Motilium - instructions for use, dose, side effects, contraindications

Excipients (For 1 tablet) lactose monohydrate 54.2 mg corn starch 20 mg microcrystalline cellulose 10 mg, 3 mg of pregelatinized starch, povidone K90 1.5 mg Magnesium stearate 0.6 mg hydrogenated cotton seed oil 0.5 mg, sodium lauryl sulfate 0.15 mg.

Film Sheath: hypromellose 2910 5mPahs, sodium lauryl sulfate 0.05 mg, purified water q.s. (removed in the process).

Description:

Round biconvex tablets,Covered with a film shell, from white to pale cream, with the inscription “JANSSEN” on one side of the tablet and M / 10 on the other. On the cross section, the core of the tablet is white.

Pharmacotherapeutic group:Antiemetic, dopamine receptor blocker central

ATX: & nbsp

A.03.F.A.03 Domperidone

Pharmacodynamics:

Domperidone is a dopamine antagonist with antiemetic properties. But, domperidone poorly penetrates the blood-brain barrier. The use of domperidone is rarely accompanied by extrapyramidal side effects actions, 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 drug concentrations found in the brain indicate a central effect of domperidone on dopamine receptors.

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

Pharmacokinetics:

When taken on an empty stomach, domperidone quickly absorbed after ingestion, peak plasma concentrations are achieved within 30-60 minutes. Low absolute bioavailability of domperidone when taken orally (approximately 15%) is associated with an intensive metabolism of the first passage in the intestinal wall and liver. Domperidone should be taken 15-30 minutes before meals. Reduction of acidity in the stomach leads to a violation of absorption of domperidone. Bioavailability during ingestion decreases with the preliminary intake of cimetidine and sodium bicarbonate. When taking the drug after a meal to achieve maximum absorption, it takes more time, and the area under the pharmacokinetic curve (AUC) slightly increases.

When ingestion, domperidone Does not accumulate or induce its own metabolism; The peak plasma level of 21 ng / ml 90 minutes after 2 weeks of oral administration at a dose of 30 mg per day was almost the same as the level of 18 ng / ml after the first dose. Domperidone binds to plasma proteins at 91-93%. Studies of distribution with a radioactive label in animals showed a significant distribution of the drug in the tissues, but low concentrations in the brain. Small amounts of the drug penetrate the placenta in rats. Domperidone is rapidly and intensely metabolized by hydroxylation and N-dealkylation. Metabolic Studies in vitro with diagnostic inhibitors have shown that CYP3A4 is the main form of cytochrome P450 involved in N-dealkylation of domperidone, at that time as CYP3A4, CYP1A2 and CYP2E1 participate in aromatic hydroxylation of domperidone. Excretion in urine and feces is 31% and 66% of the dose when taken orally, respectively. Proportion of drug, excreted in unchanged form, is small (10% - with feces and about 1% - with urine).

Plasma half-life after a single oral intake is 7-9 hours in healthy volunteers,but increases in patients with severe renal failure.

In these 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 drug concentration in the plasma is lower than in healthy volunteers . A small amount of unchanged drug (about 1%) is excreted by the kidneys.

In patients with impaired liver function of moderate severity (score of Pew 7-9, B score in Child-Pugh), AUC and C_m_Oh domperidone were 2.9 and 1.5 times higher than in healthy volunteers, respectively. The unbound fraction was increased by 25% and the half-life increased from 15 to 23 hours. In patients with mild violations of liver function, slightly reduced systemic levels of the drug were observed compared with those in healthy volunteers based on C_m_Oh and AUC, without altering the binding to proteins or half-life.

Patients with severe impairment of liver function were not studied.

Indications:

A complex of dyspeptic symptoms, often associated with delayed emptying of the stomach, gastroesophageal reflux, esophagitis:

- feeling of overflowin epigastrium, early satiety, sensation of bloating, pain in the upper abdomen;

- eructation, flatulence;

- nausea, vomiting;

- heartburn, belching gastric contents or without it.

Nausea and vomiting of a functional, organic, infectious origin, caused by radiotherapy, drug therapy or a violation of diet. A specific indication is nausea and vomiting caused by dopamine agonists if used in Parkinson's disease (such as levodopa and bromocriptine).

Contraindications:

- Established intolerance of the drug and its components;

- prolactin-secreting pituitary tumor (prolactinoma);

- simultaneous administration of oral forms of ketoconazole, erythromycin or other potent inhibitors of isoenzyme CYP3A4, causing an elongation interval QTc, such as fluconazole, voriconazole, clarithromycin, amiodarone and telithromycin (see section "Interactions");

- gastrointestinal bleeding, mechanical obstruction or perforation (i.e., when stimulation of gastric motility may be dangerous);

- violations of liver function of medium and severe degree;

- body weight less than 35 kg.

