home Audience 8 Motilium tablets: instructions for use. Motilium Express - instructions for use According to clinical studies

Motilium tablets: instructions for use. Motilium Express - instructions for use According to clinical studies

Pharmacodynamics. Domperidone is a dopamine antagonist with antiemetic properties. However, domperidone does not penetrate the blood-brain barrier well. The use of domperidone is rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the release of prolactin from the pituitary gland. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) action and antagonism of dopamine receptors in the chemoreceptor trigger zone. Animal studies and low concentrations of the drug found in the brain indicate a central effect of domperidone on dopamine receptors. When administered orally, domperidone increases the duration of antral and duodenal contractions, accelerates gastric emptying and increases lower esophageal sphincter pressure in healthy people. Domperidone has no effect on gastric secretion. Pharmacokinetics. Domperidone is rapidly absorbed after oral administration on an empty stomach, with peak plasma concentrations achieved within 30-60 minutes. The low absolute bioavailability of domperidone when taken orally (approximately 15%) is associated with intensive first-pass metabolism in the intestinal wall and liver. Domperidone should be taken 15-30 minutes before meals. Reduced acidity in the stomach leads to impaired absorption of domperidone. Oral bioavailability is reduced by prior administration of cimetidine and sodium bicarbonate. When taking the drug after a meal, it takes longer to achieve maximum absorption and the area under the pharmacokinetic curve (AUC) increases slightly. When taken orally, domperidone does not accumulate and does not induce its own metabolism; the peak plasma concentration of 21 ng/mL at 90 minutes after 2 weeks of oral dosing at a dose of 30 mg per day was essentially the same as the peak plasma concentration of 18 ng/mL after the first dose. Domperidone is 91-93% bound to plasma proteins. Distribution studies with radiolabeled drug in animals showed significant drug distribution in tissues but low concentrations in the brain. Small amounts of the drug cross the placenta in rats. Domperidone undergoes rapid and extensive metabolism by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors have shown that CYP3A4 is the major cytochrome P450 form involved in the N-dealkylation of domperidone, while CYP3A4, CYP1A2 and CYP2E1 are involved in the aromatic hydroxylation of domperidone. Excretion in urine and feces is 31% and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged is small (10% in feces and approximately 1% in urine). The plasma half-life after a single oral dose is 7-9 hours in healthy volunteers, but is increased in patients with severe renal impairment. In such patients (serum creatinine > 6 mg/100 ml, i.e. > 0.6 mmol/l), the half-life of domperidone increases from 7.4 to 20.8 hours, but plasma concentrations of the drug are lower than in healthy volunteers . A small amount of unchanged drug (about 1%) is excreted by the kidneys. In patients with moderate hepatic impairment (Pugh score 7-9, Child-Pugh B), the AUC and maximum plasma concentration of domperidone were 2.9 and 1.5 times higher than in healthy volunteers, respectively. The unbound fraction increased by 25% and the half-life increased from 15 to 23 hours. In patients with mild hepatic impairment, slightly reduced systemic levels of the drug were observed compared with those in healthy volunteers based on maximum concentration and AUC, without changes in protein binding or half-life. Patients with severe hepatic impairment have not been studied.

Excipients: lactose monohydrate - 54.2 mg, corn starch - 20 mg, microcrystalline cellulose - 10 mg, pregelatinized starch - 3 mg, K90 - 1.5 mg, magnesium stearate - 0.6 mg, hydrogenated cotton seed oil - 0.5 mg, sodium lauryl sulfate - 0.15 mg.

Film shell composition: hypromellose 2910 5 mPa×s - 2.2 mg, sodium lauryl sulfate - 0.05 mg.

30 pcs. - blisters (1) - cardboard packs.

pharmachologic effect

When taking the drug after a meal, it takes longer to reach Cmax and the AUC increases slightly.

Distribution

When taken orally, domperidone does not accumulate and does not induce its own metabolism. After taking domperidone orally for 2 weeks at a dose of 30 mg/day, C max in blood plasma after 90 minutes was 21 ng/ml and was almost the same as after taking the first dose (18 ng/ml).

Plasma protein binding - 91-93%.

Distribution studies of the radiolabeled drug in animals have shown widespread tissue distribution but low concentrations in the brain. Small amounts of the drug penetrate the placental barrier in rats.

Metabolism

Domperidone undergoes rapid and extensive metabolism by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors have shown that CYP3A4 is the major cytochrome P450 form involved in the N-dealkylation of domperidone, while CYP3A4, CYP1A2 and CYP2E1 are involved in the aromatic hydroxylation of domperidone.

breeding

Excretion by the kidneys and intestines is 31% and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged is small (10% in feces and approximately 1% in urine). Plasma T1/2 after a single oral dose is 7-9 hours in healthy volunteers, but increases in patients with severe renal failure.

