Indomethacin

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Generic Name of Indomethacin - Learn More

Indomethacin

Indomethacin Precaution - What You Need to Know

- Pregnancy: Indomethacin is contraindicated during the third trimester of pregnancy as it can cause premature closure of the ductus arteriosus in the fetus, leading to fetal pulmonary hypertension. During the first and second trimesters, it should only be used if the potential benefits outweigh the risks, under careful medical supervision.
- Breastfeeding: Indomethacin is excreted in breast milk, and while adverse effects on the infant are uncommon, it is generally recommended to avoid use in breastfeeding women unless absolutely necessary.
- Renal and Hepatic Impairment: Indomethacin should be used cautiously in patients with impaired renal or hepatic function. It can worsen renal function, leading to fluid retention and electrolyte imbalances. Regular monitoring of renal function is advised.
- Gastrointestinal Risk: As a nonsteroidal anti-inflammatory drug (NSAID), indomethacin carries a risk of gastrointestinal (GI) bleeding, ulceration, and perforation. The risk is higher in the elderly, those with a history of peptic ulcer disease, or concurrent use of anticoagulants or corticosteroids.
- Cardiovascular Risk: Indomethacin may increase the risk of cardiovascular events, including heart attack and stroke. It should be used with caution in patients with existing cardiovascular disease, and long-term use should be minimized in such individuals.
- Elderly Patients: Older adults are particularly at risk for side effects such as gastrointestinal bleeding, renal impairment, and cardiovascular events. Dosage should be adjusted, and close monitoring is necessary.
- Misuse and Dependency: While indomethacin is not typically associated with misuse or dependency, its prolonged use, especially at high doses, can lead to adverse health effects, such as renal or gastrointestinal complications.

Indomethacin Indication - Uses and Benefits

- Primary Indications:
- Rheumatoid Arthritis: Indomethacin is commonly prescribed to treat inflammatory conditions such as rheumatoid arthritis, where it reduces pain, swelling, and stiffness. It works by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the production of prostaglandins, which mediate inflammation and pain.
- Osteoarthritis: Indomethacin is used to manage pain and inflammation in osteoarthritis, improving joint function and mobility.
- Gout: It is frequently used to manage acute gout attacks, where its anti-inflammatory properties help reduce pain and swelling in affected joints.
- Ankylosing Spondylitis: Indomethacin can alleviate the pain and stiffness associated with ankylosing spondylitis, an inflammatory condition affecting the spine and sacroiliac joints.
- Off-label Uses:
- Patent Ductus Arteriosus (PDA): Indomethacin is used off-label to treat patent ductus arteriosus in preterm neonates by promoting the closure of the ductus arteriosus, a blood vessel that is supposed to close after birth.
- Bursitis and Tendonitis: It can be used off-label for inflammatory musculoskeletal conditions like bursitis and tendonitis, where it helps reduce inflammation and alleviate pain.
- Evidence-Based Context: Studies support the use of indomethacin in managing acute and chronic inflammatory conditions due to its potent anti-inflammatory and analgesic effects. However, its use is generally limited to short-term management due to its potential adverse effects on the gastrointestinal and renal systems.

Indomethacin Contraindications - Important Warnings

- Hypersensitivity: Indomethacin is contraindicated in patients with known hypersensitivity to indomethacin or other NSAIDs. It can cause serious allergic reactions such as anaphylaxis, including symptoms like hives, swelling, and difficulty breathing.
- Active Peptic Ulcer Disease: Indomethacin is contraindicated in patients with a history of gastrointestinal ulceration or active peptic ulcer disease due to its ability to cause or worsen GI bleeding and perforation.
- Severe Renal Impairment: In patients with severe renal impairment or renal failure, indomethacin should not be used as it can exacerbate kidney dysfunction and fluid retention.
- Severe Hepatic Dysfunction: This drug is contraindicated in individuals with severe hepatic dysfunction, as it can impair liver function and increase the risk of hepatotoxicity.
- Cardiovascular Disease: Indomethacin should be avoided in patients with significant cardiovascular disease or those with a history of myocardial infarction or stroke. Long-term use of NSAIDs, including indomethacin, increases the risk of heart attack, stroke, and other cardiovascular events.
- Third Trimester of Pregnancy: As mentioned, indomethacin should not be used in the third trimester of pregnancy due to the risk of fetal harm, including premature closure of the ductus arteriosus.
- Caution in Elderly: While not strictly a contraindication, indomethacin should be used with caution in elderly patients due to an increased risk of adverse gastrointestinal and cardiovascular effects.

