Motilium 10 mg 10 tablets — Made in France — Free Delivery

Pharmacological properties

Pharmacodynamics. Domperidone is a dopamine antagonist with antiemetic properties. domperidone slightly penetrates the geb. the use of domperidone is very rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the release of prolactin from the pituitary gland. its antiemetic effect is probably due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the chemoreceptor trigger zone, located outside the geb in the posterior field (area postrema). animal studies, as well as low brain concentrations, indicate a predominance of the peripheral action of domperidone on dopamine receptors.

Human studies have shown that when taken orally, domperidone increases pressure in the lower esophagus, improves antroduodenal motility, and accelerates gastric emptying. Domperidone does not affect gastric secretion.

Pharmacokinetics. Suction. Domperidone is rapidly absorbed after oral administration on an empty stomach, Cmax in blood plasma is reached after about 60 minutes. The low absolute bioavailability of oral domperidone (≈15%) is due to extensive first-pass metabolism in the intestinal wall and in the liver. Although in healthy people the bioavailability of domperidone increases when taken after meals, patients with gastrointestinal complaints should take domperidone 15-30 minutes before meals. Reduced gastric acidity reduces the absorption of domperidone. When the preparation is taken orally after a meal, the maximum absorption slows down somewhat.

Distribution. When taken orally, domperidone does not cumulate and does not induce its own metabolism; Cmax in blood plasma is reached after 90 minutes (21 ng / ml) after 2 weeks of oral administration at 30 mg / day was almost the same as after taking the first dose (18 ng / ml). Domperidone is 91–93% bound to plasma proteins. Studies of the distribution of domperidone, carried out in animals using a preparation labeled with a radioactive isotope, showed its significant distribution in tissues, but a low concentration in the brain. In animals, small amounts of the preparation  cross the placenta.

Metabolism. Domperidone is rapidly and extensively metabolized in the liver by hydroxylation and N-dealkylation.

Excretion in urine and feces accounts for 31 and 66% of the oral dose, respectively. Excretion of the preparation in unchanged form is a small proportion (10% - with feces and 1% - with urine). T½ from blood plasma after taking a single dose is 7-9 hours in healthy volunteers, but prolonged in patients with severe renal failure.

Indications

To reduce the severity of symptoms of nausea and vomiting.

Application

To reduce the severity of symptoms of nausea and vomiting, lasting 48 hours.

Adults and children over the age of 12 and weighing at least 35 kg: 1 tablet (10 mg) 3 times a day. The maximum daily dose is 3 tablets (30 mg / day).

It is recommended to take Motilium® before meals. The absorption of the preparation is somewhat delayed if taken after meals. The duration of treatment should not exceed 1 week.

Contraindications

Motilium® is contraindicated:

• patients with established hypersensitivity to the preparation or its excipients;
• patients with prolactin-secreting pituitary tumor (prolactinoma);
• patients with severe or moderate impairment of liver and / or kidney function (see SPECIAL INSTRUCTIONS);
• patients with a known lengthening of cardiac conduction intervals, in particular QTc, patients with significant electrolyte imbalance or with underlying heart diseases such as congestive heart failure (see SPECIAL INSTRUCTIONS);
• patients with liver failure;
• if stimulation of the motor function of the stomach can be dangerous, for example, with gastrointestinal bleeding, mechanical obstruction or perforation;
• concomitant use of ketoconazole, erythromycin or other potent inhibitors of CYP 3A4 is contraindicated;
• concomitant use of preparations that prolong the QT interval, such as fluconazole, erythromycin, itraconazole, oral ketoconazole, posaconazole, ritonavir, saquinavir, telaprevir, voriconazole, clarithromycin, amiodarone, telithromycinium.

Side effects

Estimation of the incidence of adverse reactions: very often (≥1 / 10); often (≥1 / 100 to 1/10); infrequently (≥1 / 1000 to 1/100); rarely (≥1 / 10,000 to 1/1000); very rare (1 / 10,000), including isolated data.

Subject to the recommendations for dosage and duration of treatment, domperidone is usually well tolerated, and adverse events occur infrequently.

From the immune system: very rarely - allergic reactions, including anaphylaxis, anaphylactic shock, hypersensitivity.

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

Mental disorders: very rarely - nervousness, irritability, agitation, depression, anxiety, decreased or lack of libido.

From the nervous system: very rarely - insomnia, dizziness, thirst, convulsions, lethargy, headache, drowsiness, akathisia, extrapyramidal disorders.

From the side of the cardiovascular system: very rarely - edema, palpitations, abnormal heart rate and rhythm, prolongation of the QT interval (frequency unknown), severe ventricular arrhythmias, ventricular arrhythmias of the torsade de pointes type, sudden death.

From the digestive tract: rarely - gastrointestinal disorders, including abdominal pain, regurgitation, changes in appetite, nausea, heartburn, constipation; very rarely - dry mouth, short-term intestinal cramps, diarrhea.

On the part of the skin and subcutaneous tissues: very rarely - itching, rash; frequency unknown - urticaria, angioedema.