Pharmacokinetics in special clinical situations

In patients with severe renal failure (serum creatinine >6 mg/100 ml, i.e. >0.6 mmol/l), T1/2 of domperidone increases from 7.4 to 20.8 hours, but plasma concentrations of the drug are lower than in patients with normal kidney function. A small amount of unchanged drug (about 1%) is excreted by the kidneys.

In patients with moderate hepatic impairment (Child-Pugh score 7-9), the AUC and C max of domperidone were 2.9 and 1.5 times higher than in healthy volunteers, respectively. The proportion of unbound fraction increased by 25%, and T1/2 increased from 15 to 23 hours. In patients with mild hepatic impairment, slightly reduced systemic drug levels were observed compared with those in healthy volunteers based on Cmax and AUC, without changes in binding to proteins or T 1/2. Patients with severe hepatic impairment have not been studied.

Indications

- to relieve symptoms of nausea and vomiting.

Contraindications

- hypersensitivity to domperidone or any other component of the drug;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- prolactinoma;

- simultaneous use of oral forms of ketoconazole, erythromycin or other drugs that increase the QT interval, or potent inhibitors of the CYP3A4 isoenzyme, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin and others;

- severe electrolyte disturbances or heart disease, such as chronic heart failure;

- bleeding from the gastrointestinal tract, mechanical intestinal obstruction, perforation of the stomach or intestines;

- liver failure of moderate and severe severity;

— body weight less than 35 kg;

- children under 12 years of age with body weight less than 35 kg;

- pregnancy;

- period of breastfeeding.

Carefully: childhood, renal dysfunction.

Dosage

Adults and adolescents over 12 years of age and children weighing ≥35 kg

Children under 12 years of age and weighing 35 kg or more- 1 tab. (10 mg) 3 times/day, the maximum daily dose is 3 tablets. (30 mg).

In pediatric practice, Motilium suspension should mainly be used.

Continuous use of the drug Motilium without consulting a doctor should not exceed 7 days. If necessary, the doctor may extend the course of treatment.

Since T1/2 of domperidone at severe renal failure(with serum creatinine levels >6 mg/100 ml, i.e. >0.6 mmol/l) increases, the frequency of taking Motilium, film-coated tablets should be reduced to 1 or 2 times a day, depending on the severity of the deficiency . It is necessary to conduct regular examination of patients with severe renal failure (see section "Pharmacological action").

The use of Motilium is contraindicated in patients with moderate to severe liver failure. U patients with mild liver failure no dose adjustment is required.

Side effects

According to clinical studies

Adverse reactions observed in ≥1% of patients taking Motilium: depression, anxiety, decreased or absent libido, headache, drowsiness, akathisia, diarrhea, rash, itching, breast enlargement/gynecomastia, pain and sensitivity in the mammary glands, galactorrhea, menstrual irregularities and amenorrhea, lactation disorders, asthenia.

Adverse reactions observed in<1% пациентов, принимавших Мотилиум : hypersensitivity, urticaria, swelling of the mammary glands, discharge from the mammary glands.

The following undesirable effects were classified as follows: very often (≥10%), often (≥1%, but<10%), нечасто (≥0.1%, но <1%), редко (≥0.01%, но <0.1%) и очень редко (<0.01%), включая отдельные случаи.

According to spontaneous reports of adverse events

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

Mental disorders: very rarely - increased excitability, nervousness, irritability.

From the nervous system: very rarely - drowsiness, headache, dizziness, extrapyramidal disorders and convulsions.

very rarely - urticaria, angioedema.

From the kidneys and urinary tract: very rarely - urinary retention.

very rarely - deviations in laboratory parameters of liver function, hyperprolactinemia.

Adverse reactions identified during post-registration clinical studies

From the immune system: frequency unknown - anaphylactic reactions, including anaphylactic shock.

Mental disorders: infrequently - increased excitability, nervousness.

From the nervous system: often - dizziness; rarely - convulsions; frequency unknown - extrapyramidal disorders.

From the cardiovascular system: frequency unknown - ventricular arrhythmia*, ventricular tachycardia of the "pirouette" type, sudden coronary death*.

From the gastrointestinal tract: frequency unknown - dry mouth.

For the skin and subcutaneous tissues: frequency unknown - angioedema.

From the kidneys and urinary tract: infrequently - urinary retention.

Laboratory and instrumental data: infrequently - deviations in laboratory parameters of liver function; rarely - hyperprolactinemia.

*Some epidemiological studies have suggested that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden death. The risk of these events is more likely in patients over 60 years of age and in patients taking the drug in a daily dose of more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose

Symptoms Overdoses occur most often in infants and children. Signs of overdose include agitation, altered consciousness, convulsions, disorientation, drowsiness and extrapyramidal reactions.

