Domperidone - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate (sugar milk) - 53.10 mg, corn starch - 20.00 mg, microcrystalline cellulose - 10.00 mg, povidone-K25 - 3.00 mg, magnesium stearate - 0.70 mg, sodium lauryl sulfate - 0, 20 mg.

Shell composition: hypromellose 1.15 mg, macrogol 4000 to 0.30 mg, titanium dioxide 0.55 mg.

Description:

Round, biconvex tablets, covered with a film shell of white or almost white color. On the cross section of the tablet, two layers are visible: the nucleus is almost white and the film membrane.

Pharmacotherapeutic group:antiemetics - dopamine receptor blocker central

ATX: & nbsp

A.03.F.A.03 Domperidone

Pharmacodynamics:

Domperidone is a dopamine antagonist with antiemetic properties. but domperidone poorly penetrates 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 of dopamine receptors in the chemoreceptor trigger zone.Animal studies and low drug concentrations found in the brain indicate a central effect of domperidone on dopamine receptors.

When administered orally domperidone prolongs the duration of antral 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:

When taken on an empty stomach, domperidone quickly absorbed after ingestion, peak plasma concentrations are achieved within 30-60 minutes.

Low absolute bioavailability of domperidone when taken orally (approximately 15%) is associated with an intensive metabolism of the first passage in the intestinal wall and liver. Domperidone should be taken 15-30 minutes before meals. Reduction of acidity in the stomach leads to a violation of absorption of domperidone.

Bioavailability during ingestion decreases with the preliminary intake of cimetidine and sodium bicarbonate. When taking the drug after a meal to achieve maximum absorption, it takes more time, and the area under the pharmacokinetic curve (AUC) increases somewhat.

Ingestion domperidone Does not accumulate or induce its own metabolism; The peak plasma level of 21 ng / ml 90 minutes after 2 weeks of oral administration 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 distribution with a radioactive label in animals showed a significant distribution of the drug in the tissues, but low concentrations in the brain. Small amounts of the drug penetrate the placenta in rats.

Domperidone undergoes rapid and intensive metabolism by hydroxylation and N-dealkylation. Metabolic Studies in vitro with diagnostic inhibitors have shown that the isoenzyme CYP3A4 is the main form of cytochrome P450 involved in the N-dealkylation of domperidone, while the CYP3A4, CYP1A2 and CYP2E1 isoenzymes participate in the aromatic hydroxylation of domperidone.

Excretion through the kidneys and through the intestine is 31% and 66% of the dose when taken orally, respectively. The proportion of the drug excreted unchanged is small (10% through the intestine and approximately 1% through the kidneys).Plasma half-life after a single oral intake is 7-9 hours in healthy volunteers, but increases in patients with severe renal failure.

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 concentration in the plasma is lower than in healthy volunteers. A small amount of unchanged drug (about 1%) is excreted by the kidneys.

In patients with impaired liver function of moderate severity (B score by Child-Pugh 7-9), AUC and C_max domperidone were 2.9 and 1.5 times higher than in healthy volunteers, respectively. The unbound fraction increased by 25% and the half-life increased from 15 to 23 hours. In patients with mild liver failure, systemic exposure is lower than in healthy patients. In patients with hepatic insufficiency of severe severity, pharmacokinetics has not been studied.

Indications:

To relieve the symptoms of nausea and vomiting.

Contraindications:

- Hypersensitivity to domperidone or any other component of the drug;

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- pronounced electrolyte disorders or heart diseases, such as chronic heart failure;

- Children under 12 years old with a body weight of less than 35 kg;

- simultaneous use of oral forms of ketoconazole, erythromycin or other drugs that increase the interval QT, or potent inhibitors of isoenzyme CYP3A4, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin, etc .;

- bleeding from the gastrointestinal tract, mechanical intestinal obstruction, perforation of the stomach or intestines;

- hepatic insufficiency of moderate and severe severity;

- prolactinoma;

- Pregnancy and the period of breastfeeding.

