intravenous powder for injection, oral capsule, oral capsule extended release, oral suspension, rectal suppository

Gastrointestinal

Very common (10% or more): Nausea (up to 34%), vomiting (up to 12%)
Common (1% to 10%): Constipation, diarrhea, dyspepsia, upper abdominal pain, abdominal pain/distress, indigestion, heartburn, epigastric pain, gastrointestinal (GI) bleeding, gastrointestinal perforation, necrotizing enterocolitis
Uncommon (0.1% to 1%): Anorexia, bloating/distention, flatulence, peptic ulcer, gastroenteritis, rectal bleeding, proctitis, ulcerations/perforations/hemorrhage of the esophagus, stomach, duodenum, or small and large intestines, intestinal ulceration, stenosis, obstruction, development of ulcerative colitis, development of regional ileitis, ulcerative stomatitis, intestinal strictures
Frequency not reported: Gastric perforation, gastritis, bleeding from sigmoid colon, perforation of existing sigmoid lesions, tenesmus, irritation of rectal mucosa, rectal burning/pain, rectal itching/discomfort, glossitis, esophageal lesions, tenesmus

Patent Ductus Arteriosus:
Common (1% to 10%): GI bleeding, GI perforation, necrotizing enterocolitis
Frequency not reported: Gross/microscopic bleeding into gastrointestinal tract, vomiting, abdominal distention, transient ileus, gastric perforation, localized perforations of small/large intestines, melena[Ref]

Hepatic

Borderline elevations of 1 or more liver function tests can occur in up to 15% of patients taking NSAIDs, including this drug. These elevations may progress, remain unchanged, or may be transient with continued treatment. Elevations of ALT or AST of 3 or more times the upper limit of normal have been reported in about 1% of patients in clinical trials with NSAIDs. Rare cases of severe hepatic reactions, including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure, some with fatal outcomes, have been reported.

Pediatric patients: There have been cases of hepatotoxicity, including fatalities, in pediatric patients with juvenile rheumatoid arthritis.[Ref]

Uncommon (0.1% to 1%): Toxic hepatitis, jaundice, elevated ALT/AST
Frequency not reported: Cholestasis, abnormal liver function[Ref]

Renal

In controlled clinical trials, renal dysfunction occurred statistically significantly more frequently during IV use in neonates than in those treated with placebo. Renal dysfunction has been reported in 41% of neonates and included at least 1 of the following: reduced urinary output, reduced urine sodium, chloride, or potassium; reduced urine osmolality, free water clearance, or GFR; elevated serum creatinine or BUN; or uremia.[Ref]

Uncommon (0.1% to 1%): Nephrotic syndrome, interstitial nephritis, elevated BUN, renal insufficiency, renal failure

Patent Ductus Arteriosus:
Very common (10% or more): Renal dysfunction (41%)
Frequency not reported: Elevated serum creatinine, renal failure, elevated BUN[Ref]

Metabolic

Common (1% to 10%): Decreased appetite
Uncommon (0.1% to 1%): Hyperglycemia, hyperkalemia, glycosuria, weight gain, fluid retention

Patent Ductus Arteriosus:
Common (1% to 10%): Hyponatremia, elevated serum potassium
Frequency not reported: Reduction in blood sugar/hypoglycemia, weight gain/fluid retention, metabolic acidosis, metabolic alkalosis[Ref]

Hematologic

Uncommon (0.1% to 1%): Leukopenia, bone marrow depression, anemia secondary to obvious or occult GI bleeding, aplastic anemia, hemolytic anemia, agranulocytosis, thrombocytopenic purpura, disseminated intravascular coagulation
Frequency not reported: Leukemia, blood dyscrasias/hematopoietic disorders, neutropenia

Patent Ductus Arteriosus:
Common (1% to 10%): Bleeding
Frequency not reported: Disseminated intravascular coagulation, decreased platelet aggregation, thrombocytopenia[Ref]

In a double blind placebo controlled trial of 405 premature infants weighing less than or equal to 1750 g with evidence of large ductal shunting, there was statistically significant greater incidence of bleeding problems, including gross or microscopic bleeding in GI tract, oozing from skin after needle stick, pulmonary hemorrhage, and disseminated intravascular coagulopathy in infants treated with this drug (n=206). There was no statistically significant difference between treatment groups of intracranial hemorrhage.[Ref]

