However, unlike these drugs, domperidone does not penetrate the blood-brain barrier. The use of domperidone, rarely accompanied by extrapyramidal side effects, especially in adults, but domperidone stimulates the release of prolactin from the pituitary. Its antiemetic effect, possibly due to a combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors in the chemoreceptor trigger zone.
When used inside testosterone propionate side effects domperidone increases the antral and duodenal contraction, accelerates gastric emptying – yield of liquid and semi-solid fraction in healthy humans and solid fractions from patients in whom this process has been slowed down, and increases the pressure of the sphincter of the lower esophagus in healthy people. Domperidone has no effect on gastric secretion.
Domperidone is rapidly absorbed when administered orally on an empty stomach, the maximum observed plasma concentration for about 30-60 minutes. The low absolute bioavailability of oral route domperidone (approximately 15%) due to extensive initial metabolism in the intestinal wall and liver.
Although healthy bioavailability of domperidone is increased when given after a meal, patients with complaints of the gastrointestinal tract should be domperidone 15 -30 minutes before a meal. Hypoacid gastric juice reduces the absorption of domperidone. Before the drug after meals for maximum absorption takes more time, and the area under the curve (AUC) increases slightly.
If oral domperidone does not accumulates and does not induce its own metabolism; maximum plasma concentration at 90 min after administration, equal to 21 ng / ml after two weeks oral administration of 30 mg per day was almost the same as after the first dose (18 ng / ml). Domperidone is 91-93% bound to plasma proteins.
The drug is metabolized in the liver by hydroxylation and N- dealkylation. When in vitro drug metabolism studies with diagnostic inhibitors was found that CYP3A4 is a major form of cytochrome-450 enzymes involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 involved in the process of hydroxylation of aromatic domperidone. Excretion of urine and feces was 31 and 66% of the oral dose, respectively. Isolation of the drug in an unmodified form of a small percentage (10% – in the feces and about 1% – in the urine). Plasma half-life period after administration of a single dose is 7-9 hours in healthy people, but lengthened in patients with severe renal insufficiency.
Indications In adults: a) Complex of dyspeptic symptoms, often associated with delayed gastric emptying, gastroesophageal reflux and esophagitis:
- feeling of fullness in the epigastrium, sense of abdominal distention, pain in the upper abdomen;
- belching, flatulence;
- nausea, vomiting;
- heartburn, belching.
b) Nausea and vomiting of functional, organic, infectious origin caused by radiotherapy, drug therapy, or violation of the diet. A specific indication is nausea and vomiting caused by dopamine agonists in the event of their application in Parkinson’s disease (such as L-dopa and bromocriptine). In pediatric patients the drug is indicated for regurgitation syndrome, cyclic vomiting, gastro-oesophageal reflux disease and other gastric motility disorders.Contraindications
- installed intolerance of the drug and its components.
- prolactin-secreting pituitary tumor (prolactinoma).
- concomitant use of oral forms of ketoconazole (See Interactions. section)
- gastrointestinal bleeding, mechanical obstruction or perforation (t. e. when the stimulation of gastric motility might be dangerous)Dosing and Administration1. Chronic dyspepsia Adults: 10 mg (1 tablet or 10 ml) 3 times a day for 15-30 min. before meals and, if necessary, before bedtime. The maximum daily dose – 80 mg. Children: 2.5 ml of suspension for oral administration for 10 kg body weight (ie, 0.25 mg domperidone per 1 kg of body weight..), 3 times a day before meals and, if necessary before going to bed. If necessary, the specified dosage can be doubled (except for children under the age of 1 year). The maximum daily dose of domperidone – 2.4 mg per 1 kg of body weight, but not more than 80 mg.
2. Nausea and vomiting Adults: 20 mg (2 tablets or 20 mL) 3-4 times a day before meals and at bedtime. The maximum daily dose – 80 mg. Children: 5 ml oral suspension for 10 kg of body weight (ie 0.5 mg domperidone per 1 kg of body weight..), 3-4 times a day before meals and at bedtime. This dose is achieved by filling the pipette twice. The maximum daily dose of domperidone -. 2.4 mg per 1 kg of body weight, but not more than 80 mg of Motilium tablets are shown only for adults and children weighing more than 35 kg in pediatric practice testosterone propionate side effects is mainly to use Motilium suspension. It is recommended for kidney failure reducing the frequency of drug administration (see. section Cautions).
DIRECTIONS FOR USE bottle before use should be shaken. The suspension packaging, protected against accidental opening of the children. The bottle should be opened as follows:
- Push down on the plastic cover of the vial, while turning it counterclockwise.
- Remove the unscrewed cap. Pipette (available only with the 100 ml bottle)
- Remove the pipette from the case and place it in a vial.
- Hold in place the lower ring, lift the top up to the mark corresponding to the weight of your child in kg.
- Hold the bottom of the ring, remove the filled pipette from the bottle.