Indomethacin Side Effects - What to Expect

- Common Side Effects:
- Gastrointestinal: Indomethacin is known to cause gastrointestinal distress, including nausea, dyspepsia, and abdominal pain. It can also increase the risk of ulcers, bleeding, or perforation in the stomach or intestines.
- Headache and Dizziness: Some patients experience headaches and dizziness, particularly when standing up quickly due to its blood pressure-lowering effect.
- Rash: A skin rash may develop as a side effect of indomethacin, usually mild but sometimes indicative of an allergic reaction.
- Fluid Retention and Edema: Due to its impact on renal function, indomethacin may cause fluid retention, leading to swelling in the legs and feet.
- Serious Side Effects:
- Gastrointestinal Bleeding: Severe bleeding, ulceration, or perforation of the gastrointestinal tract is a serious and potentially life-threatening side effect, especially in older adults.
- Renal Impairment: Indomethacin can reduce renal blood flow, causing renal dysfunction or failure, especially in patients with preexisting kidney disease.
- Cardiovascular Events: Prolonged use or high doses of indomethacin can increase the risk of serious cardiovascular events, including heart attack and stroke.
- Anaphylactic Reactions: Severe allergic reactions, including anaphylaxis, can occur, particularly in patients with a history of NSAID allergy.
- Management of Side Effects:
- Gastrointestinal Protection: To reduce the risk of GI bleeding, the use of gastroprotective agents, such as proton pump inhibitors (PPIs), may be considered, especially for long-term users.
- Hydration: Ensuring adequate fluid intake can help mitigate the risk of renal dysfunction.
- Discontinuation: If severe side effects such as gastrointestinal bleeding, anaphylaxis, or renal failure occur, the drug should be discontinued immediately.

Indomethacin Pregnancy Category ID - Safety Information

3

Indomethacin Mode of Action - How It Works

- Mechanism of Action: Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) that works primarily by inhibiting cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. These enzymes are responsible for converting arachidonic acid to prostaglandins, which play a key role in inflammation, pain, and fever. By inhibiting COX enzymes, indomethacin reduces the production of prostaglandins, leading to decreased inflammation, pain, and fever.
- Pharmacodynamics: Indomethacin’s anti-inflammatory effects are beneficial in conditions like rheumatoid arthritis, osteoarthritis, and gout, where excessive prostaglandin production contributes to pain and swelling. The analgesic and antipyretic effects are also beneficial for acute pain and fever management.
- Pharmacokinetics: Indomethacin is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1–2 hours. It is extensively metabolized in the liver and excreted primarily in the urine. Its half-life is approximately 4–5 hours, and it may take longer for the drug to be eliminated in patients with renal or hepatic impairment.
- Therapeutic Benefit: Indomethacin’s ability to effectively manage pain and inflammation, particularly in inflammatory joint diseases, makes it a potent tool in treating conditions like rheumatoid arthritis, ankylosing spondylitis, and gout. However, its use is typically limited to short-term treatment to minimize the risk of side effects.

Indomethacin Drug Interactions - What to Avoid

- Drug-Drug Interactions:
- Anticoagulants and Antiplatelet Drugs: Indomethacin may increase the risk of bleeding when used with anticoagulants (e.g., warfarin) or antiplatelet drugs (e.g., aspirin), as both increase the risk of gastrointestinal bleeding. Monitoring coagulation parameters is recommended.
- Other NSAIDs: Concurrent use of multiple NSAIDs, including indomethacin, should be avoided due to the increased risk of gastrointestinal toxicity, kidney damage, and bleeding.
- Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) and Diuretics: Indomethacin can reduce the effectiveness of ACE inhibitors and diuretics in managing blood pressure. It may also cause renal impairment when used with these agents. Close monitoring of renal function is necessary.
- Lithium: Indomethacin can increase lithium levels, potentially leading to lithium toxicity. Serum lithium levels should be closely monitored when both drugs are used together.
- Corticosteroids: The risk of gastrointestinal bleeding and ulcer formation increases when indomethacin is used with corticosteroids.
- Methotrexate: Indomethacin can increase the toxicity of methotrexate, leading to severe adverse effects, including renal and liver toxicity.
- Food and Alcohol: Alcohol can enhance the risk of gastrointestinal bleeding when used with indomethacin. It is advisable to limit alcohol intake during therapy. Additionally, taking indomethacin with food can help reduce stomach irritation, but this may also reduce its absorption rate slightly.

Indomethacin Adult Dose - Recommended Dosage

- Rheumatoid Arthritis and Osteoarthritis: The typical dose for rheumatoid arthritis or osteoarthritis is 25–50 mg taken two to three times a day. The maximum recommended daily dose is 200 mg, but this may be adjusted based on individual response and tolerability.
- Gout: For acute gout attacks, indomethacin is typically started at 50 mg three times a day, and the dose may be adjusted based on symptoms, up to a maximum of 200 mg daily.
- Ankylosing Spondylitis: A typical dose is 25 mg two to three times daily, with an upper limit of 200 mg per day.
- Administration: Indomethacin should be taken with food or milk to minimize gastrointestinal irritation. The dosage may need to be adjusted for individuals with pre-existing gastrointestinal, renal, or hepatic conditions.

Indomethacin Child Dose - Dosage for Children

- Pediatric Use: Indomethacin is occasionally used in children for conditions like patent ductus arteriosus (PDA) in premature infants. The dosage in children varies depending on the condition being treated, but it is usually given in divided doses based on the child’s weight.
- Safety Considerations: Due to the potential for significant side effects, particularly gastrointestinal bleeding, indomethacin should only be used in children when prescribed by a healthcare provider, and its use should be closely monitored.

Indomethacin Renal Dose - Dosage for Kidney Conditions

- Renal Impairment: Indomethacin should be used with caution in patients with renal impairment. Dose adjustments are generally not necessary for mild renal impairment, but the drug should be avoided in those with moderate to severe renal impairment, as it can exacerbate kidney dysfunction.
- Monitoring: Regular monitoring of renal function (e.g., serum creatinine and blood urea nitrogen) is essential during treatment, especially in long-term therapy.