Domperidone, 10 mg 30 pcs

Domperidone is a dopamine antagonist with antiemetic properties. However, domperidone poorly penetrates through the blood-brain barrier. Use of domperidone is rarely accompanied by extrapyramidal side effects especially in adults but domperidone stimulates prolactin release from pituitary gland.

Its antiemetic action may be due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the chemoreceptor trigger zone. Animal studies and low concentrations of the drug found in the brain suggest 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:

When taken on an empty stomach, domperidone is rapidly absorbed after oral administration, peak plasma concentrations are reached within 30-60 minutes.

The low absolute bioavailability of domperidone when administered orally (approximately 15%) is associated with intense first-pass metabolism in the intestinal wall and liver. Domperidone should be taken 15-30 minutes before meals. Decreased acidity in the stomach leads to impaired absorption of domperidone.

Bioavailability during oral administration is reduced if cimetidine and sodium bicarbonate are taken beforehand. When the drug is taken after meals, it takes longer to reach maximum absorption and the area under the pharmacokinetic curve (AUC) is slightly increased.

In oral administration domperidone does not accumulate and does not induce its own metabolism; the peak plasma level of 21 ng/ml after 90 minutes after 2 weeks of oral dosing of 30 mg daily was almost the same as the level of 18 ng/ml after the first dose.

Domperidone binds 91-93% to plasma proteins.

The distribution studies with the radioactively labeled drug in animals showed 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 intense metabolism by hydroxylation and N-dealkylation. In vitro metabolism studies with diagnostic inhibitors have shown that the CYP3A4 isoenzyme is the major form of cytochrome P450 involved in N-dealkylation of domperidone while the CYP3A4 isoenzymes CYP1A2 and CYP2E1 are involved in aromatic hydroxylation of domperidone.

Elevation through the kidneys and through the intestine is 31% and 66% of the dose when administered orally, respectively. The proportion of the drug excreted unchanged is small (10% – through the intestine and approximately 1% – through the kidneys). Plasma elimination half-life after a single oral administration 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. > 06 mmol/l) the half-life of domperidone is increased from 74 to 208 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 liver dysfunction of moderate degree of severity (B score according to Child-Pugh 7-9 points) AUC and Cmax of domperidone were 29 and 15 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 hepatic impairment, systemic exposure was lower than in healthy patients. In patients with severe hepatic impairment, pharmacokinetics has not been studied.

Indications

Active ingredient

Composition

Active ingredient: domperidone – 10.00 mg.

Excipients: lactose monohydrate (milk sugar) – 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 – 0.30 mg, titanium dioxide – 0.55 mg.

How to take, the dosage

Ingestion.

It is recommended to take film-coated tablets before meals if taken after meals, absorption of domperidone may be delayed.

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

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

The course of treatment usually lasts less than one week.

Peridone film-coated tablets are indicated only for adults and children over 12 years of age with body weight of 35 kg or more in pediatric practice mostly in other dosage form should be used.

Use in patients with renal failure

In patients with renal failure, correction of the single dose is not required. If repeated use, the frequency of administration of the drug should be reduced to 1-2 times per day, depending on the severity of the impairment. Dose reduction may also be required. Regular examination of such patients should be carried out (see section “Special indications”).

Patients with hepatic impairment

In patients with mild hepatic impairment, no dose adjustment is required. The drug is contraindicated in patients with moderate to severe hepatic impairment.

Interaction

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

Contraindicated combinations: QT interval prolonging drugs: Class IA antiarrhythmic drugs (e.g., disopyramide hydroquinidine quinidine) Class III antiarrhythmic drugs (e.g., amiodarone dofetilide dronedarone ibutilide sotalol) antipsychotics (e.g., haloperidol pimozide sertindol) Antidepressants (e.g., citalopram escitalopram) Antibiotics (erythromycin levofloxacin moxifloxacin spiramycin) Antifungals (e.g., pentamidine) Antimalarials (e.g., halofantrine lumefantrine) Gastrointestinalintestinal drugs (e.g., cisapride dolasetron prucalopride) antihistamines (e.g., mechitazine misolastin) anticancer drugs (e.g., toremifene vandetanib vincamine) other drugs (e.g. Bepridil difemanil methyl sulfate methadone) powerful CYP3A4 inhibitors (protease inhibitors azole antifungals some macrolide antibiotics (erythromycin clarithromycin telithromycin).

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

Combinations to be used with caution: drugs that cause bradycardia and hypokalemia as well as azithromycin and roxithromycin.

Cimetidine sodium bicarbonate other antacids and antisecretory drugs reduce the bioavailability of domperidone.

Elevate the concentration of domperidone in plasma: azole antifungal agents antibiotics of macrolide group HIV protease inhibitors nefazodone.

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

Concomitant use with paracetamol and digoxin has no effect on the blood concentrations of these drugs.

Special Instructions

It is not recommended to use Domperidone for prevention of nausea and vomiting after anesthesia.

