Motilium coated pills 10mg N30
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Active ingredients
Domperidone
Release form
Pills
Composition
Domperidone 10 mg. Additional substances: lactose monohydrate - 54.2 mg, corn starch - 20 mg, microcrystalline cellulose - 10 mg, pregelatinized starch - 3 mg, polyvidone (K-90) - 1.5 mg, magnesium stearate - 0.6 mg, hydrogenated cotton oil 0.5. mg, sodium lauryl sulfate - 0.15 mg. The composition of the film coating: hypromellose 2910 5 mPa · s - 2.2 mg, sodium lauryl sulfate - 0.05 mg, purified water (removed in the process).
Pharmacological effect
Antiemetic, central blocker of dopamine receptors. Domperidone is a dopamine antagonist with antiemetic properties. Domperidone poorly penetrates the BBB. The use of domperidone is very rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the secretion of prolactin from the pituitary gland. The antiemetic effect may be due to a combination of peripheral (gastrokinetic) action and antagonism of dopamine receptors in the chemoreceptor trigger zone located outside the BBB in the area postrema. Studies on animals, as well as low concentrations of the drug found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. When used orally in humans, domperidone increases the pressure of the lower esophageal sphincter, improves antroduodenal motility and accelerates gastric emptying. Domperidone has no effect on gastric secretion.
Pharmacokinetics
Absorption After oral administration, domperidone is rapidly absorbed from the gastrointestinal tract. Cmax in plasma is reached in approximately 30-60 minutes. Low absolute bioavailability of domperidone when administered orally (approximately 15%) is due to extensive primary metabolism in the intestinal wall and liver. Although in healthy people, the bioavailability of domperidone increases when taken after a meal, patients with complaints from the gastrointestinal tract should take domperidone 15-30 minutes before a meal . Reducing the acidity of gastric juice leads to a decrease in the absorption of domperidone. Bioavailability by ingestion decreases with the preliminary intake of cimetidine and sodium bicarbonate.When taking the drug after a meal, it takes more time to achieve maximum absorption, and the AUC slightly increases. Distribution When taken orally, domperidone does not accumulate and does not induce its own metabolism. Plasma Cmax 21 ng / ml after 90 minutes after 2 weeks of taking the drug orally at a dose of 30 mg / day was almost the same as Cmax in the blood plasma of 18 ng / ml after taking the first dose. 93%. Studies of the distribution in animals with the use of the drug labeled with a radioactive isotope, showed a significant distribution of the drug in the tissues, but low concentrations in the brain. Small amounts of the drug penetrate the placental barrier in rats. Metabolism Domperidone undergoes rapid and extensive metabolism in the liver by hydroxylation and N-dealkylation. In vitro metabolism studies using diagnostic inhibitors have shown that CYP3A4 is the main isoenzyme of the cytochrome P450 system involved in domperidone N-dealkylation, while CYP3A4, CYP1A2 and CYP2E1 isoenzymes are involved in the domperidone aromatic hydroxylation process. 31% and 66% of the dose when taken orally, respectively. The proportion of the drug released in unchanged form is small (10% with feces and approximately 1% with urine) .T1 / 2 from blood plasma after one atnogo oral administration in healthy volunteers is 7-9 ch.Farmakokinetika in special clinical sluchayahU patients with severe renal insufficiency T1 / 2 domperidone increases. In such patients (serum creatinine level> 6 mg / dL, i.e.> 0.6 mmol / l), d1 / 2 domperidone increases from 7.4 h to 20.8 h, but the plasma concentration of the drug is lower than in people with normal renal function . A small amount of unchanged drug (about 1%) is excreted by the kidneys. In patients with impaired liver function of moderate severity (7–9 points according to Pugh, class B on the Child-Pugh scale), the AUC and Cmax of domperidone are 2.9 and 1.5 times higher than in healthy people, respectively. The unbound fraction is increased by 25%, and the final T1 / 2 increases from 15 hours to 23 hours. In patients with mild hepatic impairment, systemic exposure is somewhat reduced compared to that in healthy people based on Cmax and AUC values without changing protein binding or end T1 / 2. No data is available for patients with severely impaired liver function. There are no pharmacokinetic data for children.
Indications
A complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux, esophagitis: - feeling of fullness in the epigastrium, early satiety, feeling of bloating, pain in the upper abdomen; - belching, flatulence; - nausea, vomiting; - heartburn, belching with or without gastric contents. Nausea and vomiting of functional, organic, infectious origin, as well as caused by drug therapy or a violation of the diet. A specific indication is nausea and vomiting caused by e dopamine agonists when used in Parkinson's disease (such as levodopa and bromocriptine).
