Motilium Express, 10 pcs., 10 mg, lozenges
Antiemetic, central dopamine receptor blocker
ATX:
A.03.FA03 Domperidone
Pharmacodynamics:
Domperidone is a dopamine antagonist with antiemetic properties. However, 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 in the chemoreceptor trigger zone. Animal studies and low concentrations of the drug found in the brain indicate a central effect of domperidone on dopamine receptors.
When administered orally, domperidone increases the duration of antral and duodenal contractions, accelerates gastric emptying and increases lower esophageal sphincter pressure in healthy people. Domperidone has no effect on gastric secretion.
Pharmacokinetics:
Domperidone is rapidly absorbed after oral administration on an empty stomach, with peak plasma concentrations achieved within 30-60 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 15-30 minutes before meals. Reduced acidity in the stomach leads to impaired absorption of domperidone. Oral bioavailability is reduced by prior administration 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) increases slightly.
When taken orally, domperidone does not accumulate and does not induce its own metabolism; the peak plasma concentration 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 peak plasma concentration of 18 ng/mL after the first dose. Domperidone is 91-93% bound to plasma proteins. Distribution studies with radiolabeled drug in animals showed significant drug distribution in tissues 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 in urine and feces is 31% and 66% of the oral dose, respectively. The proportion of the drug excreted unchanged is small (10% in feces and approximately 1% in urine). 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 healthy volunteers . A small amount of unchanged drug (about 1%) is excreted by the kidneys.
In patients with moderate hepatic impairment (Pugh score 7-9, Child-Pugh B), the AUC and maximum plasma concentration (Cmax) of domperidone were 2.9 and 1.5 times higher than in healthy subjects volunteers accordingly. The unbound fraction increased by 25% and the half-life increased from 15 to 23 hours. In patients with mild hepatic impairment, slightly reduced systemic drug levels were observed compared with those in healthy volunteers based on Cmax and AUC, without changes in protein binding or half-life. Patients with severe hepatic impairment have not been studied.
Motilium suspension for oral administration 1 mg/ml 100 ml bottle 1 pc. in Moscow
When using Motilium® 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®
Use in children
Motilium® in rare cases may cause neurological side effects (see section "Side effects"). In this regard, the recommended dose should be strictly adhered to (see section “Method of administration and dosage”). Neurological undesirable effects can be caused by an overdose of the drug 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 suggested that 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 imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or with bradycardia, or in patients with concomitant heart 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® 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®, the frequency of use should be reduced to one or two times a day, depending on the severity of renal dysfunction (see section "Method of administration and dosage"). 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 results from 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 section). .
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 antiarrhythmics (eg, 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 (eg, 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!
Impact on the ability to drive vehicles and machinery
Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the risk of developing adverse reactions that may affect these abilities.
