Motilium, 10 mg 30 pcs.

Gastrointestinal motility disorders, Nausea, Vomiting, Meteorism, Hiccups, Intestinal infections, Abdominal bloating, Reflux esophagitis, Heartburn For relief of symptoms of nausea and vomiting.

Indications

To relieve symptoms of nausea and vomiting.

Special instructions

Domperidone is not recommended for the prevention of nausea and vomiting after anesthesia. 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, patients taking domperidone have rarely experienced an increase in the QT interval and torsade de pointes (TdP). These adverse reactions were observed mainly in patients with risk factors, with severe electrolyte disturbances, or concomitantly taking drugs that prolong 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. It is recommended to take the drug in the minimum effective dose.

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!

Active ingredient

Domperidone

Composition

Active ingredient:

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,

cotton seed oil, hydrogenated 0.5 mg,

sodium lauryl sulfate 0.15 mg.

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

Pregnancy

MOTILIUM® is contraindicated for use during pregnancy and breastfeeding.

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 CYP34A isoenzyme, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin, etc. (see sections “Special instructions”, “Interaction with other drugs”);
– 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.

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 tenderness in the mammary glands, galactorrhea, menstrual irregularities and amenorrhea, impaired lactation, asthenia.

Adverse reactions observed in < 1% of patients taking MOTILIUM: hypersensitivity, urticaria, breast edema, breast discharge.The following undesirable effects were classified as follows: very common (≥ 10%), common (≥ 1% but < 10%), uncommon (≥ 0.1% but < 1%), rare (≥ 0.01% but < 0.1%) and very rare (< 0.01%), including isolated cases.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 convulsions.Disorders of the cardiovascular system. Frequency unknown: ventricular arrhythmia*, torsade de pointes (TdP), sudden coronary death*.Disorders of the skin 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, hyperprolactinemia.Adverse reactions identified during post-registration clinical studiesImmune system disorders. Not known: anaphylactic reactions, including anaphylactic shock. Mental disorders. Uncommon: increased excitability, nervousness.Nervous system disorders. Common: dizziness. Rarely: convulsions. Frequency unknown: extrapyramidal disorders.Disorders of the cardiovascular system. Frequency unknown: ventricular arrhythmia*, torsade de pointes (TdP), sudden coronary death*.Gastrointestinal disorders. Frequency unknown: dry mouth.Disorders of the skin and subcutaneous tissues. Frequency unknown: angioedema.Renal and urinary tract disorders. Uncommon: urinary retention.Laboratory and instrumental data. Uncommon: abnormalities in laboratory tests of liver function. Rare: 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.

Interaction

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

Contraindicated combinations: drugs that prolong the QT interval: class IA antiarrhythmic drugs (eg, disopyramide, hydroquinidine, quinidine), class III antiarrhythmic drugs (eg, amiodarone, dofetidil, dronedarone, ibutilide, sotalol), antipsychotics (eg, haloperidol, pimozide, sertindole), antidepressants (eg, citalopram, escitalopram), antibiotics (erythromycin, levofloxacin, moxifloxacin, spiramycin), antifungals (eg pentamidine), antimalarials (eg halofantrine, lumefantrine), gastrointestinal drugs (eg cisapride, dolasetron, prucalopride), antihistamines (eg mechitazine, mizolastine), anticancer drugs (for example, toremifene, vandetanib, vincamine), other drugs (for example, bepridil, difemanil methyl sulfate, methadone), strong CYP3A4 inhibitors (protease inhibitors, azole antifungals, some macrolide antibiotics (erythromycin, clarithromycin, telithromycin).

Not recommended combinations: moderate CYP3A4 inhibitors (diltiazem, verapamil, some macrolide antibiotics).

Combinations that should be used with caution: drugs that cause bradycardia and hypokalemia, as well as azithromycin and roxithromycin.

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

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

Compatible with 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.

Overdose

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

Treatment of overdose: Symptomatic, there is no specific antidote. Gastric lavage, taking activated charcoal, if extrapyramidal reactions occur – anticholinergic, antiparkinsonian drugs. Due to the potential for QT prolongation, monitor the electrocardiogram (ECG).

Clinical pharmacology

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 to 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, maximum absorption takes longer to achieve 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 is 91–93% bound to plasma proteins. Distribution studies of the radiolabeled drug in animals have shown widespread tissue distribution 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 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).

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 renal 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.

Patients with mild hepatic impairment had slightly reduced systemic drug levels compared to 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.

Storage conditions

Store at a temperature of 15 to 30° C.

Keep out of the reach of children.

Shelf life

3 years

Manufacturer

JNTL Consumer Health (France) S.A.S., France