Treatment: symptomatic, there is no specific antidote. Gastric lavage, taking activated charcoal, if extrapyramidal reactions occur - anticholinergic, antiparkinsonian drugs. Due to possible prolongation of the QT interval, ECG should be monitored.

Drug interactions

Interactions with the following drugs may increase the risk of QT prolongation.

Contraindicated combinations

Drugs that prolong the QT interval: Class IA antiarrhythmics (eg, disopyramide, hydroquinidine, quinidine), Class III antiarrhythmics (eg, amiodarone, dofetidil, dronedarone, ibutilide, sotalol), antipsychotics (eg, haloperidol, pimozide, sertindole), antidepressants (eg, citalopram, escitalopram), antibiotics (eg, erythromycin, levofloxacin, moxifloxacin, spiramycin), antifungals (eg, pentamidine), antimalarials (eg, halofantrine, lumefantrine), gastrointestinal drugs (eg, cisapride, dolasetron, prucalopride), antihistamines (eg, mechitazine, mizolastine), (eg, toremifene, vandetanib, vincamine), other drugs (eg, bepridil, difemanil methylsulfate, methadone), strong CYP3A4 inhibitors (protease inhibitors, azole antifungals, some antibiotics from the group of macrolides (erythromycin, clarithromycin, telithromycin).

Moderate CYP3A4 inhibitors (diltiazem, verapamil, some macrolide antibiotics).

Combinations to use with caution

Drugs that cause bradycardia and hypokalemia, as well as azithromycin and roxithromycin.

Cimetidine and other antacid and antisecretory drugs reduce the bioavailability of domperidone.

Increase the concentration of domperidone in the blood plasma: azole antifungals, antibiotics from the macrolide group, HIV protease inhibitors, nefazodone.

Compatible with the use of antipsychotic drugs (neuroleptics), dopaminergic receptor agonists (bromocriptine, levodopa).

Concomitant use with paracetamol and digoxin does not affect the concentration of these drugs in the blood.

special instructions

During long-term drug therapy, patients should be under regular medical supervision.

Domperidone may cause prolongation of the QT interval on the ECG. During post-marketing studies, in rare cases, an increase in the QT interval and the occurrence of torsade de pointes (TdP) were observed in patients taking domperidone. These adverse reactions were observed mainly in patients with risk factors, with severe electrolyte disturbances, or concomitantly taking drugs that increase the QT interval.

Some studies have shown that the use of domperidone may lead to an increased risk of ventricular arrhythmia or sudden coronary death (especially in patients over 60 years of age or when using a single dose of more than 30 mg, as well as in patients concomitantly taking drugs that prolong the QT interval, or CYP3A4 inhibitors).

The use of domperidone and other drugs that can cause prolongation of the QT interval in patients with severe electrolyte disturbances (hypo- and hyperkalemia, hypomagnesemia) or in patients with heart disease such as chronic heart failure. It has been shown that the presence of electrolyte disturbances in the patient (hypo- and hyperkalemia, hypomagnesemia) and bradycardia may increase the risk of developing arrhythmia. Domperidone should be discontinued if any symptoms occur that may be associated with cardiac arrhythmias. In this case, you should consult your doctor.

With simultaneous use, domperidone enhances the effect of antipsychotics. When used simultaneously with dopaminergic receptor agonists (bromocriptine, levodopa), domperidone inhibits the unwanted peripheral effects of the latter, such as indigestion, nausea and vomiting, without affecting their central effects.

If the medicine has become unusable or has expired, you should not throw it into wastewater or onto the street. It is necessary to place the medicine in a bag and place it in the trash container. These measures will help protect the environment.

Impact on the ability to drive vehicles and machinery

Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the risk of developing adverse reactions that may affect these abilities.

The use of the drug is contraindicated in case of moderate to severe liver dysfunction. For mild liver dysfunction, no dose adjustment is required.

Use in old age

Domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden death. The risk may be more likely in patients over 60 years of age.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

The drug should be stored out of the reach of children at a temperature of 15° to 30°C. Shelf life - 3 years. Do not use after the expiration date.

Disease class

Esophagitis
Gastroesophageal reflux with esophagitis
Dyspepsia
Pain localized in the upper abdomen
Nausea and vomiting
Heartburn
Flatulence and related conditions
Unacceptable diet and bad eating habits

Clinical and pharmacological group

Not indicated. See instructions

Pharmacological action

Antiemetic

Pharmacological group

Antiemetics

Motilium lozenges

Instructions for medical use of the drug

Indications for use

A complex of dyspeptic symptoms associated with delayed gastric emptying, gastroesophageal reflux, esophagitis: a feeling of fullness in the epigastrium, a feeling of bloating, pain in the upper abdomen; belching, flatulence; heartburn with or without reflux of stomach contents into the oral cavity.

Nausea and vomiting of functional, organic, infectious origin, caused by radiotherapy, drug therapy or diet disorders, as well as against the background of dopamine agonists (for example, levodopa and bromocriptine), if used for Parkinson's disease.

