Indomethacin

Indomethacin has analgesic, anti-inflammatory, antiplatelet and antipyretic effects.

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Indications Indomethacin

It is used to treat the following disorders:

• articular syndrome (this includes painful symptoms of osteoarthritis, gout, as well as rheumatoid arthritis and Bechterew's disease);
• dysmenorrhea;
• various neuralgic conditions;
• rheumatism;
• pain syndrome in the spine;
• myalgia;
• pathological conditions affecting connective tissues and having a diffuse form;
• inflammation in the area of soft tissues or joints that have a traumatic origin;
• inflammations or infections developing against the background of cystitis, adnexitis, prostatitis or diseases affecting the ENT organs (as an additional treatment).

Release form

The medication is released in the form of suppositories, tablets for oral administration, as well as ointment (tube volume 10-40 g) or gel (tube volume is 40 g).

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Pharmacodynamics

The drug is a derivative of indoleacetic acid and belongs to the category of NSAID drugs.

The drug acts by inhibiting the activity of the COX enzyme, which results in inhibition of metabolic transformations of eicosatetraenoic acid and weakening of PG binding. In addition, the drug slows down platelet aggregation processes.

Parenteral and oral use of the drug reduces the intensity of pain, especially joint pain (both during movement and at rest), reduces the symptoms of stiffness and swelling of the joints in the morning, and at the same time increases their range of motion. The anti-inflammatory effect occurs after 5-7 days of therapy.

When applied externally with gel or ointment, swelling and erythema are reduced, pain is eliminated, and in addition, the stiffness of the joints that occurs in the morning is reduced and the activity of their movements is increased.

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Pharmacokinetics

Orally administered tablets of the drug are absorbed from the gastrointestinal tract at high speed. The Cmax level in the serum is recorded after 2 hours.

After the processes of substance recirculation inside the intestine and liver, subsequent metabolic transformations are carried out inside the liver. In the plasma, unchanged active element and unbound metabolic products are found - desbenzoyl, as well as desmethyl with desmethyl-desbenzoyl.

The average half-life is about 4.5 hours. 60% of the drug is excreted through the kidneys (in an unchanged state and as metabolic products), and another 33% (as decay products) is excreted through the intestines.

Suppositories are quickly absorbed through the rectum. The bioavailability index in this case is approximately 80-90%. The connection with proteins inside the serum is about 90% of the active component.

The half-life ranges from 4 to 9 hours. Metabolic transformations occur inside the liver.

About 70% of the drug is excreted through the kidneys, and another 30% is excreted through the intestines.

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Dosing and administration

Scheme of use of tablets.

The size of the dosage portions in tablets is selected individually for each patient, taking into account the intensity of the negative manifestations of the diagnosed disease.

The medicine should be taken orally, immediately after or during meals. Usually the starting dose is 25 mg; it should be taken 2-3 times a day. If such a dosage does not bring results, it is allowed to double it (2-3 times a day 50 mg of the drug). A maximum of 0.2 g of the medicine is allowed per day.

After receiving the desired result, it is necessary to continue treatment for another 1 month, in the established or reduced dose. With long-term therapy, a maximum of 75 mg of Indomethacin per day is allowed.

At the initial stage of therapy, in case of relief of severe or acute conditions, it is necessary to use injections of the drug, and then transfer the patient to the use of suppositories or tablets. With the development of pain in the eyes, it is allowed to prescribe eye drops containing a similar active ingredient (for example, the drug Indocollyre).

Mode of application of suppositories.

Suppositories must be inserted rectally – into the rectum. This procedure is performed in the evening, before going to bed; the intestines must be cleaned beforehand. The medicine must be inserted as deeply as possible to ensure more intensive absorption.

Often, suppositories are administered in 50 mg doses, 3 times a day, or a regimen with a 1-time administration of a 0.1 g suppository is used. People with severe pain (for example, in the case of a gout attack) can be administered 0.2 g of the substance in suppositories per day (thereby supplementing the oral use of tablets).

Methods of using ointment or gel.

This form of the drug is used as an application and rubbed into the epidermis in the area where pain is felt. The medicine is applied in a thin layer. The epidermis must be cleaned before the procedure. Do not treat areas where there is any damage to the skin.

