Motilium suspension for oral use 1mg/ml, 100ml

Composition

Active ingredient (per 1 ml of suspension): domperidone 1 mg. Excipients (per 1 ml of suspension): microcrystalline cellulose and sodium carmellose 12.0 mg, liquid non-crystallized sorbitol 70% 455.4 mg, methyl parahydroxybenzoate 1.8 mg, propyl parahydroxybenzoate 0.20 mg, sodium saccharinate 0.20 mg, polysorbate 20 0.10 mg, sodium hydroxide about 10 mcg*, water up to 1.0 ml. * From 0 to 30 mcg.

Clinical Pharmacology

Pharmacodynamics : Domperidone is a dopamine antagonist with antiemetic properties. Domperidone does not penetrate well through 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 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 used orally, domperidone increases the duration of antral and duodenal contractions, accelerates gastric emptying and increases the pressure of the sphincter of the lower esophagus. Domperidone has no effect on gastric secretion. Pharmacokinetics: When taken on an empty stomach, domperidone is rapidly absorbed after oral use, with peak plasma concentrations reached within 30 to 60 minutes. The low absolute oral bioavailability of domperidone (approximately 15%) is associated with intensive presystemic 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 is reduced with prior use 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) 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 oral use 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 by 91-93%. Studies of the distribution of the drug with a radioactive label in animals showed its wide distribution in tissues, but low concentrations in the brain. Small amounts of the drug pass through the placenta in rats. Domperidone undergoes rapid and intensive metabolism by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors have shown that the CYP3A4 isoenzyme is the main form of cytochrome P450 involved in the N-dealkylation of domperidone, while the CYP3A4, CYP1A2, and CYP2E1 isoenzymes are involved in the aromatic hydroxylation of domperidone. Excretion by the kidneys and intestines is 31% and 66% of the oral dose, respectively. The proportion of the drug released unchanged is small (10% is excreted by the intestines and approximately 1% by the kidneys). The plasma half-life after a single oral dose is 7 to 9 hours in healthy volunteers, but increases in patients with severe renal insufficiency. 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 drug concentrations in plasma are lower than in patients with normal renal function. A small amount of the 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 the unbound fraction increased by 25% and the elimination half-life increased from 15 to 23 hours. Patients with mild hepatic impairment showed slightly reduced systemic levels of the drug compared to those in healthy volunteers based on Cmax and AUC, without changes in protein binding or half-life. Patients with severe hepatic impairment were not studied.

Indications

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

Use during pregnancy and lactation

Pregnancy There is insufficient data on the use of domperidone during pregnancy. To date, there is no evidence of an increased risk of malformations in humans. However, Motilium® should only be prescribed during pregnancy if its use is justified by the expected therapeutic benefits. Lactation The amount of domperidone that can enter the baby’s body with breast milk is small. The maximum relative dose for children (% ) is estimated at about 0.1% of the dose taken by the mother per body weight. It is not known whether this level has a negative effect on newborns. In this regard, when using Motilium® during lactation, breastfeeding should be discontinued.

Contraindications

• Hypersensitivity to domperidone or any component of the drug;
• prolactin-secreting tumor of the pituitary gland (a prolactinoma);
• concomitant use of oral ketoconazole, erythromycin or other potent inhibitors of CYP3A4, causing prolongation of the QTc interval, such as clarithromycin, Itraconazole, fluconazole, Posaconazole, ritonavir, saquinavir, amiodarone, telithromycin, telaprevir and voriconazole (see “Special instructions”, “Interaction with other medicines”);
• in cases where stimulation of the motor functions of the stomach can be dangerous, e. g., in gastrointestinal bleeding mechanical obstruction or perforation;
• the liver moderate or severe degree.

