Motilium Express, tablets 10 mg 30 pcs

Heartburn, Reflux esophagitis, Abdominal bloating, Intestinal infections, Nausea, GI motility disorders, Vomiting, Hiccups, Meteorism) Complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux, esophagitis:

– feeling of congestion in the epigastrium, 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 violation of diet. A specific indication is nausea and vomiting caused by dopamine agonists when used in Parkinson’s disease (such as levodopa and bromocriptine).

Indications

a) A complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal 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, 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).

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 in rare cases can cause neurological side effects (see section “Side effects”). In this regard, you should strictly adhere to the recommended dose (see section “Method of administration and dosage”). Neurological adverse effects can 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 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 known to prolong the QTc interval is not recommended in patients with existing conduction disturbances, in particular prolongation of the QTc interval, and in patients with severe electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with concomitant cardiac 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, Motilium® EXPRESS therapy 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 “Dosage and Administration”). During long-term therapy, patients should be monitored regularly.

Potential for drug interactions

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 (see section “Contraindications”).

Caution is advised when co-administering domperidone with potent 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 (see Interactions with Other Drugs).

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 antiarrhythmic drugs (for example, 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 medicines (eg dolasetron);
• certain anticancer drugs (eg toremifene, vandetanib);
• some other medicines (for example, 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!

Active ingredient

Domperidone

Composition

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.

Pregnancy

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 Motilium® EXPRESS during lactation, it is recommended to stop breastfeeding.

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 other medicines”);
• 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 kg.

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

Anticholinergic drugs may 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 Contraindications section).

It is currently unknown how elevated plasma concentrations of domperidone contribute to changes in the QTc interval.

In these studies, domperidone monotherapy (10 mg four times daily) resulted in a QTc interval prolongation of 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 a QTc interval prolongation of 3.8 ms and 2.5 ms (erythromycin study). 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 level of these drugs in the blood.

Motilium® EXPRESS can be taken simultaneously with:

• antipsychotics, 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.

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. It is recommended to closely monitor the patient’s condition and provide supportive therapy. Anticholinergics and drugs used to treat parkinsonism may be effective in stopping extrapyramidal reactions that occur.

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 in a dry place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Store in original packaging.

Shelf life

2 years. Do not use after expiration date.

Manufacturer

Catalent UK Swindon Zaydis Limited, UK