- Empty the pipette and place it back in the holster.Close the bottle.Side effects
- Gastrointestinal: gastrointestinal disorders (rare) occasion – transient intestinal cramps;
- on the part of the nervous system: extrapyramidal effects (children-very rarely, in adults – single cases); these effects are completely reversible and disappear after discontinuation of the drug;
- on the part of the immune system: allergic reaction (very rare);
- with the skin: hives;
- with the endocrine system: increase in the plasma level of prolactin caused by the fact that the pituitary is outside the blood-brain barrier;In rare cases this hyperprolactinaemia may stimulate the emergence of neuro-endocrine effects such as galactorrhoea, gynaecomastia and amenorrhoea.OverdoseSymptoms
Symptoms of overdose may include: drowsiness, disorientation and extrapyramidal reactions, especially in children.
In case of overdose, it is recommended the use of activated charcoal and close observation. Anticholinergic agents, drugs used for the treatment of Parkinson’s disease, or antihistamines can be effective in extrapyramidal reactions.
Interaction with other drugs
Anticholinergic drugs can neutralize the effect of Motilium.
The oral bioavailability is reduced Motilium after previous receiving cimetidine or sodium bicarbonate. Do not take antacids and antisecretory drugs simultaneously with Motilium, as they reduce its bioavailability after oral administration (see also Warnings and Precautions.).
The main route of metabolic transformations of domperidone – through of CYP3A4. Based on in vitro studies suggest that simultaneous reception using drugs domperidone significantly inhibiting this enzyme, may cause an increase in plasma levels of domperidone. In conducting studies (healthy volunteers) reacting domperidone ketoconazole found that ketoconazole inhibits SYRZA4 dependent primary metabolism domperidone, thereby achieving approximately threefold increase in the maximum concentration of domperidone and AUC in the plateau phase.
Examples of inhibitors of the enzyme CYP3A4 is the following medications:
- antifungals azole;
- macrolide antibiotics;
- HIV protease inhibitors;
In investigating the interaction testosterone propionate side effects of domperidone and ketoconazole shown that the combined use of domperidone 10 mg four times a day and ketoconazole at a dose of 200 mg 2 times daily lengthening QT interval observed by 10-20 msec. Monotherapy domperidone in similar doses and when receiving a daily dose of 160 mg (that is 2 times greater than the maximum daily dose), there were no clinically significant changes in QT interval.
Theoretically, since Motilium has gastrokinetic action, it could affect the absorption of both an oral preparations, particularly sustained release formulations of active substances, or preparations enterorastvorimoy coated shell. However, the use of domperidone in patients while taking paracetamol or selected treatment with digoxin did not affect the levels of these drugs in the blood.
Motilium can also be combined with:
- neuroleptics, the action of which it does not increase
- agonists of dopaminergic receptors (bromocriptine, L-dopa), whose unwanted peripheral effects such as digestive disorders, nausea, vomiting, it inhibits without neutralizing their basic properties.Cautions
When combined with the use of Motilium antacid or antisecretory drugs should be taken after the last meal and not before meals, ie should not be taken simultaneously with Motilium. Use in infants Due to the fact that the metabolic functions and the blood-brain barrier in the first months of life are not fully developed, children, infants should be given either the drug very cautiously and under close medical supervision. Since the typical absence of neurological Motilium action is mainly the result of a weak passage through the blood-brain barrier, the occurrence of neurological symptoms can not be excluded in children under the age of 1 year. Overdose can cause neurological side effects in children The use of liver diseases Given the high degree of metabolism of domperidone in the liver, it should be used with caution Motilium in patients with hepatic impairment. Use in kidney disease patients with severe renal insufficiency (serum creatinine> 6 mg / 100 ml, i.e.> 0.6 mmol / l) increased the half-life of domperidone from 7.4 to 20.8 hours, but plasma concentrations were lower than in healthy volunteers. Since a very small percentage of the drug is excreted by the kidneys in an unmodified form, it is hardly necessary correction of a single dose in patients with renal insufficiency. However, with repeated administration of assigning frequency should be reduced to one or two times a day, depending on severity of disease, and may also be necessary to reduce the dose. In patients with prolonged therapy should be regularly monitored.
Use during pregnancy and lactation
Data on the use of domperidone during pregnancy is not enough. To date there is no evidence of an increased risk of malformations in humans. However, Motilium be administered during pregnancy only when its use is justified expected therapeutic benefit. Women domperidone concentration in breast milk is from 10 to 50% of the corresponding plasma concentrations and less than 10 ng / ml. The total amount of domperidone excreted in breast milk – less than 7 micrograms per day in the application of the maximum permissible dose of domperidone. It is unknown whether this level has a negative effect on infants. In this regard, the application of Motilium during lactation should stop breastfeeding.
Effects on ability to drive and operate machinery
Motilium has no effect on ability to drive and operate machinery.
Method of production
of 10 or 30 tablets from a blister hsloynoy 3-transparent film (PVC / LDPE / PVDC), and aluminum foil. 1 blister with instructions for use in a cardboard box.
Bottles of 100 or 200 ml of a suspension for oral administration of 0.1%, with a graduated pipette 5 ml or 10 ml of a measured cap.
steroids anabolic for sale buy tbol buy steroid online