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Pharmacological properties of the drug Domrid

Domperidone is a dopamine antagonist and has an antiemetic effect. It practically does not penetrate the BBB, so the use of domperidone is rarely accompanied by extrapyramidal disorders, especially in adults, while domperidone stimulates the release of prolactin from the pituitary gland. The antiemetic effect is due to a combination of gastrokinetic action and antagonism to dopamine receptors in the chemoreceptor trigger zone, which is located outside the BBB. When taken orally, domperidone increases the duration of antral and duodenal contractions, accelerates passage through the stomach - the excretion of liquid and semi-solid fractions in healthy people and solid fractions in patients in whom this process has been slowed down, and also increases compression of the sphincter of the lower esophagus in healthy people. Domperidone does not affect gastric secretion. Domperidone is rapidly absorbed when administered orally on an empty stomach, reaching Cmax within 30–60 minutes. The bioavailability of domperidone when taken orally is about 15% due to intensive metabolism in the intestinal wall and in the liver. In healthy people, the bioavailability of domperidone increases when taken after meals; patients with gastrointestinal disorders should take domperidone 15–30 minutes before meals; in patients with reduced gastric acidity, the absorption of domperidone decreases. After taking cimetidine or sodium bicarbonate, the bioavailability of the drug when taken orally decreases. Domperidone is metabolized in the liver by hydroxylation and N-dealkylation. When studying the metabolism of the drug in vitro using diagnostic inhibitors, it was found that the CYP 3A4 isoenzyme is the main isoenzyme of the cytochrome P450 system, which takes part in the process of N-dealkylation of domperidone, while the CYP 3A4, CYP 1A2 and CYP 2E1 isoenzymes are involved in the process of aromatic hydroxylation domperidone. Plasma protein binding is 91–93%. Excreted in urine (31%) and feces (66%). Only a small amount of the drug is excreted unchanged (10% in feces and 1% in urine). Tmax from blood plasma after a single dose is 7–9 hours, but may increase in severe renal failure.

Domperidone

Domperidone

(lat.
domperidonum
, English
domperidone
) - a drug for the treatment of functional intestinal disorders, prokinetic, antiemetic.
Chemical compound
: 5-chloro-1-[1-[3-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)propyl]-4-piperidinyl]-1,3-dihydro-2H- benzimidazole-2-OH.
Empirical formula: C22H24Cl N5O2. Domperidone is the international nonproprietary name (INN) of the drug.
According to the pharmacological index, it belongs to the group “Gastrointestinal motility stimulants, including emetics.” According to ATC, it belongs to the group “Gastrointestinal motility stimulants” and has code A03FA03. Domperidone blocks dopamine D2 receptors and thus eliminates dopamine inhibition of the motor activity of the digestive system. Increases the duration of gastric antrum and duodenal peristalsis, prevents slow gastric emptying, and increases the tone of the lower esophageal sphincter. The antiemetic effect of domperidone is due to a combination of gastrokinetic action and blockade of chemoreceptors of the trigger zone of the vomiting center. Domperidone prevents the development or reduces the severity of vomiting and nausea.

Domperidone increases the level of prolactin in the blood.
After oral administration, domperidone is rapidly absorbed from the gastrointestinal tract. Food or low acidity of gastric juice slows down and reduces absorption. The maximum concentration of domperidone in the blood is reached after 0.5–1 hour. Found in small quantities in breast milk. It is subjected to intensive metabolism in the intestinal wall and liver (by hydroxylation and N-dealkylation) with the formation of hydroxydomperidone and 2,3-dihydro-2-oxo-1-H-benzimidazole-1-propionic acid, respectively. The half-life after a single dose is 7 hours and increases in chronic renal failure. 31% is excreted by the kidneys, of which 1% is excreted unchanged and 66% is excreted by the intestines (10% unchanged). Domperidone may accumulate in patients with liver disease.

Domperidone belongs to the second generation gastrokinetics and, unlike metoclopramide (trade names Cerucal , Reglan

etc.), does not penetrate the blood-brain barrier (BBB) ​​and does not cause extrapyramidal disorders characteristic of metoclopramide: spasm of the facial muscles, trismus, rhythmic protrusion of the tongue, bulbar type of speech, spasm of the extraocular muscles, spasmodic torticollis, opisthotonus, muscle hypertonicity, etc. . Also, unlike metoclopramide, domperidone does not cause parkinsonism: hyperkinesis, muscle rigidity. When taking domperidone, side effects of metoclopramide such as drowsiness, fatigue, tiredness, weakness, headaches, increased anxiety, confusion, and tinnitus are less common and less pronounced.

