Motilium 10 mg, 30 pcs.

Active substance:

domperidone;

Excipients:

lactose,

corn starch,

microcrystalline cellulose,

pregelatinized potato starch,

polyvidone

magnesium stearate,

hydrogenated vegetable oil,

sodium lauryl sulfate and hypromellose;

Motilium - antiemetic.

Pharmacodynamics 

Domperidone is a dopamine antagonist, which, similarly to metoclopramide and some antipsychotics, has antiemetic properties. However, unlike these drugs, domperidone does not penetrate the blood-brain barrier poorly.

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 is probably due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the trigger zone of chemoreceptors.

When used internally, domperidone increases the duration of antrum 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 

Domperidone is rapidly absorbed when taken orally on an empty stomach, the maximum plasma concentrations are observed for about 1 hour. The low absolute bioavailability of oral domperidone (approximately 15%) is due to extensive primary metabolism in the intestinal wall and liver. 

Domperidone should be taken 15-30 minutes before a meal. Hypoacidity of gastric juice reduces the absorption of domperidone. When taking the drug after meals, it takes longer to achieve maximum absorption, and the area under the curve (AUC) increases slightly. 
When taken orally, domperidone does not cumulate and does not induce its own metabolism. The maximum concentration in plasma 90 minutes after ingestion at a dose of 30 mg per day for 2 weeks was 21 ng / ml, almost no different from the maximum concentration after a single dose (18 ng / ml). Domperidone binds to plasma proteins by 91-93%. The concentration of domperidone in breast milk of lactating women is 4 times lower than the corresponding plasma concentration. 

The drug is metabolized in the liver by hydroxylation and N-dealkylation. Excretion with urine and feces is 31 and 66% of the oral dose, respectively. The excretion of the drug unchanged is a small percentage (10% with feces and approximately 1% with urine). The plasma half-life after taking a single dose is 7–9 hours in healthy people, but is extended in patients with severe renal failure (20.8 hours).

• a feeling of fullness in the epigastrium, a feeling of bloating, pain in the upper abdomen;
• belching, flatulence;
• nausea, vomiting;
• heartburn, belching. 

• established intolerance to the drug and its components;
• prolactin-secreting pituitary tumor (prolactinoma);
• concomitant use of oral forms of ketoconazole;
• gastrointestinal bleeding, obstruction or perforation (i.e., when stimulation of the motor function of the stomach can be dangerous).
• children's age up to 5 years.

With caution: given the high degree of domperidone metabolism in the liver, Motilium should be prescribed with caution to patients with liver failure.

From the gastrointestinal tract: gastrointestinal disorders (rarely), in some cases - transient intestinal cramps;

From the side of the nervous system: extrapyramidal effects (in children it is very rare, in adults - isolated cases); these phenomena are completely reversible and disappear after stopping the drug;

On the part of the immune system: allergic reactions (very rare);

From the skin: urticaria;

From the endocrine system: increased plasma prolactin, due to the fact that the pituitary gland is outside the blood-brain barrier; in rare cases, this hyperprolactinemia can stimulate the appearance of neuro-endocrine phenomena such as galactorrhea, gynecomastia and amenorrhea.

Anticholinergic drugs can neutralize the effects of Motilium. The oral bioavailability of Motilium decreases after the previous administration of cimetidine or sodium bicarbonate.

Antacids and antisecretory drugs should not be taken simultaneously with Motilium, since they reduce its bioavailability after oral administration. 

The main pathway of metabolic transformations of domperidone is through CYP3A4. Based on in vitro studies, it can be assumed that concomitant use of domperidone with drugs that significantly inhibit this enzyme may cause an increase in plasma domperidone levels.

When conducting a study (on healthy volunteers) of the interaction of domperidone with ketoconazole, ketoconazole inhibits the CYPZA4-dependent primary metabolism of domperidone, resulting in an approximately three-fold increase in the maximum concentration of domperidone and AUC in the plateau phase. 

The following drugs are also examples of CYP3A4 enzyme inhibitors:

• azole antifungal drugs;
• antibiotics from the macrolide group;
• HIV protease inhibitors;
• nefazodone. 

In a study of the interaction of domperidone and ketoconazole, it was shown that with the combined use of domperidone at a dose of 10 mg 4 times a day and ketoconazole at a dose of 200 mg 2 times a day, the QT interval is prolonged by 10-20 ms. When monotherapy with domperidone, both in similar doses and when taking a daily dose of 160 mg (which is 2 times the maximum allowable daily dose), there were no clinically significant changes in the QT interval. 
Theoretically, since Motilium has a gastrokinetic effect, it could affect the absorption of simultaneously used oral drugs, in particular, drugs with delayed release of the active substance, or enteric-coated preparations. However, the use of domperidone in patients with paracetamol or selected digoxin therapy did not affect the level of these drugs in the blood. 

Motilium may also be combined with:

• antipsychotics, the effect of which he does not enhance
• agonists of dopaminergic receptors (bromocriptine, levodopa), whose undesirable peripheral effects, such as digestive disorders, nausea, vomiting, it suppresses, without neutralizing their basic properties.

Inside, 15-30 minutes before meals and at bedtime (if necessary).

Chronic dyspepsia: adults - 10 mg (1 tablet) 3 times a day; in case of inefficiency, the dose can be doubled (with the exception of children under 1 year old). The maximum daily dose is 2.4 mg / kg, but not more than 80 mg.

Nausea and vomiting: adults - 20 mg (2 tablets) 3-4 times a day (maximum daily dose - 80 mg). The maximum daily dose is 2.4 mg / kg, but not more than 80 mg.

Motilium® tablets are indicated only for adults and children weighing more than 35 kg; in pediatric practice, Motilium® suspension should be mainly used. In renal failure, a decrease in the frequency of taking the drug is recommended.

Symptoms: drowsiness, disorientation and extrapyramidal reactions, especially in children. 

Treatment: in case of overdose, the use of activated carbon and careful monitoring are recommended. Anticholinergics, drugs used to treat parkinsonism, or antihistamines may be effective in the event of extrapyramidal reactions.

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