Indomethacin

Indomethacin is an active ingredient that is used to treat mild to moderate pain, fever and inflammation. It belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs). The active ingredient is available in prolonged-release capsule form, as eye drops and as a solution. Prolonged-release capsules are special capsules that release the active ingredients with a delay. They are usually hard capsules that dissolve in the stomach and release micro-pellets. These have an enteric coating that dissolves in the small intestine with a time delay. Only then can the active ingredient be absorbed by the small intestine. Indomethacin is an indole acetic acid derivative that is often present as a white/yellowish crystalline powder and is insoluble in water. Indometacin is also available as a prodrug in the form of acemetacin. A prodrug is an inactive substance that is only converted into its active form in the body, where it is supposed to work.

Indomethacin works by inhibiting the enzyme cyclooxygenase, or COX for short. This is often referred to as a COX inhibitor. By binding the active ingredient to the binding site, the actual substrate, namely arachidonic acid, cannot bind to the receptor. The inhibition of cyclooxygenase leads to a decrease in prostaglandin synthesis. Prostaglandins, in turn, are involved in inflammatory reactions. There are several cyclooxygenase enzymes and indomethacin inhibits all of them. Unlike other NSAIDs, it also inhibits the enzyme phospholipase A2. It is responsible for the release of arachidonic acid from phospholipids.

Indomethacin is broken down in the liver. The bioavailability, i.e. the percentage of the active ingredient that is available in the blood, is 90%. This high figure is probably due to the fact that indomethacin is not subject to the first-pass effect (this has not yet been fully clarified). The first-pass effect occurs with most active substances that are absorbed in the stomach or small intestine. The active substance is absorbed through the mucous membrane of the stomach or small intestine and transported through the portal vein (vena portae) to the liver. In the liver, before the active ingredient enters the systemic circulation, it is metabolized for the first time, so that the active ingredient is then available to the body to a lesser extent. The first-pass effect has a major influence on the bioavailability of the respective active ingredients in the body. The half-life, i.e. the time the body needs to excrete half of the active ingredient, is 4.5 hours. The maximum plasma concentration (Cmax), i.e. the maximum concentration of the active ingredient in the blood plasma (liquid cell-free part of the blood), is reached after around 1 to 1.5 hours.

Always take indomethacin exactly as described in the package leaflet or as advised by your doctor.

Adults:

The usual recommended dose is 75 mg twice daily .

The maximum daily dose of 200 mg should NOT be exceeded.

Children & adolescents:

Use under the age of 18 is NOT recommended!

The following side effects may occur:

Very common:

• Headache
• dizziness
• Drowsiness

Frequent:

• Depression
• Fatigue
• Nausea
• Loss of appetite
• vomiting
• abdominal pain
• constipation
• Diarrhea

Occasionally:

• Noises in the ears (tinnitus)
• Hearing disorders
• Bleeding in the gastrointestinal tract
• Breakthrough of existing intestinal damage
• Flatulence
• Inflammation of the gastric mucosa (gastritis) or the oral mucosa
• Fluid retention
• Hair loss

Rarely:

• Hypersensitivity reactions (itching, (skin) rash)
• Inflammation of blood vessels in the skin
• Inflammatory, pressure-sensitive skin nodules
• Breathing difficulties
• shortness of breath
• drop in blood pressure
• shock
• Swelling in the area of the face
• pulmonary edema
• Mental disorders
• psychotic states
• confusion
• blurred vision
• double vision
• Pain in the area of the eyeball
• anxiety
• fainting
• drowsiness
• Tingling and numbness in the extremities
• speech disorders
• Nervous disorders
• insomnia
• Worsening of epilepsy or Parkinson's disease
• Muscle twitching
• muscle weakness
• convulsions
• coma
• Hearing loss
• tachycardia
• arrhythmias
• palpitations
• Cardiac insufficiency
• chest pain
• high blood pressure
• low blood pressure
• Liver inflammation with jaundice
• Ulcers and bleeding in the gastrointestinal tract (incl. oesophagus)
• Bleeding in the vagina
• breast changes
• Sensitivity to touch
• hot flushes
• Increased sweating
• nosebleeds
• Changes in blood values
• Excretion of sugar via the urine
• Increase in urea and nitrogen in the blood

Very rare:

• Changes in blood count
• Life-threatening coagulation disorders
• Deposits and pathological changes in the eye area
• Protein excretion via the urine
• kidney diseases
• Severe skin reactions (blistering, peeling)

Frequency unknown:

• Pancreatitis

Interactions may occur if the following medicines are taken at the same time:

• Medication containing cortisone
• other NSARs
• Medication to inhibit blood clotting
• Medication to lower blood sugar levels
• lithium
• Selective serotonin reuptake inhibitors (SSRIs)
• probenecid
• Drugs for dehydration
• Antihypertensive medication
• digitalis preparations
• phenylpropanolamine
• cyclosporine
• methotrexate
• phenytoin
• alcohol

Indomethacin must NOT be taken in the following cases:

• if you are allergic to indomethacin
• if you have had an allergic reaction to other NSAIDs in the past
• past gastrointestinal bleeding with the use of other NSAIDs
• current ulcers or bleeding in the gastrointestinal tract
• cerebral hemorrhage or other active bleeding
• in the case of unexplained blood formation and coagulation disorders
• for cardiac insufficiency
• for pain treatment after bypass operations

Indomethacin can be used from the age of 18.

Pregnancy

In pregnancy, indomethacin should NOT be used in the last two trimesters of pregnancy (2nd and 3rd trimester).

The experience with indomethacin is moderate, although high for the group of NSAIDs. In the first trimester of pregnancy (1st trimester), no correlation between the use of indomethacin and an increased risk of malformation in the unborn baby could be established. However, there are only a few reports on this, but also no reports that prove an increased risk of malformations.

The group of NSAIDs can cause a blockage of the ductus arteriosus botalli in the unborn child in the 2nd and 3rd trimester. This is a vascular connection between the heart and lungs (between the aorta and the pulmonary trunk). The blockage can lead to kidney dysfunction, high blood pressure and intestinal inflammation (small and large intestine) in the newborn. There are many reports on this, especially from the 28th week of pregnancy.

Alternatives to indomethacin are:

• Paracetamol, which can be used throughout pregnancy
• Ibuprofen, which pregnant women can use in the 1st and 2nd trimester of pregnancy

Breastfeeding

Indomethacin should NOT be used while breastfeeding, as it can lead to serious side effects in the infant, such as cerebral hemorrhage or kidney failure. Accidental ingestion of indomethacin does not require restriction of breastfeeding.

As an alternative, breastfeeding mothers can use the following active ingredients:

• Ibuprofen
• diclofenac