INDOMETHACIN (indomethacin)

There are 5 contraindications. Absolute contraindication.

Contraindication List
Aspirin exacerbated respiratory disease
Cerebrovascular accident
Post-operative from CABG surgery
Pregnancy
Renal transplant

There are 23 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Blurred vision
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Corneal deposits
Depression
Diverticular disease
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
Hemorrhoids
History of kidney donation
Hyperkalemia
Hypertension
Increased risk of bleeding due to coagulation disorder
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Proctitis
Rectal bleeding
Systemic mastocytosis
Thrombotic disorder
Ulcerative colitis

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Asthma
Disease of liver
Parkinsonism
Psychotic disorder
Stomatitis

There are 75 severe adverse reactions.

More Frequent	Less Frequent
Edema	Depression

Rare/Very Rare

Abnormal hepatic function tests Abnormal vaginal bleeding Acute eruptions of skin Acute myocardial infarction Acute pancreatitis Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angioedema Aphthous stomatitis Aplastic anemia Bloody stools Bloody vomit Blurred vision Bronchospastic pulmonary disease Bruising Bullous dermatitis Cardiac arrhythmia Cerebrovascular accident Chest pain Chest tightness Chronic heart failure Colitis Contact dermatitis Corneal deposits Cystitis Diplopia Disseminated intravascular coagulation DRESS syndrome Drug-induced hepatitis Dysarthria Dyspnea Epistaxis Erythema multiforme Esophageal ulcer Esophagitis Exfoliative dermatitis Gastric ulcer Gastroenteritis Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Hallucinations Hematuria Hemolytic anemia Hepatitis Hyperkalemia Hypertension Interstitial nephritis Jaundice Kidney disease with reduction in glomerular filtration rate (GFr) Laryngeal edema Leukopenia Nephrotic syndrome Nephrotoxicity Ocular pain Pancytopenia Peptic ulcer Proteinuria Pulmonary edema Rectal bleeding Renal failure Seizure disorder Skin rash Stevens-johnson syndrome Syncope Thrombocytopenic disorder Toxic epidermal necrolysis Urticaria Vasculitis Visual changes Wheezing

There are 31 less severe adverse reactions.

More Frequent	Less Frequent
Acute abdominal pain Dizziness Dyspepsia Gastric acid hypersecretory conditions Headache disorder Nausea	Constipation Diarrhea Drowsy Hyperhidrosis Tinnitus Vomiting

Rare/Very Rare
Abdominal distension Acute cognitive impairment Anorexia Body fluid retention Ecchymosis Fatigue Flatulence Flushing Hearing loss Insomnia Irritability Mouth irritation Nervousness Palpitations Peripheral neuropathy Pruritus of skin Skin photosensitivity Tachycardia Xerostomia

Use of NSAIAs during pregnancy at about 30 weeks' gestation or later can cause premature closure of the fetal ductus arteriosus, and use at about 20 weeks' gestation or later has been associated with fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, use of NSAIAs should be avoided in pregnant women at about 30 weeks' gestation or later; if NSAIA therapy is necessary between about 20 and 30 weeks' gestation, the lowest effective dosage and shortest possible duration of treatment should be used. Monitoring of amniotic fluid volume via ultrasound examination should be considered if the duration of NSAIA treatment exceeds 48 hours; if oligohydramnios occurs, the drug should be discontinued and follow-up instituted according to clinical practice.

Pregnant women should be advised to avoid use of NSAIAs beginning at 20 weeks' gestation unless otherwise advised by a clinician; they should be informed that NSAIAs should be avoided beginning at 30 weeks' gestation because of the risk of premature closure of the fetal ductus arteriosus and that monitoring for oligohydramnios may be necessary if NSAIA therapy is required for longer than 48 hours' duration between about 20 and 30 weeks' gestation. Fetal renal dysfunction resulting in oligohydramnios and, in some cases, neonatal renal impairment has been observed, on average, following days to weeks of maternal NSAIA use, although oligohydramnios has been observed infrequently as early as 48 hours after initiation of NSAIA therapy. Oligohydramnios is often, but not always, reversible following discontinuance of NSAIA therapy.

Complications of prolonged oligohydramnios may include limb contracture and delayed lung maturation. A limited number of case reports have described maternal NSAIA use and neonatal renal dysfunction, in some cases irreversible, without oligohydramnios. Some cases of neonatal renal dysfunction have required treatment with invasive procedures such as exchange transfusion or dialysis.

Methodologic limitations of these postmarketing studies and case reports include lack of a control group; limited information regarding dosage, duration, and timing of drug exposure; and concomitant use of other drugs. These limitations preclude establishing a reliable estimate of the risk of adverse fetal and neonatal outcomes with maternal NSAIA use. Available data on neonatal outcomes generally involved preterm infants, and the extent to which certain reported risks can be generalized to full-term infants is uncertain.

Animal data indicate that prostaglandins have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, inhibitors of prostaglandin synthesis, such as indomethacin, were associated with increased pre- and post-implantation losses. Prostaglandins also have an important role in fetal kidney development.

In animal studies, inhibitors of prostaglandin synthesis impaired kidney development at clinically relevant doses. Reproduction studies in mice and rats at dosages of 0.5-4 mg/kg daily have revealed no increase in fetal malformations other than retarded fetal ossification, which was observed at the highest dosage and was attributed to decreased average fetal weight.

Administration of indomethacin to mice and rats during the last 3 days of gestation at a dosage of 4 mg/kg daily was associated with an increased incidence of neuronal necrosis in the diencephalon in live-born fetuses; no increase in neuronal necrosis was observed at a dosage of 2 mg/kg daily, and administration of the drug to the offspring during the first 3 days of life at a dosage of 0.5 or 4 mg/kg daily did not result in an increase in neuronal necrosis. The effects of indomethacin on labor and delivery are unknown. In studies with rats, drugs that inhibit prostaglandin synthesis, including NSAIAs, increased the incidence of dystocia, delayed parturition, and increased the incidence of stillbirth.

Based on available data, indomethacin may be present in human milk. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for indomethacin and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Indomethacin should be used with caution in geriatric individuals >=65 years of age since increasing age may be associated with increased risk of adverse reactions. Geriatric individuals appear to be at a greater risk for fatal adverse GI effects (See Cautions: GI Effects). Indomethacin may cause confusion or, rarely, psychosis; clinicians should remain alert to the possibility of such adverse reactions in geriatric individuals.

Indomethacin is eliminated mainly by the kidneys and individuals with renal impairment may be at increased risk for toxic reactions to the drug. Because geriatric patients frequently have decreased renal function, particular attention should be paid to indomethacin dosage and it may be useful to monitor renal function in these patients.