Side effects

According to clinical studiesnotable reactions observed in ≥ 1% of patients taking MOTILIUM: depression, anxiety, decreased or no libido, headache, drowsiness, akathisia, diarrhea, rash, pruritus, breast enlargement/gynecomastia, breast pain and sensitivity, galactorrhea, menstrual disorders and amenorrhea, lactation disorders, asthenia. Adverse reactions observed in patients with The following adverse effects were classified as very common (≥ 10%), common (≥ 1%, but < 10%), uncommon (≥ 0.1%, but < 1%), rare (≥ 0.01%, but < 0.1%), and very rare (Based on spontaneous reports of adverse events. Immune system disorders. Very rare: anaphylactic reactions, including anaphylactic shock. Mental disorders. Very rare: increased excitability, nervousness, irritability. Nervous system disorders. Very rare: drowsiness, headache, dizziness, extrapyramidal disorders and seizures. Disorders of the cardiovascular system. Frequency unknown: ventricular arrhythmia*, pirouette-type ventricular tachycardia, sudden coronary death*. Skin and subcutaneous tissue disorders. Very rare: urticaria, angioedema. Disorders of the kidneys and urinary tract. Very rare: urinary retention. Laboratory and instrumental data. Very rare: abnormalities in laboratory parameters of liver function, hyperprolactinemia. Adverse reactions identified in post-marketing clinical trials Immune system disorders. Frequency unknown:   anaphylactic reactions, including anaphylactic shock. Mental disorders. Infrequently:   increased excitability, nervousness. Nervous system disorders. Common: dizziness. Rare: convulsions. Frequency unknown:  extrapyramidal disorders. Disorders of the cardiovascular system. Frequency unknown: ventricular arrhythmia*, pirouette-type ventricular tachycardia, sudden coronary death*. Disorders of the gastrointestinal tract. Frequency unknown: dry mouth. Skin and subcutaneous tissue disorders. Frequency unknown: angioedema. Disorders of the kidneys and urinary tract. Infrequently: urinary retention. Laboratory and instrumental data. Infrequently: abnormalities in laboratory parameters of liver function. Rare: hyperprolactinemia. * Some epidemiological studies have shown that domperidone use 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.

Interaction

Anticholinergic drugs can neutralize the effect of Motilium ® EXPRESS. Oral bioavailability of Motilium EXPRESS decreases after previous use of cimetidine or sodium bicarbonate. Do not take antacids and antisecretory medications simultaneously with domperidone, as they reduce its bioavailability after oral use (see the section “Special instructions”). The main role in the metabolism of domperidone is played by the isoenzyme CYP3A4. The results of in vitro studies and clinical experience show that concomitant use of drugs that significantly inhibit this isoenzyme can cause an increase in plasma concentrations of domperidone. Strong inhibitors of the CYP3A4 isoenzyme include:* Azole antifungal medications 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 extend the QTc interval (see section “Contraindications”). )A number of studies on the pharmacokinetic and pharmacodynamic interactions of domperidone with oral ketoconazole and oral erythromycin in healthy volunteers have shown that these drugs significantly inhibit the primary metabolism of domperidone, carried out by the CYP3A4 isoenzyme. When taking 10 mg of domperidone 4 times a day and 200 mg of ketoconazole 2 times a day at the same time, the QTc interval lengthened by an average of 9.8 ms during the entire follow-up period, at some points the changes ranged from 1.2 to 17.5 ms. When taking 10 mg of domperidone 4 times a day and 500 mg of erythromycin 3 times a day at the same time, the QTc interval lengthened by an average of 9.9 ms during the entire follow-up period, at some points the changes ranged 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”). Currently, it is not known what contribution to the change in the QT interval is made by increased plasma concentrations of domperidone. In these studies, domperidone monotherapy (10 mg four times daily) resulted in QTc interval prolongation 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) resulted in QTc interval prolongation by 3.8 and 4.9 ms, respectively, over the entire follow-up period. In another multi-dose study, no significant prolongation of the QTc interval was found in healthy volunteers during inpatient domperidone monotherapy (40 mg four times daily, total daily dose 160 mg, significantly higher than the recommended maximum daily dose). At the same time, domperidone concentrations in plasma 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 simultaneously used oral drugs, in particular, drugs with a prolonged release of the Active ingredient, or drugs coated with an enteric coating. However, the use of domperidone in patients taking paracetamol or digoxin did not affect the level of these drugs in the blood. 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 undesirable peripheral effects, such as digestive disorders, nausea and vomiting, without affecting their central effects.

How to take, course of use and dosage

It is recommended to take Motilium® before meals, if taken after meals, the absorption of domperidone slows down slightly. Adults and adolescents over 12 years of age with a body weight of 35 kg or more and children under 12 years of age with a body weight of 35 kg or more: 10 ml 3 times/day. The maximum daily dose is 30 ml (30 mg). The dose should be determined very carefully, taking into account body weight and not exceeding the recommended maximum daily dosage. In patients of all age categories, usually 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 persist for more than one week, the patient should consult their doctor again. For other indications, the duration of therapy is 4 weeks. If the symptoms do not disappear within 4 weeks, the patient should be re-examined and evaluated for the need to continue therapy. Use in patients with impaired renal functionas the elimination half-life of domperidone increases with severe renal impairment, with repeated use, the frequency of taking Motilium® should be reduced to 1-2 times a day, depending on the severity of the disorders, and a dose reduction may also be required. With long-term therapy, such patients should be regularly examined. Use in patients with impaired liver function The use of Motilium® is contraindicated in patients with moderate (7-9 according to the Child-Pugh classification) or severe (> 9 according to the Child-Pugh classification) hepatic insufficiency (see the section “Contraindications”). In patients with mild (5 – 6 according to the Child-Pugh classification) hepatic insufficiency, no dose adjustment is required.

