Motilium tablets 10mg, no. 30

Inside. It is recommended to take MOTILIUMЃ tablets 15-30 minutes before meals; if the drug is taken after meals, the absorption of domperidone may slow down.

Adults and children over 12 years old with a body weight of 35 kg or more

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

Children under 12 years old 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, the MOTILIUMЃ suspension should generally be used.

Continuous use of MOTILIUMЃ without consulting a doctor should not exceed 7 days in duration. If necessary, the doctor can extend the course of treatment.

Use in patients with renal impairment

Since the half-life of domperidone in severe renal failure (serum creatinine level> 6 mg / 100 ml, i.e.> 0.6 mmol / L) increases, the frequency of taking MOTILIUMЃ 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 properties').

Use in patients with hepatic impairment

The use of MOTILIUMЃ is contraindicated in patients with moderate to severe hepatic impairment (see section 'Contraindications'). In patients with mild hepatic impairment, dose adjustment is not required (see section 'Pharmacological properties').

Composition (for 1 tablet):

active substance: domperidone 10 mg;

excipients: lactose monohydrate 54.2 mg, corn starch 20 mg, microcrystalline cellulose 10 mg, pregelatinized starch 3 mg, povidone K90 1.5 mg, magnesium stearate 0.6 mg, hydrogenated cottonseed oil 0.5 mg, sodium lauryl sulfate 0.15 mg.

Film shell: hypromellose 2910 5 mPax 2.2 mg, sodium lauryl sulfate 0.05 mg.

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

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

• prolactinoma;

• simultaneous application of oral forms of ketoconazole, erythromycin or other potent inhibitors of isoenzyme CYP3A4, causing the lengthening of the interval QT (such as clarithromycin, itraconazole, fluconazole, posaconazole, ritonavir, saquinavir, amiodarone, telithromycin, telaprevir and voriconazole) except apomorphine (see. Forums ' Interaction with other medicinal products 'and' Special instructions ') ;

• 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 a body weight of less than 35 kg;

• pregnancy;

• period of breastfeeding.

Pharmacotherapeutic group: antiemetic agent - central dopamine receptor blocker.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics

Domperidone is a dopamine antagonist with antiemetic properties. Domperidone poorly penetrates the blood-brain barrier. 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 to dopamine receptors in the chemoreceptor trigger zone, which is 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 the sphincter pressure of 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 reached 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 to 30 minutes before meals. A decrease in acidity in the stomach leads to a deterioration in the absorption of domperidone. Oral bioavailability decreases with prior administration of cimetidine and sodium bicarbonate. When taking the drug after meals, it takes more time to achieve maximum absorption, and the area under the pharmacokinetic curve (AUC) slightly increases.

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

Domperidone is rapidly and extensively metabolized by hydroxylation and N-dealkylation. In vitro metabolic studies with diagnostic inhibitors have shown that the isoenzyme CYP3A4 is the main form of cytochrome P450 involved in N-dealkylation of domperidone, while isoenzymes CYP3A4, CYP1A2 and CYP2E1 are involved in aromatic hydroxylation of domperidone.

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% is excreted by the intestines and approximately 1% by the kidneys). Plasma half-life after a single oral administration is 7-9 hours in healthy volunteers, but increases in patients with severe renal failure.

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

INDICATIONS FOR USE

For the relief of 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 potent inhibitors of isoenzyme CYP3A4, causing the lengthening of the interval QT (such as clarithromycin, itraconazole, fluconazole, posaconazole, ritonavir, saquinavir, amiodarone, telithromycin, telaprevir and voriconazole) except apomorphine (see sections. 'Interaction with other medicinal products' and 'Special instructions') ;

- severe electrolyte disturbances or heart diseases 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 a body weight of less than 35 kg;

- pregnancy;

- the period of breastfeeding.

Carefully

- childhood;

- impaired renal function.

APPLICATION DURING PREGNANCY AND DURING BREASTFEEDING

MOTILIUM Ѓ is contraindicated for use during pregnancy and during breastfeeding.

DOSAGE AND APPLICATION

Inside. It is recommended to take MOTILIUMЃ tablets 15-30 minutes before meals; if the drug is taken after meals, the absorption of domperidone may slow down.

