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

Excipients: lactose 54.2 mg; corn starch 23.05 mg; microcrystalline cellulose 10.0 mg; povidone K30 1.5 mg; sodium lauryl sulfate 0.15 mg; magnesium stearate 0.6 mg; silicon dioxide colloid 0.5 mg.

Description:

White, round, biconvex tablets with application of "Dm 10 "on one side.

Pharmacotherapeutic group:antiemetics - dopamine receptor blocker central

ATX: & nbsp

A.03.F.A.03 Domperidone

Pharmacodynamics:

Domperidone is a dopamine antagonist possessing, similarly metoclopramide and some neuroleptics, antiemetic properties. However, unlike these drugs domperidone, poorly penetrating the blood-brain barrier, primarily blocks peripheral and less central (in the trigger zone of the brain) dopamine receptors, eliminating the inhibitory effect of dopamine on the motor function of the gastrointestinal tract (GI tract). 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. Increases the duration of peristaltic contractions of the antral part of the stomach and duodenum,accelerates the emptying of the stomach in case of slowing down of this process, increases the reduced pressure in the esophagus, eliminates the development of nausea and vomiting. Domperidone has no effect on gastric secretion.

A placebo-controlled, direct comparative study of the effect on the interval QT two doses of domperidone (10 mg and 20 mg) with the same dosing regimen 4 times a day. The maximum elongation of the interval QT an average of 3.4 ms was noted on the fourth day of the study with a high dose of domperidone.

Pharmacokinetics:

After oral administration on an empty stomach domperidone quickly absorbed from the gastrointestinal tract, reaching a maximum concentration (C_m_Oh) in the blood plasma after 1 hour. The values of the area under the curve "concentration-time" (AUC) and the maximum plasma concentration (C_m_Oh) increase proportionally with an increase in the dose from 10 mg to 20 mg. Two-three-fold increase AUC was observed with the application of domperidone 4 times a day on the fourth day of admission. Low absolute bioavailability of oral domperidone (approximately 15%) is due to extensive primary metabolism in the wall of the intestine and liver.Although healthy volunteers the bioavailability of domperidone increases with admission after meals, patients with gastrointestinal complaints should take domperidone for 15-30 minutes before meals. Reducing the acidity of the stomach can reduce the absorption of domperidone.

The bioavailability of domperidone decreases with the simultaneous use of cimetidine and sodium bicarbonate.

Domperidone is widely distributed in various tissues, in the brain tissues its concentration is low. Binding to plasma proteins is 91-93%.

It is subject to intensive metabolism in the liver and intestinal wall and by hydroxylation and N-dealkylation with isozymes CYP3A4, CYP1A2 and CYP2E1.

It is excreted through the intestine (66%) and kidneys (31%), with 10% and 1% of the accepted dose in the unchanged form, through the corresponding elimination route. Half-life (T_1/2) from plasma of blood after taking a single dose in healthy volunteers is 7-9 hours.

When severe renal failure (clearance creatinine (CK) less than 30 ml / min) T_1/2increases from 7.4 to 20.8 hours, butthe concentration of the drug in the blood plasma is lower than that of healthy volunteers. Since the kidneys show a smallamount of the drug in unchanged form (1%), then correction of a single dose in patients with renal insufficiency is not required. However, with repeated use, the frequency of admission should be reduced to one or two times a day, depending on the severity of renal failure.

Have patients with moderate hepatic impairment (7-9 points on the Child-Pugh scale) values AUC and C_m_Oh in 2.9 and 1.5 times, respectively, higher than in healthy volunteers. The volume of unbound faction increases by 25%, T_1/2may increase to 23 hours. In patients with mild liver failure, systemic exposure is lower than in healthy patients. There is no data on patients with hepatic impairment of severe severity.

Indications:To relieve the symptoms of nausea and vomiting.

Contraindications:

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

- prolactin-secreting pituitary tumor (prolactinoma);

- hepatic insufficiency of moderate and severe severity;

- simultaneous use of oral forms of ketoconazole, erythromycin or other medications,increasing the interval QT, or potent inhibitors of isoenzyme CYP34A, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin, etc. (see section "Interaction with other drugs");

- severe electrolyte disturbances or heart disease, such as chronic heart diseaseMr.insufficiency;

- gastrointestinal bleeding, mechanical obstruction or perforation of the digestive tract (ie, when stimulation of gastric motility may be dangerous);

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

- children under 12 years of age with a body weight of less than 35 kg (for this dosage form);

- pregnancy, the period of breastfeeding.

Carefully:Renal failure.

Pregnancy and lactation:

Controlled studies on the use of domperidone in pregnant women have not been conducted. The use of the drug during pregnancy is contraindicated.

Domperidone is excreted in small amounts into breast milk. Infants who are breastfed may develop unwanted reactions from the cardiovascular system.The use of the drug in the period of breastfeeding is contraindicated.

Dosing and Administration:

Dosing and Administration Inside, 15-20 minutes before meals, without chewing, squeezed enough water.

It is recommended to take it regularly at a certain time. If you miss one dose, take the next tablet as soon as possible. If the time of taking the next dose of the drug is appropriate, an additional dose of the drug should not be taken to compensate for the missed dose. Do not take two doses of the drug at the same time.

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

Adults and children over 12 years of age with a body weight of more than 35 kg: 1 tablet (10 mg) 3 times a day.