On the part of the reproductive system and mammary glands: rarely - galactorrhea, enlargement of the mammary glands / gynecomastia, breast sensitivity, discharge from the mammary glands, amenorrhea, edema of the mammary glands, pain in the mammary glands, impaired lactation, irregular menstrual cycle.

From the musculoskeletal system and connective tissue: rarely - pain in the legs.

From the urinary system: very rarely - urinary retention, dysuria, frequent urination.

General disorders: rarely - asthenia.

From the side of the organ of vision: the frequency is unknown - oculogyric crises.

Other: conjunctivitis, stomatitis.

Changes in laboratory parameters: very rarely - an increase in the level of ALT, AST and CS; infrequently - deviation from the norm of indicators of liver function tests; rarely - an increase in the level of prolactin in the blood.

Since the pituitary gland is outside the BBB, domperidone can cause an increase in prolactin levels. In isolated cases, such hyperprolactinemia can lead to neuroendocrine side effects such as galactorrhea, gynecomastia, and amenorrhea.

During the period of post-marketing use of the preparation, no differences were found in the safety profile of domperidone in adults and children, with the exception of extrapyramidal disorders and other phenomena (convulsions, agitation) associated with the central nervous system, noted mainly in children.

Special instructions

Motilium® is not recommended for motion sickness.

Motilium® should be used with caution in elderly patients or patients with a history of heart disease or heart disease.

Cardiovascular Effects. Domperidone has been associated with prolongation of the QT interval on the ECG. During post-marketing surveillance, there were very rare cases of QT prolongation and flutter / ventricular fibrillation in patients taking domperidone. These reports included information about patients with other risk factors, electrolyte disturbances, and concomitant therapy that may be contributing factors.

According to the ICH-El4 guidelines, a study was conducted with a thorough study of the QT interval in healthy individuals. The lengthening of the QT interval, which was observed in the study with the use of domperidone, according to the recommended dosing regimen in usual therapeutic doses (10 or 20 mg 4 times a day), has no clinical significance.

Cautions Domperidone should be used with caution in patients with mild hepatic and / or renal impairment.

Due to the increased risk of ventricular arrhythmia, Motilium® is contraindicated in patients with prolonged cardiac conduction intervals, in particular QTc, in patients with significant electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with underlying heart diseases such as congestive heart failure. It is known that electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) and bradycardia are conditions that increase the proarrhythmogenic risk.

If signs or symptoms appear that may be associated with cardiac arrhythmias, the use of Motilium® should be discontinued and the patient should immediately consult a doctor.

Impaired renal function. T ½ of domperidone in severe renal impairment is lengthened. With prolonged use, the dosing frequency of domperidone should be reduced to 1-2 times a day, depending on the severity of the disorder. It may also be necessary to reduce the dose.

Antacids or antisecretory preparations should not be taken concomitantly with oral forms of Motilium®, as they reduce the oral bioavailability of domperidone (see INTERACTIONS). When used in combination, Motilium® should be taken before meals, and antacids or antisecretory preparations should be taken after meals.

Application with ketoconazole. In studies of interaction with the oral form of ketoconazole, a prolongation of the QT interval was noted. Although the significance of this study is not clearly established, an alternative treatment should be chosen if antifungal therapy with ketoconazole is indicated (see INTERACTIONS).

Motilium® tablets contain lactose, therefore, the preparation should not be used in patients with lactose intolerance, galactosemia and glucose / galactose malabsorption.

The following information should be considered regarding the risk of developing complications of cardiovascular diseases caused by preparations containing domperidone:

• some epidemiological studies have shown that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death;
• the risk of serious ventricular arrhythmias or sudden cardiac death may be higher in patients aged 60 years or older or with oral administration of doses of the preparation 30 mg / day. Therefore, Motilium® should be used with caution in elderly patients. Patients over the age of 60 should consult a doctor before taking Motilium®;
• domperidone should be administered to adults and children at the lowest effective dose.

The risk-benefit ratio of domperidone remains favorable.

Use during pregnancy and lactation. There are limited data on post-marketing use of domperidone in pregnant women. Therefore, Motilium® during pregnancy should be prescribed only when, in the opinion of the doctor, the expected positive effect for the mother outweighs the potential risk for the fetus.

The amount of domperidone that can enter an infant's body through breast milk is extremely low. The maximum relative dose for infants (%) is estimated at about 0.1% of the mother's dose, adjusted for body weight. It is not known if it will harm a baby, so mothers taking Motilium® should refrain from breastfeeding. Caution should be exercised in the presence of risk factors for QTc interval prolongation in breastfed infants. After exposure as a result of penetration of the preparation with breast milk, the appearance of side effects, in particular cardiological, cannot be excluded.

Children. The preparation is used to treat children aged 12 years and older and weighing at least 35 kg. Domperidone should be given to children at the lowest effective dose for the shortest possible period.

Influence on the ability to drive vehicles or work with other mechanisms. Given the side effects from the nervous system, patients need to be careful when driving or working with other mechanisms.

