Indometacin

Indometacin (:中文 吲哚美辛 ) also known as Indomethacin, is a nonsteroidal anti-inflammatory drug, an NSAID. As an NSAID, indomethacin is an analgesic, anti-inflammatory and antipyretic.

Clinical indications for indomethacin include:

• rheumatoid arthritis
• alkylosing spondylitis
• osteoarthritis
• gouty arthritis

It is also be used in menstrual pain, headaches, dental pain, postoperative and postpartum pain.

Drug name

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Indomethacin Capsule 25 mg		P1S1S3

Mechanism of Action

Non-opioid Analgesic (NSAID) Anti-inflammatory agent, Nonselective COX inhibitor, inhibits COX-1 and COX-2

Dosage

Chronic musculoskeletal and joint disorders	Oral : 25 mg two to three times daily, increased if required by 25 to 50 mg at weekly intervals to 150 to 200mg daily. To alleviate night pain and morning stiffness, up to 100 mg of the total daily dose may be given orally, or rectally as a suppository, on retiring. Alternatively, the total daily dose may be given retally as 100 mg in the morning and at night. The total daily combined oral and rectal doses should not exceed 200 mg.
Acute gout	Oral : 150 to 200 mg in divided doses until all symptoms and signs subsided
Dysmenorrhea	Oral : 75 mg daily

Indomethacin Eyedrops :

0.1% eye drops	Prevent miosis (瞳孔縮小) during cataract surgery; the usual dose is 2 drops 3 hours before and 2 drops 1 hour before surgery.
0.5% eye drop	Prevent miosis and inflammation associated with cataract surgery

In other inflammatory eye disorders, the usual dose is 1 drop of 0.1% indomethacin eye drop 4 to 6 times daily until symptoms are resolved.

Administration in children

Aged 1 month to 17 years	Oral : 0.5 to 1 mg/kg twice daily.

Side Effects

For NSAIDs in general

Common side effects	heartburn, nausea, dyspepsia, diarrhoea, constipation, gastrointestinal ulceration/bleeding, headache, dizziness, rashes, salt and fluid retention, and high blood pressure.
Adverse side effects	depression, drowsiness, tinnitus, confusion, insomnia, psychiatric disturbances, convulsion.

It also increases the risk of heart attack, stroke, kidney failure and liver failure.

Rectal irritation and bleeding have been reported occasionally in patients using indomethacin suppositories.

Blood	localized spontaneous bleeding, bruising and prolonged bleeding time have been reported
Asthma	Can be worsen
Cardiovascular risk	Chronic ibuprofen use has been found correlated with risk of progression to hypertension and myocardial infarction (heart attack). Both the U.S. Food and Drug Administration (FDA) and The European Medicines Agency (EMA) issues warnings of increased heart attack and stroke risk.
Skin	NSAIDs have been associated with the onset of bullous pemphigoid. It can also cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, which can be fatal.
Stomach ulcers	Naproxen poses an intermediate risk of stomach ulcers compared with ibuprofen, which is low-risk, and indomethacin which is high-risk.

Rectal irritation and bleeding have been reported occasionally in patients using indomethacin suppositories.

Drug Management

Efficiency: Pain and inflammation control The frequency and severity of side effects and the availability of better tolerated alternatives such as diclofenac, make indomethacin today a drug of second choice.

Monitoring

• Regular physical examination to detect edema and signs of central nervous side effects.
• Blood pressure checks will reveal development of hypertension.
• Periodic serum electrolyte (sodium, potassium, chloride) measurements,
• complete blood counts and
• assessment of liver enzymes as well as creatinine (renal function) should be performed.

Drug Interaction

• Increases the blood thinning effects of warfarin because it displaces them from their plasma protein binding and increases their free concentrations in the bloodstream.
• Increase the risk of adverse effects of lithium, methotrexate and cardiac glycosides by lowering their excretion via the kidneys.
• Risk of nephrotoxicity may be increased if given with ACE inhibitors, ciclosporin, tacrolimus or diuretics
• Combination with antihypertensive drugs such as ACE inhibitors, sartans and diuretics can decrease their effectiveness as well as increase the risk for kidney toxicity.
• Antihypertensive effects of ACEIs, beta blockers and diuretics may be reduced
• Use of more than one NSAID together (including aspirin) should be avoided because of the increased risk of adverse effects.
• It adds to the risk of gastrointestinal bleeding and ulceration when used with steroids, the SSRIs, the SNRI venlafaxaine, the antiplatelet clopidogrel, bisphosphonates or pentoxifylline.

Many NSAIDs, but particularly indomethacin, cause lithium retention by reducing its excretion by the kidney. Thus indomethacin users have an elevated risk of lithium toxicity. For patients taking lithium (e.g. for treatment of bipolar disorder), less toxic NSAIDs such as sulindac is preferred.

All NSAIDs, including indomethacin, also increase plasma renin activity and aldosterone levels, and increase sodium and potassium retention. Vasopressin activity is also enhanced. Together these may lead to:

• Edema (swelling due to fluid retention)
• Hyperkaelemia (high potassium levels)
• Hypernatremia (high sodium levels)
• Hypertension

Contraindication

• Allergy to indomethacin, aspirin or other NSAIDs
• History of allergic reactions (bronchospasm, rhinitis, urticaria) following the use of other NSAIDs such as aspirin
• Third-trimester pregnancy
• Active stomach and/or duodenal ulceration or gastrointestinal bleeding, or history of peptic ulcer disease
• Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis
• Severe congestive heart failure (NYHA III/IV)
• Severe liver damage
• Severe chronic kidney disease (creatinine clearance <30 mi/min)
• Caution in patients with pre-existing hepatic porphyria, as diclofenac may trigger attacks
• Caution in patients with severe, active bleeding such as cerebral hemorrhage
• Caution in patients with Parkinson’s disease, epilepsy, psychotic disorders (indomethacin may worsen these conditions)
• Concurrent with potassium sparing diuretics
• Can lead to onset of new hypertension or worsening of pre-existing hypertension

How should I take the tablet?

Should always be taken with food. Nearly all patients benefit from an ulcer protective drug (e.g. antacids, or famotidine 20mg or omeprazole 20 mg at bedtime).

What should I avoid while taking?

Avoid alcohol consumption.

What happen if I overdose?

Contact your primary care docotor If emergency situation, call 999

What happen if I miss a dose?

Take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.