Instructions for Motorix film-coated tablets 10 mg blister No. 10
Composition
active ingredient: domperidone;
1 tablet contains domperidone 10 mg;
Excipients: lactose monohydrate; pregelatinized starch; croscarmellose sodium; microcrystalline cellulose; sodium lauryl sulfate; povidone; magnesium stearate;
shell: Opadry II White film coating mixture (hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol; titanium dioxide (E 171); triacetin).
Dosage form
Film-coated tablets.
Main physicochemical properties: film-coated tablets, white in color, with a biconvex surface, with a score.
Pharmacotherapeutic group
Peristaltic stimulants. ATX code A03F A03.
Pharmacological properties
Pharmacodynamics.
Domperidone is a dopamine antagonist with antiemetic properties. Domperidone crosses the blood-brain barrier to a limited extent. Extrapyramidal side effects are very rare with domperidone, especially in adults, but domperidone stimulates the release of prolactin from the pituitary gland. Its antiemetic effect is probably due to a combination of peripheral (gastrokinetic) action and antagonism of dopamine receptors in the chemoreceptor trigger zone, which is located outside the blood-brain barrier in the area postrema. The low concentrations of domperidone detected in the brain indicate a peripheral effect of the drug on dopamine receptors.
When administered orally, domperidone increases pressure in the lower esophagus, improves antroduodenal motility, and accelerates gastric emptying. Domperidone does not affect gastric secretion.
Pharmacokinetics.
Domperidone is rapidly absorbed after oral administration on an empty stomach, with peak plasma concentrations occurring approximately 30-60 minutes after oral administration. The low absolute bioavailability of oral domperidone (approximately 15%) is due to extensive first-pass metabolism in the intestinal wall and liver. Although in healthy subjects the bioavailability of domperidone is increased when administered after a meal, patients with gastrointestinal complaints should take domperidone 15-30 minutes before a meal. Reduced gastric acidity reduces the absorption of domperidone. When the drug is administered orally after a meal, peak absorption is somewhat delayed.
When administered orally, domperidone does not accumulate and does not induce its own metabolism. Domperidone is 91-93% bound to plasma proteins. Distribution studies of domperidone have shown its significant distribution in tissues, but low concentrations in the brain. In animals, small amounts of the drug cross the placenta.
Domperidone is rapidly and extensively metabolized in the liver by hydroxylation and N-dealkylation.
Urinary and fecal excretion account for 31% and 66% of the oral dose, respectively. Excretion of unchanged drug is small (10% in feces and approximately 1% in urine). The plasma half-life after a single dose is 7-9 hours in healthy volunteers, but is prolonged in patients with severe renal impairment.
Indication
For the relief of symptoms of nausea and vomiting lasting less than 48 hours.
Contraindication
Motorix is contraindicated:
- patients with established hypersensitivity to the drug or excipients;
- patients with a prolactin-secreting pituitary tumor (prolactinoma);
- patients with severe or moderate liver and/or kidney dysfunction;
- patients with known prolongation of the QT interval, which is the basis of cardiac disorders or diseases;
- patients with liver failure.
Motorix should not be used if stimulation of gastric motor function could be dangerous, for example in the presence of gastrointestinal bleeding, mechanical obstruction or perforation.
Concomitant use of ketoconazole, erythromycin or other potent CYP3A4 inhibitors, medicinal products that prolong the QT interval, such as fluconazole, erythromycin, itraconazole, oral ketoconazole, posaconazole, ritonavir, saquinavir, telaprevir, voriconazole, clarithromycin, amiodarone, telithromycin is contraindicated (see sections “Special warnings and precautions for use” and “Interaction with other medicinal products and other forms of interaction”).
Interaction with other medicinal products and other types of interactions
Anticholinergic drugs may neutralize the antidyspeptic effect of Motorix.
Antacids and antisecretory drugs should not be taken simultaneously with Motorix, as they reduce its bioavailability after oral administration (see section "Special instructions").
Domperidone is metabolized primarily by CYP3A4. In vitro studies have shown that concomitant use of medicinal products that significantly inhibit this enzyme may lead to increased plasma levels of domperidone.
