Domperidone

Pharmacological properties

domperidone - a stimulator of motility of the gastrointestinal tract. the mechanism of action is due to the blockade of dopamine d2 receptors, thereby eliminating the inhibitory effect of dopamine on the motor function of the gastrointestinal tract. increases the duration of peristaltic contractions of the antrum and duodenum, accelerates the motility of the stomach, increases the tone of the lower esophageal sphincter. does not affect gastric secretion. it has an antiemetic effect due to a combination of the gastrokinetic effect and antagonism of dopamine receptors in the trigger zone of chemoreceptors located outside the GEB. Eliminates hiccups and nausea.

Pharmacokinetics Quickly and completely absorbed in the digestive tract. It undergoes intensive metabolism in the wall of the intestine and liver, resulting in low bioavailability - about 15%. Eating and decreasing the acidity of gastric juice slow down and reduce the absorption of domperidone. C_max in the blood is reached after 60 minutes. Binding to blood plasma proteins - 91–93%. It penetrates poorly through the BBB. It is distributed into breast milk, where its level is approximately ¼ of the plasma concentration. Biotransformed by hydroxylation and N-desalination. T_½ is 7–9 hours, with severe renal failure increases. It is excreted from the body with feces (66%) and urine (33%), including unchanged - 7–10 and 0.4–1%, respectively.

Indications

Adults nausea and vomiting, a feeling of fullness of the stomach, pain in the upper abdomen, heartburn with casting of the contents of the stomach or without casting.

Children. Nausea and vomiting.

Application

Domidon is recommended for oral administration, before meals. when taken after meals, absorption slows down somewhat.

Adults and children (over 12 years old 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.

With renal failure, it is necessary to reduce the frequency of taking the drug; with liver failure, the patient should not be prescribed the drug.

Contraindications

Hypersensitivity to domperidone or other components of the drug.

Cases where stimulation of the motor activity of the gastrointestinal tract can be dangerous (for example, gastrointestinal bleeding, mechanical intestinal obstruction, perforation of the stomach or intestines).

Patients with a prolactin-secreting pituitary tumor (prolactinoma).

The simultaneous use of oral forms of ketoconazole, erythromycin or other potent inhibitors of CYP 3A4, drugs that prolong the Q – T interval, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin (see INTERACTIONS).

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;

from the nervous system: often - dry mouth, headache; infrequently - insomnia, dizziness, thirst, lethargy, irritability; rarely - extrapyramidal side effects; very rarely - drowsiness, convulsions;

on the part of the cardiovascular system: rarely - edema, palpitations; violation of the frequency and rhythm of heart contractions: lengthening of the Q – T interval, ventricular arrhythmias;

from the gastrointestinal tract: rarely - gastrointestinal disorders, including abdominal pain, diarrhea, regurgitation, changes in appetite, nausea, heartburn, constipation; very rarely - short-term intestinal cramps;

on the part of the skin and subcutaneous tissue: rarely - itching, rash;

from the reproductive system and mammary glands: rarely - galactorrhea, gynecomastia, amenorrhea;

from the urinary system: rarely - frequent urination, dysuria;

from the musculoskeletal system and connective tissue: rarely - pain in the legs, asthenia;

others: rarely - conjunctivitis, stomatitis;

change in laboratory parameters: increased levels of AlAT, AsAT and cholesterol.

Since the pituitary gland is outside the BBB, the use of domperidone can lead to an increase in prolactin levels. Rarely, hyperprolactinemia can cause neuroendocrine side effects, such as galactorrhea, gynecomastia, and amenorrhea.

Very rarely, extrapyramidal effects have been observed in adults. These adverse reactions disappear completely after stopping the use of the drug.

Other side effects associated with the nervous system — cramps, agitation, and drowsiness — were very rare.

special instructions

Domidon should not be taken simultaneously with antacid 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.

Given the high level of domperidone metabolism in the liver, the drug should not be prescribed to patients with liver failure.

In patients with severe renal failure (plasma creatinine level 6 mg / 100 ml, i.e. 0.6 mmol / L) T_½ domperidone increased from 7.4 to 20.8 hours, but the concentration of the drug in blood plasma was lower than in healthy volunteers. Since a small percentage of the drug is excreted unchanged in the urine, a single dose can not be corrected. But 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 impairment. 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 a risk factor for prolongation of the Q – T interval, including hyperkalemia, severe hypermagnesemia, organic heart disease, and the simultaneous use of drugs that extend the Q – T interval.

Use during pregnancy and lactation. Domidon is not recommended for use during pregnancy. The drug passes into breast milk, therefore it is not recommended to use the drug during lactation.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. You should refrain from driving and working with other mechanisms during treatment with the drug.

Children. Children under the age of 12 years with a body weight of 35 kg are not recommended to prescribe the drug in this dosage form. The drug is used to treat children over the age of 12 years with a body weight of ≥35 kg.

Interactions

Anticholinergics can neutralize the effect of domidone. the oral bioavailability of the drug decreases after the previous administration of cimetidine or sodium bicarbonate. do not take antacid and antisecretory drugs simultaneously with domidone, as they reduce its bioavailability after oral administration. the main pathway of metabolic transformations of domperidone occurs with the participation of the cyp 3a4 isoenzyme 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 blood plasma is possible. The following drugs are examples of inhibitors of the cyp 3a4 isoenzyme: azole-type antifungal drugs (fluconazole, intraconazole, ketoconazole, voriconazole), macrolide antibiotics (clarithromycin, erythromycin), HIV protease inhibitors (amprenavir, atosfirvirnavirnirvirnavirinvirfavirnirvirnavirnirvirnavirnirvirnavirnirvirnavirnirvirnavirnirvirnavirnirvirnavirnirvirnavirin saquinavir), calcium antagonists (diltiazem, verapamil), amiodarone, aprepitant, nefazodone, telithromycin.

With the simultaneous use of the drug with M-anticholinergics and narcotic analgesics, the effect of domperidone on the motor-evacuation activity of the stomach and intestines decreases.

Concomitant use with ketoconazole, erythromycin, or other potential CYP 3A4 inhibitors may increase the Q – T interval.

With the 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, an extension of the Q – T interval by 10–20 ms was observed. When monotherapy with domperidone, both in the same dosage and in the daily dose of 160 mg (which is two times higher than the maximum allowable daily dose), clinically significant changes in the Q – T interval were not observed.

The concomitant use of domperidone with digoxin or paracetamol does not affect the level of these drugs in the blood.

Domidone can also be combined with antipsychotics, the effect of which it does not enhance; agonists of dopaminergic receptors (bromocriptine, L-dopa), whose undesirable peripheral effects, such as digestive disorders, nausea, vomiting, it suppresses without neutralizing their basic properties.

Overdose

Symptoms: drowsiness, disorientation, extrapyramidal disorders.

Treatment: drug withdrawal, intake of activated carbon. To eliminate extrapyramidal symptoms, anticholinergic drugs, agents for treating parkinsonism, or antihistamines with an anticholinergic effect are used.

Storage conditions

In the dark place at a temperature of no higher than 25 ° C.