Domperidone-Teva

The main metabolism of domperidone occurs with the participation of the CYP3A4 isoenzyme. in
vitro
study has demonstrated that concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma concentrations of domperidone.

Separate in
vivo
pharmacokinetic/pharmacodynamic interaction studies of domperidone with oral ketoconazole or erythromycin in healthy volunteers confirmed significant inhibition of the CYP3A4-mediated first pass metabolism of domperidone by these drugs.

Increased risk of interval prolongation

QT
due to pharmacodynamic and/or pharmacokinetic interactions
When domperidone 10 mg orally administered four times daily and ketoconazole 200 mg twice daily was coadministered, a mean QT prolongation of 9.8 ms was observed during the observation period, with individual time variations points in the range of 1.2-17.5 ms. When co-administered with domperidone 10 mg orally four times daily and erythromycin 500 mg orally three times daily, the mean QT prolongation during the observation period was 9.9 ms, with individual time point variations ranging from 1.6 to 14. 3 ms. The Cmax and AUC of domperidone at steady state were increased approximately threefold in each of these interaction studies. In these studies, domperidone monotherapy 10 mg orally four times daily caused an increase in mean QTc interval of 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), whereas ketoconazole monotherapy (200 mg twice daily) day) and erythromycin monotherapy (500 mg three times daily) resulted in an increase in the QTc interval of 3.8 and 4.9 ms during the observation period, respectively.

Concomitant use with the following medications is contraindicated:

Drugs that prolong the QTc interval

- class IA antiarrhythmic drugs (for example, disopyramide, hydroquinidine, quinidine);

- class III antiarrhythmic drugs (for example, amiodarone, dofetilide, drondarone, ibutilide, sotalol);

- some antipsychotic drugs (for example, haloperidol, pimozide, sertindole):

- some antidepressants (for example, citalopram, escitalopram);

- some antibiotics (for example, erythromycin, levofloxacin, moxifloxacin, spiramycin);

- some antifungal drugs (for example, pentamidine);

- some antimalarial drugs (especially halofantrine, lumefantrine);

- some gastrointestinal drugs (for example, cisapride, dolasetron, prucalopride);

- some antihistamines (for example, mequitazine, mizolastine);

- some drugs used for cancer (for example, toremifene, vandetanib, vincamine);

- some other medications (for example, bepridil, difemanil, methadone);

- potent inhibitors of CYP3A4 (regardless of the effects that prolong the QT interval), namely: HIV protease inhibitors; systemic azole antifungals; some macrolides (eg, erythromycin, clarithromycin and telithromycin).

Concomitant use of the following medications is not recommended

Moderate inhibitors of the CYP3A4 isoenzyme, namely diltiazem, verapamil and some macrolides.

Concomitant use of the following drugs requires caution

Caution should be exercised during the simultaneous use of drugs that induce bradycardia and hypokalemia, as well as macrolides that prolong the QT interval: azithromycin and roxithromycin (clarithromycin is contraindicated because it is a potent inhibitor of the CYP3A4 isoenzyme). The above list of drugs is typical and not exhaustive.

Buy Domperidone film-coated tablets 10 mg No. 30 in pharmacies

Trade name of the drug:

Domperidone-Teva

International nonproprietary name:

domperidone

Dosage form:

film-coated tablets

Compound

1 tablet contains:

active ingredient: domperidone (domperidone maleate) 10.0 (12.73) mg;

excipients: lactose monohydrate 50.00 mg, corn starch 10.00 mg, sodium lauryl sulfate 0.20 mg, povidone-K30 3.00 mg, microcrystalline cellulose 23.32 mg, colloidal silicon dioxide 0.25 mg, magnesium stearate 0 .50 mg; shell (hypromellose 2.80 mg, propylene glycol 0.30 mg, talc 0.70 mg, titanium dioxide E171 1.20 mg).

Description

White or off-white, round, biconvex, film-coated tablets, debossed with “Do 10” on one side. On a cross section, the core is white.

Pharmacotherapeutic group:

antiemetic - dopamine receptor blocker central

Pharmacological properties

Pharmacodynamics

Domperidone is a dopamine receptor blocker with antiemetic effects. The antiemetic effect is due to a combination of peripheral (gastrokinetic) action and inhibition of dopamine receptors in the trigger zone of brain chemoreceptors located outside the blood-brain barrier in the area postrema. When taken orally, domperidone increases the reduced pressure in the esophagus, improves antroduodenal motility and accelerates gastric emptying without affecting gastric secretion. Domperidone increases the secretion of prolactin in the pituitary gland.

