Indometacinum

Indometacinum Uses, Dosage, Side Effects, Food Interaction and all others data.

Indometacinum is a non-steroidal anti-inflammatory drug (NSAID) having properties of antipyretic and analgesic effects. A great number of pharmacological studies have proved that Indometacinum has strong anti-inflammatory, analgesic and antipyretic properties. Unlike the corticosteroids, the effect of Indometacinum is not related to the pituitary gland or the adrenals.

Indometacin is an NSAID with analgesic and antipyretic properties that exerts its pharmacological effects by inhibiting the synthesis of factors involved in pain, fever, and inflammation. Its therapeutic action does not involve pituitary-adrenal stimulation. Indometacin primarily works by suppressing inflammation in rheumatoid arthritis by providing relief of pain as well as reducing fever, swelling, and tenderness. This effectiveness has been demonstrated by a reduction in the extent of joint swelling, the average number of joints displaying symptoms of inflammation, and the severity of morning stiffness. Increased mobility was demonstrated by a decrease in total walking time and by improved functional capability seen as an increase in grip strength. In clinical trials, indometacin was shown to be effective in relieving the pain, reducing the fever, swelling, redness, and tenderness of acute gouty arthritis. Due to its pharmacological actions, the use of indometacin is associated with the risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, as well as gastrointestinal effects such as bleeding, ulceration, and perforation of the stomach or intestines.

In a study of healthy individuals, acute oral and intravenous indometacin therapy resulted in a transiently diminished basal and CO2 stimulated cerebral blood flow; this effect disappeared in one study after one week of oral treatment. The clinical significance of this effect has not been established. Compared to other NSAIDs, it is suggested that indometacin is a more potent vasoconstrictor that is more consistent in decreasing cerebral blood flow and inhibiting CO2 reactivity. There have been studies that show indometacin directly inhibiting neuronal activity to some extent in the trigeminocervical complex after either superior salivatory nucleus or dural stimulation.

Trade Name Indometacinum
Availability Prescription only
Generic Indomethacin
Indomethacin Other Names Indometacin, Indometacina, Indometacine, Indometacinum, Indomethacin
Related Drugs Humira, Buprenex, aspirin, prednisone, ibuprofen, acetaminophen, tramadol, meloxicam, duloxetine, cyclobenzaprine
Type
Formula C19H16ClNO4
Weight Average: 357.788
Monoisotopic: 357.076785712
Protein binding

Indometacin is a weak organic acid that is 90-99% bound to protein in plasma over the expected range of therapeutic plasma concentrations . Like other NSAIDs, indometacin is bound to plasma albumin but it does not bind to red blood cells.

Groups Approved, Investigational
Therapeutic Class Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)
Manufacturer
Available Country
Last Updated: September 19, 2023 at 7:00 am
Indometacinum
Indometacinum

Uses

Indometacinum is used for the treatment of rheumatoid arthritis, ankylosing spondylitis, osteoarthritis (degenerative joint disease), gout, acute non-articular rheumatism (bursitis, synovitis, tendinitis).

Indometacinum is also used to associated treatment for these conditions: Acute Gouty Arthritis, Joint Pain, Moderate to Severe Osteoarthritis, Moderate to Severe Rheumatoid Arthritis, Moderate to severe ankylosing spondylitis, Patent Ductus Arteriosus (PDA), Soreness, Muscle, Acute Shoulder Pain

