Domperidone-Teva, 10 mg 30 pcs

Pharmacotherapeutic group: antipyretic drug – dopamine receptor blocker central

ATX code: A03FA03

Pharmacological properties

Pharmacodynamics

Domperidone is a dopamine receptor blocker with antiemetic effects. The antiemetic action is due to a combination of peripheral (gastrokinetic) action and inhibition of dopamine receptors in the trigger zone of brain chemoreceptors located outside the blood-brain barrier in the area postrema. When administered orally, domperidone increases decreased esophageal pressure, improves antroduodenal motility and accelerates gastric emptying without affecting gastric secretion. Domperidone increases prolactin secretion in the pituitary gland.

Pharmacokinetics

When taken orally on an empty stomach, domperidone is rapidly absorbed, its maximum plasma concentrations are reached within 30-60 min. 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 when taken after meal, patients with gastrointestinal complaints should take domperidone 15-30 min before meal. When gastric acidity decreases, impaired absorption of domperidone is observed. Pre-taking cimetidine and sodium bicarbonate reduces the bioavailability of domperidone. When administered orally after a meal, a slightly longer time is required to achieve maximum absorption.

When administered orally domperidone does not cumulate and does not induce its own metabolism. Domperidone is 91-93% bound to plasma proteins. Domperidone is distributed in various tissues of the body, is found in breast milk, but does not penetrate through the blood-brain barrier. The concentration of domperidone in breast milk is 10-50% of the concentration in blood plasma.

The metabolism of domperidone occurs in the liver and in the intestinal wall by hydroxylation and N-dealkylation with participation of CYP3A4, CYP1A2 and CYP2E1 isoenzymes.

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

Pharmacokinetics in special groups of patients

In patients with serum creatinine concentration more than 0.6 mmol/l the half-life is from 7.4 to 20.8 hours, with decreased plasma concentration of domperidone.

Indications

Active ingredient

Composition

How to take, the dosage

Overly, before meals, with plenty of water. When using the drug after a meal, absorption of the drug may be slightly delayed.

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. The duration of use should not exceed 1 week. Further use of the drug is possible after consultation with a physician.

Patients should try to take each dose at the scheduled time. If a scheduled dose is missed, it should be eliminated and the medication should be restarted as usual. The medication should not be duplicated to make up for a missed dose.

In moderate to severe hepatic impairment the use of Domperidone-Teva is contraindicated.

In mild hepatic impairment no dose adjustment is required.

In renal failure it is recommended to reduce the frequency of administration of the drug Domperidone-Teva to 1-2 times per day.

Interaction

The main metabolism of domperidone involves CYP3A4 isoenzyme. Studies in vitro have demonstrated that co-administration of drugs that significantly inhibit this enzyme may cause increased plasma concentrations of domperidone.

Separate studies in vivo pharmacokinetic/pharmacodynamic interactions of domperidone with ketoconazole or oral erythromycin in healthy volunteers have confirmed significant inhibition of CYP3A4-mediated presystemic metabolism of domperidone by these drugs.

Elevated risk of prolongation of the interval QT due to pharmacodynamic and/or pharmacokinetic interactions

. When domperidone 10 mg for oral administration four times daily and ketoconazole 200 mg twice daily were coadministered, a mean QT interval prolongation of 9.8 ms was observed over the observation period with individual time point changes ranging from 1.2-17.5 ms. When domperidone 10 mg for oral administration four times daily and erythromycin 500 mg for oral administration three times daily were used together, the mean QT interval prolongation during the observation period was 9.9 ms with individual time point changes ranging from 1.6-14.3 ms. Cmax and AUC of domperidone at equilibrium were increased approximately three-fold in each of these interaction studies. In these studies, monotherapy with domperidone 10 mg for oral administration four times daily caused an increase in the mean QTc interval of 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), whereas ketoconazole monotherapy (200 mg twice daily) and erythromycin monotherapy (500 mg three times daily) led to increases in the QTc interval of 3.8 and 4.9 ms during the follow-up period, respectively.

Contraindications for co-administration with the following drugs

Special Instructions

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

Since only very small amounts of domperidone are excreted unchanged by the kidneys, it is unlikely that adjustment of the single dose in patients with renal impairment is necessary. When repeated use, the dosing frequency should be reduced to 1-2 times per day depending on the severity of the failure; a dose reduction may also be required. These patients should be monitored regularly during long-term therapy.

Taking the drug after meals slows its absorption.

The use of domperidone may cause prolongation of the QT interval on electrocardiogram. During the post-registration follow-up of patients receiving domperidone, there have been reports of very rare cases of prolongation of the QT interval and ventricular tachycardia of the “pirouette” type. These reports contained information about patients with concomitant risk factors, electrolyte imbalances, and co-therapies that may have contributed to adverse events.