Release form

lozenges 10 mg; blister 10, cardboard pack 3;
lozenges 10 mg; blister 10, cardboard pack 1;

Pharmacodynamics

Domperidone does not penetrate the blood-brain barrier well, so the use of domperidone is rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the release of prolactin from the pituitary gland. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) action and antagonism of dopamine receptors in the chemoreceptor trigger zone. Domperidone has no effect on gastric secretion.

Pharmacokinetics

Suction

After oral administration, it is quickly absorbed from the gastrointestinal tract. It has low bioavailability (about 15%). Reduced acidity of gastric contents reduces the absorption of domperidone. Cmax in plasma is reached after 1 hour.

Distribution

Domperidone is widely distributed in tissues; its concentration in brain tissue is low. Plasma protein binding is 91–93%.

Metabolism

Subject to intensive metabolism in the intestinal wall and liver.

breeding

Excreted through the intestines (66%) and kidneys (33%), unchanged, 10 and 1% of the dose, respectively. T1/2 - 7–9 hours (with severe renal failure, it lengthens).

Use during pregnancy

When administered to animals in doses up to 160 mg/kg/day, it has no teratogenic effect. Use in the first trimester of pregnancy is possible if the expected effect of therapy exceeds the potential risk to the fetus. There is currently no evidence of an increased risk of developmental defects in humans. In women, concentrations of domperidone in breast milk are 4 times lower than the corresponding concentrations in plasma. It is unknown whether this level has a negative effect on newborns. Therefore, if the mother is taking Motilac, breastfeeding is not recommended unless the expected benefit justifies the potential risk.

Contraindications for use

Hypersensitivity, gastrointestinal bleeding, mechanical intestinal obstruction, perforation of the stomach or intestines (stimulation of peristalsis may aggravate these conditions), hyperprolactinemia, prolactinoma; children under 5 years of age and children weighing up to 20 kg - for tablets.

Side effects

From the gastrointestinal tract: spasm of smooth muscles of the gastrointestinal tract, dry mouth, stomatitis, thirst, heartburn, changes in appetite, constipation/diarrhea.

From the nervous system and sensory organs: extrapyramidal disorders (in children and patients with increased permeability of the blood-brain barrier), headache, asthenia, irritability, nervousness, drowsiness, leg cramps, lethargy, conjunctivitis (itching, redness, pain, swelling of the eyes).

Allergic reactions: skin rash, itching, hives, swelling (of the face, arms, legs or feet).

Other: increased levels of prolactin in the blood plasma, galactorrhea, gynecomastia, menstrual irregularities, mastalgia, changes in urination frequency, dysuria (burning, difficulty and pain when urinating), palpitations.

Dosage and administration

Orally, 15–30 minutes before meals and before bedtime (if necessary).

Chronic dyspepsia: adults - 10 mg (1 tablet) 3 times a day; in case of ineffectiveness, the dose can be doubled (except for children under 1 year). The maximum daily dose is 2.4 mg/kg, but not more than 80 mg.

Nausea and vomiting: adults - 20 mg (2 tablets) 3-4 times a day (maximum daily dose - 80 mg). The maximum daily dose is 2.4 mg/kg, but not more than 80 mg.

Motilium tablets are indicated only for adults and children weighing more than 35 kg; in pediatric practice, the Motilium suspension should mainly be used. In case of renal failure, it is recommended to reduce the frequency of taking the drug.

Overdose

Symptoms: drowsiness, arrhythmia, disorientation, extrapyramidal disorders (especially in children), decreased blood pressure.

Treatment: the use of activated carbon, if extrapyramidal reactions occur - anticholinergics or antihistamines with anticholinergic activity, drugs used to treat parkinsonism. There is no specific antidote.

Interactions with other drugs

Antacid and antisecretory drugs reduce bioavailability, anticholinergic drugs weaken the effect of domperidone. Inhibitors of the cytochrome P450 CYP3A4 isoenzyme (azole antifungals, macrolide antibiotics, HIV protease inhibitors) can block the metabolism of domperidone and increase its plasma level (combined use requires caution). Use with caution simultaneously with MAO inhibitors. It is possible that concomitantly used drugs with sustained release of the active substance may have an effect on absorption. Domperidone does not affect the level of paracetamol and digoxin in the blood.

Precautions for use

Should not be prescribed for the prevention of postoperative vomiting.

Storage conditions

At a temperature of 15–30 °C.

Best before date

ATX classification:

A Digestive tract and metabolism

A03 Drugs for the treatment of functional disorders of the gastrointestinal tract

A03A Drugs used for intestinal dysfunction

A03F Gastrointestinal motility stimulants

A03FA Gastrointestinal motility stimulants

The antiemetic effect of motilium is due to a combination of gastrokinetic action and blockade of chemoreceptors of the trigger zone of the vomiting center. Motilium prevents the development or reduces the severity of vomiting and nausea.