Domperidone should be used with caution in combination with potent CYP3A4 inhibitors that have not been shown to prolong the QT interval, or with medicinal products that may prolong the QT interval (see section 4.4).
Theoretically, since Motorix has a prokinetic effect on the stomach, this may affect the absorption of concomitant oral medications, in particular prolonged-release or enteric-coated formulations. However, in patients whose condition has already stabilized, concomitant use of domperidone with digoxin or paracetamol has not affected the blood levels of these medications.
In separate in vivo pharmacokinetic/pharmacodynamic interaction studies with concomitant oral administration of ketoconazole or erythromycin in healthy volunteers, it was confirmed that these drugs significantly inhibit the CYP3A4-mediated first-pass metabolism of domperidone.
Examples of strong CYP3A4 inhibitors with which Motorix is not recommended are:
- azole antifungal medicines such as fluconazole*, itraconazole, ketoconazole* and voriconazole*;
- macrolide antibiotics such as clarithromycin* and erythromycin*;
- HIV protease inhibitors such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir and saquinavir;
- calcium antagonists such as diltiazem and verapamil;
- amiodarone*;
- amrepitant;
- nefazodone;
- telithromycin*.
*prolong the QTc interval.
Motorix can be combined with:
- neuroleptics, the effect of which it enhances;
- dopaminergic agonists (bromocriptine, L-dopa), whose undesirable peripheral effects (such as indigestion, nausea, vomiting) it suppresses without neutralizing the basic properties.
Possible interactions with other medications
The main metabolic pathway of domperidone is mediated by CYP3A4. It is known that concomitant use of medicinal products that significantly inhibit this enzyme may lead to increased plasma levels of domperidone. Concomitant use of domperidone with potent CYP3A4 inhibitors that may cause QT prolongation is contraindicated (see section 4.3).
Domperidone should be used with caution when used concomitantly with potent CYP3A4 inhibitors that have not been shown to prolong the QT interval, such as indinavir; patients should be closely monitored for signs or symptoms of adverse reactions.
Domperidone should be used with caution with medicinal products that prolong the QT interval and patients should be closely monitored for signs or symptoms of cardiovascular adverse reactions. Such medicinal products include, for example:
- class IA antiarrhythmic drugs
- class III antiarrhythmic drugs
- some neuroleptic drugs
- some antidepressants
- some antibiotics
- some antifungal medications
- some antimalarial drugs
- some gastrointestinal medications
- some medicines used for cancer
- some other medicines.
The above list is representative but not exhaustive.
Application features
Antacids or antisecretory drugs should not be taken simultaneously with Motorix, as they reduce the oral bioavailability of domperidone (see section "Interaction with other medicinal products and other types of interactions"). When used together, Motorix should be taken before meals, antacids or antisecretory drugs after meals.
Patients whose nausea and vomiting last more than 48 hours should consult a doctor.
Use with ketoconazole: In studies of the interaction of domperidone with oral ketoconazole, prolongation of the QT interval was observed, therefore alternative treatment should be chosen if antifungal therapy with ketoconazole is indicated (see section “Interaction with other medicinal products and other types of interactions”).
Domperidone should be used with caution in patients with risk factors for QT prolongation, including hypokalemia, severe hypomagnesemia, organic heart disease, and in patients with mild hepatic and/or renal impairment.
It has been established that the prolongation of the QT interval observed with domperidone, according to the recommended dosage regimen at usual therapeutic doses (10 mg or 20 mg 4 times a day), is of no clinical significance.
Due to the increased risk of ventricular arrhythmias, Motorix is not recommended for use in patients with prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with underlying cardiac disease such as congestive heart failure. Electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia are known to be conditions that increase the proarrhythmic risk.
Motorix tablets contain lactose, so the drug should not be used in patients with lactose intolerance, galactosemia and glucose/galactose malabsorption.
