Indomethacin

# Indomethacin ## Overview - **Classification**: Nonsteroidal Anti-inflammatory Drug (NSAID) - **Mechanism**: Inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, reducing prostaglandin synthesis. This leads to anti-inflammatory, analgesic, and antipyretic effects. ## Primary Indications 1. **Rheumatoid Arthritis/Osteoarthritis/Ankylosing Spondylitis**: For moderate to severe inflammatory pain and stiffness. 2. **Acute Gouty Arthritis**: Rapid relief of pain and inflammation in acute gout attacks. 3. **Bursitis/Tendonitis**: Management of acute pain and inflammation. 4. **Patent Ductus Arteriosus (PDA)**: Closure of hemodynamically significant PDA in preterm infants. ## Adult Dosing ### Standard Dosing **Acute Gouty Arthritis** - **Dose**: **50 mg** initially, then **25-50 mg** every 6-8 hours. - **Frequency**: Up to 3-4 times daily. - **Route**: Oral (capsule, suspension), Rectal (suppository). - **Duration**: Continue for 1-2 days after symptoms subside. Max **7 days**. **Rheumatoid Arthritis, Osteoarthritis, Ankylosing Spondylitis** - **Dose**: **25 mg** 2-3 times daily, may increase by **25 mg** increments. - **Frequency**: Up to 3-4 times daily. - **Route**: Oral (capsule, suspension). - **Maximum Dose**: **200 mg/day**. (Sustained Release: **75 mg** 1-2 times daily, max **150 mg/day**) **Acute Bursitis/Tendonitis** - **Dose**: **25-50 mg** 2-3 times daily. - **Frequency**: Up to 3-4 times daily. - **Route**: Oral (capsule, suspension). - **Duration**: Continue until inflammation subsides. ### Dose Adjustments - **Renal Impairment**: Avoid use if CrCl < **30 mL/min**. For CrCl 30-60 mL/min, use lowest effective dose, monitor renal function closely. - **Hepatic Impairment**: No specific guidelines. Use with caution, consider reduced dose, monitor LFTs. - **Elderly Patients**: Start with lower doses (**25 mg** 1-2 times daily) due to increased risk of GI, renal, and CNS adverse effects. Avoid chronic use. ## Pediatric Dosing ### Neonates (0-28 days) - For Patent Ductus Arteriosus (PDA) - **Indication**: Closure of hemodynamically significant PDA. - **Dose**: Administer in **3 IV doses** at 12-24 hour intervals. - **1st dose**: **0.2 mg/kg** - **2nd dose**: **0.1 mg/kg** (if <48 hrs old), **0.2 mg/kg** (if 2-7 days old), **0.25 mg/kg** (if >7 days old) - **3rd dose**: **0.1 mg/kg** (if <48 hrs old), **0.2 mg/kg** (if 2-7 days old), **0.25 mg/kg** (if >7 days old) - **Route**: Intravenous (IV) infusion over 20-30 minutes. - **Maximum**: Total cumulative dose of **0.6-0.75 mg/kg** per course. - **Special Notes**: Ensure adequate urine output before each dose. Contraindicated in active bleeding, severe renal dysfunction, thrombocytopenia. ### Infants (1-12 months) - **Indication**: Not routinely used due to significant side effects. Consult specialist for specific indications (e.g., severe juvenile arthritis, off-label). - **Dose**: Generally avoided. If used, dose selection by specialist. - **Safety**: High risk of GI, renal, and CNS side effects. ### Children (1-12 years) - **Indication**: Generally avoided; other NSAIDs preferred. Consult specialist for specific conditions (e.g., severe juvenile arthritis, off-label). - **Dose**: If used off-label, initial dose of **1-2 mg/kg/day** divided 2-4 times daily. - **Maximum**: Max **4 mg/kg/day** or **150-200 mg/day** (adult max). - **Special Notes**: Use lowest effective dose for shortest duration. Monitor for GI, renal, and CNS effects. ### Adolescents (13-18 years) - **Indication**: Use adult dosing guidelines for conditions like gout, inflammatory arthritis, or musculoskeletal pain. - **Dose**: Follow adult dosing for specific indications. - **Maximum**: Adult maximum dose limits apply (**200 mg/day**). - **Special Notes**: Consider starting with lower adult doses in younger adolescents. ## Safety Information ### Contraindications - **Absolute**: History of aspirin/NSAID-induced asthma, urticaria, or allergic-type reactions. - **Absolute**: Peri-operative pain in the setting of CABG surgery. - **Absolute**: Severe renal impairment (CrCl < **30 mL/min**). - **Absolute**: Active gastrointestinal bleeding or ulceration. - **Absolute**: Third trimester of pregnancy (risk of premature ductus arteriosus closure). - **Relative**: Severe uncontrolled hypertension, severe heart failure. ### Common Adverse Effects - **Very Common (>10%)**: Headache, dizziness, dyspepsia, nausea, abdominal pain. - **Common (1-10%)**: Vomiting, diarrhea, constipation, tinnitus, edema, rash, vertigo. - **Serious but Rare**: GI bleeding/perforation, acute kidney injury, cardiovascular thrombotic events (MI, stroke), severe skin reactions (SJS/TEN), anaphylaxis, aseptic meningitis, hyperkalemia. ### Key Drug Interactions - **Anticoagulants (Warfarin, Heparin)**: Increased risk of bleeding. Monitor INR/aPTT, observe for signs of bleeding. - **Diuretics (Furosemide, Thiazides)**: Decreased diuretic and antihypertensive effects. Increased risk of renal impairment. Monitor BP and renal function. - **ACE Inhibitors/ARBs**: Decreased antihypertensive effect. Increased risk of renal impairment and hyperkalemia. Monitor BP, renal function, potassium. - **Lithium**: Increased lithium levels, leading to toxicity. Reduce lithium dose, monitor lithium levels closely. - **SSRIs/SNRIs**: Increased risk of GI bleeding. Use with caution. - **Methotrexate**: Increased methotrexate levels, enhancing toxicity. Avoid concomitant use or closely monitor for methotrexate toxicity. ## Monitoring & Follow-up - **Before Treatment**: Complete blood count (CBC), renal function (BUN, Cr), liver function tests (LFTs), blood pressure (BP). - **During Treatment**: - **Chronic Use**: CBC, renal function, LFTs every **3-6 months**. - **All Patients**: Monitor BP regularly. - **Clinical Signs**: Monitor for signs of GI bleeding (black/tarry stools, severe abdominal pain), edema, rash, changes in vision, or unusual bruising/bleeding. - **Clinical Signs**: Watch for signs of fluid retention, increased BP, or worsening cardiac function. ## Clinical Pearls - 💡 **Timing**: For acute gout, start indomethacin as early as possible after symptom onset for best efficacy. - 💡 **GI Protection**: Consider a proton pump inhibitor (PPI) or H2 blocker for patients at high risk of GI side effects, especially with chronic use. - 💡 **Administration**: Take with food or milk to minimize GI upset. Rectal suppositories can be an alternative if oral route is problematic. - 💡 **Pediatric PDA**: Ensure neonate has good urine output and normal platelet count before administering IV indomethacin. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.