Pharmacokinetics

When taken orally on an empty stomach, domperidone is rapidly absorbed, its maximum plasma concentrations are reached within 30-60 minutes. Low absolute bioavailability after oral administration (about 15%) is due to the “first pass” effect through the liver. Although in healthy volunteers the bioavailability of domperidone is increased when taken after a meal, patients with gastrointestinal complaints should take domperidone 15-30 minutes before meals. With a decrease in the acidity of gastric juice, a violation of the absorption of domperidone is observed. Pre-administration of cimetidine and sodium bicarbonate reduces the bioavailability of domperidone. When taken orally after a meal, it takes slightly longer to achieve maximum absorption.

When taken orally, domperidone does not accumulate or induce its own metabolism. Domperidone is 91-93% bound to plasma proteins. Domperidone is distributed in various tissues of the body, is found in breast milk, but does not penetrate the blood-brain barrier. The concentration of domperidone in breast milk is 10-50% of the concentration in blood plasma.

Metabolism of domperidone occurs in the liver and in the intestinal wall by hydroxylation and N-dealkylation with the participation of the isoenzymes CYP3A4, CYP1A2 and CYP2E1.

Domperidone is excreted by the intestines (66%) and kidneys (33%), incl. unchanged (10% and 1%, respectively). The half-life is 7-9 hours.

Pharmacokinetics in special groups of patients

In patients with a serum creatinine concentration of more than 0.6 mmol/l, the half-life ranges from 7.4 to 20.8 hours, while the concentration of domperidone in the blood plasma is reduced.

Indications for use

To relieve symptoms of nausea and vomiting.

Contraindications for use

- Hypersensitivity to domperidone or any other component of the drug. — Prolactin-secreting tumor of the pituitary gland (prolactinoma). - Gastrointestinal bleeding. — Perforation of the gastrointestinal tract. — Mechanical obstruction of the intestine. - Liver failure of moderate to severe severity. - In patients with prolongation of cardiac conduction intervals, especially the QTc interval, in patients with severe electrolyte imbalance or concomitant cardiac diseases, such as chronic heart failure. - Simultaneous use with drugs that prolong the QT interval, with the exception of apomorphine (see sections “Interaction with other drugs” and “Special instructions”). - Concomitant use of ketoconazole for oral administration, erythromycin for oral administration or other potent inhibitors of the CYP3A4 isoenzyme that cause prolongation of the QT interval, such as fluconazole, clotrimazole, clarithromycin, amiodarone and telithromycin (see section "Interaction with other drugs"). - Hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption. - Breastfeeding period. - Pregnancy. — Children under 12 years of age or weighing less than 35 kg.

Carefully

Kidney failure; simultaneous use of drugs that induce the development of bradycardia and hypokalemia, as well as macrolides that prolong the QT interval - azithromycin and roxithromycin.

Use during pregnancy and breastfeeding

There are limited post-marketing data on the use of domperidone in pregnant women.

An animal study demonstrated reproductive toxicity at high maternal dose levels. The possible risk to humans is unknown. Therefore, domperidone should be used during pregnancy only if the expected therapeutic benefit for the mother is justified.

Domperidone is excreted in breast milk in lactating female rats (mainly as metabolites: maximum concentrations of 40 and 800 mg/ml after oral or intravenous administration of 2.5 mg/kg, respectively).

Domperidone is excreted in women's breast milk, and breastfed infants may receive less than 0.1% of the maternal weight-adjusted dose. We cannot exclude the possibility of undesirable effects, especially cardiac ones, in infants during breastfeeding.

It is necessary to make a decision to stop breastfeeding or discontinue/abstain from domperidone therapy, assessing the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Caution is advised if there are risk factors for QTc prolongation in breastfeeding infants.

Directions for use and doses

Inside, before meals, with a sufficient amount of water. When using the drug after a meal, the absorption of the drug may slow down somewhat.

Adults and children over 12 years of age weighing more than 35 kg

1 tablet 3 times a day. The maximum daily dose is 30 mg/day. The duration of treatment should not exceed 1 week. Further use of the drug is possible after consulting a doctor.

Patients should try to take each dose at the scheduled time. If a scheduled dose is missed, it should be omitted and the usual dosage regimen should be resumed. Do not duplicate doses of the drug to make up for a missed dose.

In case of moderate to severe liver failure, the use of Domperidone-Teva is contraindicated.

For mild liver failure, no dose adjustment is required.

In case of renal failure, it is recommended to reduce the frequency of taking Domperidone-Teva to 1-2 times a day.

Side effect

Adverse reactions are systematized according to the World Health Organization (WHO) Classification: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100) , rare (from ≥1/10000 to <1/1000), very rare (<1/10000), frequency unknown (cannot be determined based on available data).

Allergic reactions: very rarely - allergic reactions, including anaphylaxis, anaphylactic shock, anaphylactoid reactions and angioedema.

