Pharmacological properties
Pharmacodynamics. Domperidone is a stimulant of gastrointestinal motility. The mechanism of action is due to the blockade of dopamine D2 receptors, which eliminates the inhibitory effect of dopamine on the motor function of the gastrointestinal tract. Increases the duration of peristaltic contractions of the antrum of the stomach and duodenum, accelerates gastric motility, increases the tone of the lower esophageal sphincter. Does not affect gastric secretion. Has an antiemetic effect due to the combination of the gastrokinetic effect and antagonism to dopamine receptors in the trigger zone of chemoreceptors located outside the blood-brain barrier. Eliminates hiccups and nausea.
Pharmacokinetics. Quickly and completely absorbed in the digestive tract. It is subject to intensive metabolism in the intestinal wall and liver, as a result of which it has a low bioavailability - about 15%. Food intake and a decrease in the acidity of gastric juice slow down and reduce the absorption of domperidone. C max in the blood is achieved after 60 minutes. Binding to plasma proteins is 91-93%. It penetrates poorly through the blood-brain barrier. It enters breast milk, where its level is approximately ¼ of the concentration in blood plasma. It is biotransformed by hydroxylation and N-dealkylation. T ½ is 7-9 hours, with severe renal failure it increases. It is excreted from the body with feces (66%) and urine (33%), including 7-10 and 0.4-1% in unchanged form, respectively.
Indication
Adults: nausea and vomiting, feeling of fullness in the stomach, pain in the upper abdomen, heartburn with or without regurgitation of gastric contents.
Children. Nausea and vomiting.
Application
Domidon is recommended to be taken orally, before meals. When taken after meals, absorption is somewhat slower.
Adults and children (over 12 years of age with a body weight of 35 kg or more) are prescribed 10-20 mg (1-2 tablets) 3 times a day 15-30 minutes before meals and, if necessary, before bedtime.
The maximum daily dose of the drug is 80 mg.
The duration of the initial treatment is 4 weeks. The doctor determines the need for further use of the drug.
In case of renal failure, the frequency of administration of the drug should be reduced; in case of hepatic failure, the drug should not be prescribed to the patient.
Contraindication
Hypersensitivity to domperidone or to other components of the drug.
Cases where stimulation of gastrointestinal motor activity may pose a risk (e.g. gastrointestinal bleeding, mechanical intestinal obstruction, perforation of the stomach or intestines).
Patients with a prolactin-secreting pituitary tumor (prolactinoma).
Concomitant use of oral forms of ketoconazole, erythromycin or other potent CYP 3A4 inhibitors, drugs that prolong the QT interval, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin (see Interactions with other drugs).
Side effects
On the part of the immune system: very rarely - anaphylactic reactions, including anaphylactic shock, angioedema, urticaria, allergic reactions;
From the endocrine system: rarely - increased prolactin levels;
Mental disorders: rarely - nervousness; very rarely - agitation;
Nervous system: often - dry mouth, headache; infrequently - insomnia, dizziness, thirst, lethargy, irritability; rarely - extrapyramidal side effects; very rarely - drowsiness, convulsions;
Cardiovascular system: rarely - edema, palpitations; heart rate and rhythm disturbances: QT interval prolongation, ventricular arrhythmias;
Gastrointestinal disorders: rarely - gastrointestinal disorders, including abdominal pain, diarrhea, regurgitation, change in appetite, nausea, heartburn, constipation; very rarely - short-term intestinal spasms;
Skin and subcutaneous tissue disorders: rarely - itching, rashes;
From the reproductive system and mammary glands: rarely - galactorrhea, gynecomastia, amenorrhea;
From the urinary system: rarely - frequent urination, dysuria;
Musculoskeletal and connective tissue disorders: rarely - leg pain, asthenia;
others: rarely - conjunctivitis, stomatitis;
changes in laboratory parameters: increased levels of ALT, AST and cholesterol.
Because the pituitary gland is located outside the blood-brain barrier, domperidone use may result in elevated prolactin levels. Rarely, hyperprolactinemia may cause neuroendocrine side effects such as galactorrhea, gynecomastia, and amenorrhea.