Nervous system

Very common (10% or more): Headache (up to 16%), dizziness (up to 15%)
Common (1% to 10%): Presyncope, somnolence, syncope, intracranial bleeding, fainting
Uncommon (0.1% to 1%): Drowsiness, lightheadedness, paresthesia, aggravation of epilepsy and Parkinsonism, coma, peripheral neuropathy, convulsion, dysarthria, aseptic meningitis, optic neuritis

Patent Ductus Arteriosus:
Very common (10% or more): Intraventricular hemorrhage (up to 14.3%), intracranial hemorrhage (up to 10.5%)
Common (1% to 10%): Intracranial bleeding, periventricular leukomalacia[Ref]

Psychiatric

Common (1% to 10%): Depression, listlessness
Uncommon (0.1% to 1%): Anxiety, nervousness, insomnia, muzziness, psychic disturbances, psychotic episodes, mental confusion, depersonalization
Frequency not reported: Hallucinations[Ref]

Cardiovascular

Common (1% to 10%): Hot flush
Uncommon (0.1% to 1%): Congestive heart failure, hypertension, hypotension, tachycardia, chest pain, arrhythmia, palpitations, angiitis
Frequency not reported: Thrombophlebitis, rapid fall in blood pressure resembling shock, cardiac failure, thrombotic events

Patent Ductus Arteriosus:
Frequency not reported: Bradycardia, hypertension, cardiac failure[Ref]

Dermatologic

Common (1% to 10%): Pruritus, rash, sweating/hyperhidrosis, flushing, urticaria
Uncommon (0.1% to 1%): Petechiae, ecchymosis, exfoliative dermatitis, erythema nodosum, loss of hair/alopecia, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, angioedema, purpura
Very rare (less than 0.01%): Eczema
Frequency not reported: Fulminant necrotizing fasciitis, photosensitivity[Ref]

Hypersensitivity

Uncommon (0.1% to 1%): Acute anaphylaxis
Very rare (less than 0.01%): Allergy-induced vasculitis
Frequency not reported: Hypersensitivity reactions

Patent Ductus Arteriosus:
Frequency not reported: Hypersensitivity reactions[Ref]

Ocular

Uncommon (0.1% to 1%): Corneal deposits, retinal disturbances, blurred vision, diplopia
Frequency not reported: Orbital/periorbital pain, double vision

Patent Ductus Arteriosus:
Very common (10% or more): Retinopathy of prematurity (up to 21.1%)
Common (1% to 10%): Retrolental fibroplasia
Uncommon (0.1% to 1%): Blindness[Ref]

Other

Very common (10% or more): Post-procedural edema (up to 26%), post-procedural hemorrhage (up to 11%)
Common (1% to 10%): Post-procedural swelling, vertigo, fatigue, malaise, tinnitus, asthenia, exhaustion
Uncommon (0.1% to 1%): Hearing disturbances, deafness, edema, fever
Postmarketing reports: Exacerbation of infection

Patent Ductus Arteriosus:
Frequency not reported: Exacerbation of infection, edema[Ref]

General

The most frequently reported adverse effects were nausea, headache, dizziness, vomiting, constipation, pruritus, diarrhea, dyspepsia, presyncope, rash, upper abdominal pain, somnolence, pruritus, hyperhidrosis, decreased appetite, hot flush, and syncope.

Patent Ductus Arteriosus: The most frequently reported adverse effects were bleeding problems, transient oliguria, and elevated serum creatinine.[Ref]

Genitourinary

Uncommon (0.1% to 1%): Hematuria, vaginal bleeding, proteinuria, breast enlargement/tenderness, gynecomastia
Frequency not reported: Urinary frequency

Patent Ductus Arteriosus:
Very common (10% or more): Oliguria (44%)
Frequency not reported: Transient oliguria[Ref]

Information from various medical literature states that 44% of infants treated with this drug had oliguria. Renal dysfunction appears to be dose related; renal function usually returns to normal 24 hours following discontinuation.[Ref]

Local

Patent Ductus Arteriosus:
Frequency not reported: Bleeding/oozing from skin following needle puncture[Ref]

Musculoskeletal

Uncommon (0.1% to 1%): Muscle weakness, involuntary muscle movements
Frequency not reported: Hypercreatininemia, acceleration of cartilage degeneration[Ref]

Respiratory

Uncommon (0.1% to 1%): Dyspnea, acute respiratory distress, asthma, pulmonary edema, epistaxis
Frequency not reported: Bronchospasm, pulmonary eosinophilia, alveolitis

Patent Ductus Arteriosus:
Frequency not reported: Pulmonary hemorrhage, pneumothorax, pulmonary hypertension, apnea, exacerbation of preexisting pulmonary infection[Ref]

Some side effects of Indocin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.