Also, while inferior in terms of its effect on gastrointestinal motility to the more effective prokinetic agent cisapride, domperidone does not have its serious side effects (ventricular arrhythmias, cardiac arrest, and even sudden death due to long QT syndrome). Therefore, domperidone is a more preferable prokinetic agent than metoclopramide and cisapride.

.

In case of overdose

With domperidone, the above extrapyramidal disorders and sedative effects are possible.
In this case, the use of activated carbon, anticholinergics or antihistamines is indicated. Indications for use
.
Nausea and vomiting, including in the presence of infections, with toxemia, radiation therapy, diet disorders, during endoscopic and radiopaque studies of the digestive tract, hiccups, postoperative or other atony of the stomach and intestines.
Feelings of bloating, fullness in the epigastrium, pain in the upper abdominal cavity, belching, flatulence, heartburn, reflux of gastric contents into the oral cavity. At the Department of Children's Diseases No. 2 of the Russian State Medical University, at the Russian Children's Clinical Hospital and the Moscow Research Institute of Pediatrics and Pediatric Surgery, studies were carried out in which it was found that taking domperidone (as opposed to mebeverine) leads to an increase in the rhythmicity coefficient of contractions of the gastrointestinal tract parts studied using electrogastroenterography compared to basal ones. values.

At the same time, there are studies showing that the prescription of dompidone as a prokinetic drug in the complex treatment of GERD in patients with diabetes mellitus is less effective in a number of parameters, such as the intensity of the reduction of esophageal symptoms (heartburn, regurgitation, dysphagia, odynophagia), in the normalization of pH-metry and peripheral electrogastroenterography compared with itopride (Fedorchenko Yu.L.).

Contraindications.

Hypersensitivity to domperidone, bleeding in the stomach or intestines, perforation of the stomach or intestines, mechanical intestinal obstruction, hyperprolactinemia, prolactinoma, pregnancy.
For children under 5 years of age and weighing less than 20 kg, taking domperidone tablets is not recommended. Part of domperidone passes into breast milk, so it is not recommended during breastfeeding (the Russian Ministry of Health* proposed to amend the instructions for film-coated tablets, 10 mg, in particular, the list of contraindications for use has been added: moderate and severe liver failure, pregnancy , breastfeeding period, children under 12 years of age or body weight up to 35 kg, simultaneous use of drugs that increase the QT interval and inhibitors of the CYP34A
).

Dosage forms

:
preparations containing domperidone are available in the form of an oral suspension, tablets, lozenges, film-coated tablets.
Side effects.

Digestive system:
spasm of smooth muscles of the gastrointestinal tract, dry mouth, stomatitis, thirst, heartburn, changes in appetite, constipation or diarrhea. Nervous system and sensory organs:
extrapyramidal disorders in overdose, headache, asthenia, irritability, nervousness, drowsiness, leg cramps, lethargy, conjunctivitis.
Allergic reactions:
skin rash, itching, urticaria, swelling.
Urinary system:
change in frequency of urination, burning, difficulty and pain when urinating.
Others:
increased levels of prolactin in the blood plasma, galactorrhea, gynecomastia, menstrual irregularities, mastalgia, palpitations.
( The letter* has added the list of side effects for film-coated tablets, 10 mg: very rarely - urticaria, anaphylactic shock, angioedema shock, convulsions, increased excitability and irritability, drowsiness, headache, changes in liver function tests; frequency unknown - ventricular tachycardia of the “pirouette” type, sudden coronary death.
)

Interaction.

Antacids and antisecretory drugs reduce bioavailability. Anticholinergics weaken the effect of domperidone. Antifungal drugs of the azole group, antibiotics of the macrolide group, and HIV protease inhibitors can block the metabolism of domperidone and increase its plasma level, so their combined use with domperidone requires caution. Concomitant use with monoamine oxidase inhibitors also requires caution. Domperidone does not affect the level of digoxin and paracetamol in the blood.

Trade names of drugs with active ingredients

domperidone: Damelium, Domet, Domperidone, Domperidone Hexal, Domstal, Motilak, Motilium, Motinorm, Motonium, Passazhiks.

Ukraine: Domrid, Domrid SR.

Domperidone is not approved by the FDA for use in the United States. Unlike the USA, in Canada, Japan, China, Israel, Great Britain and most European countries it has such permission.

Medicines with the complex active ingredient domperidone + omeprazole: Omez D and Omez DSR.

