Domperidone tablets 10mg, Teva No. 30

Dyspeptic symptoms such as:

• nausea

• vomiting

• a feeling of fullness in the epigastric region

• discomfort in the upper abdomen and regurgitation of gastric contents.

Inside before eating, drinking plenty of water. When using the drug after a meal, the absorption of the drug may slow down somewhat.

Adults and children over 12 years old weighing more than 35 kg:

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

Patients should try to take each dose at the scheduled time.

If the planned dose is missed, it should be excluded and the usual dosage regimen should be resumed. Do not duplicate the dose of the drug to make up for the missed dose.

In case of hepatic insufficiency of moderate and severe severity, the use of the drug Domperidone-Teva is contraindicated.

With mild hepatic impairment, dose adjustment is not required.

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

1 tablet contains:

active substance: 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).

• Hypersensitivity to domperidone or any other component of the drug;

• prolactin-secreting pituitary tumor (prolactinoma);

• gastrointestinal bleeding;

• perforation of the gastrointestinal tract;

• mechanical obstruction of the intestine;

• liver failure of moderate and severe severity;

• in patients with prolongation of cardiac conduction intervals, especially the QTc interval; in patients with severe electrolyte imbalance or concomitant heart diseases such as chronic heart failure;

• the simultaneous use of ketoconazole for oral administration of erythromycin for oral administration or other potent inhibitors of the CYP3A4 isoenzyme causing prolongation of the QT interval, such as fluconazole clotrimazole clarithromycin amiodarone and telithromycin (see the section 'Interaction with other medicinal products');

• hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

• breastfeeding period;

• children under 12 years old and weighing less than 35 kg.

With care: pregnancy; renal failure; simultaneous use of drugs that induce the development of bradycardia and hypokalemia, as well as macrolides that lengthen the QT interval: azithromycin and roxithromycin.

Trade name of the drug

Domperidone-Teva

International non-proprietary name

Domperidone

Dosage form

film-coated tablets

Composition

1 tablet contains:

active substance: 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 with 'Do 10' engraving on one side. Cross-section - white core.

Pharmacotherapeutic group

antiemetic agent - dopamine receptor blocker central

ATX code

A03FA03

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. The 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 increases when taken after meals, 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-intake of cimetidine and sodium bicarbonate reduces the bioavailability of domperidone. When taken orally after a meal, it takes a little longer to achieve maximum absorption.

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

Domperidone metabolism occurs in the liver and in the intestinal wall by hydroxylation and N-dealkylation with the participation of 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 patient groups

In patients with a serum creatinine concentration of more than 06 mmol / L, the half-life is from 74 to 208 hours, while the concentration of domperidone in the blood plasma is reduced.

Indications:

Dyspeptic symptoms such as:

• nausea

• vomiting

• a feeling of fullness in the epigastric region

• discomfort in the upper abdomen and regurgitation of gastric contents.

Contraindications:

• Hypersensitivity to domperidone or any other component of the drug;

• prolactin-secreting pituitary tumor (prolactinoma);

• gastrointestinal bleeding;

• perforation of the gastrointestinal tract;

• mechanical obstruction of the intestine;

• liver failure of moderate and severe severity;

• in patients with prolongation of cardiac conduction intervals, especially the QTc interval; in patients with severe electrolyte imbalance or concomitant heart diseases such as chronic heart failure;

• the simultaneous use of ketoconazole for oral administration of erythromycin for oral administration or other potent inhibitors of the CYP3A4 isoenzyme causing prolongation of the QT interval, such as fluconazole clotrimazole clarithromycin amiodarone and telithromycin (see the section 'Interaction with other medicinal products');

• hereditary lactose intolerance, lactase deficiency or glucose-galactose malabsorption;

• breastfeeding period;

• children under 12 years old and weighing less than 35 kg.

With care: pregnancy; renal failure; simultaneous use of drugs that induce the development of bradycardia and hypokalemia, as well as macrolides that lengthen the QT interval: azithromycin and roxithromycin.

Pregnancy and lactation:

There are limited post-marketing data on the use of domperidone in pregnant women. Animal studies have demonstrated reproductive toxicity at a high dose maternal toxicity. The possible risk to humans is unknown.

Therefore, domperidone should be used during pregnancy only if the intended therapeutic benefit to the mother is justified. Domperidone is excreted in breast milk in lactating female rats (mainly as metabolites: the maximum concentration is 40 and 800 ng / ml after oral administration or intravenous administration of 25 mg / kg, respectively).