Contraindications
- prolactin-secreting pituitary tumor (prolactinoma); - simultaneous administration of oral forms of ketoconazole, erythromycin or other strong inhibitors of the CYP3A4 isoenzyme that cause prolongation of the QT interval, such as fluconazole, voriconazole, clarithromycin, amiodarone, and telithromycin; stomach can be dangerous, for example, in case of gastrointestinal bleeding, mechanical obstruction or perforation; - moderate or severe liver dysfunction; - increased sensitivity awn to domperidone or any of the components of the drug. With care: renal dysfunction; violation of the rhythm and conduction of the heart, including prolongation of the QT interval, electrolyte imbalance, congestive heart failure.
Precautionary measures
Use for violations of the liver, Motilium should be used with caution in patients with liver failure, given the high degree of metabolism of domperidone in the liver. The use of renal dysfunction during renal failure is recommended to increase the interval between taking the drug. Since Since a very small percentage of the drug is excreted by the kidneys unchanged, there is hardly a need to correct a single dose in patients with renal insufficiency. However, when reappointment frequency should be reduced to 1-2 times / day, depending on the severity of renal failure, may also require dose reduction. Use in children Possible use in children according to indications. Motilium in rare cases can cause neurological side effects.The risk of neurological side effects in young children is higher because metabolic functions and BBB in the first months of life are not fully developed. In this regard, you should very accurately calculate the dose of Motilium for newborns, children of the first year of life and children of early preschool age and strictly adhere to this dose. Neurological adverse effects may be caused in children by overdose of the drug, but other possible causes of such effects must be taken into account.
Use during pregnancy and lactation
Data on the use of the drug Motilium during pregnancy is not enough. To date, there is no data on the increased risk of malformations in humans. However, Motilium should be prescribed during pregnancy only when the expected benefit of therapy for the mother exceeds the potential risk to the fetus. In women, the concentration of domperidone in breast milk is 10-50% of the corresponding plasma concentration and does not exceed 10 ng / ml. The total amount of domperidone excreted into breast milk is less than 7 mcg / day when the maximum permissible dose is applied. It is not known whether this level has a negative effect on newborns. Therefore, if necessary, the use of the drug Motilium during lactation, breastfeeding should be stopped.
Dosage and administration
It is recommended to take Motilium pills before meals, in case of taking after eating, domperidone absorption may slow down. Adults and adolescents over 12 years old are prescribed 1-2 tab. 3 or 4 times / day, the maximum daily dose is 80 mg. Children are prescribed 1 tab. 3-4 times / day In the absence of the desired effect, the indicated dose can be doubled. The maximum daily dose is 80 mg. Motilium pills are indicated only for adults and children weighing more than 35 kg, Motilium suspension should be used in pediatric practice. In case of renal failure, a single dose adjustment is not required. When reappointment frequency should be reduced to 1 or 2 times / day, depending on the severity of insufficiency, and it may be necessary to reduce the dose. With long-term therapy, patients should be monitored regularly.
Side effects
According to studies , galactorrhea, amenorrhea, pain in the area of the mammary glands, menstrual disorders, violation of lactation, asthenia. discharge from the mammary glands. According to spontaneous reports of adverse events, the following adverse effects were classified as follows: very often (≥10%), often (≥1%, but <10%), infrequently (≥0.1%, but <1%), rarely (≥0.01% but <0.1%) and very rarely (<0.01%), including individual cases. From the immune system: very rarely - anaphylactic reactions, including anaphylactic shock. Mental disorders: very rarely - agitation, nervousness (mainly in newborns and children in the first year of life). From the nervous system: very rarely - ex rapiramide disorders, convulsions (mainly in newborns and children in the first year of life). On the cardiovascular system: very rarely - prolonged QT interval, serious ventricular arrhythmias, sudden coronary death. On the side of the skin and subcutaneous tissues: very rarely - angioedema, urticaria. From the urinary system: very rarely - urinary retention. Laboratory and instrumental data: very rarely - deviations of laboratory parameters of liver function, increased prolactin levels in the blood.
Overdose
Symptoms: drowsiness, disorientation and extrapyramidal reactions, especially in children. Treatment: domperidone specific antidote does not exist. In case of overdose, gastric lavage and the use of activated carbon are recommended. It is recommended to closely monitor the patient's condition and carry out maintenance therapy. Anticholinergics, drugs used to treat parkinsonism, or antihistamines can be effective when extrapyramidal reactions occur.