Adults and children over 12 years old with a body weight of 35 kg or more

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

Children under 12 years old 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, the MOTILIUMЃ suspension should generally be used.

Continuous use of MOTILIUMЃ without consulting a doctor should not exceed 7 days in duration. If necessary, the doctor can extend the course of treatment.

Use in patients with renal impairment

Since the half-life of domperidone in severe renal failure (serum creatinine level> 6 mg / 100 ml, i.e.> 0.6 mmol / L) increases, the frequency of taking MOTILIUMЃ 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 properties').

Use in patients with hepatic impairment

The use of MOTILIUMЃ is contraindicated in patients with moderate to severe hepatic impairment (see section 'Contraindications'). In patients with mild hepatic impairment, dose adjustment is not required (see section 'Pharmacological properties').

SIDE EFFECT

According to clinical trials

Adverse reactions seen in? 1% of patients taking MOTILIUMO: depression, anxiety, decreased or lack of libido, headache, drowsiness, akathisia, diarrhea, rash, itching, breast enlargement / gynecomastia, pain and tenderness in the mammary glands, galactorrhea, menstrual irregularities and amenorrhea , violation of lactation, asthenia.

Adverse reactions observed in <1% of patients taking MOTILIUMO: hypersensitivity, urticaria, edema of the mammary glands, discharge from the mammary glands.

The following undesirable effects were classified as follows: very often (? 10%), often (? 1%, but <10%), infrequently (? 0.1%, but <1%), rarely

(? 0.01%, but <0.1%) and very rarely (<0.01%), including isolated cases.

According to spontaneous reports of adverse events

Immune system disorders. Very rare: anaphylactic reactions, including anaphylactic shock.

Mental disorders. Very rare: hyperexcitability, nervousness, irritability.

Nervous system disorders. Very rare: drowsiness, headache, dizziness, extrapyramidal disorders and seizures.

Violations of the cardiovascular system. Frequency unknown: ventricular arrhythmia , pirouette-type ventricular tachycardia, sudden coronary death .

Skin and subcutaneous tissue disorders. Very rare: urticaria, angioedema.

Kidney and urinary tract disorders. Very rare: urinary retention.

Laboratory and instrumental data. Very rare: abnormalities in laboratory parameters of liver function, hyperprolactinemia.

* Some epidemiological studies have shown that the use of domperidone may be associated with an increased risk of severe ventricular arrhythmias or sudden death. The risk of these phenomena 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. The use of domperidone in the lowest effective dose in adults and children is recommended.

Adverse reactions identified during post-marketing clinical trials

Immune system disorders. Frequency not known: anaphylactic reactions, including anaphylactic shock.

Mental disorders. Uncommon: hyperexcitability, nervousness.

Nervous system disorders. Often: dizziness. Rarely: convulsions. Frequency unknown: extrapyramidal disorders.

Violations of the cardiovascular system. Frequency unknown: ventricular arrhythmia , pirouette-type ventricular tachycardia, sudden coronary death .

Disorders from the gastrointestinal tract. Frequency not known: dry mouth.

Skin and subcutaneous tissue disorders. Frequency unknown: angioedema.

Kidney and urinary tract disorders. Uncommon: urinary retention.

Laboratory and instrumental data. Uncommon: abnormalities in laboratory parameters of liver function. Rare: hyperprolactinemia.

* Some epidemiological studies have shown that the use of domperidone may be associated with an increased risk of severe ventricular arrhythmias or sudden death. The risk of these phenomena 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. The use of domperidone in the lowest effective dose in adults and children is recommended.

OVERDOSE

Overdose symptoms are most common in infants and children. Signs of overdose are agitation, altered consciousness, seizures, disorientation, drowsiness, and extrapyramidal reactions.

Overdose treatment: Symptomatic, there is no specific antidote. Gastric lavage, intake of activated carbon, in the event of extrapyramidal reactions - anticholinergic, antiparkinsonian drugs. Due to the possible increase in the QT interval, an electrocardiogram (ECG) should be monitored.