5% topical medications are applied 3-4 times per day. But applications of 10% medications should be performed 2-3 times per day. Single and maximum doses of Indomethacin are selected by calculating the amount (in cm) of ointment or gel taken from the tube.

For an adult, 4-5 cm of the medicine is enough; in this case, a maximum of 15-20 cm of the substance is allowed per day. A child should use dosages that are halved.

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Use Indomethacin during pregnancy

Suppositories with tablets should not be used during lactation or pregnancy.

The ointment and gel should not be used in the 3rd trimester (if the medicine needs to be applied to large areas of the body). Doctors believe that external forms of Indomethacin can be used with caution and in small doses during lactation and in the 1st and 2nd trimesters of pregnancy.

Contraindications

Main contraindications (suppositories and tablets):

• regional enteritis;
• liver failure or active liver disease;
• presence of intolerance;
• ulcerative colitis;
• BA;
• acute rhinitis or urticaria that developed as a result of previous use of NSAIDs;
• diagnosed hyperkalemia;
• ulcers that appear in the gastrointestinal tract;
• CRF (creatinine clearance level is below 30 ml/minute) or progressive kidney disease;
• presence of bleeding;
• recent coronary artery bypass grafting;
• disorders of blood clotting processes;
• congenital heart defects;
• problems with hematopoietic function (including leukopenia or anemia).

Suppositories are also not used in cases of signs of proctitis, symptoms of hemorrhoids or bleeding in the rectal area.

Caution is required when using in the following disorders:

• parkinsonism;
• somatic forms of diseases that have a severe degree of expression, as well as coronary heart disease and cerebrovascular disorders;
• depression, epilepsy, CHF;
• hyper- or dyslipidemia;
• mental disorders, as well as alcoholism or nicotine addiction;
• diseases in the area of peripheral arteries;
• elevated blood pressure, thrombocytopenia;
• diabetes mellitus, history of gastrointestinal ulcers;
• hyperbilirubinemia, as well as chronic renal failure (CC level is within 30-60 ml/minute);
• long-term use of other NSAIDs;
• presence of the bacterium H.pylori;
• liver cirrhosis, against the background of which portal hypertension is observed;
• combination with oral corticosteroids (eg, prednisolone), anticoagulants (such as warfarin), SSRIs (including citalopram, fluoxetine, and sertraline with paroxetine), and antiplatelet agents (such as aspirin or clopidogrel);
• appointment for elderly people.

Ointments and gels are prohibited to use in the following cases:

• damage to the integrity of the epidermis in the areas where treatment is performed;
• the presence of hypersensitivity.

External types of medication should be used with caution in the following disorders:

• any combinations when the patient has polyposis in the nose or paranasal sinuses, bronchial asthma and hypersensitivity to NSAIDs;
• ulcer in the gastrointestinal tract during the acute stage;
• problems with blood clotting processes;
• children under 6 years of age.

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Side effects Indomethacin

The use of suppositories and tablets may lead to the appearance of side effects:

• digestive disorders: vomiting, jaundice, bloating, anorexia, nausea, bleeding inside the gastrointestinal tract, gastritis, diarrhea or constipation and stomatitis. In addition, there is pain or discomfort in the abdominal area, ulcers, erosions or perforations inside the gastrointestinal tract, intestinal strictures, hepatitis and bleeding from the sigmoid colon or diverticulum;
• problems with the functioning of the nervous system: fainting, dysarthria, muscle weakness, headaches, paresthesia, depression and dizziness. In addition, there is a feeling of fatigue, anxiety or drowsiness, parkinsonism, sleep disorders, polyneuropathy, as well as mental disorders (depersonalization and psychotic manifestations), involuntary muscle contractions and cramps;
• disorders of the cardiovascular system: swelling, palpitations, hematuria, increase or decrease in blood pressure, cardiac insufficiency (in congestive form), arrhythmia, tachycardia and pain in the sternum;
• damage to the hematopoietic function: purpura, thrombocyto- or leukopenia, petechiae, hemolytic or aplastic anemia, and in addition, consumption coagulopathy and ecchymosis;
• urinary disorders: kidney problems, proteinuria, nephrotic syndrome, renal failure and tubulointerstitial nephritis;
• problems with the functioning of the sense organs: visual or hearing impairment, deafness, tinnitus, diplopia, as well as periorbital pain;
• metabolic disorders: glucosuria and hyperkalemia or -glycemia;
• signs of allergy: rash, urticaria, itching, alopecia, anaphylactic symptoms, angiitis and bronchial asthma. In addition, a sudden decrease in blood pressure, nodular erythema, pulmonary edema and exfoliative dermatitis. Dyspnea, Quincke's edema, Stevens-Johnson syndrome, RDSS, erythema multiforme and TEN also develop;
• Others: vaginal or nasal bleeding, hot flashes, gynecomastia, hyperhidrosis, and enlarged or tense breasts.