Patients on long-term therapy with the drug should be under regular medical supervision.

Domperidone may cause prolongation of the QT interval on ECG. During the post-marketing studies in patients receiving domperidone in rare cases prolongation of the QT interval and the occurrence of ventricular tachycardia by “pirouette” type were noted. These adverse reactions were noted mainly in patients with risk factors with significant electrolyte disturbances or concomitantly taking drugs prolonging the QT interval.

In some studies it has been shown that domperidone administration can increase the risk of ventricular arrhythmias or sudden coronary death (especially in patients older than 60 years of age or when using a single dose greater than 30 mg, and in patients concomitantly taking agents that increase QT interval or CYP3A4 inhibitors).

The use of Domperidone or other drugs which may prolong the QT interval is contraindicated in patients with prolonged cardiac conduction intervals, particularly prolonged QT intervals in patients with significant electrolyte disturbances (hypo- and hyperkalemia hypomagnesemia) or in patients with heart disease, such as chronic heart failure.

It has been shown that patients with electrolyte disturbances (hypo- and hyperkalemia hypomagnesemia) and bradycardia may increase the risk of arrhythmias. The drug should be discontinued in case of any symptoms that may be associated with arrhythmia. In this case, a physician should be consulted.

Domperidone increases the effect of neuroleptics when used simultaneously.

In concomitant use of Domperidone with dopaminergic receptor agonists (bromocriptine levodopa), the drug inhibits adverse peripheral effects of the latter such as digestive disorders, nausea and vomiting, while not affecting their central effects.

The drug is recommended at the lowest effective dose.

Contraindications

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

– lactose intolerance lactase deficiency glucose-galactose malabsorption;

– significant electrolyte abnormalities or heart conditions such as chronic heart failure;

–

– concurrent use of oral forms of ketoconazole erythromycin or other QT-increasing drugs or potent CYP3A4 isoenzyme inhibitors, such as fluconazole voriconazole clarithromycin amiodarone telithromycin, etc.

– bleeding from the gastrointestinal tract mechanical intestinal obstruction gastric or intestinal perforation;

– moderate to severe hepatic impairment;

– prolactinoma;

– pregnancy and breastfeeding.

Side effects

According to clinical studies

Indesirable reactions observed in ≥ 1% of patients taking domperidone: depression anxiety decreased or absent libido headache somnolence akathisia dry mouth diarrhea rash pruritus galactorrhea gynecomastia pain and sensitivity in the breast menstrual cycle disorders and amenorrhea lactation disorders asthenia.

Unwanted reactions observed in < 1% of patients taking domperidone: hypersensitivity urticaria swelling and mammary gland discharge.

According to spontaneous reports of adverse events

The frequency of adverse reactions listed below was determined according to the following (World Health Organization classification): Very common > 1/10 common from > 1/100 to < 1/10 infrequent from > 1/1000 to < 1/100 rare from > 1/10000 to < 1/1000 very rare from < 1/10000 including individual reports.

Immune system disorders

Very rare: allergic reactions including anaphylaxis anaphylactic shock anaphylactic reactions angioedema.

Gastrointestinal disorders

Rare: gastrointestinal including transient intestinal cramps; very rare: diarrhea.

Nervous system disorders

very rarely: extrapyramidal disorders convulsions increased excitability and irritability sleepiness headache.

Cardiovascular system disorders

Very rare: prolongation of the QT interval; frequency unknown: pirouette-type ventricular tachyarrhythmia* sudden coronary death*.

Skin and subcutaneous tissue disorders

Very rare: Quincke’s edema pruritus skin urticaria.

River and urinary tract disorders

very rarely: urinary retention.

Others

Very rare: changes in liver function tests.

Rare: hyperprolactinemia galactorrhea gynecomastia amenorrhea.

*In some epidemiologic studies, it has been shown that domperidone use may be associated with an increased risk of serious ventricular arrhythmias or sudden death. The risk of occurrence of these phenomena is more probable in patients over 60 years old and in patients taking the drug in daily dose more than 30 mg. It is recommended to use domperidone in the lowest effective dose in adults and children.

Overdose

Symptoms of overdose are most common in children. Signs of overdose are agitation altered consciousness convulsions disorientation somnolence and extrapyramidal reactions.

The treatment of overdose: symptomatic no specific antidote. Gastric lavage administration of activated charcoal in case of extrapyramidal reactions – anticholinergic antiparkinsonian agents. Due to possible prolongation of the QT interval, the electrocardiogram (ECG) should be monitored.

Pregnancy use

There are not enough data on the use of domperidone during pregnancy. The use of the drug during pregnancy is contraindicated.

In women the concentration of domperidone in breast milk is from 10 to 50% of the corresponding concentration in plasma and does not exceed 10 ng/ml. In breastfed infants adverse cardiovascular reactions may occur.

In this regard, when using domperidone during breastfeeding, breastfeeding should be stopped.

Similarities