The maximum daily dose is 30 mg.

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

Have patients with hepatic insufficiency mild dose correction is not required. The drug is contraindicated in patients with hepatic insufficiency of moderate and severe severity.

Have patients with renal insufficiency correction of a single dose is not required. However, with repeated use, it is recommended to reduce the dose, as well as reduce the frequency of application up to 1-2 times a day, depending on the severity of renal failure.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their developmental frequency 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); frequency Unknown - according to available data to establish the frequency of occurrence was not possible

Immune system disorders

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

Disorders from the gastrointestinal tract

often: dryness of the oral mucosa.

rarely: gastrointestinal disorders, including transient intestinal spasms;

rarely: diarrhea.

Disturbances from the nervous system

rarely: extrapyramidal disorders, convulsions, increased excitability and irritability, drowsiness (in adults the above symptoms are extremely rare), headache.

Extrapyramidal disorders, as a rule, are reversible and disappear when treatment with domperidone is discontinued;

frequency is unknown: syndrome of restless legs (worsening of the manifestations of restless legs syndrome in patients with Parkinsonism).

Disturbances on the part of the organ of sight

frequency is unknown: involuntary movement of the eyes.

Disorders from the cardiovascular system

frequency is unknown: ventricular arrhythmia, lengthening of the interval QT, ventricular tachycardia as pirouette, sudden coronary death (see section "Special instructions").

Disturbances from the skin and subcutaneous tissue

rarely: skin rash, itching of the skin, urticaria.

Other

rarely: hyperprolactinemia, galactorrhea, gynecomastia, amenorrhea;

rarely: change in indicators of functional liver samples.

Overdose:

Symptoms overdose were observed mainly in children. Symptoms of overdose may include increased excitability, drowsiness, convulsions, disorientation and extrapyramidal reactions.

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

Interaction:

Antacids and antisecretory drugs Do not take at the same time with oral forms of domperidone, i.e.in the case of joint therapy with these drugs domperidone must be taken before meals, antacids or antisecretory drugs - after meal.

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 grade III (eg, amiodarone, dofetilide, dronedaron, ibutilide, sotalol), antipsychotic facilities (eg, haloperidol, pimozide, sertindole), antidepressants (eg, citalopram, escitalopram), antibiotics (erythromycin, levofloxacin, moxifloxacin, spiramycin), antifungal agents (e.g., pentamidine), antimalarial drugs (in particular, halofantrine, lumefantrine), gastrointestinal drugs (e.g., cisapride, dolasetron, prukalopride), antihistamines (eg, mechitazine, misolastine), anti-cancer drugs (eg, toremifene, vandetanib, wincamine), other drugs (e.g., bepridil, diphemanyl methyl sulfate, methadone), powerful inhibitors CYP3A4 (protease inhibitors, antifungal azole agents, some antibiotics from the macrolide group (erythromycin, clarithromycin, telithromycin)).

Levodopa: an increase in the concentration of levodopa in blood plasma (by 30-40%).

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

Combinations that follow use carefully: drugs that cause bradycardia and hypokalemia, and azithromycin and roxithromycin.

Cimetidine, sodium hydrogen carbonate, others antacids and antisecretory drugs reduce bioavailability domperidone.

Anticholinergics can neutralize the action of domperidone.

Increase the concentration of domperidone in blood plasma: antifungal agents azole series, antibiotics from the macrolide group, HIV protease inhibitors, nefazodone. Compatible with reception antipsychotic drugs (neuroleptics), agondopaminergic receptors (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 use the drug Domridon for the prevention of nausea and vomiting after anesthesia.

With prolonged therapy with the drug Domiridon, patients should be under regular supervision of a doctor.

Renal insufficiency

The half-life of domperidone increases with severe renal failure. When a single dose is not required to reduce dosage, but for course appointments, the frequency of reception should not exceed 1-2 times a day, depending on the severity of the insufficiency; a dose reduction may also be required.

Influence on the cardiovascular system

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, increasing the interval QT.

In some studies, it was 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 simultaneous drugs increasing the range QT, or inhibitors CYP3A4).

The use of domperidone and other drugs that can cause lengthening of the interval QT, contraindicated in patients who are experiencing an elongation of the intervals of cardiac conduction, 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 in the patient may increase the risk of arrhythmia.

Reception of domperidone should be discontinued if any symptoms occur that may be associated with a heart rhythm disorder. In this case it is necessary to consult a doctor.

Joint application with levodopa

Despite the fact that dose adjustment of levodopa is not required, with its joint application with domperidone, an increase in the concentration of levodopa in the blood plasma (up to 30-40%) was observed.

Joint application with antipsychotics

The drug Domridon intensifies the action of neuroleptics with simultaneous application.

Joint application with agonists of dopaminergic receptors

With simultaneous use with dopaminergic agonists receptors (bromocriptine, levodopa), the drug Domridon depresses their unwanted peripheral effects, such as digestive disorders, nausea and vomiting, without affecting their central effects.

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

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

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

When taking Domrindon, 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, 10 mg.

Packaging:

For 10 tablets in a contour mesh package of PVC / aluminum foil.

1, 2, 3, 4 or 5 blisters per pack with instructions for use.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-002051

Date of registration:09.11.2011 / 21.04.2015

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp18.01.2016

Illustrated instructions

Instructions

Domridon (Domridone)