Indomethacin

BRAND NAMES:

Indocin- Its primary component, indomethacin, is a drug frequently used to treat pain, edema, and stiffness in the joints.  It can be purchased as a suppository. Tendinitis, gout, and arthritis are among the ailments for which this medication is frequently administered.

Tivorbex- It contains the active ingredients of indomethacin. It is available in the form of capsules used to treat the pains, swelling, and joint stiffness.

MECHANISM OF ACTION:

The cyclo-oxygenase or prostaglandin G/H synthase enzyme is reversibly and nonspecifically inhibited by indomethacin. COX comes in two recognised isoforms: COX-2 is produced in response to inflammation or damage, whereas COX-1 is ubiquitous in most human tissues and implicated in the manufacture of prostaglandins and thromboxane A2. generated prostaglandin (PG) G2 and PGH2 from arachidonic acid by constitutively expressing the COX-1 enzymes implicated in kidney, platelet, and stomach mucosal protection. When a baby is born prematurely, they may have congenital heart abnormalities where PGE1 acts in opposition to oxygen to cause patent ductus arteriosus. Distal arterioles dilate in response to PGE1. Domethacin facilitates the closure of ductus arterioles by preventing prostaglandin production.

PHARMACOKINETICS:

Absorption: The bioavailability of the drug is approximately 100%.

Distribution: The volume of distribution ranged from 0.34-1.57L/kg.

Metabolism: Indomethacin enters enterohepatic circulation and is metabolized via demethylation and ceacylation pathways. The major metabolites include O-deschlorobenoyl-indomethacin and their glucuronide conjugates.

Excretion: Approximately 60% of administered indomethacin is excreted in urine via renal tubular secretion, with the remainder excreted in feces following biliary secretion.

PHARMACODYNAMICS:

Indomethacin, like most other NSAIDs, works by blocking the formation of prostaglandins. Cyclooxygenase enzymes predominantly create prostaglandins, important mediators of inflammation, fever, and pain. They also support renal function, gastrointestinal mucosa, and platelet activity. NSAIDs can block the COX enzyme, which might cause various side effects.

DOSAGE AND ADMINISTRATION:

The dose of this medicine will be different patients

• These are available in capsules with strengths of 20mg, 25mg, 40mg, and 50mg.

• Extended-release capsules are available in the strengths of 75mg

• Powder for injection with 1mg

• Oral suspensions with 25mg/5ml.

• Suppository with 50mg.

Indomethacin is available in three forms: capsules, extended-release capsules, and an oral suspension. Indomethacin capsules and liquids are commonly taken twice to four times each day. Indomethacin capsules, extended-release capsules, and suspension should be consumed with food, shortly after meals, or with antacids. Take indomethacin at the same time every day. Take the extended-release pills whole. Don't split, chew, or crush them. Shake the suspension before each use to ensure the medication is evenly mixed.

DRUG INTERACTIONS:

Drug interactions with indomethacin include

• Pain relivers- Ibuprofen, Naproxen and Aspirin

• Depression medicines- Duloxetine

• Hypertension drugs- Metoprolol

• Arthritis-Celecoxib, Prednisone

Patients who have a history of NSAID-induced hypersensitivity and atopic responses, such as urticarial, asthma, exfoliative, dermatitis, toxic epidermal necrolysis, or Stevens-Johnson syndrome, should avoid indomethacin. Patients who have previously undergone coronary artery bypass graft surgery should not use indomethacin. Indomethacin usage can result in premature closure of the fetal ductus arteriosus, hence it is not recommended for pregnant women beginning in the third trimester.

SIDE EFFECTS:

Indomethacin may cause side effects

• Headache

• Dizziness

• Vomiting

• Diarrhea

• Constipation

• Ringing in the ear

Some side effects can be serious, they may include

• Unexplained weight gain

• Shortness of breath or difficulty breathing

• Swelling in the abdomen, ankles, feet or legs

• Fever, rash, lymph node swelling, or facial swelling

• Blisters

• Itching

• Hives

• Pale skin

• Fast heartbeat

• Lack of energy

• Nausea

• Backpain

• Blurred vision

OVERDOSE:

Overdose of indomethacin may include

• Nausea

• Vomiting

• Headache

• Dizziness

• Confusion

• Extreme tiredness

• Seizures

TOXICITY:

Healthcare providers should offer patients supportive and symptomatic care following indomethacin dosage. A specific antidote for indomethacin toxicity is not available. For adult patients, administering 60 to 100 grams of activated charcoal should be considered to decrease the absorption of NSAIDs from the upper gastrointestinal tract. Osmotic cathartics may be used in symptomatic patients observed within 4 hours of overdose or in patients who ingested 5 to 10 times the recommended dosage of indomethacin. The local poison control center should be contacted for detailed information on the treatment protocol. 

STORAGE:

Keep out of the reach of children. Store at room temperature between 15⁰ and 30⁰ C (59 ⁰and 86 ⁰F). Protect from light and moisture. Keep the container tightly closed.