Indomethacin

OVERVIEW

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that is widely used to reduce various symptoms associated with inflammation and pain.

DOSAGE

Adult Dosage

Rheumatoid Arthritis, Ankylosing Spondylitis, Osteoarthritis

Immediate-release capsules:

Starting dose: 25 mg taken 2 to 3 times daily.

Maintenance dose: Increase by 25-50 inches per week as needed, up to a maximum of 200 mg daily.

Extended-release capsules:

75 mg once or twice daily (maximum 150 mg per day).

Acute Gouty Arthritis

Take 50 mg three times daily until symptoms improve.

Bursitis or Tendinitis

Immediate-release: 75 to 150 mg daily in divided doses (3 or 4 doses).

Extended-release: 75 mg once or twice daily (maximum 150 mg daily).

Acute Pain Management

Typically, the dose ranges from 20 to 40 mg, taken 2 to 3 times a day, depending on the severity of the pain.

Rectal Suppositories

50 mg rectally up to three times daily for various conditions.

Pediatric Dosage

Dosing for children is typically based on weight.

Immediate-release capsules: Starting dose may be 1-2 mg/kg per day, divided into 2-4 doses.

Maximum dose: 3 mg/kg per day or 200 mg per day, whichever is less.

MECHANISM OF ACTION

Inhibition of Cyclooxygenase Enzymes

COX-1: This enzyme is involved in the production of protective prostaglandins that maintain the gastric mucosa, support kidney function, and facilitate platelet aggregation.

COX-2: This enzyme is usually induced during inflammatory processes and is responsible for the production of prostaglandins that increase pain and inflammation.

Reduction of Prostaglandin Synthesis

Decreased inflammation: Lower levels of inflammation-causing prostaglandins result in decreased swelling and pain.

Pain relief: The analgesic effect is due to decreased sensitivity of pain receptors to inflammatory mediators.

Antipyretic effect: Indomethacin can reduce fever by acting on the hypothalamus to increase peripheral blood flow and promote heat dissipation.

Additional Mechanisms

Vasoconstrictor: It may have potent vasoconstrictor effects, particularly within the cerebral circulation, which may be beneficial in the treatment of certain headache disorders.

Inhibition of phospholipase A2: This enzyme releases arachidonic acid from membrane phospholipids, which further enhances its anti-inflammatory effects.

Antiviral activity: Preliminary studies suggest that indomethacin may have antiviral properties by reducing viral replication, although more research is needed in this area.

ADVERSE DRUG REACTIONS

Cardiovascular events: Indomethacin may increase the risk of serious cardiovascular events, including heart attack and stroke. This risk can occur at any time during treatment but is more pronounced with long-term use or in patients with pre-existing cardiac conditions. It is contraindicated in the setting of coronary artery bypass graft (CABG) surgery because of this risk.

Gastrointestinal Issues:

• Ulceration
• Bleeding (which can be fatal)
• Perforation of the stomach or intestines

Kidney problems: Indomethacin can cause damage to the kidneys, including changes in urine output, swelling, and rapid weight gain. Patients should be monitored for signs of kidney dysfunction.

Liver damage: Indomethacin can cause serious liver disease. Symptoms include persistent nausea/vomiting, loss of appetite, dark urine, severe abdominal pain, and jaundice (yellowing of the skin or eyes).

Allergic reactions: Serious allergic reactions may occur, including symptoms such as hives, difficulty breathing, swelling of the face or throat, and severe skin reactions (e.g., blistering or peeling of the skin) that may require immediate medical attention.

Central nervous system: Headache, dizziness, drowsiness, and vertigo are common. Some patients may experience mood changes or confusion.

Gastrointestinal symptoms: Stomach upset, heartburn, nausea, vomiting, and diarrhea are common side effects. These symptoms can be mild but can lead to more serious GI problems if not monitored.

Fluid retention: Indomethacin can cause fluid retention and edema, which may aggravate heart failure in sensitive individuals.

Hypertension: Indomethacin may increase blood pressure; regular monitoring is advised.

Asthma exacerbation: In patients with a history of asthma or allergy to NSAIDs or aspirin, indomethacin may make symptoms worse and should be used with caution.

DRUG-DRUG INTERACTIONS

Anticoagulants: Indomethacin may increase the effects of anticoagulants (eg, warfarin, apixaban), increasing the risk of bleeding. Close monitoring is necessary when these drugs are used together.

Other NSAIDs: The risk of gastrointestinal bleeding and ulceration may be increased when indomethacin is used concomitantly with other NSAIDs (e.g., ibuprofen, naproxen). It is generally recommended to avoid using multiple NSAIDs simultaneously.

ACE Inhibitors and ARBs: Indomethacin may decrease the effectiveness of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), which may lead to hypertension and worsening of kidney function.

Diuretics: The use of indomethacin with diuretics may reduce diuretic efficacy and increase the risk of kidney damage, especially in patients with pre-existing kidney problems.

Lithium: Indomethacin may increase the levels of lithium in the blood, which may lead to lithium toxicity. It is important to monitor lithium levels when these medications are used together.

Methotrexate: Co-administration of indomethacin may increase plasma concentrations of methotrexate, which may increase the risk of methotrexate toxicity. Regular monitoring for signs of toxicity is recommended.

Corticosteroids: Combining corticosteroids with indomethacin increases the risk of gastrointestinal ulceration and bleeding.

Selective Serotonin Reuptake Inhibitors (SSRIs): Using SSRIs (eg, sertraline, fluoxetine) with indomethacin may increase the risk of gastrointestinal bleeding.

Antidepressants: Some antidepressant medications such as venlafaxine may also react with indomethacin, so caution is needed.

Alcohol and Food Interactions: There are known interactions between indomethacin and alcohol, which can increase gastrointestinal side effects and increase the risk of bleeding. Patients are generally advised to limit alcohol intake while taking this medication.

USE

Rheumatoid arthritis: Indomethacin is commonly prescribed to reduce pain and inflammation associated with rheumatoid arthritis.

Osteoarthritis: It helps in managing symptoms like pain and stiffness in patients suffering from osteoarthritis.

Ankylosing spondylitis: This medicine is used to treat inflammation and pain associated with ankylosing spondylitis, a type of inflammatory arthritis affecting the spine.

Gouty arthritis: Indomethacin is effective in treating acute attacks of gout by reducing inflammation and pain.

Bursitis and Tendonitis: It is indicated for the treatment of acute painful shoulder conditions including bursitis and tendonitis.

Headaches: Because of its ability to reduce cerebral blood flow and intracranial pressure, it is uniquely effective in treating certain types of headaches, especially indomethacin-sensitive headaches.