Epidemiological studies have demonstrated that domperidone use has been associated with an increased risk of serious ventricular arrhythmias or sudden coronary death (see section “Adverse effects”).

The highest risk was observed in patients over 60 years of age, patients receiving domperidone in daily doses greater than 30 mg, and in patients concomitantly taking drugs prolonging the QT interval or CYP3A4 inhibitors.

Domperidone-Teva should be used in adults and children at the lowest effective dose.

The drug Domperidone-Teva is contraindicated for use in patients with a history of prolonged cardiac conduction intervals, especially QTc interval, in patients with significant electrolyte balance disorders (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with concomitant heart diseases, such as chronic heart failure, due to the increased risk of ventricular arrhythmias (see section “Contraindications”). Electrolyte balance disorders (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia are known to increase proarrhythmogenic risk.

Domperidone is contraindicated when co-administered with drugs that prolong the QT interval, except for apomorphine. Co-administration with apomorphine is possible only if the benefit of co-administration of domperidone with apomorphine exceeds the risks and only if the recommended precautions for co-administration of the drugs mentioned in the instructions for medical use of apomorphine are strictly observed.

The treatment with Domperidone-Teva should be discontinued if signs and symptoms occur that may be associated with cardiac arrhythmias, and patients should consult their physician.

Patients should be advised to immediately report any cardiac abnormalities to their physician.

Influence on the ability to drive vehicles, mechanisms

. During the use of the drug Domperidone-Teva care should be taken when driving vehicles and engaging in other potentially dangerous activities requiring high concentration and quick psychomotor reactions due to the possible risk of extrapyramidal disorders, seizures, drowsiness, headache.

Synopsis

Contraindications

Cautions

Renal failure; concomitant use of drugs that induce bradycardia and hypokalemia, as well as macrolides that prolong the QT interval – azithromycin and roxithromycin.

Side effects

The adverse reactions are categorized according to the World Health Organization (WHO) Classification: very common (≥1/10), common (≥1/100 to < 1/10), infrequent (≥1/1000 to < 1/100), rare (≥1/10000 to < 1/1000), very rare (< 1/10000), frequency unknown (cannot be determined based on available data).

Allergic reactions: very rare allergic reactions, including anaphylaxis, anaphylactic shock, anaphylactoid reactions, and angioedema.

From the endocrine system: frequently – increase in prolactin concentrations.

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

Cardiovascular system side: frequency unknown – QT interval prolongation, ventricular arrhythmia, sudden cardiac death (see “Special Instructions”).

Digestive system disorders: rarely – gastrointestinal disorders; very rarely – intestinal spasm, diarrhea.

Skin disorders: very rarely – skin itching, skin rash, urticaria.

Reproductive system and mammary glands: frequently – galactorrhea, gynecomastia, amenorrhea.

Laboratory findings: very rarely – deviation of liver function test values from the normal.

Description of individual adverse reactions

As the pituitary gland is located outside the blood-brain barrier, domperidone may cause increased prolactin concentration. In rare cases, this hyperprolactinemia may 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 exceptional in adults. These side effects resolve spontaneously and completely when treatment is discontinued.

Other nervous system-related effects: seizures, agitation, and somnolence are also very rare and are mostly reported when used in infants and children.

Overdose

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

Treatment. There is no specific antidote. In case of overdose, gastric lavage and use of activated charcoal may be effective. Close monitoring and supportive therapy are recommended.

In order to stop extrapyramidal disorders m-cholinoblockers and drugs used for treatment of Parkinsonism may be effective.

Pregnancy use

There are limited post-registration data on the use of domperidone in pregnant women.

An animal study has demonstrated reproductive toxicity at a high dose toxic to the maternal body. The possible risk to humans is unknown. Therefore, domperidone should be used in pregnancy only if the therapeutic benefit to the mother is substantiated.

Domperidone is excreted with breast milk in lactating female rats (mainly as metabolites: maximum concentrations of 40 and 800 mg/ml after oral administration or intravenous injection of 2.5 mg/kg, respectively).

Domperidone is excreted with breast milk in women, and infants during breastfeeding may receive less than 0.1% of the maternal dose adjusted for body weight. The possibility of adverse effects, especially cardiac, in infants during breastfeeding cannot be excluded.

The decision should be made to discontinue breastfeeding or to discontinue/abstain from domperidone therapy, assessing the benefit of breastfeeding for the baby and the benefit of the treatment for the mother.

Caution should be exercised if there are risk factors for QTc interval prolongation in infants during breastfeeding.

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