Carefully:Pkidney failure.

Pregnancy and lactation:

Data on the use of domperidone during pregnancy is not enough. Application drug during pregnancy is contraindicated.

In women, the concentration of domperidone in breast milk is 10 to 50% of the corresponding plasma concentration and does not exceed 10 ng / ml. Infants who are breastfed may develop unwanted reactions from the cardiovascular system.

In this regard, when using domperidone during breastfeeding should stop breastfeeding.

Dosing and Administration:

Inside.

It is recommended to take tablets covered with a film membrane before meals, in case of their reception after eating, the absorption of domperidone may slow down.

Adults and children over 12 years of age weighing 35 kg or more:

1 tablet (10 mg) 3 times a day. The maximum daily dose is 3 tablets (30 mg).

Usually the duration of the course of treatment does not exceed one week.

Application the children

Domperidone tablets covered with a film coat are shown only for adults and children over 12 years of age with a body weight of 35 kg or more; in children's practice, domperidone in another dosage form.

Application the patients with renal insufficiency

In patients with renal insufficiency, a single dose adjustment is not required. With repeated use, the frequency of taking the drug should be reduced to 1-2 times a day, depending on the severity of the disorders. A dose reduction may also be required. A regular examination of such patients should be carried out (see section "Special instructions").

Application the patients with hepatic insufficiency

In patients with mild heredity, a dose adjustment is not required. The drug is contraindicated in patients with hepatic insufficiency of moderate and severe severity.

Side effects:

According to clinical studies

Undesirable reactions observed in ≥1% of patients taking domperidone: depression, anxiety, decreased or absent libido, headache, drowsiness, akathisia, dry mouth, diarrhea, rash, itching, galactorrhea, gynecomastia, pain and sensitivity in the area of dairy glands, menstrual irregularities and amenorrhea, lactation, asthenia.

Undesirable reactions observed in <1% of patients taking domperidone: hypersensitivity, urticaria, swelling and discharge from the mammary glands.

According to spontaneous reports of undesirable phenomena

The incidence of adverse reactions listed below was determined according to the following (World Health Organization classification): Often > 1/10, often from> 1/100 to <1/10, infrequently from> 1/1000 to <1/100, rarely from> 1/10000 to <1/1000, rarely from <1/10000, including individual messages.

Immune system disorders

Very rarely: allergic reactions, including anaphylaxis, anaphylactic shock, anaphylactic reactions, angioedema.

Disorders from the gastrointestinal tract

Rarely: gastrointestinal, including transient intestinal spasms; very rarely: diarrhea.

Disturbances from the nervous system

Very rarely: extrapyramidal disorders, convulsions, increased irritability and irritability, drowsiness, headache.

Disorders from the cardiovascular system

Very rarely: lengthening the interval QT; frequency unknown: ventricular tachyarrhythmia of the type "pirouette" *, sudden coronary death *.

Disturbances from the skin and subcutaneous tissues

Very rarely: Quincke's edema, itching of the skin, hives.

Disorders from the kidneys and urinary tract

Very rarely: retention of urine.

Other

Very rarely: a change in the indicators of functional liver samples.

Rarely: hyperprolactinemia, galactorrhea, gynecomastia, amenorrhea.

* Some epidemiological studies have shown that the use of domperidone may be associated with an increased risk of developing 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 at a daily dose of more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose:

Overdose Symptoms are found most often in children. Signs of overdose are agitation, altered consciousness, convulsions, disorientation, drowsiness and extrapyramidal reactions.

Treatment of overdose: symptomatic, there is no specific antidote. Gastric lavage, reception of activated charcoal, in case of occurrence of extrapyramidal reactions - anticholinergic, antiparkinsonian agents. Due to the possible increase in the QT interval, an electrocardiogram (ECG) should be monitored.

