* Administration * Carefully consider the potential benefits and risks of indomethacin and other treatment options before deciding to use Indomethacin Suppositories. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals . * After observing the response to initial therapy with Indomethacin Suppositories, the dose and frequency should be adjusted to suit an individual patient’s needs. * Indomethacin is available as 50 mg suppositories for rectal use. This section makes reference to capsule dosage for guidance in using suppositories.
* Adverse reactions appear to correlate with the size of the dose of indomethacin in most patients but not all. Therefore, every effort should be made to determine the smallest effective dosage for the individual patient. * Adult dose * Dosage Recommendations for Active Stages of the Following: * Moderate to severe rheumatoid arthritis including acute flares of chronic disease; moderate to severe ankylosing spondylitis; and moderate to severe osteoarthritis. Suggested Dosage: 1. Indomethacin capsules 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. 2. 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. 3. If minor adverse effects develop as the dosage is increased, reduce the dosage rapidly to a tolerated dose and observe the patient closely. 4. 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. 5.
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, indomethacin should be used with greater care in the elderly. * Acute painful shoulder (bursitis and/or tendonitis). 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. * Acute gouty arthritis Suggested Dosage:
Indomethacin capsules 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. * Pediatric Dosage * Safety and effectiveness in pediatric patients 14 years of age and younger has not been established. * Indomethacin 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.
* 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 mg/kg/day given in divided doses. Maximum daily dosage should not exceed 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. * Overdose warning * 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.
* Allergic warning * allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue. * A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash,itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing * Liver demage warning * Damage or injury to the liver caused by exposure to indomethacin. Indomethacin is a relatively uncommon cause of liver damage. Symptoms vary depending on the degree of exposure and hence extent of the liver damage or injury.
Mild liver damage may cause few if any symptoms whereas severe damage can ultimately result in liver failure. Symptoms may be acute, subacute or chronic depending on the severity of the exposure. Factors such as age, race, gender, overall health and underlying liver problems may also influence a person’s risk of developing liver problems and the severity of the symptoms. More detailed information about the symptoms, causes, and treatments of Drug-induced liver damage \ SAFETY DATA * Allergy and hypersensitivity * Allergy.
* Severe allergic reaction (rash, hiver, itching, difficulty breathing, tightness in the chest, swelling of the mouth, face, lips or tongue), blood in vomit, stool or urine, dark,tarry stools, decreased urination, slow heartbear, unusual bruising or bleeding, unusual weight gain. * Hypersensitivity * Hypersensitivity reactions include urticaria, angioedema, dyspnea, bronchospasm, hypotension, fever, angiitis, arthropathy, purpura, and anaphylaxis. * Gastrointestinal effects * Gastrointestinal side effects reported frequently include dyspepsia, nausea, abdominal pain, and diarrhea.
Constipation, anorexia, flatulence, gastroenteritis, proctitis and stomatitis have been reported. More serious gastrointestinal hemorrhage, with or without perforation, ileal and colonic strictures, and pancreatitis. * Single and multiple ulcerations may occur in the esophagus, stomach, and duodenum, as well as in the small and large intestines, and may be fatal in some patients. In rare case, intestinal ulceration has been associated with stenosis and abstruction. * Patients with a history of serious gastrointestinal event or alcohol abuse are at increased risk for severe gastrointestinal side effects.
Indomethacin should be used with caution in these patients. * Indomethacin should be administered with food or antacids to reduce gastric irritation. * Hepatics effects * Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including indomethacin. 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 indomethacin. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g. , eosinophilia, rash, etc. ), indomethacin should be discontinued. * Pregnancy and laction * Pregnancy :- *
In late pregnancy, as with other NSAIDs, indomethacin should be avoided because it may cause premature closure of the ductus arteriosus. * Laction :- * In vitro data suggest that indomethacin passes into human milk by simple diffusion. The excretion of indomethacin into human milk was evaluated in 16 women treated with dose ranging from 0. 94 to 4. 29 mg/kg/day. All but one patient was less than 10 days post partum.
Milk concentration ranged from less than 20 mcg/L to 115 mcg. L and did not correlate with meternal dose. The median milk to meternal plasma concentrationratio was 0. 37. Plasma samples were obtained from seven nursing infants. In six infants, indomethacin plasma conxentration were below the level of detection (less than 20 mcg/L). in one infant, the plasma concentration was 47 mcg/L at approximately 1. 2 hours after nursing. Seizures have beem reported in a seven-day-old infant whose mother was treated with indomethasin in doses up to 200 mg per day during the puerperium.
In the absence of a definitive cause, the outhors speculated that the seizures were related to indomethacin exposure via breast milk. Causality in this case in unknown. * indomethacin is excreted in the milk of lactating mothers. Indomethacin not recommended by the manufactured for use in nursing mothers. * Renal effect * 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 overt 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, 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, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state * Pontential drug-drug interaction * Dogoxin * INDOCIN (indomethacin) given concomitantly with digoxin has been reported to increase the serum concentration and prolong the half-life of digoxin. Therefore, when INDOCIN (indomethacin) and digoxin are used concomitantly, serum digoxin levels should be closely monitored.
* NSAIDs * The concomitant use of INDOCIN (indomethacin) with other NSAIDs is not recommended due to the increased possibility of gastrointestinal toxicity, with little or no increase in efficacy. * ASPIRIN * When INDOCIN (indomethacin) is administered with aspirin, its protein binding is reduced, although the clearance of free INDOCIN (indomethacin) is not altered. The clinical significance of this interaction is not known. * The use of INDOCIN (indomethacin) in conjunction with aspirin or other salicylates is not recommended.
Controlled clinical studies have shown that the combined use of INDOCIN (indomethacin) and aspirin does not produce any greater therapeutic effect than the use of INDOCIN (indomethacin) alone. In a clinical study of the combined use of INDOCIN (indomethacin) 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%.