After oral administration, motilium is quickly absorbed from the gastrointestinal tract. Food or low acidity of gastric juice slows down and reduces absorption. The maximum concentration in the blood is reached after 0.5–1 hour. Motilium is found in small amounts in breast milk. It is subjected to intensive metabolism in the intestinal wall and liver 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.

Motilium belongs to the second generation prokinetics and, unlike the first generation prokinetics: cerucal, raglan and others (the active substance metoclopramide) does not penetrate well through the blood-brain barrier (BBB). Therefore, Motilium does not cause extrapyramidal disorders: spasms of the facial muscles, trismus, rhythmic protrusion of the tongue, bulbar type of speech, spasms of the extraocular muscles, spastic torticollis, opisthotonus, muscle hypertonicity and others. Motilium does not cause parkinsonism: hyperkinesis, muscle rigidity. Motilium less frequently and to a lesser extent than Cerucal and Raglan causes side effects such as drowsiness, fatigue, tiredness, weakness, headaches, increased anxiety, confusion, and tinnitus.

011655/01-050617

Tradename

Motilium® EXPRESS

International Nonproprietary Name (INN)

domperidone

Dosage form

lozenges

Compound

Active ingredient (per 1 tablet): domperidone 10 mg.

Excipients (per 1 tablet): gelatin 5.513 mg, mannitol 4.136 mg, aspartame 0.750 mg, mint essence 0.300 mg, poloxamer 188 1.125 mg.

Description

White or almost white round lozenges.

Pharmacotherapeutic group

antiemetic, central dopamine receptor blocker.

ATX code– A03FA03

Pharmacological properties

Pharmacodynamics

Domperidone is a dopamine antagonist with antiemetic properties. Domperidone does not penetrate the blood-brain barrier well.

The use of domperidone is rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the release of prolactin from the pituitary gland. Its antiemetic effect may be due to a combination of peripheral (gastrokinetic) action and antagonism of dopamine receptors at the chemoreceptor trigger zone, which is located outside the blood-brain barrier.

Animal studies and low concentrations of the drug detected in the brain indicate a predominantly peripheral effect of domperidone on dopamine receptors.

When administered orally, domperidone increases the duration of antral and duodenal contractions, accelerates gastric emptying and increases sphincter pressure in the lower esophagus. Domperidone has no effect on gastric secretion.

Pharmacokinetics

When taken on an empty stomach, domperidone is rapidly absorbed after oral administration, with peak plasma concentrations achieved within 30 to 60 minutes. The low absolute bioavailability of domperidone when taken orally (approximately 15%) is associated with intensive first-pass metabolism in the intestinal wall and liver. Domperidone should be taken 15-30 minutes before meals. Reduced acidity in the stomach leads to poor absorption of domperidone. Oral bioavailability is reduced by prior administration of cimetidine and sodium bicarbonate. When taking the drug after a meal, it takes longer to achieve maximum absorption and the area under the pharmacokinetic curve (AUC) increases slightly.

When taken orally, domperidone does not accumulate and does not induce its own metabolism; the peak plasma level of 21 ng/mL at 90 minutes after 2 weeks of oral dosing at a dose of 30 mg per day was essentially the same as the level of 18 ng/mL after the first dose. Domperidone binds to plasma proteins by 91 - 93%. Studies of the distribution of the radiolabeled drug in animals have shown a wide distribution in tissues, but low concentrations in the brain. Small amounts of the drug cross the placenta in rats.

Excretion in urine and feces is 31% and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged is small (10% in feces and approximately 1% in urine). The plasma half-life after a single oral dose is 7-9 hours in healthy volunteers, but is increased in patients with severe renal impairment.

In such patients (serum creatinine > 6 mg/100 ml, i.e. > 0.6 mmol/l), the half-life of domperidone increases from 7.4 to 20.8 hours, but plasma concentrations of the drug are lower than in patients with normal kidney function. A small amount of unchanged drug (about 1%) is excreted by the kidneys.

In patients with moderate hepatic impairment (Child-Pugh score 7-9), the AUC and Cmax of domperidone were 2.9 and 1.5 times higher than in healthy volunteers, respectively. The proportion of unbound fraction increased by 25% and the half-life increased from 15 to 23 hours. In patients with mild hepatic impairment, slightly reduced systemic drug levels were observed compared with those in healthy volunteers based on Cmax and AUC, with no changes in protein binding or half-life. Patients with severe hepatic impairment have not been studied.

Indications

a) A complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux, esophagitis:
- a feeling of fullness in the epigastrium, a feeling of bloating, pain in the upper abdomen;
- belching, flatulence;
- nausea, vomiting;
- heartburn, belching.
b) Nausea and vomiting of functional, organic, infectious origin, as well as caused by radiotherapy, drug therapy or diet disorders. A specific indication is nausea and vomiting caused by dopamine agonists when used in Parkinson's disease (such as levodopa and bromocriptine).