Carefully:

- Childhood;

- impaired renal function.

Pregnancy and lactation:

Data on the use of domperidone during pregnancy is not enough. To date, there is no evidence of an increased risk of human developmental malformations,not less, Motilium® should be administered during pregnancy Only if its use is justified by the expected therapeutic benefit.

In women, the concentration of domperidone in breast milk is 10 to 50% of the corresponding plasma concentration and does not exceed 10 ng / ml. The total amount of domperidone excreted into breast milk is less than 7 μg per day when the maximum permissible doses of domperidone are administered. It is not known whether this level has a negative effect on infants. In this regard, when using MOTILUM® during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside. It is recommended to take MOTHILIUM® tablets before meals, if they are taken after eating, the absorption of domperidone may slow down.

The duration of continuous use of the drug without a doctor's recommendation should not exceed 28 days.

Adults and children over 12 years of age and weighing 35 kg or more: 1-2 tablets of 10 mg 3-4 times a day.The maximum daily dose is 8 tablets (80 mg).

Children under 12 years of age and weighing 35 kg or more: 0,25 - 0,5 mg per 1 kg of body weight 3-4 times a day. The maximum daily dose of domperidone is 2.4 mg per 1 kg of body weight, but not more than 8 tablets (80 mg).

Use in children

Motilium® tablets are indicated only for adults and children with a body weight of 35 kg or more, in pediatric practice, the MOTILIUM® suspension should generally be used.

Use in patients with impaired renal function

The frequency of taking Motilium® should be reduced to 1-2 times a day, depending on the severity of the disorders, a dose reduction may also be required. A regular examination of such patients should be carried out (see section "Special instructions").

Use in patients with impaired hepatic function

Do not apply MOTILIUM® for violations of the liver function of moderate and severe severity. With light violations of liver function, dose adjustment is not required.

Side effects:

According to clinical studies

Unwanted reactions observed in ≥1% of patients taking MOTILIUM®: depression, anxiety, the decrease or absence of libido, headache, drowsiness, akathisia,dry mouth, diarrhea, rash, itching, galactorrhea, gynecomastia, pain and sensitivity in the mammary glands, menstrual irregularities and amenorrhea, lactation, asthenia.

Unwanted reactions observed in <1% of patients taking MOTILIUM®: hypersensitivity, urticaria, swelling and discharge from the mammary glands.

According to spontaneous reports of undesirable phenomena

The undesirable effects listed below were classified as follows: very frequent (≥10%), frequent (≥ 1%, but <10%), infrequent (≥ 0.1% but <1%), rare (≥ 0.01%, but <0.1%) and very rare (<0.01%), including individual cases.

Impaired immune system. Very rarely: anaphylactic reactions, including anaphylactic shock.

Mental disorders. Very rarely: agitation, nervousness (mainly in newborns and children).

Violations from the nervous system. Very rarely: extrapyramidal phenomena, seizures (mainly in newborns and children).

Disorders from the cardiovascular system. Very rarely: lengthening the interval QTc, ventricular arrhythmia *, sudden coronary death *.

Disturbances from the skin and subcutaneous tissues. Very rarely: Quincke's edema, hives.

Disorders from the kidneys and urinary tract. Very rarely: retention of urine.

Laboratory and instrumental data. Very rarely: abnormalities in laboratory parameters of liver function, increased prolactin levels of blood.

* Some epidemiological studies have shown that the use of domperidone may be associated with an increased risk of developing 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 at a daily dose of more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose:

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

Treatment of overdose: there is no specific domperidone antidote. In case of overdosage, gastric lavage and the use of activated charcoal are recommended.It is recommended to closely monitor the patient's condition and conduct supportive therapy. Anticholinergics, drugs used to treat parkinsonism, or antihistamines may be effective in the occurrence of extrapyramidal reactions.

Interaction:

Anticholinergic drugs can neutralize the effect of MOTILUM®.

The oral bioavailability of MOTILIUM® is reduced after previous administration of cimetidine or sodium bicarbonate. Do not take antacid and antisecretory drugs at the same time as domperidone, as they reduce its bioavailability after ingestion (see section "Special instructions").

The main role in the metabolism of domperidone is played by the isoenzyme CYP3A4. Research results in vitro and clinical experience show that simultaneous use of drugs that significantly inhibit this isoenzyme may cause an increase in domperidone concentrations in plasma. Among the strong inhibitors CYP3A4 relate:

- Azole antifungal drugs, such as fluconazole *, itraconazole, ketoconazole * and voriconazole *;

- Antibiotics-macrolides, for example clarithromycin * and erythromycin *;

- HIV protease inhibitors, for example amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir and saquinavir;

- Calcium antagonists, such as diltiazem and verapamil;

- Amiodarone *;

- Aprepitant;

- Nefazodone.

