Indomethacin

Camber Pharmaceuticals, Inc.
Hetero Labs Limited

Indomethacin Extended Release Capsules, USPRx only

FULL PRESCRIBING INFORMATION: CONTENTS*

• BOXED WARNING
• INDOMETHACIN DESCRIPTION
• CLINICAL PHARMACOLOGY
• INDICATIONS & USAGE
• INDOMETHACIN CONTRAINDICATIONS
• WARNINGS
  • Cardiovascular Effects
  • Gastrointestinal Effects
  • Renal Effects
  • Anaphylactoid Reactions
  • Skin Reactions
  • Pregnancy
• PRECAUTIONS
  • General Precautions
  • Hepatic Effects
  • Hematological Effects
  • Preexisting Asthma
  • Information for Patients
  • Laboratory Tests
  • Drug Interactions
  • Drug & OR Laboratory Test Interactions
  • Carcinogenesis & Mutagenesis & Impairment Of Fertility
  • Pregnancy
  • Labor & Delivery
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• INDOMETHACIN ADVERSE REACTIONS
• OVERDOSAGE
• DOSAGE & ADMINISTRATION
• HOW SUPPLIED
• SPL MEDGUIDE
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

FULL PRESCRIBING INFORMATION

INDOMETHACIN DESCRIPTION

CLINICAL PHARMACOLOGY

Indomethacin is a nonsteroidal drug with anti-inflammatory, antipyretic and analgesic properties. Its mode of action, like that of other anti-inflammatory drugs, is not known. However, its therapeutic action is not due to pituitary-adrenal stimulation.

Indomethacin is a potent inhibitor of prostaglandin synthesis in vitro. Concentrations are reached during therapy which have been demonstrated to have an effect in vivo as well. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Moreover, prostaglandins are known to be among the mediators of inflammation. Since indomethacin is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues.

Indomethacin has been shown to be an effective anti-inflammatory agent, appropriate for long-term use in rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.

Indomethacin affords relief of symptoms; it does not alter the progressive course of the underlying disease.

Indomethacin suppresses inflammation in rheumatoid arthritis as demonstrated by relief of pain and reduction of fever, swelling and tenderness. Improvement in patients treated with indomethacin 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.

Indomethacin has been reported to diminish basal and CO₂ stimulated cerebral blood flow in healthy volunteers following acute oral and intravenous administration. In one study, after one week of treatment with orally administered indomethacin, this effect on basal cerebral blood flow had disappeared. The clinical significance of this effect has not been established.

INDICATIONS & USAGE

Carefully consider the potential benefits and risks of indomethacin extended-release capsules and other treatment options before deciding to use indomethacin extended-release capsules. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS ).

Indomethacin extended-release capsules have been found effective in active stages of the following:

INDOMETHACIN CONTRAINDICATIONS

WARNINGS

Cardiovascular Effects

Gastrointestinal Effects

Risk of Ulceration,Bleeding and Perforation

Renal Effects

Anaphylactoid Reactions

Skin Reactions

NSAIDs, including indomethacin extended-release capsules, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Pregnancy

PRECAUTIONS

General Precautions

Indomethacin extended-release capsules cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids.

The pharmacological activity of indomethacin extended-release capsules in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.

Hepatic Effects

Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs, including indomethacin extended-release capsules. 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 values has occured, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with indomethacin extended-release capsules. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), indomethacin extended-release capsules should be discontinued.

Hematological Effects

Preexisting Asthma

Information for Patients

Patients should be informed of the following information before initiating therapy with a NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.

7. In late pregnancy, as with other NSAIDs, indomethacin extended-release capsules should be avoided because it will cause premature closure of the ductus arteriosus.

Laboratory Tests

Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs should have their CBC and a chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, indomethacin extended-release capsules should be discontinued.

Drug Interactions

Drug & OR Laboratory Test Interactions

Carcinogenesis & Mutagenesis & Impairment Of Fertility

Pregnancy

Labor & Delivery

Nursing Mothers

Pediatric Use

Geriatric Use

INDOMETHACIN ADVERSE REACTIONS

^*Reactions occurring in 3% to 9% of patients treated with indomethacin. (Those reactions occurring in less than 3% of the patients are unmarked.)

Hematologic : Although there have been several reports of leukemia, the supporting information is weak.

Genitourinary : Urinary frequency

OVERDOSAGE

DOSAGE & ADMINISTRATION

HOW SUPPLIED

SPL MEDGUIDE

These are not all the side effects with NSAID medicines. Talk to your healthcare provider or pharmacist for more information about NSAID medicines.

  Other information about Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)

 ·     Aspirin is an NSAID medicine but it does not increase the chance of a heart attack.Aspirin can cause bleeding in the brain, stomach, and intestines. Aspirin can alsocause ulcers in the stomach and intestines.

·     Some of these NSAID medicines are sold in lower doses without a prescription(over-the-counter). Talk to your healthcare provider before using over-the-counterNSAIDS for more than 10 days.

NSAID medicines that need a prescription

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL