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INDOMETHACIN (INDOCIN)



Indomethacin is an analgesic (pain reliever), anti-pyretic (fever reducer) of the NSAID (non-steroidal anti-inflammatory) class which exerts its pharmacological effect by non specific prostaglandin inhibition in peripheral tissues which mediate inflammation and desensitizes afferent nerves (nerves providing information to the brain) thus preventing the potential effect of bradykinin (a chemical that conveys pain) to induce pain. The drug is indicated for long-term use in rheumatoid arthritis (RA), ankylosing spondylitis, and osteoarthritis (DJD).

The response in RA is manifested by pain relief, reduction of fever, swelling, joint tenderness, and morning stiffness. The benefit of adding indomethacin to the RA regiment is reduction in steroid usage in some cases.

Its anti-inflammatory and analgesic effects provide relief for the acute gout patient during attack. Gout, the precipitation of uric acid crystals in the joints, usually of the lower extremity especially the large toe and ankle joints, is a very painful ‘overnight ,waking up to morning pain’ usual presentation. It is characterized by swelling, erythema (heat), very guarded rom (range of motion) on exam, compensated gait.)

As with all pain medication, the lowest possible effective dose should be started, and adjusted to both subjective(patient response) and objective(observed in examination) for the shortest time necessary.

INDICATIONS



Indomethacin is indicated for:

-moderate to severe RA including acute flare-ups of chronic stages

-moderate to severe ankylosing spondylitis

-moderate to severe DJD

-acute should pain (bursitis, tendonitis)

-acute gouty arthritis

CONTRAINDICATIONS



The initial dose of 25-50mg orally is absorbed achieving blood levels in two hours. The drug crosses the blood/brain barrier and placenta, and is NOT RECOMMENDED IN PREGNANT OR BREAST FEEDING WOMEN.

The drug should be avoided in patients with history of easily precipitated severe asthmatic attacks, urticaria( significant rash with itching), or those patients with aspirin or allergy to any other NSAID. It is NOT for use in post-operative patients, especially in those who have undergone coronary artery bypass grafts(CABG) due to its anti-platelet activity and increased bleeding time. The suppository form of the drug should be avoided in patients with rectal bleeding or proctitis.

SIDE EFFECTS



Indomethacin along with many NSAIDs, even the COX-2 inhibitors (celebrex), may increase the risk of severe cardiovascular events such as stroke(CVA), myocardial infarction(MI-heart attack), worsened hypertension(high blood pressure) or may precipitate high blood pressure. Patients on loop (furosemide) or thiazide (hydrochlorothiazide, chlorothiazide) diuretics may experience a reduced effect in urinary excretion due to the concomitant use of indomethacin.

Through its mechanism of prostaglandin inhibition, necessary for cardiovascular compensation mechanisms, the drug may aggravate congestive heart failure or induce hyponatremia (reduced plasma sodium level concentrations). With the non specific inhibition(COX 1&2), there is increased risk of gastrointestinal problems, such as bleeding, ulceration, perforation, which is additive when aspirin , corticosteroids are used along with patients who smoke and drink alcohol. The risk is elevated in the elderly, debilitated patient and is also a function of duration of the drug. IT SHOULD BE AVOIDED IN PATIENTS ON ANTICOAGULANT MEDICATION.

Long term use may lead to renal(kidney) disease especially in those patients with established reduced renal clearance, heart failure, liver dysfunction, and dehydration. Serum potassium (K+) may be elevated in the hyponatremia (low sodium) patient. Anaphylactic (sudden) and fatal allergic reactions may occur in patients a history of rhinitis(significant nasal inflammation) nasal polyps, and bronchospasms, skin reactions such as exfoliate dermatitis(severe shedding of skin),Stevens-Johnson Syndrome(SJS) with severe redness of the skin, edema) may occur and the medication should be immediately discontinued and proper supportive therapy initiated. Corneal, retinal, and macula changes with blurred vision may occur with prolonged therapy of indomethacin., CNS-central nervous system depression and various psychiatric problems, epilepsy and Parkinson’s may be aggravated by the drug, headaches and drowsiness may occur.

Drug interactions may occur in those patients also taking various medications-

Anti-hypertensive-reducing the blood pressure effect

ACE- inhibitors, angiotensin II antagonists, Beta-blockers

Aspirin- reduces the effects of indomethacin due to common protein binding sites

Diflunisal, another anti-inflammatory similar to aspirin, will reduce the clearance of indomethacin, and thus increasing plasma levels.

Digoxin, a cardio tonic medication, will have increased half –life, thus providing enhanced reactions possibly harmful

Diuretics efficacy are reduced with indomethacin

Lithium, a medication used in various psychiatric conditions, (whose blood concentration must be closely monitored,) clearance is reduced, thus elevating plasma concentration to possible toxic levels.

Indomethacin is contraindicated in patients less than 14 years of age, and in those patients, especially aging with comorbidities of the renal, gastric or hepatic system should be monitored closely with possible reduction in dosage.

DOSING



Indomethacin is available in oral capsular form in 25 and 50mg and oral suspension of 25mg/5cc (teaspoonful) or rectal suppository of 75mg. The usual dosage prescribed is 25-50mg po(orally) tid(3 times daily) pc (after meals) for moderate to severe pain relief of RA, DJD, ankylosing spondylitis up to 150-200mg/day. For painful acute bursitis/tendonitis , doses of 75-150mg daily in 3-4 divided doses is beneficial. The drug is also available for injection.

REFERENCES

PDR, Physicians’ Desk Reference, 61st edition, 2005

MPR, Monthly Physician Reference

‘Conquering Pain’, Institute for Natural Resources, First edition (02-11)

COMMENTS

As a physician, my patient population usually presents with tendonitis, bursitis, and acute gout. It is my drug of choice, for those not taking anticoagulants (blood thinners) or history of gastric disease (ulcers, gastritis). For acute gout and dosed at 50mg by mouth three times per day x 3 days then 25mg by mouth three times per day for 7-10days it provides excellent relief and is usually tolerated very well. Similar favorable responses occur for acute painful ankle sprains and lower extremity tendon problems.



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