Indomethacin

(in doh METH a sin)

Introduced: 1963

Prescription: USA: Yes Canada: Yes

Available as Generic: USA: Yes Canada: No

Class: Mild analgesic, antiinflammatory

Controlled Drug: USA: No Canada: No

Brand Names: Apo-Indomethacin, Indameth, Indocid, Indocid PDA, Indocin, Indocin-SR, Novomethacin

Principal Uses

As a Single Drug Product: Used primarily to relieve mild to moderately severe pain associated with (1) musculoskeletal injuries; (2) acute and chronic gout, rheumatoid arthritis and osteoarthritis; (3) dental, obstetrical and orthopedic surgery; (4) menstrual cramps; and (5) vascular (migrainelike) headaches.

How This Drug Works: Not completely established. It is thought that this drug reduces the tissue concentrations of prostaglandins (and related compounds), chemicals involved in the production of inflammation and pain.

Available Dosage Forms and Strengths

Capsules — 25 mg, 50 mg, 75 mg Capsules, prolonged-action — 75 mg

Oral suspension — 25 mg per 5-ml teaspoonful Suppositories — 50 mg

Usual Adult Dosage Range: For arthritis and related conditions: 25 to 50

mg 2 to 4 times daily. If needed and tolerated, dose may be increased by 25 or 50 mg/day at intervals of 1 week. For acute gout: 100 mg initially; then 50 mg 3 times/day until pain is relieved. Total daily dosage should not exceed 200 mg. Note: Actual dosage and administration schedule must be determined by the physician for each patient individually.

Dosing Instructions: Take with or following food to prevent stomach irritation. Take with a full glass of water and remain upright (do not lie down) for 30 minutes. The regular capsule may be opened for adminis­tration, but not the prolonged-action capsule.

Usual Duration of Use: Continual use on a regular schedule for 1 to 2 weeks is usually necessary to determine this drug's effectiveness in relieving the discomfort of arthritis. The usual length of treatment for bursitis or tendinitis is 7 to 14 days. Long-term use requires supervision and periodic evaluation by the physician. Consult your physician on a regular basis.

This Drug Should Not Be Taken If

• you have had an allergic reaction to it previously.

• you are subject to asthma or nasal polyps caused by aspirin.

• you are pregnant or breast-feeding.

• you have active peptic ulcer disease or any form of gastrointestinal ulceration or bleeding.

• you have a bleeding disorder or a blood cell disorder.

• you have severe impairment of kidney function.

Inform Your Physician Before Taking This Drug If

• you are allergic to aspirin or to other aspirin substitutes.

• you have a history of peptic ulcer disease, Crohn's disease, ulcerative colitis or any type of bleeding disorder.

• you have a history of epilepsy, Parkinson's disease or mental illness (psychosis).

• you have impaired liver or kidney function.

• you have high blood pressure or a history of heart failure.

• you are taking any of the following: acetaminophen, aspirin or other aspirin substitutes, anticoagulants, oral antidiabetic drugs.

Possible Side-Effects (natural, expected and unavoidable drug actions) Drowsiness, ringing in ears, fluid retention.

Possible Adverse Effects (unusual, unexpected and infrequent reactions) If any of the following develop, consult your physician promptly for guidance.

Mild Adverse Effects

Allergic Reactions: Skin rash, hives, itching, localized swellings of face and/or extremities.

Headache, dizziness, feelings of detachment.

Mouth sores, indigestion, nausea, vomiting, diarrhea.

Temporary loss of hair. Serious Adverse Effects

Allergic Reactions: Asthma, difficult breathing, mouth irritation.

Blurred vision, confusion, depression.

Active peptic ulcer, with or without bleeding.

Liver damage with jaundice .

Kidney damage with painful urination, bloody urine, reduced urine for­mation.

Rare bone marrow depression - fatigue, weakness, fever, sore throat, abnormal bleeding or bruising.

Peripheral neuritis.

Possible Effects on Sexual Function

Enlargement and tenderness of both male and female breasts. Nonmenstrual vaginal bleeding.