Suppositories can also cause tenesmus, irritation of the mucous membranes inside the rectum and exacerbation of colitis or hemorrhoids.

The use of ointment or gel may lead to such negative symptoms: manifestations of allergy, skin hyperemia or dryness, rashes or itching in the application area and a burning sensation. With prolonged use, general symptoms occur. Exacerbation of existing psoriasis occurs sporadically.

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Overdose

The development of signs of poisoning with the drug is usually noted when using its rectal or oral forms: a feeling of disorientation, memory impairment, nausea, dizziness, vomiting and severe headaches. In severe cases of intoxication, convulsions with paresthesia or numbness in the limbs appear.

Therapy is selected taking into account the negative symptoms recorded.

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Interactions with other drugs

Combination with lithium agents, methotrexate and digoxin increases their serum levels, which may increase their toxic properties.

Combined use with GCS, drugs containing ethyl alcohol, corticotropins and colchicine may increase the likelihood of bleeding within the gastrointestinal tract.

Combination with medications containing paracetamol increases the likelihood of developing nephrotoxic effects.

Concomitant use with insulin and other antidiabetic drugs potentiates their properties.

Use together with thrombolytics, anticoagulants, and antiplatelet agents with indirect activity potentiates their effect, as a result of which the likelihood of bleeding increases.

Combination with cyclosporine or gold drugs leads to increased nephrotoxicity (most likely due to suppression of PG binding processes in the kidneys).

Combination with potassium-sparing diuretics leads to a weakening of their effectiveness, resulting in an increased likelihood of developing hyperkalemia.

Treatment in which plicamycin, cefamandole, valproic acid, as well as cefoperazone and cefotetan are used with Indomethacin increases the risk of bleeding and increases the incidence of hypoprothrombinemia.

Combination with uricosuric or antihypertensive drugs causes a weakening of their medicinal activity.

Combined use with GCS, estrogens and other NSAIDs leads to an increase in their characteristic negative reactions.

Antacids, as well as cholestyramine, weaken the absorption of the drug.

Use together with zidovudine may provoke an increase in its toxic properties (due to the suppression of metabolic processes).

Combination with myelotoxic substances enhances their hematotoxic effect.

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Storage conditions

Indomethacin must be kept at temperatures not exceeding 25°C.

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Shelf life

Indomethacin can be used within 3-5 years from the date of manufacture of the therapeutic drug.

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Application for children

The tablet form of the medicine and suppositories are prohibited for use in children under 14 years of age, but the gel or ointment is allowed to be used from the age of 1 year.

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Analogues

Analogues of the drug are Adolor, Dicloran and Bioran with Diclofenac and Voltaren, as well as Aertal, Ortofen, Rapten with Diclac, Naklofen with Ketalgin and Ketorol with Piroxicam and Nise. Also on the list are Ketanov, Ibuprofen, etc.

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Reviews

Indomethacin (suppositories and tablets) often receives positive reviews regarding its anti-inflammatory and analgesic effect. Most people note that with its help they were able to eliminate swelling and pain that arose in the back, muscles and joints due to various diseases of the musculoskeletal system, without leading to the development of negative symptoms. But there are also comments from those to whom the drug did not help, on the contrary, causing the appearance of its characteristic negative manifestations. From all of the above, we can conclude that the medication is not suitable for everyone, so the selection of a drug from the NSAID category must be made individually for each patient.

The degree of effectiveness of the ointment or gel is also determined by the individual characteristics of the human body, but in such cases, even if the therapy does not produce results, the appearance of negative symptoms is unlikely.