Domperidone is excreted in breast milk in women and infants during breastfeeding may receive less than 01% of the maternal weight-adjusted dose. The possibility of undesirable effects, especially cardiological, in infants during breastfeeding cannot be ruled out. A decision must be made to discontinue breastfeeding or to discontinue / abstain from domperidone therapy, assessing the benefits of breastfeeding for the child and the benefits of treatment for the mother.

Care should be taken if there are risk factors for QTc prolongation in breastfeeding infants.

Method of administration and dosage:

Inside before eating, drinking plenty of water. When using the drug after a meal, the absorption of the drug may slow down somewhat.

Adults and children over 12 years old weighing more than 35 kg:

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

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

In case of hepatic insufficiency of moderate and severe severity, the use of the drug Domperidone-Teva is contraindicated.

With mild hepatic impairment, dose adjustment is not required.

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

Side effects:

The frequency of adverse events is classified as follows: very often (? 1/10) often (? 1/100 - <1/10) infrequently (? 1/1000 - <1/100) rarely (? 1/10000 - <1/1000 ) very rarely (<1/10000) the frequency is unknown (cannot be determined from the available data).

From the side of the immune system: very rarely - allergic reactions including anaphylaxis, anaphylactic shock, anaphylactoid reactions and angioedema.

From the endocrine system: rarely - an increase in the concentration of prolactin.

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

From the side of the cardiovascular system: frequency is unknown - prolongation of the QT interval; ventricular arrhythmia; sudden cardiac death (see the section 'Special instructions').

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

On the part of the skin and subcutaneous tissues: very rarely - itchy skin rash urticaria.

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

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

Description of selected adverse reactions

'Since the pituitary gland is located outside the blood-brain barrier, domperidone can cause an increase in the concentration of prolactin. 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 neonates and infants, and exceptional in adults. These side effects resolve spontaneously and completely immediately upon discontinuation of treatment.

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

Overdose:

Overdose symptoms include drowsiness, disorientation, and extrapyramidal disorders, 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 observation and supportive therapy are recommended.

For the relief of extrapyramidal disorders, m-anticholinergics and drugs used to treat parkinsonism may be effective.

Interaction:

The main metabolism of domperidone occurs with the participation of the isoenzyme CYP3A4. An in vitro study demonstrated that the combined use of drugs that significantly inhibit this enzyme can cause elevated plasma concentrations of domperidone.

Separate in vivo studies of pharmacokinetic / pharmacodynamic interactions of domperidone with ketoconazole or erythromycin for oral administration with the participation of healthy volunteers have confirmed a significant inhibition of CYPZA4-mediated first-pass metabolism of domperidone by these drugs.

Increased risk of lengthening the interval Q T due pharmacodynamic and / or pharmacokinetic interactions

With the combined use of domperidone 10 mg for oral administration four times a day and ketoconazole 200 mg twice a day, an average lengthening of the QT interval of 98 ms was observed during the observation period with changes in individual time points in the range of 12-175 ms. With the combined use of domperidone 10 mg for oral administration four times a day and erythromycin 500 mg for oral administration three times a day, the average QT prolongation during the observation period was 99 ms with changes in individual time points in the range of 16-143 ms. The steady state Cmax and AUC of domperidone were increased approximately threefold in each of these interaction studies.In these studies, monotherapy with domperidone 10 mg for oral administration four times a day caused an increase in the mean QTc interval of 16 ms (ketoconazole study) and 25 ms (erythromycin study), while monotherapy with ketoconazole (200 mg twice daily) and erythromycin monotherapy (500 mg three times a day) led to an increase in the QTc interval of 38 and 49 ms during the observation period, respectively.

Joint use with the following drugs is contraindicated

Medicines 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 (such as pentamidine);

- some antimalarial drugs (especially halofantrine lumefantrine);

- some gastrointestinal agents (for example, cisapride dolasetron prucaloprid);

- некоторые антигистаминные препараты (например меквитазин мизоластин);

- некоторые лекарственные препараты примен¤емые при онкологических заболевани¤х (например торемифен вандетаниб винкамин);

- некоторые другие лекарственные препараты (например бепридил дифеманил метадон);

- мощные ингибиторы CYP3A4 (независимо от эффектов удлин¤ющих интервал QT) а именно: ингибиторы ¬»„-протеазы; системные азольные противогрибковые препараты; некоторые макролиды (например эритромицин кларитромицин и телитромицин).

Ќе рекомендуетс¤ совместное применение следующих лекарственных препаратов

”меренные ингибиторы изофермента CYP3A4 а именно дилтиазем верапамил и некоторые макролиды.