The following information should be considered regarding the risk of cardiovascular complications caused by medicines containing domperidone:
Some epidemiological studies have shown that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death; the risk of serious ventricular arrhythmias or sudden cardiac death may be higher in patients over 60 years of age or at oral doses of the drug greater than 30 mg per day. Therefore, Motorix should be used with caution in elderly patients. Patients over 60 years of age should consult a doctor before using Motorix; domperidone should be prescribed to adults and children at the lowest effective dose.
The risk-benefit ratio of domperidone remains favorable.
Use during pregnancy or breastfeeding
Data on the use of domperidone in pregnant women are limited. Therefore, Motorix should be prescribed during pregnancy only if, in the opinion of the physician, the expected positive effect for the mother outweighs the potential risk to the fetus.
The amount of domperidone that can reach the infant through breast milk is extremely low. The maximum relative dose for infants (%) is estimated to be about 0.1% of the maternal dose adjusted for body weight. It is not known whether it harms the infant, so mothers taking Motorix should refrain from breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given the side effects on the nervous system, patients should be careful when driving or operating other machinery.
Method of administration and doses
For the relief of symptoms of nausea and vomiting lasting less than 48 hours.
Adults and children over 12 years of age and weighing at least 35 kg: 1 tablet (10 mg) 3 times a day.
The maximum daily dose is 3 tablets (30 mg per day).
The maximum duration of treatment is 48 hours without consulting a doctor.
It is recommended to use the drug Motorix before meals. The absorption of the drug is somewhat delayed if it is used after meals. The duration of treatment should not exceed 1 week.
Children.
The medicine should be used to treat children aged 12 years and over and weighing at least 35 kg.
Domperidone should be given to children at the lowest effective dose.
Overdose
Symptoms: Symptoms of overdose may include agitation, impaired consciousness, convulsions, disorientation, drowsiness, and extrapyramidal reactions.
Treatment. There is no specific antidote for domperidone, but in the case of a significant overdose, gastric lavage within 1 hour after taking the drug and the use of activated charcoal are recommended, as well as close patient observation and supportive therapy. Anticholinergic drugs, drugs for the treatment of Parkinson's disease may be effective in controlling extrapyramidal reactions.
Adverse reactions
Provided that the dosage and duration of treatment recommendations are followed, domperidone is usually well tolerated and adverse events occur infrequently.
Immune system disorders: allergic reactions, including anaphylaxis, anaphylactic shock, hypersensitivity.
On the part of the endocrine system: increased prolactin levels.
Mental disorders: nervousness, irritability, agitation, depression, anxiety, decreased or absent libido.
Nervous system: insomnia; dizziness, thirst, convulsions, lethargy, headache, drowsiness, akathisia, extrapyramidal disorders.
Cardiovascular system: edema, palpitations, heart rate and rhythm disturbances, QT interval prolongation; serious ventricular arrhythmias, sudden cardiac death.
Gastrointestinal: gastrointestinal disorders, including abdominal pain, regurgitation, changes in appetite, nausea, heartburn, constipation; dry mouth, short-term intestinal spasms, diarrhea.
Skin and subcutaneous tissue disorders: itching, rash; urticaria, angioedema.
Reproductive system and breast disorders: galactorrhea, breast enlargement/gynecomastia, breast tenderness, breast discharge, amenorrhea, breast swelling, breast pain, lactation disorder, irregular menstrual cycle.
Musculoskeletal and connective tissue disorders: leg pain.
From the urinary system: urinary retention, dysuria, frequent urination.
General disorders: asthenia.
Other: conjunctivitis, stomatitis.
Changes in laboratory parameters: increased levels of ALT, AST and cholesterol; abnormal liver function tests; increased levels of prolactin in the blood.
During post-marketing use of the drug, no differences in the safety profile of its use in adults and children were noted, with the exception of extrapyramidal disorders and other phenomena, seizures and agitation related to the central nervous system, which were observed mainly in children.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 ºС.
Keep out of reach of children.
Packaging
10 tablets in a blister; 1 or 3 blisters in a pack.
Vacation category
Without a prescription.
Producer
PJSC "Kyiv Vitamin Plant".
Location of the manufacturer and its business address
04073, Ukraine, Kyiv, Kopylivska St., 38.
Website: www.vitamin.com.ua.