Interactions

Anticholinergic preparations can neutralize the antidispeptic effect of Motilium®. due to pharmacodynamic and / or pharmacokinetic interactions, the risk of lengthening the qt interval increases.

You should not take antacids and antisecretory preparations simultaneously with Motilium®, since they reduce its bioavailability after oral administration (see SPECIAL INSTRUCTIONS).

Domperidone is metabolized primarily by CYP 3A4. According to in vitro studies, the combined use of preparations that significantly inhibit this enzyme can lead to an increase in the level of domperidone in the blood plasma.

When domperidone was used concurrently with potent CYP 3A4 inhibitors capable of prolonging the QT interval, clinically significant changes in the QT interval were observed. Therefore, the simultaneous use of domperidone with certain preparations is contraindicated (see CONTRAINDICATIONS).

The simultaneous use of the following preparations together with domperidone is contraindicated

All preparations that prolong the QT interval:

• class IA antiarrhythmics (eg disopyramide, quinidine, hydroquinidine);
• class III antiarrhythmic preparations (amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
• some antipsychotics (eg haloperidol, pimozide, sertindole);
• some antidepressants (eg citalopram, escitalopram);
• some antibiotics (eg levofloxacin, moxifloxacin, erythromycin, spiramycin);
• some antifungal preparations (such as pentamidine);
• some antimalarial preparations (eg halofantrine, lumefantrine);
• some gastrointestinal preparations (eg cisapride, dolasetron, prucaloprid);
• some antihistamines (eg mequitazine, mizolastine);
• some preparations used for cancer (for example, toremifene, vandetanib, vincamine);
• some other preparations (eg bepridil, methadone, diphemanil).

Examples of strong CYP 3A4 inhibitors with which Motilium® is contraindicated:

• azole antifungals such as fluconazole *, itraconazole, ketoconazole *, and voriconazole *;
• macrolide antibiotics such as clarithromycin * and erythromycin *; protease inhibitors *;
• HIV protease inhibitors such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir;
• calcium antagonists such as diltiazem and verapamil; amiodarone *;
• aprepitant; nefazodone;
• telithromycin *.

* Prolong the QTc interval.

The simultaneous use of the following substances requires caution

Use with caution with preparations that cause bradycardia and hypokalemia, as well as with the following macrolides that can cause prolongation of the QT interval: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent inhibitor of CYP 3A4).

Domperidone should be used with caution in conjunction with potent CYP 3A4 inhibitors that did not cause QT prolongation, such as indinavir, and patients should be closely monitored for signs or symptoms of side effects.

The above list is representative but not exhaustive.

Motilium can be combined with:

• antipsychotics, the effect of which it does not enhance;
• dopaminergic agonists (bromocriptine, L-dopa), the undesirable peripheral actions of which, such as indigestion, nausea, vomiting, it suppresses without neutralizing the main properties.

In separate studies of the pharmacokinetic / pharmacodynamic interaction in vivo with the simultaneous oral administration of ketoconazole or erythromycin in healthy volunteers, it was confirmed that these preparations significantly suppress the presystemic metabolism of domperidone, mediated by CYP 3A4. With the simultaneous use of 10 mg of domperidone orally 4 times a day and 200 mg of ketoconazole orally 2 times a day during the observation period, there was an increase in the QTc interval by an average of 9.8 ms; individual values ​​ranged from 1.2 to 17.5 ms. With the simultaneous use of 10 mg of domperidone 4 times a day and 500 mg of erythromycin orally 3 times a day, the QTc interval during the observation period was extended by an average of 9.9 ms, the interval of individual values ​​ranged from 1.6 to 14.3 ms. The equilibrium values ​​of Cmax and AUC of domperidone increased approximately threefold in each of these interaction studies. The effect of elevated plasma concentrations of domperidone on the observed QTc effect is unknown. In these studies, in the case of monotherapy with domperidone (10 mg orally 4 times a day), the QTc interval was prolonged by an average of 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), while the use of ketoconazole alone (200 mg 2 times a day) or erythromycin (500 mg 3 times a day) led to an increase in the QTc interval during the observation period by 3.8 and 4.9 ms, respectively.

In theory, since Motilium has a prokinetic effect on the stomach, it can affect the absorption of oral preparations used simultaneously, in particular, slow-release or enteric dosage forms. However, in patients whose condition had already stabilized with the use of digoxin or paracetamol, the simultaneous use of domperidone did not affect the levels of these preparations in the blood.

Overdose

Overdose symptoms may include agitation, impaired consciousness, seizures, disorientation, drowsiness, and extrapyramidal reactions.

Treatment. There is no specific antidote for domperidone, but in case of a significant overdose, gastric lavage is recommended for 1 hour after taking the preparation and the use of activated charcoal, as well as careful monitoring of the patient's condition and supportive therapy. Anticholinergics, preparations for the treatment of Parkinson's disease can be effective in controlling extrapyramidal reactions.

Storage conditions

No special storage conditions are required. shelf life is 3 years.