—овместное применение следующих лекарственных препаратов требует осторожности

—ледует про¤вл¤ть осторожность при одновременном применении лекарственных препаратов индуцирующих брадикардию и гипокалиемию а также макролидов удлин¤ющих интервал QT: азитромицина и рокситромицина (кларитромицин противопоказан так как ¤вл¤етс¤ мощным ингибитором изофермента CYP3A4). ¬ышеуказанный список препаратов ¤вл¤етс¤ типичным и не исчерпывающим.

ќсобые указани¤:

ѕрепарат ?омперидон-“ева содержит лактозу поэтому его не следует примен¤ть у пациентов с непереносимостью лактозы галактоземией или нарушением абсорбции глюкозы или галактозы.

“ак как только очень небольшое количество домперидона выводитс¤ почками в неизмененном виде то вр¤д ли необходима коррекци¤ разовой дозы у пациентов с почечной недостаточностью. ѕри повторном применении частота дозировани¤ должна быть снижена до 1-2 раз в сутки в зависимости от т¤жести недостаточности; также может потребоватьс¤ снижение дозы. ѕри длительной терапии такие пациенты должны находитьс¤ под регул¤рным наблюдением.

ѕрием препарата после еды замедл¤ет его всасывание.

ѕри применении домперидона возможно удлинение интервала QT на электрокардиограмме. ¬ период пострегистрационного наблюдени¤ за пациентами получающими домперидон поступали сообщени¤ об очень редких случа¤х удлинени¤ интервала QT и желудочковой тахикардии типа 'пируэт'.

?анные сообщени¤ содержали информацию о пациентах с сопутствующими факторами риска нарушени¤ми электролитного баланса и о совместной терапии котора¤ могла способствовать развитию нежелательных ¤влений.

Ёпидемиологические исследовани¤ продемонстрировали что применение домперидона было св¤зано с повышенным риском развити¤ серьезных желудочковых аритмий или внезапной сердечной смерти (см. раздел 'ѕобочное действие'). Ќаиболее высокий риск наблюдалс¤ у пациентов старше 60 лет пациентов получавших домперидон в суточных дозах превышающих 30 мг и у пациентов параллельно принимающих лекарственные препараты удлин¤ющие интервал QT или ингибиторы CYP3A4.

ѕрепарат ?омперидон-“ева должен примен¤тьс¤ у взрослых и детей в минимальной эффективной дозе.

ѕрепарат ?омперидон-“ева противопоказан дл¤ применени¤ у пациентов с удлинением интервалов сердечной проводимости в анамнезе особенно интервала QTc у пациентов с выраженными нарушени¤ми электролитного баланса (гипокалиеми¤ гиперкалиеми¤ гипомагниеми¤) или брадикардией или у пациентов с сопутствующими заболевани¤ми сердца например хронической сердечной недостаточностью в св¤зи с повышением риска развити¤ желудочковых аритмий (см. раздел 'ѕротивопоказани¤'). Ќарушени¤ электролитного баланса (гипокалиеми¤ гиперкалиеми¤ гипомагниеми¤) или брадикарди¤ известны как состо¤ни¤ повышающие проаритмогенный риск.

Ћечение препаратом ?омперидон-“ева необходимо прекратить при возникновении признаков и симптомов которые могут быть св¤заны с сердечной аритмией а пациентам следует проконсультироватьс¤ со своим врачом.

Ќеобходимо рекомендовать пациентам немедленно сообщать о любых нарушени¤х со стороны сердца лечащему врачу.

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

ѕри приеме препарата ?омперидон-“ева следует соблюдать осторожность при управлении транспортными средствами и зан¤ти¤х другими потенциально опасными видами де¤тельности требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций из-за возможного риска возникновени¤ экстрапирамидных расстройств судорог сонливости головной боли.

‘орма выпуска/дозировка:

“аблетки покрытые пленочной оболочкой 10 мг.

”паковка:

ѕо 10 таблеток в блистеры из ѕ¬’/алюминиевой фольги; 1 или 3 блистера вместе с инструкцией по применению в картонную пачку.

”слови¤ хранени¤:

ѕри температуре не выше 25 ?—.

’ранить в недоступном дл¤ детей месте.

—рок годности:

4 года.

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

Vacation conditions

On prescription

Manufacturer

Teva Pharmaceutical Works Private Limited Company, Pallagi ut. 13, Debrecen, 4042, Hungary, Hungary

Marketing Authorization Holder / Organization Receiving Consumer Claims:

Teva Pharmaceutical Enterprises Co., Ltd