All drugs containing domperidone as an active ingredient, including combination drugs, have been transferred from over-the-counter to prescription

.**

Patient materials in English

(for UK, pdf):

• "Patient Information Leaflet for Domperidone Stomach Discomfort Relief Tablets (Domperidone 10 mg)", May 2012.
• "Domperidone 1 mg/ml Oral Suspension. Patient Information Leaflet", 05.11.2012
• "Package Leaflet: Information for the User. Domperidone 10 mg Tablets. Domperidone maleate"

* Letter from the Director of the Department of State Regulation of Medicines of the Ministry of Health of the Russian Federation A.G. Tsyndymeev No. 20-3/162 dated 03/05/2015 ** Letter from the Director of the Department of State Regulation of Medicines of the Ministry of Health of the Russian Federation A.G. Tsyndymeev No. 20-3/100 dated January 31, 2017

Resources for healthcare professionals regarding the use of domperidone

Printed publications

• Alekseeva E.V., Fominykh V.P., Tropinskaya N.S., Popova T.S. Use of the prokinetic drug domperidone in patients in the early postoperative period // Surgery. - No. 3. – pp. 62–69. – 2010.
• Ponomareva A.P., Rachkova N.S., Belmer S.V., Khavkin A.I. Peripheral electrogastroenteromyography in pediatric gastroenterology / M.: 2007, 48 p.
• Rebrov V.G., Loginov A.F., Kalinin A.V. Changes in the electrical activity of the stomach and intestines under the influence of motilium / Russian Journal of Gastroenterology, Hepatology, Coloproctology. —1997. - No. 4. - With. 42–45.
• Starostin B.D., Starostina G.A. Clinical and economic effectiveness of motilak in gastroesophageal reflux disease // News of Universities. North Caucasus region. Natural Sciences. Special issue. - 2005. - p. 51–52.
• Arkhipov V.V., Serebrova S.Yu. Safety of the use of prokinetics in the practice of a therapist using the example of domperidone (Motilac) // Russian Medical Journal. - 2007. - Volume 15. - No. 16. - p. 1218.
• Maev I.V., Dicheva D.T., Andreev D.N. Possibilities of using Domperidone in the complex therapy of GERD // Medical Council. 2012. No. 12. pp. 56–60.
• Fedorchenko Yu.L. Comparative characteristics of prokinetics in the treatment of gastroesophageal reflux disease in patients with diabetes // Experimental and clinical gastroenterology. 2013. No. 5. pp. 42–58.
• Kosenko P.M., Rudnev A.F., Mikhailenko P.A., Matveeva E.A. Electrophysiological assessment of the influence of prokinetics on the motility of the gastrointestinal tract // Young scientist. — 2021. — No. 17 (151). — pp. 125-127.

On the website GastroScan.ru in the “Literature” section there is a subsection “Prokinetics”, containing articles on the use of prokinetics in the treatment of diseases of the gastrointestinal tract.

Video

Still from video: Shavkuta G.V. Combined functional disorders of the esophagus and stomach: actual clinical practice and modern recommendations for patient management

Still from the video (with simultaneous translation into Russian): Serhat Bor (Turkey).
Diagnosis and treatment of GERD: what's new? On the website GastroScan.ru in the “Video” section there is a subsection for patients “Popular Gastroenterology” and a subsection “For Doctors”, containing video recordings of reports, lectures, webinars in various areas of gastroenterology for healthcare professionals.
Domperidone has contraindications, side effects and application features; consultation with a specialist is necessary. Back to section

Indications for use of the drug Domrid

A complex of dyspeptic symptoms that is associated with delayed evacuation of stomach contents, gastroesophageal reflux, esophagitis: a feeling of fullness, bloating, epigastric pain; belching, flatulence; nausea, vomiting; heartburn with or without belching stomach contents. Nausea and vomiting of functional, organic origin, due to food intake, as well as caused by radiation or drug therapy. A specific indication is nausea and vomiting caused by the use of dopamine agonists in Parkinson's disease (levodopa, bromocriptine).

Use of the drug Domrid

Domrid is recommended to be taken orally before meals. When taking the drug after a meal, absorption slows down somewhat. For chronic dyspepsia: - adults and children over 12 years old - 1 tablet (10 mg) 3 times a day 15-30 minutes before meals and, if necessary, before bedtime. If necessary, the indicated dose can be doubled. The maximum daily dose is 2.4 mg/kg body weight, but not more than 80 mg. For acute and subacute conditions (nausea, vomiting): - adults and children over 12 years old - 2 tablets (20 mg) 3-4 times a day 15-30 minutes before meals and, if necessary, before bedtime, but no more 80 mg per day.