Interaction:

Interaction with the following drugs may increase the risk of increasing the interval QT:

Contraindicated combinations: drugs that increase the interval QT: antiarrhythmic drugs class IA (e.g., disopyramide, hydroquinidine, quinidine), antiarrhythmic drugs of class III (for example, amiodarone, dofetilide, dronedaron, ibutilide, sotalol), antipsychotics (for example, haloperidol, pimozide, sertindole), antidepressants (for example, citalopram, escitalopram), antibiotics (erythromycin, levofloxacin, moxifloxacin, spiramycin), antifungal medications (eg, pentamidine), antimalarial drugs (in particular halophthrin, lumefantrine), gastrointestinal drugs (eg, cisapride, dolasetron, prukalopride), antihistamines (for example, mechitazine, misolastine), antitumor drugs (for example, toremifene, vandetanib, wincamine), other drugs (for example, bepridil, diphemanyl methyl sulfate, methadone), potent inhibitors CYP3A4 (protease inhibitors, antifungal azole agents, some antibiotics from the macrolide group (erythromycin, clarithromycin, telithromycin)).

Unsupported combinations: moderate inhibitors CYP3A4 (diltiazem, verapamil, some antibiotics from the macrolide group).

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

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

Increase the concentration of domperidone in the blood plasma: antifungal agents of the azole series, antibiotics from the macrolide group, HIV protease inhibitors, nefazodone.

Compatible with the use of antipsychotic drugs (neuroleptics), dopaminergic receptor agonists (bromocriptine, levodopa).

Simultaneous use with paracetamol and digoxin does not affect the concentration of these drugs in the blood.

Special instructions:

It is not recommended to apply the drug Domperidone for the prevention of nausea and vomiting after anesthesia.

With prolonged therapy with the drug, patients should be under regular medical supervision.

Domperidone may cause lengthening of the interval QT on the ECG. During post-marketing research in patients taking domperidone, in rare cases there was an increase in the interval QT and the occurrence of ventricular tachycardia as pirouette. These adverse reactions were noted mainly in patients with risk factors, with severe electrolyte disturbances, or concomitantly taking drugs that increase the range QT.

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 with a single dose of more than 30 mg, as well as in patients taking both drugs that increase the interval QT, or inhibitors CYP3A4).

Application of the drug Domperidone and other drugs that can cause lengthening of the interval QT, is contraindicated in patients who experience prolongation of cardiac conduction intervals, especially the interval QT, in patients with severe electrolyte disorders (hypo- and hyperkalemia, hypomagnesemia) or in patients with heart disease, such as chronic heart failure.

It was shown that the presence of electrolyte disorders (hypo- and hyperkalemia, hypomagnesemia) and bradycardia may increase the risk of arrhythmia. The drug should be discontinued if there are any symptoms that may be associated with a heart rhythm disorder. In this case it is necessary to consult a doctor.

A drug Domperidone enhances the effect of neuroleptics with simultaneous application.

With the simultaneous use of the drug Domperidone with dopaminergic receptor agonists (bromocriptine, levodopa) inhibits unwanted peripheral effects of the latter, such as digestive disorders, nausea and vomiting, without affecting their central effects.

The drug is recommended to take in the minimum effective dose.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, due to the risk of side effects that may affect these abilities.

Form release / dosage:

Tablets coated with a film coating, 10.0 mg.

Packaging:

For 10, 30, 50 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets in cans of polyethylene terephthalate for medicines, sealed with screw caps with a first opening control or a "push-turn"polypropylene or polyethylene cans or cans of polypropylene for medicines sealed with lids pull-up with the control of the first opening from polyethylene or cans of polypropylene for medicines sealed with caps tightened with the control of the first opening of high pressure polyethylene.

One jar or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a cardboard package.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003751

Date of registration:26.07.2016

Expiration Date:26.07.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp30.08.2016

Illustrated instructions

Instructions

Domperidone (Domperidone)