INTERACTION WITH OTHER DRUGS

Interaction with the following drugs may increase the risk of QT interval prolongation. Contraindicated combinations - drugs that increase 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 (erythromycin, levofloxacin, moxifloxacin, spiramycin), antifungals (eg pentamidine), antimalarial drugs (eg halofantrine, lumefantrine) (eg gastrointestinal cyzapantrine , dolasetron, prucaloprid), antihistamines (eg mechitazine, mizolastine), antineoplastic drugs (eg toremifene, vandetanib,vincamine), other drugs (eg, bepridil, diphemanil methyl sulfate, methadone), potent CYP3A4 inhibitors (protease inhibitors, azole antifungals, some macrolide antibiotics (erythromycin, clarithromycin, telithromycin). verapamil, some antibiotics from the macrolide group). Combinations that should be used with caution: drugs that cause bradycardia and hypokalemia, as well as azithromycin and roxithromycin. Cimetidine, sodium bicarbonate, other antacids and antisecretory drugs reduce the bioavailability of domperidone concentration in blood. : antifungal agents of the azole series, antibiotics from the macrolide group, HIV protease inhibitors, nefazodone.Domperidone is compatible with taking antipsychotic drugs (neuroleptics), dopaminergic receptor agonists (bromocriptine, levodopa). Simultaneous use with paracetamol and digoxin does not affect the concentration of these drugs in the blood. Co-administration with apomorphine is only possible if the benefits of co-administration outweigh the risks and only if the recommended precautions for co-administration are strictly followed.if the advantage of joint use outweighs the risks and only if the recommended precautions for joint use of drugs are strictly followed.if the advantage of joint use outweighs the risks and only if the recommended precautions for joint use of drugs are strictly followed.

SPECIAL INSTRUCTIONS

Domperidone is not recommended for the prevention of nausea and vomiting after anesthesia. With prolonged drug therapy, patients should be under regular medical supervision.

Domperidone can cause prolongation of the QT interval on the ECG. In the course of post-marketing studies in patients taking domperidone, in rare cases, there was an increase in the QT interval and the occurrence of ventricular tachycardia of the 'pirouette' type. These adverse reactions were observed mainly in patients with risk factors, with severe electrolyte disturbances, or at the same time taking drugs that increase the QT interval.

Some studies have shown that the use of domperidone can 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 who are simultaneously taking drugs that increase the QT interval , or CYP3A4 inhibitors). Domperidone is contraindicated when taken together with drugs that prolong the QT interval, with the exception of apomorphine. The use in conjunction with apomorphine is possible only if the advantage of the combined use of domperidone with apomorphine outweighs the risks and only if the recommended precautions for the joint use of drugs mentioned in the instructions for medical use of apomorphine are strictly followed.

ѕрименение домперидона и других препаратов, способных вызвать удлинение интервала QT, не рекомендовано у пациентов с выраженными электролитными нарушени¤ми (гипо- и гиперкалиеми¤, гипомагнезиеми¤) или у пациентов с заболевани¤ми сердца, такими как хроническа¤ сердечна¤ недостаточность. Ѕыло показано, что наличие у пациента электролитных нарушений (гипо- и гиперкалиеми¤, гипомагнезиеми¤) и брадикардии может увеличить риск развити¤ аритмии. ѕрием домперидона следует прекратить при возникновении любых симптомов, которые могут быть ассоциированы с нарушением ритма сердца. ¬ этом случае необходимо проконсультироватьс¤ с врачом.

ѕри одновременном применении домперидон усиливает действие нейролептиков. ѕри одновременном применении препарата с агонистами дофаминергических рецепторов (бромокриптин, леводопа) домперидон угнетает нежелательные периферические эффекты последних (такие как нарушение пищеварени¤, тошнота и рвота), не вл褤 при этом на их центральные эффекты. ѕрепарат рекомендуетс¤ принимать в минимальной эффективной дозе.

?сли лекарственное средство пришло в негодность или истек срок годности, не выбрасывайте его в сточные воды и на улицу. ѕоместите лекарственное средство в пакет и положите в мусорный контейнер. Ёти меры помогут защитить окружающую среду!

¬Ћ»яЌ»? Ќј —ѕќ—ќЅЌќ—“№ ”ѕ–ј¬Ћя“№ “–јЌ—ѕќ–“Ќџћ» —–??—“¬јћ», ћ?’јЌ»«ћјћ»

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