Extrapyramidal reactions have been reported very rarely in adults. These adverse reactions disappear completely after discontinuation of the drug.
Other side effects related to the nervous system - seizures, agitation and drowsiness - have been observed very rarely.
Special instructions
Domidon should not be taken simultaneously with antacids or antisecretory drugs.
The drug contains lactose, so it should not be prescribed to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
In patients with severe renal insufficiency (plasma creatinine level 6 mg / 100 ml, i.e. 0.6 mmol / l) T ½ domperidone increased from 7.4 to 20.8 h, but the concentration of the drug in the blood plasma was lower than in healthy volunteers. Since a small percentage of the drug is excreted in the urine unchanged, a single dose may not be adjusted. However, with prolonged use of domperidone, the frequency of taking the drug should be reduced to 1-2 times a day, depending on the severity of renal dysfunction. It may also be necessary to reduce the dose. With prolonged therapy, these patients should be under regular medical supervision.
Domperidone should be used with caution in patients with risk factors for QT prolongation, including hyperkalemia, severe hypermagnesemia, organic heart disease, and concomitant use of drugs that prolong the QT interval.
Use during pregnancy and breastfeeding. Domidon is not recommended for use during pregnancy. The drug passes into breast milk, so it is not recommended to use the drug during breastfeeding.
Ability to influence the reaction rate when driving or operating other mechanisms. You should refrain from driving or operating other mechanisms during treatment with the drug.
Children. It is not recommended to prescribe the drug in this dosage form to children under 12 years of age with a body weight of 35 kg. The drug is used to treat children over 12 years of age with a body weight of ≥35 kg.
Interactions
Anticholinergic drugs can neutralize the effect of the drug Domidon. The bioavailability of the drug when taken orally is reduced after prior administration of cimetidine or sodium bicarbonate. Antacids and antisecretory drugs should not be taken simultaneously with the drug Domidon, as they reduce its bioavailability after oral administration. The main pathway of metabolic transformations of domperidone occurs with the participation of the isoenzyme CYP 3A4 of the cytochrome P450 system, therefore, with the simultaneous use of domperidone and drugs that significantly inhibit this isoenzyme, an increase in the level of domperidone in the blood plasma is possible. Examples of CYP 3A4 inhibitors include the following drugs: azole antifungals (fluconazole, itraconazole, ketoconazole, voriconazole), macrolide antibiotics (clarithromycin, erythromycin), HIV protease inhibitors (amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, saquinavir), calcium antagonists (diltiazem, verapamil), amiodarone, aprepitant, nefazodone, telithromycin.
With simultaneous use of the drug with M-cholinolytics and narcotic analgesics, the effect of domperidone on the motor-evacuation activity of the stomach and intestines is reduced.
Concomitant use with ketoconazole, erythromycin or other potential CYP 3A4 inhibitors may lead to an increase in the QT interval.
With simultaneous use of domperidone at a dose of 10 mg 4 times a day and ketoconazole at a dose of 200 mg 2 times a day, a prolongation of the QT interval by 10-20 ms was noted. With monotherapy with domperidone both in a similar dosage and in a daily dose of 160 mg (which is twice the maximum permissible daily dose), no clinically significant changes in the QT interval were noted.
Concomitant administration of domperidone with digoxin or paracetamol does not affect the levels of these drugs in the blood.
Domperidone can also be combined with neuroleptics, the effect of which it does not enhance; dopaminergic receptor agonists (bromocriptine, L-dopa), the undesirable peripheral effects of which, such as indigestion, nausea, vomiting, it suppresses, without neutralizing their basic properties.
Overdose
Symptoms: drowsiness, disorientation, extrapyramidal disorders.
Treatment: drug withdrawal, administration of activated charcoal. To eliminate extrapyramidal symptoms, anticholinergic drugs, drugs for the treatment of parkinsonism, or antihistamines with anticholinergic action are used.
Storage conditions
In a place protected from light at a temperature not exceeding 25 °C.