Possible Delayed Adverse Effects: Mild anemia due to "silent" blood loss from the stomach (less than that caused by aspirin).

Adverse Effects That May Mimic Natural Diseases or Disorders

Liver reaction may suggest viral hepatitis.

Natural Diseases or Disorders That May Be Activated by This Drug

Peptic ulcer disease, ulcerative colitis.

Possible Effects on Laboratory Tests

Complete blood cell counts: decreased red cells, hemoglobin, white cells and platelets.

Prothrombin time: increased.

Blood lithium level: increased.

Liver function tests: increased liver enzymes (ALT/GPT, AST/GOT and

alkaline phosphatase), increased bilirubin. Kidney function tests: increased blood creatinine and urea nitrogen

(BUN) levels (kidney damage). Fecal occult blood test: positive.

CAUTION

1. Dosage should always be limited to the smallest amount that produces reasonable improvement.

2. This drug may mask early indications of infection. Inform your physician if you think you are developing an infection of any kind.

Precautions for Use

By Infants and Children: This drug frequently causes impairment of kidney function in infants. Fatal liver reactions have occurred in children between 6 and 12 years of age; avoid the use of this drug in this age group.

By Those over 60 Years of Age: Adverse effects are very common in this age group. Small doses are advisable until tolerance is determined. Observe for any indications of liver or kidney toxicity, fluid retention, dizziness, confusion, impaired memory, depression, peptic ulcer or diarrhea, often with rectal bleeding.

Advisability of Use During Pregnancy

Pregnancy Category: D (tentative). See Pregnancy Code inside back cover.

Animal studies: Significant toxicity and birth defects reported in mice and rats.

Human studies: Information from adequate studies of pregnant women is not available. However, birth defects have been attributed to the use of this drug during pregnancy.

The manufacturer recommends that this drug not be taken during pregnancy.

Advisability of Use if Breast-Feeding

Presence of this drug in breast milk: Yes. Avoid drug or refrain from nursing.

The manufacturer recommends that this drug not be taken while breast feeding.

Habit-Forming Potential: None.

Effects of Overdosage: Drowsiness, agitation, confusion, nausea, vomiting, diarrhea, disorientation, seizures, coma.

Possible Effects of Long-Term Use: Eye changes: deposits in the cornea, alterations in the retina.

Suggested Periodic Examinations While Taking This Drug (at physician's

discretion)

Complete blood cell counts, liver and kidney function tests, complete eye examinations if vision is altered in any way.

While Taking This Drug, Observe the Following

Foods: No restrictions.

Nutritional Support: Take 50 mg of vitamin С (ascorbic acid) daily.

Beverages: No restrictions. May be taken with milk.

> Alcohol: Use with caution. The irritant action of alcohol on the stomach

lining, added to the irritant action of this drug in sensitive individuals, can increase the risk of stomach ulceration and/or bleeding. Tobacco Smoking: No interactions expected.

> Other Drugs

Indomethacin may increase the effects of

• acetaminophen (Tylenol, etc.), and increase the risk of kidney damage; avoid prolonged use of this combination.

• anticoagulants (Coumadin, etc.), and increase the risk of bleeding; monitor prothrombin time, adjust dose accordingly.

• lithium, and cause lithium toxicity. Indomethacin may decrease the effects of

• beta blocker drugs (see Drug Class, Section Four), and reduce their antihypertensive effectiveness.

• bumetanide (Bumex).

• captopril (Capoten).

• ethacrynic acid (Edecrin).

• furosemide (Lasix).

Indomethacin taken concurrently with the following drugs may in­crease the risk of bleeding; avoid these combinations: aspirin.

diflunisal (Dolobid). dipyridamole (Persantine). sulfinpyrazone (Anturane). valproic acid (Depakene).

Driving, Hazardous Activities: This drug may cause drowsiness, dizziness or impaired vision. Restrict activities as necessary.

Aviation Note: The use of this drug may be a disqualification for piloting. Consult a designated Aviation Medical Examiner.

Exposure to Sun: No restrictions.

TEXT 12. Read the following text and choose the abstract about advisability of use if breast-feeding.