How Indometacinum works

Indometacin is a nonspecific and reversible inhibitor of the cyclo-oxygenase (COX) enzyme or prostaglandin G/H synthase. There are two identified isoforms of COX: COX-1 is universally present in most body tissues and is involved in the synthesis of the prostaglandins and thromboxane A2, while COX-2 is expressed in response to injury or inflammation. Constitutively expressed, the COX-1 enzyme is involved in gastric mucosal protection, platelet, and kidney function by catalyzing the conversion of arachidonic acid to prostaglandin (PG) G2 and PGG2 to PGH2. COX-2 is constitutively expressed and highly inducible by inflammatory stimuli. It is found in the central nervous system, kidneys, uterus, and other organs. COX-2 also catalyzes the conversion of arachidonic acid to PGG2 and PGG2 to PGH2. In the COX-2-mediated pathway, PGH2 is further converted to PGE2 and PGI2 (also known as prostacyclin). PGE2 is involved in mediating inflammation, pain, and fever. Decreasing levels of PGE2 leads to reduced inflammatory reactions. Indometacin is known to inhibit both isoforms of COX, however, with greater selectivity for COX-1, which accounts for its increased adverse gastric effects relative to other NSAIDs. It binds to the enzyme's active site and prevents the interaction between the enzyme and its substrate, arachidonic acid. Indometacin, unlike other NSAIDs, also inhibits phospholipase A2, the enzyme responsible for releasing arachidonic acid from phospholipids. The analgesic, antipyretic and anti-inflammatory effects of indomethacin as well as adverse reactions associated with the drug occur as a result of decreased prostaglandin synthesis. Its antipyretic effects may be due to action on the hypothalamus, resulting in increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

The exact mechanism of action of indometacin in inducing closure of a patent ductus arteriosus is not fully understood; however, it is thought to be through inhibition of prostaglandin synthesis. At birth, the ductus arteriosus is normally closed as the tension of the oxygen increases significantly after birth. Patent ductus arteriosus in premature infants is associated with congenital heart malformations where PGE1 mediates an opposite effect to that of oxygen. PGE1 dilates the ductus arteriosus through smooth muscle relaxation and prevents the closure of the ductus arteriosus. By inhibiting the synthesis of prostaglandins, indometacin promotes the closure of ductus arteriosus.

Indometacin has been described as possessing anticancer and antiviral properties through activation of protein kinase R (PKR) and downstream phosphorylation of eIF2α, inhibiting protein synthesis.

Dosage

Indometacinum dosage

Indometacinum is available for oral administration as a 25 mg capsule and as a rectal suppository containing 100 mg of indomethacin.

The recommended dosage of Indometacinum is 50 mg to 200 mg daily in divided doses and should be individually adjusted to the patient's response and tolerance. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals.

Unlike some other potent antirheumatic agents, an initial high "loading" dose of Indometacinum is not necessary. In chronic rheumatic disorders, initiating therapy with low doses, increasing gradually when necessary, and continuing for an adequate period (up to one month is recommended) will produce maximum benefit and minimise adverse reactions.

In patients with persistent night pain and/or morning stiffness, a dose of up to 100 mg at bedtime may be helpful in affording relief. It is rarely necessary to exceed a dosage of 200 mg per day.

In the treatment of acute gouty arthritis, the recommended daily dosage is 150 mg to 200 mg until all symptoms and signs subside.

In primary dysmenorrhoea, the recommended dosage is 25 mg three times a day starting with onset of cramps or bleeding and continuing for as long as the symptoms usually last.

To minimise the possibility of gastrointestinal disturbances, it is recommended that oral Indometacinum be taken with food, milk, or an antacid.

Side Effects

Headache, usually in the morning and mild vertigo may occur during the early weeks of therapy. These symptoms are transient and usually disappear with continued use or by reduction of the dose. Gastrointestinal reactions such as nausea, vomiting, diarrhea, epigastric and abdominal pain are often due to large doses of the drug and disappear when the dose is reduced.

Toxicity

Acute oral LD50 is 2.42 mg/kg in rats and 13 mg/kg in mice. The oral LD50 of indomethacin in mice and rats (based on 14-day mortality response) was 50 and 12 mg/kg, respectively.

Symptoms of overdose may be characterized by nausea, vomiting, intense headache, dizziness, mental confusion, disorientation, or lethargy. In addition, there have been reports of paresthesias, numbness, and convulsions. In case of an overdose, the patient should receive symptomatic and supportive treatment with stomach emptying through induced vomiting or gastric lavage. The patient should then be closely monitored for any signs of gastrointestinal ulceration and hemorrhage. Antacids may be useful.

Interaction

It may interact with anticoagulants, lithium, diuretics, ß-blockers, diflunisal, aspirin, probenecid and sulfonylureas.

