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

Excipients: lactose monohydrate 50.00 mg, corn starch 10.00 mg, sodium lauryl sulfate 0.20 mg, povidone-K30 3.00 mg, microcrystalline cellulose 23.32 mg, silicon dioxide colloid 0.25 mg, magnesium stearate 0.50 mg ; sheath (hypromellose 2.80 mg, propylene glycol 0.30 mg, talc 0.70 mg, titanium dioxide E171 1.20 mg).

Description:

White or almost white, round, biconvex tablets, covered with a film sheath, engraved with "Do 10 "on one side, on the cross section - the core of white color.

Pharmacotherapeutic group:antiemetics - dopamine receptor blocker central

ATX: & nbsp

A.03.F.A.03 Domperidone

Pharmacodynamics:

Domperidone is a blocker of dopamine receptors, which has an antiemetic effect. Antiemetic action is caused by a combination of peripheral (gastrokinetic) action and inhibition of dopamine receptors in the trigger zone of chemoreceptors of the brain located outside the blood-brain barrier in the region area postrema. Ingestion domperidone increases the decreased pressure in the esophagus, improves anthroduodenal motility and accelerates the emptying of the stomach without exerting an effect on gastric secretion. Domperidone increases the secretion of prolactin in the pituitary gland.

Pharmacokinetics:

When administered on an empty stomach domperidone quickly absorbed, its maximum plasma concentrations are reached within 30-60 minutes. Low absolute bioavailability after oral administration (about 15%) is due to the effect of "first passage" through the liver. Although in healthy volunteers the bioavailability of domperidone increases with admission after meals, patients with gastrointestinal complaints should take domperidone for 15-30 minutes before meals. With a decrease in the acidity of gastric juice, there is a violation of absorption of domperidone. Preliminary intake of cimetidine and sodium bicarbonate reduces the bioavailability of domperidone. When taken orally after a meal, it takes a little longer to achieve maximum absorption.

Ingestion domperidone Does not cumulate or induce its own exchange. Domperidone on 91-93% binds to blood plasma proteins. Domperidone is distributed in various tissues of the body, is found in breast milk, but does not penetrate the blood-brain barrier.The concentration of domperidone in breast milk is 10-50% of the concentration in the blood plasma.

Metabolism domperidona occurs in the liver and in the wall of the intestine by hydroxylation and N-dealkylation with the participation of isoenzymes CYP3A4, CYP1A2 and CYP2E1.

Domperidone is excreted by the intestine (66%) and kidneys (33%), incl. in unchanged form (10% and 1% respectively). The half-life is 7-9 hours.

Pharmacokinetics in specific patient groups

In patients with a serum creatinine concentration greater than 0.6 mmol / L, the half-life is 7.4 to 20.8 hours, with a decrease in domperidone concentration in the blood plasma.

Indications:

Dyspeptic symptoms, such as nausea, vomiting, a feeling of overflow in the epigastric region, discomfort in the upper abdomen and regurgitation of gastric contents.

Contraindications:

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

- prolactin secretant tumor pituitary (prolactinoma);

- gastrointestinal bleeding;

- perforation of the gastrointestinal tract;

- mechanical intestinal obstruction;

- hepatic insufficiency of moderate and severe severity;

- in patients with lengthening intervals cardiac conduction, especially interval QTc, in patients with severe impairment electrolyte balance or concomitant diseases of the heart, for example, chronic cardiac insufficiency;

- simultaneous application ketoconazole for oral administration, erythromycin for oral administration or other potent inhibitors of isoenzyme CYP3A4, causing an elongation interval QT, such as fluconazole, clotrimazole, clarithromycin, amiodarone and telithromycin (see section "Interaction with other medicinal products");

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

- the period of breastfeeding;

- Children under 12 years of age and weighing less than 35 kg.

Carefully:

- Pregnancy;

- kidney failure;

- simultaneous use of drugs that induce the development of bradycardia and hypokalemia, as well as macrolides that extend the interval QT: azithromycin and roxithromycin.

Pregnancy and lactation:

ANDlimited postregistration data on the use of domperidone in pregnant women. Research on animals demonstrated reproductive toxicity at a high dose, toxic to the mother's body. The possible risk to man is unknown.

therefore domperidone should apply pregnancy only in case of justification of the alleged therapeutic benefit for the mother. Domperidone is excreted in breast milk in lactating female rats (primarily as metabolites: maximum concentration 40 and 800 ng / ml after ingestion or intravenous administration of 2.5 mg / kg, respectively).