From the endocrine system: rarely - increased concentration of prolactin.

From the nervous system: very rarely - extrapyramidal disorders, agitation, nervousness, convulsions, drowsiness, headache; frequency unknown - restless legs syndrome (exacerbation in patients with Parkinson's disease).

From the cardiovascular system: frequency unknown - prolongation of the QT interval, ventricular arrhythmia, sudden cardiac death (see section "Special Instructions").

From the digestive system: rarely - gastrointestinal disorders; very rarely - intestinal spasm, diarrhea.

From the skin: very rarely - itching, skin rash, urticaria.

From the reproductive system and mammary glands: rarely - galactorrhea, gynecomastia, amenorrhea.

Laboratory indicators: very rarely - deviation of liver function tests from the norm.

Description of selected adverse reactions

Since the pituitary gland is located outside the blood-brain barrier, domperidone may cause an increase in prolactin concentrations. In rare cases, such hyperprolactinemia can lead to the development of neuroendocrine side effects such as galactorrhea, gynecomastia and amenorrhea.

Extrapyramidal side effects are very rare in newborns and infants and exceptional in adults. These side effects resolve spontaneously and completely when treatment is stopped.

Other effects related to the nervous system, such as seizures, agitation and drowsiness, are also very rare and are mainly reported in infants and children.

Overdose

Symptoms of overdose include drowsiness, confusion and extrapyramidal disturbances, especially in children.

Treatment. There is no specific antidote. In case of overdose, gastric lavage and the use of activated charcoal may be effective. Close monitoring and supportive care are recommended.

To relieve extrapyramidal disorders, m-anticholinergic blockers and drugs used to treat parkinsonism may be effective.

Interaction with other drugs

The main metabolism of domperidone occurs with the participation of the CYP3A4 isoenzyme. An in vitro study has demonstrated that concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma concentrations of domperidone.

Separate in vivo pharmacokinetic/pharmacodynamic interaction studies of domperidone with oral ketoconazole or erythromycin in healthy volunteers confirmed significant inhibition of CYP3A4-mediated first pass metabolism of domperidone by these drugs.

Increased risk of QT prolongation due to pharmacodynamic and/or pharmacokinetic interactions

When coadministered with domperidone 10 mg orally four times daily and ketoconazole 200 mg twice daily, a mean QT prolongation of 9.8 ms was observed during the observation period, with individual time point changes ranging from 1.2 to 17. 5 ms. When co-administered with domperidone 10 mg orally four times daily and erythromycin 500 mg orally three times daily, the mean QT prolongation during the observation period was 9.9 ms, with individual time point variations ranging from 1.6 to 14. 3 ms. The Cmax and AUC of domperidone at steady state were increased approximately threefold in each of these interaction studies. In these studies, domperidone monotherapy 10 mg orally four times daily caused an increase in mean QTc interval of 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), whereas ketoconazole monotherapy (200 mg twice daily) day) and erythromycin monotherapy (500 mg three times daily) resulted in an increase in the QTc interval of 3.8 and 4.9 ms during the observation period, respectively.

Concomitant use with the following medications is contraindicated:

Drugs that prolong the QTc interval:

- class IA antiarrhythmic drugs (for example, disopyramide, hydroquinidine, quinidine); - Class III antiarrhythmic drugs (for example, amiodarone, dofetilide, dronedarone, ibutilide, sotalol); - some antipsychotic drugs (for example, haloperidol, pimozide, sertindole); - some antidepressants (for example, citalopram, escitalopram); - some antibiotics (for example, erythromycin, levofloxacin, moxifloxacin, spiramycin); - some antifungal drugs (for example, pentamidine); - some antimalarial drugs (especially halofantrine, lumefantrine); - some gastrointestinal drugs (for example, cisapride, dolasetron, prucalopride); - some antihistamines (for example, mequitazine, mizolastine); - some drugs used for cancer (for example, toremifene, vandetanib, vincamine); - some other medications (for example, bepridil, difemanil, methadone); - use together with apomorphine is possible only if the benefits of joint use outweigh the risks, and only if the recommended precautions for joint use of drugs are strictly followed; - potent inhibitors of CYP3A4 (regardless of effects that prolong the QT interval), namely: HIV protease inhibitors, systemic azole antifungals, some macrolides (for example, erythromycin, clarithromycin and telithromycin).

Concomitant use of the following medications is not recommended

Moderate inhibitors of the CYP3A4 isoenzyme, namely diltiazem, verapamil and some macrolides.

Concomitant use of the following drugs requires caution

Combined use with levodopa

Domperidone can be used in combination with levodopa; no dose adjustment of levodopa is required. When used together, an increase in plasma concentrations of levodopa may be observed (maximum 30-40%).