Food Interaction

  • Avoid alcohol. Ingestion of alcohol can increase the risk of GI bleeding.
  • Take with or without food. Food has no effect on drug absorption. However, food may decrease the extent of gastrointestinal irritation caused by indomethacin.

Indometacinum Alcohol interaction

[Moderate] GENERALLY AVOID:

The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss.

The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.



Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

Indometacinum Hypertension interaction

[Major] Fluid retention and edema have been reported in association with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).

Therapy with NSAIDs should be administered cautiously in patients with preexisting fluid retention, hypertension, or a history of heart failure.

Blood pressure and cardiovascular status should be monitored closely during the initiation of NSAID treatment and throughout the course of therapy.

Hypertension interaction

[Moderate] Nonsteroidal anti-inflammatory drugs (NSAIDs), including topicals, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which can contribute to the increased incidence of cardiovascular events.

NSAIDs should be used with caution in patients with hypertension.

Blood pressure should be monitored closely during the initiation of NSAID therapy and throughout the course of therapy.

Volume of Distribution

The volume of distribution ranged from 0.34 to 1.57 L/kg following oral, intravenous, or rectal administration of single and multiple doses of indometacin in healthy individuals. Indometacin is distributed into the synovial fluid and is extensively bound to tissues . It has been detected in human breast milk and placenta. Although indometacin has been shown to cross the blood-brain barrier (BBB), its extensive plasma protein binding allows only the small fraction of free or unbound indometacin to diffuse across the BBB.

Elimination Route

Indometacin displays a linear pharmacokinetics profile where the plasma concentrations and area under the curve (AUC) are dose-proportional, whereas half-life (T1/2) and plasma and renal clearance are dose-dependent. Indometacin is readily and rapidly absorbed from the gastrointestinal tract. The bioavailability is virtually 100% following oral administration and about 90% of the dose is absorbed within 4 hours. The bioavailability is about 80-90% following rectal administration.

The peak plasma concentrations following a single oral dose were achieved between 0.9 ± 0.4 and 1.5 ± 0.8 hours in a fasting state. Despite large intersubject variation as well using the same preparation, peak plasma concentrations are dose-proportional and averaged 1.54 ± 0.76 μg/mL, 2.65 ± 1.03 μg/mL, and 4.92 ± 1.88 μg/mL following 25 mg, 50 mg, and 75 mg single doses in fasting subjects, respectively. With a typical therapeutic regimen of 25 or 50 mg t.i.d., the steady-state plasma concentrations of indomethacin are an average 1.4 times those following the first dose.

Half Life

Indometacin disposition from the plasma is reported to be biphasic, with a half-life of 1 hour during the initial phase and 2.6–11.2 hours during the second phase. Interindividual and intraindividual variations are possible due to the extensive and sporadic nature of the enterohepatic recycling and biliary discharge of the drug.

The mean half-life of oral indomethacin is estimated to be about 4.5 hours. The disposition of intravenous indometacin in preterm neonates was shown to vary across premature infants. In neonates older than 7 days, the mean plasma half-life of intravenous indometacin was approximately 20 hours, ranging from 15 hours in infants weighing more than 1000 g and 21 hours in infants weighing less than 1000 g.

Clearance

In a clinical pharmacokinetic study, the plasma clearance of indometacin was reported to range from 1 to 2.5 mL/kg/min following oral administration.

Elimination Route

Indometacin is eliminated via renal excretion, metabolism, and biliary excretion. It is also subject to enter the enterohepatic circulation through excretion of its glucuronide metabolites into bile followed by resorption of indometacin after hydrolysis . The extent of involvement in the enterohepatic circulation ranges from 27 to 115%.

About 60 percent of an oral dosage is recovered in urine as drug and metabolites (26 percent as indomethacin and its glucuronide), and 33 percent in the feces (1.5 percent as indomethacin).

Pregnancy & Breastfeeding use

Use in pregnancy: Not recommended for pregnant women, because at the present time clinical studies are insufficient.

Use in children: Not recommended for children.

Contraindication

Indometacinum is contraindicated in patients with ulcer, gastritis, active ulcerative colitis, and should be used with caution in patients with a history of these disorders. It is also contraindicated in previously hypersensitive patient.