Domperidone excreted in breast milk in women, and infants during breastfeeding may receive less than 0.1% of the maternal dose adjusted by body weight. It is impossible to exclude the possibility of undesirable effects, especially cardiological effects, in infants during breastfeeding. It is necessary to decide whether to stop breastfeeding or to cancel / abstain from therapy domperidone, assessing the benefits of breastfeeding for the baby and the benefit of treatment for the mother.

Care should be taken if there are risk factors for lengthening the interval QTc in infants during breastfeeding.

Dosing and Administration:

Inside, before eating, squeezed with enough water. When applying the drug after eating, the absorption of the drug may be somewhat slowed down.

Adults and children over 12 years of age with a body weight of more than 35 kg:

1 tablet 3 times a day. The maximum daily dose is 30 mg / day. Duration of admission should not exceed 1 week. Further administration of the drug is possible after consultation with a doctor.

Patients should try to take each dose at the scheduled time. If a planned dose is missed, it should be deleted and the usual regimen of the drug should be resumed. Do not duplicate the dose of the drug to replenish the missed dose.

With hepatic insufficiency of moderate and severe severity application of Domperidone-Teva it is contraindicated.

With mild hepatic insufficiency correction of the dose is not required.

With renal insufficiency It is recommended to reduce the frequency of taking Domperidone-Teva to 1-2 times a day.

Side effects:

The incidence of adverse events is classified as follows: very often (≥1 / 10), often (≥1 / 100 - <1/10),infrequently (≥1 / 1000 - <1/100), rarely (≥1 / 10000 - <1/1000), very rarely (<1/10000), the frequency is unknown (can not be determined based on available data).

From the immune system: very rarely - allergic reactions, including anaphylaxis, anaphylactic shock, anaphylactoid reactions and angioedema.

From the endocrine system: rarely - an increase in the concentration of prolactin.

From the nervous system: very rarely - extrapyramidal disorders, agitation, nervousness, convulsions, drowsiness, headache; frequency unknown - "restless legs" syndrome (exacerbation in patients with Parkinson's disease).

From the cardiovascular system: frequency unknown - interval elongation QT, ventricular arrhythmia, sudden cardiac death (see section "Special instructions").

From the digestive system: rarely - gastrointestinal disorders; very rarely - intestinal spasm, diarrhea.

From the skin and subcutaneous tissues: very rarely - skin itching, skin rash, hives.

On the part of the reproductive system and mammary glands: rarely - galactorrhea, gynecomastia, amenorrhea.

Laboratory indicators: very rarely - the deviation of indicators of functional liver samples from normal.

Description of individual adverse reactions

'As the pituitary gland is located outside the blood-brain barrier, domperidone can cause an increase in the concentration of prolactin. In rare cases, such hyperprolactinemia can lead to the development of neuroendocrine side effects, such as galactorrhea, gynecomastia and amenorrhea. Extrapyramidal side effects are very rare in newborns and infants and are exceptional in adults. These side effects are resolved spontaneously and completely, immediately upon discontinuation of treatment.

Other effects associated with the nervous system: seizures, agitation and drowsiness, are also very rare and are mainly reported when used in infants and children.

Overdose:

Overdose Symptoms include drowsiness, disorientation and extrapyramidal disorders, especially in children.

Treatment

There is no specific antidote. In case of an overdose, gastric lavage and the use of activated charcoal may be effective. Careful observation and maintenance therapy is recommended.

To stop extrapyramidal disorders, m-cholinoblockers and drugs used to treat parkinsonism may be effective.

Interaction:

The main metabolism of domperidone occurs with the participation of isoenzyme CYP3A4. Study in vitro demonstrated that the combined use of drugs that significantly inhibit this enzyme can cause the appearance of elevated concentrations of domperidone in the blood plasma.

Individual research in vivo pharmacokinetic / pharmacodynamic interactions of domperidone with ketoconazole or erythromycin for oral administration with the participation of healthy volunteers confirmed a significant inhibition of SURCA4-mediated presystemic metabolism of domperidone with these drugs.

Increased risk of lengthening the interval QT as a result of pharmacodynamic and / or pharmacokinetic interactions

With the combined use of domperidone 10 mg for oral administration four times a day and ketoconazole 200 mg twice daily, the average elongation interval QT, equal to 9.8 ms, was observed during the observation period with changes in individual time points in the range 1.2-17.5 ms. With the combined use of domperidone 10 mg for oral administration four times a day and erythromycin 500 mg for oral administration three times a day, the average elongation QT during the observation period was 9.9 ms with changes in individual time points in the range 1.6-14.3 ms. FROM_m_Oh and AUC domperidone in the equilibrium state were increased approximately three-fold in each of the studies of interactions. In these studies, monotherapy with domperidone 10 mg for oral administration four times a day, caused an increase in the mean interval QTc, (study of ketoconazole) and 2.5 ms (study of erythromycin), whereas monotherapy with ketoconazole (200 mg twice daily) and monotherapy with erythromycin (500 mg three times a day) resulted in an increase interval QTc, which amounted to 3.8 and 4.9 ms during the observation period respectively.