Overdose

Symptoms and symptoms of overdose have been reported mainly in children and older children. Symptoms of overdose may include increased excitability, altered consciousness, seizures, disorientation, drowsiness, and extrapyramidal reactions. There is no treatment-specific antidote for domperidone. In case of overdose, gastric lavage is recommended within one hour of taking the drug and the use of activated charcoal. It is recommended to carefully monitor the patient’s condition and conduct maintenance therapy. Anticholinergic agents and drugs used to treat Parkinsonism may be effective in stopping the occurrence of extrapyramidal reactions.

Description

Homogeneous suspension of white color

Special instructions

When Motilium EXPRESS is co-administered with antacids or antisecretory medications, the latter should be taken after meals, not before meals, i. e. they should not be taken simultaneously with Motilium EXPRESS. Motilium ® EXPRESS resorption tablets contain aspartame, so they should not be used in patients with hyperphenylalaninemia. Use in children of Imotilium ® EXPRESS in rare cases may cause neurological side effects (see the section “Side effects”). In this regard, you should strictly adhere to the recommended dose (see the section “Dosage and use”). Neurological adverse effects may be caused in adolescents by overdose of the drug, but other possible causes of such effects should also be taken into account. Application in diseases of the cardiovascular system. Some epidemiological studies have shown that the use of 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 disturbances (hypokalemia, hyperkalemia, hypomagnesemia) or with bradycardia, or in patients with concomitant heart diseases, such as congestive heart failure. As you know, against the background of electrolyte imbalance and bradycardia, the risk of arrhythmias increases. If signs or symptoms that may be associated with cardiac arrhythmia appear, Motilium® EXPRESS therapy should be discontinued and a doctor should be consulted. Use in kidney diseases. Since a very small percentage of the drug is excreted unchanged by the kidneys, a single dose adjustment is not required in patients with renal insufficiency. However, when Motilium ® EXPRESS is re-prescribed, the frequency of use should be reduced to one to two times a day, depending on the severity of renal dysfunction (see the section “Dosage and use”). With long-term therapy, patients should be regularly monitored. Drug interaction potencythe main pathway of domperidone metabolism is mediated by the CYP3A4 isoenzyme. In vitro data and results of human studies show that concomitant use of drugs that significantly inhibit this enzyme may be accompanied by an increase in plasma concentrations of domperidone. Concomitant use of domperidone with potent inhibitors of the CYP3A4 isoenzyme, which, according to the data obtained, cause prolongation of the QT interval, is contraindicated (see the section “Contraindications”). Caution should be exercised when domperidone is co-administered with strong inhibitors of the CYP3A4 isoenzyme that do not cause prolongation of the QT interval, such as indinavir, and patients should be carefully monitored for signs or symptoms of adverse reactions (seesection “Interaction with other medicinal products”). Caution should be exercised when using domperidone concomitantly with medications that have been reported to cause prolongation of the QT interval, and patients should be carefully monitored for signs or symptoms of cardiovascular adverse reactions. Examples of such medicines:* Class IA antiarrhythmic agents (e. g. disopyramide, quinidine);• class III antiarrhythmic drugs (e. g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol•; * certain antipsychotics (e. g., haloperidol, pimozide, sertindol);• certain antidepressants (e. g., citalopram, escitalopram);• certain antibiotics (for example, levofloxacin, moxifloxacin);• certain antifungal agents (for example, pentamidine);• certain antimalarials (for example, halofantrine);• certain gastrointestinal medications (for example, dolasetron);• certain antitumor medications (for example, toremifene, vandetanib);• certain other medications (for example, bepridil, methadone). If the medicine has become unusable or the expiration date has expired, do not throw it into the sewage system or on the street! Place the medicine in a plastic bag and put it in the trash can. These measures will help protect the environment!

Form of production

Oral suspension

Storage conditions

Store at a temperature of 15 to 30° C. Keep out of the reach of children.

Shelf life

3 years

Active ingredient

Domperidone

Conditions of release from pharmacies

By prescription

Dosage form

suspension for oral use

Purpose

Children as prescribed by a doctor, Pregnant women as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Gastrointestinal motility disorders, Intestinal infections, Reflux esophagitis, Flatulence