How should the drug be stored correctly?

This medicine should be kept at a temperature of 15 to 25 degrees in a dark room. In addition, it is worth limiting children's access to this drug, because in large dosages it can cause significant harm to the baby’s body.

The drug can be stored for no more than two years. After this period has expired, the medicine should be thrown into the trash bin, because it will no longer be useful.

Factors influencing gastric motility

Side effects of the drug Domrid

Isolated cases of intestinal spasms have been observed; sometimes - extrapyramidal disorders in children and extremely rarely in adults, which disappear after stopping treatment. Domrid can induce an increase in plasma prolactin levels. In some cases, hyperprolactinemia can stimulate neuroendocrine manifestations (galactorrhea, gynecomastia, amenorrhea). With increased permeability of the BBB, the possibility of neurological symptoms cannot be excluded. Allergic reactions were extremely rarely detected: skin rash, itching.

Domperidone overdose, symptoms and treatment

Symptoms of overdose may include drowsiness, disorientation and extrapyramidal disorders, especially in children. In case of overdose, gastric lavage, intake of activated charcoal and medical supervision are recommended. To eliminate extrapyramidal symptoms, anticholinergic drugs, drugs for the treatment of parkinsonism, or antihistamines with anticholinergic effects are used.

List of pharmacies where you can buy Domperidone:

• Moscow
• Saint Petersburg

Special instructions for the use of the drug Domrid

It is recommended to take antacid or antisecretory drugs simultaneously with Domrid. Prescribe Domrid with caution to patients with liver failure, given the high degree of metabolism of domperidone in the liver. During long-term therapy, patients should be monitored regularly. In patients with severe renal failure (serum creatinine 6 mg/100 ml, i.e. 0.6 mmol/l), the half-life of domperidone is increased. Since a small percentage of the drug is excreted unchanged by the kidneys, there is no need for single dose adjustment for patients with renal failure, but when repeated administration, the frequency of dosing should be reduced to 1-2 times a day, depending on the severity of renal failure, a dose reduction may also be necessary . Use during pregnancy and breastfeeding During pregnancy and breastfeeding, the use of Domrid is possible if the expected benefit to the mother outweighs the potential risk to the fetus or child. The ability to influence the reaction rate when driving vehicles or working with other mechanisms Domrid in therapeutic doses does not affect the reaction rate when driving a car or working with other mechanisms.

Price

It is important to understand that the price of a medicine consists of several factors, namely:

• Pharmacy markup;
• Transportation costs;
• The price at which the goods were purchased.

It is worth understanding that the article shows average prices. If you need to know the price, please contact your nearest pharmacy. The drug is freely available.

Russia

In this country, the price for this drug was set at 353 rubles.

Ukraine

In this country, you will have to pay an average of 189 hryvnia for medicine.

Drug interactions Domrid

Anticholinergic drugs can neutralize the antidyspeptic effect of Domrid. Antacids and antisecretory drugs should not be taken simultaneously with Domrid, because they reduce its bioavailability. The main metabolic pathway of domperidone is mediated by cytochrome P450. With simultaneous use of domperidone with cytochrome P450 inhibitors (azole antifungals, macrolide antibiotics, HIV protease inhibitors, nefazodone), it is possible to increase the level of domperidone in the blood plasma. Studies of the interaction of domperidone and ketoconazole have shown that with the simultaneous use of domperidone at a dose of 10 mg 4 times a day and ketoconazole at a dose of 200 mg 2 times a day, a prolongation of the QT interval by 10-20 ms is observed. With domperidone monotherapy, both in similar doses and when taken in a daily dose of 160 mg (2 times higher than the maximum permissible daily dose), no clinically significant changes in the QT interval were observed. Concomitant use of domperidone with digoxin or paracetamol does not affect the level of these drugs in the blood. Domrid can be combined with antipsychotics, the effect of which it enhances; agonists of dopaminergic receptors (bromocriptine, levodopa), the side effects of which (digestive disorders, nausea, vomiting) it suppresses without inhibiting the main properties.

Reviews from people

If suddenly you have ever encountered the use of this remedy, then please leave your review about it. It is your opinion that can be very important for someone.

One of the most commonly used drugs for the treatment of the digestive system is the drug Domidon. Reviews about this product can be found in large numbers on the Internet. Having considered all the reviews, it becomes clear that the picture has a positive orientation

However, it is worth noting that at the first stage of treatment, people experience depression, nausea, and mood swings. In addition, the medicine has a relatively high cost, which not everyone likes, so they prefer cheaper analogues.