Contraindicated joint use with the following drugs

Drugs that extend the interval QTc:

- antiarrhythmic drugs class IA (e.g., disopyramide, hydroquinidine, quinidine);

- antiarrhythmic drugs of class III (eg, amiodarone, dofetilide, drondrone, ibutilide, sotalol);

- some antipsychotics (eg, haloperidol, pimozide, sertindole):

- some antidepressants (for example, citalopram, escitalopram);

- Some antibiotics (for example, erythromycin, levofloxacin, moxifloxacin, spiramycin);

- some antifungal medicinal preparations (for example, pentamidine);

- some antimalarial drugs (especially halofantrine, lumefantrine);

- some gastrointestinal agents (e.g., cisapride, dolasetron, prukalopride);

- some antihistamines (eg, mequitazine, misolastine);

- some drugs used in cancer (for example, toremifene, vandetanib, wincamine);

- Some other medications (for example, beprideal, diphenemann, methadone);

- powerful inhibitors CYP3A4 (regardless of the effects that extend the interval QT), namely: HIV protease inhibitors; systemic azole antifungal drugs; some macrolides (eg, erythromycin, clarithromycin and telithromycin).

It is not recommended joint use of the following drugs

Moderate inhibitors of isoenzyme CYP3A4, namely diltiazem, verapamil and some macrolides.

Joint use of the following medicines requires caution

Caution should be exercised with the simultaneous use of drugs that induce bradycardia and hypokalemia, as well as macrolides that extend the interval QT: azithromycin and roxithromycin (clarithromycin is contraindicated, since it is a potent inhibitor of isoenzyme CYP3A4). The above list of drugs is typical and not exhaustive.

Special instructions:

The drug Domperidone-Teva contains lactose, so it should not be used in patients with lactose intolerance, galactosemia or impaired absorption of glucose or galactose.

Since only a very small amount of domperidone is excreted by the kidneys unchanged, it is hardly necessary to correct a single dose in patients with renal insufficiency. At repeated application the frequency of dosing should be reduced to 1-2 times a day, depending on the severity of the insufficiency; can also a dose reduction is required. With prolonged therapy, such patients should be under regular supervision.

Taking the drug after a meal slows its absorption.

When using domperidone, an interval may be lengthened QT on an electrocardiogram. During the period post-registration monitoring of patients receiving domperidone, there were reports of very rare cases of lengthening the interval QT and ventricular tachycardia of the "pirouette" type.

These reports included information about patients with concomitant risk factors, electrolyte balance disorders, and joint therapy, which could contribute to the development of adverse events.

Epidemiological studies demonstrated that the use of domperidone was associated with increased risk of developing serious ventricular arrhythmias or sudden cardiac death (see section "Side effect"). The highest risk was observed in patients older than 60 years, patients receiving domperidone in daily doses exceeding 30 mg, and in patients taking medications in parallel, lengthening the interval QT or inhibitors CYP3A4.

The drug Domperidone-Teva should be used in adults and children in the minimum effective dose.

The drug Domperidone-Teva is contraindicated for use in patients with prolonged intervals of cardiac conduction in the anamnesis, especially the interval QTc, in patients with severe electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with concomitant heart disease, such as chronic heart failure, due to increased risk of developing ventricular arrhythmias (see "Contraindications"). Disorders of electrolyte balance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia are known as conditions that increase pro-arrhythmic risk.

Treatment with Domperidone-Teva should be discontinued if there are signs and symptoms that may be associated with cardiac arrhythmia, and patients should consult their physician.

It is necessary to recommend patients to immediately report any violations from the heart to the treating doctor.

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

When taking Domperidone-Teva, caution should be exercised when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions because of the possible risk of extrapyramidal disorders, seizures, drowsiness, headache.

Form release / dosage:

Tablets, film-coated, 10 mg.

Packaging:

For 10 tablets in PVC / aluminum foil blisters; 1 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 of the year.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000316

Date of registration:22.02.2011

Date of cancellation:2016-02-22

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp18.01.2016

Illustrated instructions

Instructions

Domperidone-Teva (Domperidone-Teva)