Contraindications

hypersensitivity to domperidone or any of the components of the drug;
prolactin-secreting tumor of the pituitary gland (prolactinoma);
simultaneous use of oral forms of ketoconazole, erythromycin or other potent inhibitors of the CYP3A4 isoenzyme that cause prolongation of the QTc interval, such as clarithromycin, itraconazole, fluconazole, posaconazole, ritonavir, saquinavir, amiodarone telithromycin, telaprevir and voriconazole (see sections "Special Instructions","Interaction with othersmedicines");
gastrointestinal bleeding, mechanical obstruction or perforation (i.e., when stimulation of gastric motility may be dangerous);
moderate to severe liver dysfunction;
phenylketonuria;
body weight less than 35 kg;
children under 12 years of age with body weight<35 кг.

Carefully

renal dysfunction;
disturbances of cardiac rhythm and conduction, including prolongation of the QT interval, electrolyte imbalance, congestive heart failure.

Use during pregnancy and breastfeeding

Use during pregnancy

There is insufficient data on the use of domperidone during pregnancy.
To date, there is no evidence of an increased risk of developmental defects in humans. However, Motilium® EXPRESS should be prescribed during pregnancy only if its use is justified by the expected therapeutic benefit.

Use during lactation

The amount of domperidone that can enter a baby's body through breast milk is small.

The maximum relative dose for infants (%) is estimated to be about 0.1% of the maternal dose based on body weight. It is unknown whether this level has a negative effect
on newborns. In this regard, when using the drug

Dosage and administration

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

Children under 12 years of age and weighing 35 kg or more

1 tablet (10 mg) 3 times a day, the maximum daily dose is 3 tablets (30 mg).

In pediatric practice, MOTILIUM® suspension should mainly be used.

Typically, for the treatment of acute nausea and vomiting, the maximum duration of continuous use of the drug should not exceed one week. If nausea and vomiting continues for more than one week, the patient should reconsult with their doctor. For other indications, the duration of therapy is 4 weeks. If symptoms do not resolve within 4 weeks, the patient should be re-evaluated and the need for continued therapy assessed.

Use in patients with renal failure

Since the half-life of domperidone in severe renal impairment (serum creatinine level > 6 mg/100 ml, i.e., > 0.6 mmol/l) is increased, the frequency of dosing of Motilium® EXPRESS, lozenges, should be reduced to 1 or 2 times a day, depending on the severity of the deficiency.

Patients with severe renal impairment should be regularly monitored (see section"Pharmacological properties").

Use in patients with liver failure

The use of MOTILIUM® EXPRESS is contraindicated in patients with moderate (7 - 9 according to the Child-Pugh classification) or severe (> 9 according to the Child-Pugh classification) liver failure (see section"Contraindications"). In patients with mild (5 - 6 according to the Child-Pugh classification) liver failure, no dose adjustment of the drug is required (see section “Pharmacological properties”).

DIRECTIONS FOR USE

Since lozenges are quite fragile, they should not be pressed through the foil to avoid damage. In order to remove a tablet from a blister, you need to do the following: take the foil by the edge and completely remove it from the cell in which the tablet is located (Fig. 1);

Press gently from below (Fig. 2);

Remove the tablet from the package
(Fig.3).

Place the tablet on your tongue. Within a few seconds it will disintegrate on the surface of the tongue and can be swallowed with saliva without washing it down with water.

SIDE EFFECTS

According to clinical studies

Unwantedreactions, observed in > 1% of patients,who tookMotilium®EXPRESS: depression, anxiety, decreased or absent libido, headache, drowsiness, akathisia, dry mouth, diarrhea, rash, itching, breast enlargement/gynecomastia, breast pain and tenderness, galactorrhea, menstrual irregularities and amenorrhea, disorder lactation, asthenia.

Unwantedreactions, observed in< 1% пациентов, who tookMotilium®EXPRESS: hypersensitivity, urticaria, swelling of the mammary glands, discharge from the mammary glands.

The following undesirable effects were classified as follows: Often(> 10 %), often(> 1%, but< 10 %), infrequently(>0.1%, but< 1 %), rarely(>0.01%, but< 0,1 %) и very rarely(< 0,01 %), включая отдельные случаи.

According to spontaneous reports of adverse events

Very rare: anaphylactic reactions, including anaphylactic shock.

Mental disorders.

Very rare: increased excitability (mainly in newborns and children), nervousness.

Nervous disorderssystems.

Very rare: dizziness, extrapyramidal

disorders and seizures

(mainly in newborns and children).

Cardiovascular disorders
vascular system.

Very rare: QT prolongation, ventricular arrhythmia*, sudden coronary death*.