- Telithromycin *

(Drugs marked with an asterisk, in addition, extend the interval QTc (see the section "Contraindications")).

In a number of studies on the pharmacokinetic and pharmacodynamic interactions of domperidone with oral ketoconazole and oral erythromycin in healthy volunteers, it has been shown that these drugs significantly inhibit the primary metabolism of domperidone by isoenzyme CYP3A4. When simultaneous administration of 10 mg of domperidone 4 times a day, and 200 mg of ketoconazole 2 times daily observed lengthening the interval QTc on average by 9.8 ms during the whole observation period, at some moments 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, the interval QTc on average by 9.9 ms during the whole period of observation, at some moments the changes varied from 1.6 to 14.3 ms. In each of these studies, C_m_Oh and AUC domperidone were increased approximately three-fold (see Fig.section "Contraindications").

At present, it is not known what contribution to changing the interval QTc increased concentrations of domperidone in plasma.

In these studies, monotherapy with domperidone (10 mg four times a day) resulted in lengthening of the interval QTc at 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), whereas monotherapy with ketoconazole (200 mg twice daily) and monotherapy with erythromycin (500 mg three times a day) resulted in lengthening of the interval QTc at 3.8 and 4.9 msec respectively during the entire observation period.

In another study using multiple doses in healthy volunteers, there was no significant lengthening of the interval QTc during stationary monotherapy with domperidone (40 mg four times a day, total daily dose of 160 mg, which is 2 times the recommended maximum daily dose). At the same time, the concentrations of domperidone in plasma were similar to those in studies of the interaction of domperidone with other drugs.

Theoretically, since MOTILIUM® has a gastrokinetic effect, it could affect the absorption of concomitant oral preparations, in particular, sustained-release preparations or enteric-coated preparations.However, the use of domperidone in patients on paracetamol or digoxin did not affect the level of these drugs in the blood.

MOTILIUM® can be taken at the same time as:

- Neuroleptics, the effect of which it does not enhance;

- with dopaminergic receptor agonists (bromocriptine, levodopa), as it depresses their unwanted peripheral effects, such as digestive disorders, nausea and vomiting, without affecting their central effects.

Special instructions:

When combined with MOTILIUM® with antacid or antisecretory drugs, the latter should be taken after a meal, and not before a meal, i.e. they should not be taken concomitantly with MOTILUM®.

Mothilium® film-coated tablets contain lactose, so they should not be used in patients with lactose intolerance, galactosemia, and a violation of absorption of glucose and galactose.

Use in children

Motilium® in rare cases can cause neurological side effects (see section "Side Effects"). The risk of neurological side effects in young children is higher, since the metabolic functions and the blood-brain barrier in the first months of life is not completely developed. In this regard, the recommended dose should be strictly adhered to (see section "Method of administration and dose"). Neurological adverse effects may be caused in children by an overdose of the drug, but other possible causes of such effects should be taken into account.

Application in diseases of the kidneys

Since a very small percentage of the drug is excreted by the kidneys unchanged, the correction of a single dose in patients with renal insufficiency is not required. However, with the re-appointment of MOTILIUM®, the frequency of application should be reduced to one or two times a day, depending on the severity of renal dysfunction, and it may also be necessary to reduce the dose. With prolonged therapy, patients should be under regular supervision.

Effects on the cardiovascular system

In some epidemiological studies, it has been shown that the use of domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden death (see "Side Effects" section).Risk may be more likely in patients over 60 years of age and in patients taking the drug at daily doses of more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

The use of domperidone and other drugs that lead to lengthening of the interval QTc, requires caution in patients with existing conduction disorders, in particular, lengthening the interval QTc, and in patients with severe electrolyte imbalance or concomitant diseases of the cardiovascular system, such as congestive heart failure.

If the medicine has become unusable, or the expiration date has expired, do not throw it into the waste water and into the street! Place the drug in a bag and put it in the trash. These measures will help protect the environment!

Effect on the ability to drive transp. cf. and fur:

Motilium® does not have or has a negligible impact on the ability to drive and work with machinery.

Form release / dosage:Tablets, film-coated 10 mg.

Packaging:For 10 or 30 tablets in a PVC blister/Alu. For 1 blister together with instructions for medical use in a cardboard bundle.

Storage conditions:

Store at temperatures between 15 and 30 ° C. Keep out of the reach of children.

Shelf life:

5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:П N014853 / 01-2003

Date of registration:09.02.2009 / 18.05.2012

Expiration Date:Unlimited

The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia

Manufacturer: & nbsp

JANSSEN-CILAG, S.A. France

Representation: & nbspJohnson & Johnson LLC Johnson & Johnson LLC Russia

Information update date: & nbsp01.06.2018

Illustrated instructions

Instructions

Motilium® (Motilium®)