Indomethacin in pregnancy and its possible consequences

Indomethacin belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) of non-selective action.

This drug is produced almost under four dozens of trade names: Indocid, Indopal, Intaban, Articin, Dolopas, Matarril and others.

The main question that many pregnant women ask are whether Indomethacin can be used during pregnancy.

Medicaid answer to it is known: use Indomethacin during pregnancy is contraindicated, which, in fact, is indicated in the instructions to the drug.

Read the instructions for prescribing medicines so as not to harm your health and not endanger the future child.

[1], [2], [3]

Indications Indomethacin in pregnancy

In addition to anti-inflammatory action, NSAIDs can cope with the pain of any etiology and localization, fever and swelling. And Indomethacin indications include headache and toothache; otitis, pharyngitis and tonsillitis; arthritis, arthrosis, gout, myositis and neuralgia.

Like other non-steroidal anti-inflammatory drugs, this drug is taken with pain accompanied by menstruation, inflammation of the bladder and kidneys, uterus, appendages, prostate, as well as thrombophlebitis and varicose veins.

However, in obstetrical practice, Indomethacin is sometimes given from a tonus during pregnancy, that is, with  hypertension of the uterus, which in some pregnant women is accompanied by painful pain. But Indomethacin does not affect the cause of this condition, and with constantly increased stress of the muscular walls of the uterus, according to the treatment regimen, spasmolytics, magnesium and pyridoxine (vitamin B6) are usually used, and various relaxation techniques are used.

Such variants are also not excluded, when obstetricians prescribe antibacterial and diuretics, as well as Indomethacin in case of polyhydramnios of pregnancy - if an excess of physiological norm of amniotic (amniotic fluid) is detected.

[4], [5], [6]

Release form

Indomethacin is available in the form of tablets and capsules (25 mg each); rectal suppositories (candles of 0.05 and 0.1 g); solution for injection (in ampoules of 1 ml); 10% of ointment (in tubes of 40 g).

[7], [8], [9]

Pharmacodynamics

The versatile therapeutic effect of Indomethacin on derivatives of indoacetic acid is provided by the inactivation of the enzyme cyclooxygenase (COX1 and 2), resulting in certain changes in the metabolism of unsaturated fatty arachidonic acid (cis-5,8,11,14-eicosatetraene) acid. In turn, the formation of prostaglandins (mediators of the nociceptive system), prostaglandins E-1 (pyrogenic mediators) and thromboxanes (providing the process of platelet aggregation) that are produced during the metabolism of arachidonic acid ceases or significantly decreases.

Due to the suppression of inflammatory reactions, pain stops and inflammation and swelling pass.

[10], [11], [12], [13]

Pharmacokinetics

Indomethacin is well absorbed when using all forms. The level of bioavailability of the drug taken in the form of tablets inside is 98%, in the form of rectal suppositories - 90%, in the form of ointment - about 80%. With the blood serum proteins bind almost 90% of the active substance with reaching a maximum concentration after 60-100 minutes.

Indomethacin overcomes the blood-brain barrier and penetrates the placenta, enters the breast milk.

Biotransformation of the drug passes in the liver, and elimination from the body (partially unchanged) occurs with urine and feces.

[14], [15]

Dosing and administration

The standard single dose of the tablet form of Indomethacia is 25 mg, the number of doses taken during the day is no more than three. The maximum permissible daily dose is 100-125 mg.

Suppositories are applied rectally - one twice a day (the second time before going to bed).

Overdose of this drug leads to an increase in its side effects and the development of acidosis, seizures and fainting.

[18], [19], [20]

Contraindications

In the list of contraindications Indomethacin is noted:

• stomach ulcers and duodenal ulcers;
• enterokolit;
• bronchial asthma;
• congenital heart disease and chronic heart failure;
• arterial hypertension;
• pronounced functional insufficiency of the liver and kidneys;
• low platelet count in the blood;
• mental disorders and mental illness;
• age is less than 14 years.

Indomethacin is contraindicated in pregnancy (why - read further).

In addition, the rectal suppository is not used for hemorrhoids and proctitis.

Why is it contraindicated to use Indomethacin in pregnancy?

Studies concerning NSAIDs, which can be recommended to pregnant women by under-qualified doctors, are carried out for many years. And their results confirm the risk of negative effects of drugs of this pharmacological group.

Possible consequences for the fetus of any form of indomethacin, including the effects on the child of indomethacin in suppositories during pregnancy are manifested by a decrease in the volume of amniotic fluid (leading to congenital anomalies), a violation of acid-base balance of the body (acidosis), kidney deficiency.

You can not use Indomethacin in early pregnancy because of the increased risk of delaying intrauterine development of the fetus, as well as the development  of left ventricular hypoplasia syndrome  . This may be due to the lack of phospholipids necessary for the formation of cellular and cytoplasmic membranes of the organ-forming tissues of the embryo and fetus.

Indomethacin and most NSAIDs are contraindicated and at later stages of pregnancy. And the reasons for this are very serious. First, too early closure of the botulinum duct can occur-the arterial duct, which connects the pulmonary arterial blood vessel and the dorsal aorta emanating from the right ventricle of the heart. The result of premature closure of this duct is the development of congenital heart disease. Also, the fetus may have increased pulmonary blood flow with  persistent pulmonary hypertension of newborns.

As studies have shown, in the last trimester of pregnancy, closer to the term of delivery, the activity of specific enzymes of the placenta tissues for cleavage of phospholipids significantly increases, which is explained by the beginning of the process of preparation for childbirth. The fact is that for their initiation, a sufficient high level of prostaglandins (referred to in the description of the pharmacodynamics of indomethacin) is necessary, and the source for their synthesis is free fatty arachidonic acid.

Thus, if you use Indomethacin suppository in the 3rd trimester of pregnancy, the fetoplacental system will receive less arachidonic acid, and this can cause weakness of labor and various complications of labor.

Also, due to a violation of the metabolism of arachidonic acid and its lack, the secretion of thromboxanes decreases, which ensure normal coagulation of the blood. That is why the use of any NSAIDs at late gestation may lead to the birth of infants with platelet-like disorders and hemorrhagic syndrome.

[16]

Side effects Indomethacin in pregnancy

In addition to an allergic reaction down to anaphylaxis, indomethacin can have side effects that manifest themselves:

• nausea, vomiting, abdominal pain, impaired intestinal function;
• increased activity of liver enzymes and bilirubin levels;
• tachycardia and arrhythmia, increased blood pressure;
• headache, increased fatigue, sleep disorders, depressive condition;
• deterioration of vision (with opacity of the cornea) and hearing, taste disorders;
• a violation of the kidneys (with damage to nephrons and renal papillae) and a decrease in the volume of excreted urine;
• increased blood glucose and urine, increased potassium ions in blood plasma.

[17]

Interactions with other drugs

The combination of indomethacin with drugs of the corticosteroid group can lead to gastric bleeding.

NSAIDs, including indomethacin, potentiate the action of insulin and indirect anticoagulants. In addition, indomethacin reduces the antihypertensive effect of drugs of the group of beta-adrenoblockers (used at elevated blood pressure), as well as diuretic diuretic diuretic effect and contraceptive effect of hormonal birth control pills.

[21], [22], [23], [24], [25]

Reviews

The difficult question is: should the future mother trust the doctor watching the course of pregnancy, or should all precautions be taken for all prescriptions? At the same time, no feedback about this or that drug on various women's online forums for pregnant women will not help to solve their health problems ...

Only reliable information about medicines that can be prescribed during pregnancy will help to protect yourself from possible negative consequences.