Storage Condition

Should be stored in cool and dry place

Innovators Monograph

You find simplified version here Indometacinum

Indometacinum contains Indomethacin see full prescribing information from innovator Indometacinum Monograph, Indometacinum MSDS, Indometacinum FDA label

FAQ

What is Indometacinum used for?

Indometacinum is a nonsteroidal anti-inflammatory drug commonly used as a prescription medication to reduce fever, pain, stiffness, and swelling from inflammation.

How safe is Indometacinum?

Indometacinum can increase your risk of fatal heart attack or stroke, even if you don't have any risk factors. Do not use this Indometacinum just before or after heart bypass surgery (coronary artery bypass graft, or CABG). Indometacinum may also cause stomach or intestinal bleeding, which can be fatal.

How does Indometacinum work?

Indometacinum works by blocking an enzyme in your body that leads to inflammation.

What are the common side effects of Indometacinum?

Common side effects of Indometacinum are include:

  • headache.
  • dizziness.
  • vomiting.
  • diarrhea.
  • constipation.
  • ringing in the ears.

Is Indometacinum safe during pregnancy?

Women who are more than 32 weeks pregnant should avoid taking Indometacinum, given the potential for heart problems in the baby.

Is Indometacinum safe during breastfeeding?

Because of the low levels of Indometacinum in breastmilk and therapeutic administration directly to infants, it is acceptable to use in nursing mothers.

Can I drink alcohol with Indometacinum?

Heavy drinking alcohol can increase your risk of stomach bleeding. Avoid taking alcohol unless your doctor tells you to.

Can I drive after taking Indometacinum?

Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert.

How many time can I take Indometacinum daily?

Extended-release capsules are usually taken one or two times a day.

Can I take Indometacinum at night?

Indometacinum is commonly prescribed at night to relieve morning stiffness in patients with rheumatoid arthritis.

When should be taken of Indometacinum?

Indometacinum capsules, extended-release capsules, and suspension should be taken with food, immediately after meals, or with antacids. Take Indometacinum at around the same times every day.

How much Indometacinum can I take daily?

Adults 25 milligrams (mg) two or three times a day. Your doctor may increase your dose by 25 or 50 mg per day, as needed. However, the total dose is usually not more than 200 mg per day. Children 15 years of age and older. Dose is based on body weight and must be determined by your doctor.

How long does Indometacinum take to work?

This Indometacinum usually begins to work within 1 week, but in severe cases up to two weeks or even longer may pass before you begin to feel better. Also, several weeks may pass before you feel the full effects of this medicine.

How long does Indometacinum stay in my system?

The mean half- life of Indometacinum is estimated to be about 4.5 hours.

How long can I take Indometacinum?

Indometacinum should be discontinued after the signs and symptoms of inflammation have been controlled for several days. The usual course of therapy is 7-14 days.

Who should not take Indometacinum?

Talk to your doctor about the risks and benefits of taking Indometacinum if you are 65 years of age or older. Older adults usually should not take Indometacinum because it is not as safe as other medications that can be used to treat the same condition.

Is Indometacinum bad for my heart?

Indometacinum can increase your risk of fatal heart attack or stroke, even if you don't have any risk factors. Do not use this medicine just before or after heart bypass surgery.

Can Indometacinum affects my liver?

Indometacinum is rarely mentioned as a cause of acute liver failure. Rechallenge may lead to recurrence and should be avoided.

Is Indometacinum bad for kidneys?

Any medication may have some drug interaction that affect the kidneys. Of the medication that you take, Indomethacin can cause kidney function to decline.

What happen If I stop taking Indometacinum?

If you experience any of the following symptoms, stop taking indomethacin and call your doctor: stomach pain, heartburn, vomit that is bloody or looks like coffee grounds, blood in the stool, or black and tarry stools. Keep all appointments with your doctor and the laboratory.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

What happens if I overdose?

Seek emergency medical attention. Overdose symptoms may include severe drowsiness, stomach pain, or vomiting.

*** Taking medicines without doctor's advice can cause long-term problems.
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