The above list of drugs is typical and not exhaustive.

special instructions

Domperidone-Teva contains lactose and should not be used in patients with lactose intolerance, galactosemia, or impaired absorption of glucose or galactose.

Since only a very small amount of domperidone is excreted unchanged by the kidneys, single dose adjustment is unlikely to be necessary in patients with renal failure. When repeated use, the dosing frequency should be reduced to 1-2 times a day, depending on the severity of the deficiency; a dose reduction may also be required. During long-term therapy, such patients should be monitored regularly.

Taking the drug after meals slows down its absorption.

When using domperidone, prolongation of the QT interval on the electrocardiogram is possible. During post-marketing surveillance of patients receiving domperidone, there have been reports of very rare cases of QT prolongation and torsade de pointes (TdP). These reports included information about patients with underlying risk factors, electrolyte imbalances, and concomitant therapies that may contribute to adverse events.

Epidemiological studies have demonstrated that the use of domperidone was associated with an increased risk of developing serious ventricular arrhythmias or sudden coronary death (see section "Side effects").

The highest risk was observed in patients over 60 years of age, patients receiving domperidone in daily doses exceeding 30 mg, and in patients concurrently taking drugs that prolong the QT interval or CYP3A4 inhibitors.

Domperidone-Teva should be used in adults and children in the minimum effective dose.

Domperidone-Teva is contraindicated for use in patients with a history of prolonged cardiac conduction intervals, especially the QTc interval, in patients with severe electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with concomitant cardiac diseases, such as chronic heart disease. insufficiency, due to an increased risk of developing ventricular arrhythmias). Electrolyte imbalances (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia are known to increase proarrhythmogenic risk.

Domperidone is contraindicated when co-administered with drugs that prolong the QT interval, with the exception of apomorphine. Use together with apomorphine is possible only if the benefits of combined use of domperidone with apomorphine outweigh the risks, and only if the recommended precautions for combined use of drugs mentioned in the instructions for medical use of apomorphine are strictly followed.

Treatment with Domperidone-Teva should be discontinued if signs and symptoms that may be associated with cardiac arrhythmia occur, and patients should consult their physician.

Patients should be advised to immediately report any cardiac abnormalities to their physician.

Impact on the ability to drive vehicles and machinery

When taking Domperidone-Teva, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the possible risk of extrapyramidal disorders, convulsions, drowsiness, and headaches.

Release form

Film-coated tablets, 10 mg.

10 tablets in PVC/aluminum foil blisters; 1 or 3 blisters along with instructions for use in a cardboard box with first opening control.

Storage conditions

Store at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Best before date

4 years.

Do not use after the expiration date stated on the package.

Vacation conditions

Dispensed by prescription.

Domperidone

The antiemetic drug domperidone is a very important component of a traveler's first aid kit, because in addition to inhibiting inappropriately excessive “cleansing” activity of the body, it is used, among other things, to correct such dyspeptic phenomena as a feeling of fullness in the stomach, abdominal pain, excessive gas formation, heartburn and belching - all that can await a pilgrim in countries with extreme -exotic cuisine.

In pharmacological terminology, domperidone belongs to the group of dopamine receptor blockers. Vomiting can be induced at many different stages of the physiological ladder. At its lowest level - at the level of local irritation of the stomach - astringents and coating agents, as well as local anesthetics, cope well with vomiting. Domperidone reveals its “weapon” at the highest level - at the source of the generation of vomiting impulses, which is the trigger zone of the vomiting center, located in the medulla oblongata. The latter contains, among other things, dopamine-reactive receptors, blockade of which by domperidone causes a decrease in the excitability of the vomiting center. Clinically, the pharmacological effect of domperidone is manifested by activation of peristalsis of the antrum (bordering the duodenum) of the stomach, stimulation of gastric emptying when difficulties arise in this delicate process, increased muscle tone of the lower esophageal sphincter, elimination of nausea and vomiting.

It is believed that in addition to the central action, domperidone also has peripheral (gastrokinetic) activity. The drug does not affect gastric secretion. Another positive point is the inability of domperidone to penetrate the blood-brain barrier, which protects the patient from extrapyramidal adverse reactions (impaired muscle tone and motor activity). This circumstance is especially relevant for adults.

For chronic dyspeptic symptoms, domperidone is taken 15-30 minutes before meals, 10 mg (1 tablet) three times a day. It is possible to take the drug before bedtime. For children over 5 years of age, the dose is calculated based on body weight: 2.5 mg per 10 kg of weight when taken three times a day. As directed by your doctor, the given doses of domperidone can be doubled. For conditions accompanied by nausea and vomiting, the recommended single dose of the drug is 20 mg 3-4 times a day.

Renal failure is not a reason to stop taking the drug: it is only necessary to reduce its dosage by half.