Skin disorders and
subcutaneous tissues.

Very rare: urticaria, angioedema.

Renal and urinary tract disorders.

Very rare: urinary retention.

Laboratory and instrumental
data.

Very rare: abnormalities in laboratory tests of liver function, increased blood prolactin levels.

Adverse reactions identified during post-registration clinical studies

Immune system disorders.

Not known: anaphylactic reactions, including anaphylactic shock.

Mental disorders.

Uncommon: increased excitability (mainly in newborns and children), nervousness.

Nervous disorders
systems. Common: dizziness. Rarely: seizures (mainly in newborns and children). Frequency unknown: extrapyramidal disorders (mainly in neonates and children).

Disorders of the cardiovascular system. Not known: QT prolongation, ventricular arrhythmia*, sudden coronary death*.

Skin and subcutaneous disordersfabrics.

Frequency unknown: angioedema.

Kidney disorders andurinary tract.

Uncommon: urinary retention.

Laboratory and instrumental data.

Uncommon: abnormalities in laboratory tests of liver function. Rarely: increased blood prolactin levels. *Some epidemiological studies have suggested that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden death. The risk of these events is more likely in patients over 60 years of age and in patients taking the drug in a daily dose of more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose

Symptoms

Cases of overdose have been reported mainly in infants and older children. Symptoms of overdose may include increased excitability, changes in consciousness, convulsions, disorientation, drowsiness and extrapyramidal reactions.

Treatment There is no specific antidote for domperidone. In case of overdose, gastric lavage is recommended within one hour from the moment of taking the drug and the use of activated carbon.

Anticholinergics and drugs used to treat parkinsonism may be effective in stopping extrapyramidal reactions that occur.

Interaction with other drugs

Anticholinergic drugs can neutralize the effect of Motilium® EXPRESS. The oral bioavailability of Motilium® EXPRESS decreases after previous administration of cimetidine or sodium bicarbonate. Antacids and antisecretory drugs should not be taken simultaneously with domperidone, as they reduce its bioavailability after oral administration (see section"Special instructions"). The main role in the metabolism of domperidone is played by the CYP3A4 isoenzyme. In vitro studies and clinical experience indicate that concomitant use of drugs that significantly inhibit this isoenzyme may cause increased plasma concentrations of domperidone.

Strong inhibitors of the CYP3A4 isoenzyme include:

Azole antifungals such as fluconazole*, itraconazole, ketoconazole* and voriconazole*;
Macrolide antibiotics, such as clarithromycin* and erythromycin*;
HIV protease inhibitors, such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir;
Calcium antagonists such as diltiazem and verapamil;
Amiodarone*;
Aprepitant;
Nefazodone;
Telithromycin*.

(Drugs marked with an asterisk also prolong the QTc interval (see section “Contraindications”)).
In a number of studies of the pharmacokinetic and pharmacodynamic interactions of domperidone with oral ketoconazole and oral erythromycin in healthy volunteers, these drugs have been shown to significantly inhibit the primary metabolism of domperidone by the CYP3A4 isoenzyme.

With simultaneous administration of 10 mg of domperidone 4 times a day and 200 mg of ketoconazole 2 times a day, there was an increase in the QTc interval by an average of 9.8 ms during the entire observation period, at certain points the changes varied from 1.2 to 17.5 ms. With simultaneous administration of 10 mg of domperidone 4 times a day and 500 mg of erythromycin 3 times a day, there was an increase in the QTc interval by an average of 9.9 ms during the entire observation period, at certain points the changes varied from 1.6 to 14.3 ms. In each of these studies, the Cmax and AUC of domperidone were increased approximately threefold (see section"Contraindications").

It is currently unknown
what contribution does increased plasma domperidone concentrations make to changes in the QTc interval? In these studies, domperidone monotherapy (10 mg four times daily) resulted in a prolongation of the QTc interval by 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), whereas ketoconazole monotherapy (200 mg twice daily) and erythromycin monotherapy (500 mg three times daily) led to a prolongation of the QTc interval by 3.8 and 4.9 ms, respectively, during the entire observation period.

In another multiple-dose study in healthy volunteers, there was no significant prolongation of the QTc interval during inpatient domperidone monotherapy (40 mg four times daily, total daily dose of 160 mg, which is significantly higher than the recommended maximum daily dose). However, plasma concentrations of domperidone were similar to those in studies of the interaction of domperidone with other drugs.

Theoretically, since Motilium® EXPRESS has a gastrokinetic effect, it could affect the absorption of concomitantly administered oral drugs, in particular sustained-release or enteric-coated drugs. However, the use of domperidone in patients taking paracetamol or digoxin did not affect the blood levels of these drugs. Motilium® EXPRESS can be taken simultaneously with:

neuroleptics, the effect of which it does not enhance;
with dopaminergic receptor agonists (bromocriptine, levodopa), since it inhibits their unwanted peripheral effects, such as digestive disorders, nausea and vomiting, without affecting their central effects.

special instructions

When using Motilium® EXPRESS together with antacid or antisecretory drugs, the latter should be taken after meals and not before meals, i.e. they should not be taken simultaneously with Motilium® EXPRESS.