Interaction with other drugs
Anticholinergic drugs can neutralize the action of Motilium. The bioavailability of oral Motilium is reduced after previous administration of cimetidine or sodium bicarbonate. Do not take antacid and antisecretory drugs simultaneously with Motilium, because they reduce its bioavailability. CYP3A4 isoenzyme plays a major role in the metabolism of domperidone. The results of in vitro studies and clinical experience show that the simultaneous use of drugs that significantly inhibit this isoenzyme, can cause an increase in plasma domperidone concentrations. The potent inhibitors of CYP3A4 include: azole antifungal agents 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 *; aprepitant; nefazodone. (Preparations marked with an Golden Star, in addition, prolong the QTc interval.) In a number of studies on the pharmacokinetic and pharmacodynamic interactions of domperidone with oral ketoconazole and oral erythromycin in healthy volunteers, it was shown that these drugs significantly inhibit the primary metabolism of domperidone carried out by isomers and isomers and isomers. 10 mg of domperidone 4 times / day and 200 mg of ketoconazole 2 times / day showed an elongation of the QTc interval by an average of 9.8 ms during the entire observation period, in the department moments of the changes ranged from 1.2 to 17.5 msec. With simultaneous administration of 10 mg of domperidone 4 times / day and 500 mg of erythromycin 3 times / day, the QTc interval was lengthened by an average of 9.9 ms during the entire observation period, at some moments changes ranged from 1.6 to 14.3 ms. In each of these studies, Cmax and AUC of domperidone were increased about 3 times. At present, it is not known how the increased concentrations of domperidone in plasma contribute to the change in the QTc interval. In these studies, domperidone monotherapy (10 mg 4 times / day) resulted in lengthening the QTc interval by 1.6 ms (ketoconazole study) and 2.5 ms (erythromycin study), while ketoconazole monotherapy (200 mg 2 times / day) and erythromycin monotherapy (500 mg 3 times / day) resulted in a prolongation of the QTc interval by 3.8 and 4.9 ms respectively during the whole Heat-nablyudeniya.V another study with multiple doses in healthy volunteers,no significant prolongation of the QTc interval was observed during inpatient domperidone monotherapy (40 mg 4 times / day, total daily dose of 160 mg, which is 2 times the recommended maximum daily dose). At the same time, plasma domperidone concentrations were similar to those in studies of the interaction of domperidone with other drugs. Theoretically (since the drug has a gastrokinetic effect) Motilium could affect the absorption of simultaneously used oral drugs, in particular, drugs with a slow release of the active substance or drugs, enteric-coated. However, the use of domperidone in patients with paracetamol or digoxin did not affect the concentration of these drugs in the blood. Motilium can be taken simultaneously with neuroleptics, the effect of which it does not increase; dopamine receptor agonists (bromocriptine, levodopa), the undesirable peripheral effects of which, such as digestive disorders, nausea, vomiting, it suppresses without affecting their central effects.
special instructions
When combined use of the drug Motilium with antacid or antisecretory drugs, the latter should be taken after meals and not before meals, i.e. They should not be taken simultaneously with the drug Motilium. The suspension of Motilium contains sorbitol, therefore it should not be taken in patients with intolerance to sorbitol. Use for kidney disease 1-2 times / day, depending on the severity of renal dysfunction, and it may also be necessary to reduce the dose. With long-term therapy, such patients should be regularly examined. Effects on the cardiovascular system In some epidemiological studies, it has been shown that domperidone may be associated with an increased risk of serious ventricular arrhythmias or sudden coronary death. The risk may be more likely in patients older than 60 years and in patients taking the drug in daily doses of more than 30 mg. The use of domperidone in the smallest effective dose in adults and children is recommended. Use in pediatrics Motilium in rare cases can cause neurological side effects. The risk of neurological side effects in young children is higher because metabolic functions and BBB in the first months of life are not fully developed.In this regard, you should very accurately calculate the dose of Motilium for newborns, children of the first year of life and children of early preschool age and strictly adhere to this dose. Neurological undesirable effects can be caused in children by overdose of the drug, but other possible causes of such effects must be taken into account. Effect on the ability to drive vehicles and control mechanisms the patient should be informed that if the drug has become unusable or has expired, it is not it should be disposed of in sewage or on the street. It is necessary to put the drug in the bag and put it in the trash. These measures will help protect the environment.