Motilium® EXPRESS lozenges contain aspartame and should not be used in patients with hyperphenylalaninemia.

Use in children
Motilium® EXPRESS may in rare cases cause neurological side effects In this regard, you should strictly adhere to the recommended dose (see section “Method of application”Anddoses"). Neurological adverse effects may be caused by drug overdose in adolescents, but other possible causes of such effects must be taken into account.

Use for diseases of the cardiovascular system.

Some epidemiological studies have shown that domperidone may
be associated with an increased risk of serious ventricular arrhythmias or sudden coronary death
(see section "Side effects"). The risk may be more likely in patients over 60 years of age and in patients taking the drug in daily doses of more than 30 mg.

Patients over 60 years of age should take Motilium® EXPRESS with caution. The use of domperidone and other drugs that lead to prolongation of the QTc interval is not recommended in patients with existing conduction disorders, in particular, prolongation of the QTc interval, and in patients with severe electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or with bradycardia, or in patients with concomitant heart diseases such as congestive heart failure. As is known, against the background of electrolyte imbalance and bradycardia, the risk of arrhythmias increases.

If signs or symptoms appear that may be associated with cardiac arrhythmia, therapy with Motilium® EXPRESS should be discontinued and a physician should be consulted.

Use for kidney diseases.

Since a very small percentage of the drug is excreted unchanged by the kidneys, single dose adjustment is not required in patients with renal failure. However, when re-prescribing Motilium® EXPRESS, the frequency of use should be reduced to one or two times a day, depending on the severity of renal dysfunction (see section "Methodapplication and dose"). During long-term therapy, patients should be monitored regularly.

Potentialmedicinal interaction

The main route of metabolism of domperidone is through the CYP3A4 isoenzyme.

In vitro data and human studies indicate that concomitant use of drugs that significantly inhibit this enzyme may be associated with increased plasma concentrations of domperidone. The combined use of domperidone with potent inhibitors of the CYP3A4 isoenzyme, which, according to data obtained, cause prolongation of the QT interval is contraindicated { cm.chapter"Contraindications").

Caution is advised when coadministering domperidone with strong CYP3A4 inhibitors that do not prolong the QT interval, such as indinavir, and patients should be closely monitored for signs or symptoms of adverse reactions. (cm.chapter"InteractionWithothers medicines").

Caution is advised when coadministering domperidone with drugs known to cause QT prolongation, and patients should be closely monitored for signs or symptoms of cardiovascular adverse reactions. Examples of such medicines:

class IA antiarrhythmics (eg, disopyramide, quinidine);
Class III antiarrhythmics (eg, amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
certain antipsychotics (eg, haloperidol, pimozide, sertindole);
certain antidepressants (eg, citalopram, escitalopram);
certain antibiotics (eg, levofloxacin, moxifloxacin);
certain antifungals (eg, pentamidine);
certain antimalarials (eg, halofantrine);
certain gastrointestinal drugs (eg, dolasetron);
certain anticancer drugs (eg, toremifene, vandetanib);
some other medicines (eg, bepridil, methadone).

If the medicine has become unusable or has expired, do not throw it into wastewater or onto the street! Place the medication in a bag and place it in the trash. These measures will help protect the environment!

Impact on the ability to drive vehicles and machinery

Release form

Primary packaging: 10 lozenges in a blister made of PVC-PE-PVDC/aluminum.
Secondary packaging: 1 or 3 blisters along with instructions for medical use in a cardboard box.

Storage conditions

Store in a dry place at a temperature not exceeding 25 °C.
Keep out of the reach of children.
Store in original packaging.

Best before date

2 years. Do not use after expiration date.

Vacation conditions

On prescription

Manufacturer

Manufacturer of finished dosage form and packer(primary packaging):

Catalent UK Swindon Zydis Limited, United Kingdom

Actualaddress productionsites:

Frankland Road, Blagrove, Swindon, SN5 8RU, United Kingdom

Packer (secondary packaging) and releasing quality control:

Janssen Cilag S.p.A., Italy; Janssen-Cilag, France/Janssen-Cilag, France

Actualaddress production site:

Via C. Janssen (loc. Borgo S. Michele) - 04100 Latina, Italy/Via C. Janssen (loc. Borgo S. Michele) - 04100 Latina, Italy;

Domaine de Maigremont, Val-de-Reuil, 27100, France

Host organization claims:

Johnson & Johnson LLC, Russia 121614, Moscow, st. Krylatskaya, 17, bldg. 2