For medical use
active substance: domperidone maleate;
1 tablet contains domperidone maleate equivalent to domperidone 30 mg;
excipients: lactose monohydrate, povidone, quinoline yellow (Е 104), crosscarmellose sodium, magnesium stearate, hydrophobic colloidal silicon dioxide, hydroxypropylmethicellulose, talcum.
Pharmaceutical form:long-acting tablets.
Peristalsis stimulanst (propulsive agents). ATC code А03F А03.
– Nausea and vomiting (to relieve symptoms);
– feeling of fullness in the stomach;
– bloat in the epigastric region;
– heartburn with or without reflux of gastric contents, observed after a meal.
– Hypersensitivity to the components of the drug.
– Do not use the drug if the stimulation of the stomach motor function can be dangerous, such as gastrointestinal bleeding, mechanical obstruction or perforation.
– Prolactin-secreting pituitary tumor (prolactinoma).
– Simultaneous administration of ketoconazole, erythromycin or other drastic inhibitors CYP3A4, drugs that prolong the QT interval, such as fluconazole, voriconazole, clarithromycin, amiodarone, telithromycin (see "Drug interactions and other kinds of interactions").
– Severe or moderate renal disorder or liver function abnormality.
Administration and Dosage:
Acute conditions (mainly nausea, vomiting).
Adults. 1 tablet 1 time per day 15-30 min before meal and, if necessary, one more tablet before bedtime.
The maximum duration of treatment is 48 hours.
Chronic conditions (mainly dyspepsia).
Adults. 1 tablet 1 time per day 15-30 min before meal and, if necessary, one more tablet before bedtime.
The maximum duration of treatment is 2 weeks.
The maximum daily dose is 60 mg.
Evaluation of side effects frequency: very often (≥ 1/10); often (≥ 1/100, < 1/10); unoften (≥ 1/1000, < 1/100); rarely (≥ 1/10 000, < 1/1000); very rarely (< 1/10 000), including isolated cases.
Immune system: very rarely - anaphylactic reactions, including anaphylactic shock, angioedema, facial oedema, main succulente, oedema of shin and feet, urticaria fever, allergic reactions.
Endocrine system: rarely – increasing of plasma prolactin levels.
Mental disorders: rarely – nervosism; very rarely – agitation.
Nervous system: often - dry mouth, headache; unoften – hyposomnia, vertigo, thirst, atony, irritation, nervousness; rarely - extrapyramidal disorders; very rarely – drowsiness, convulsions.
Cardio-vascular system: rarely – oedema, palpitation, arrhythmia, prolongation of the QT interval, ventricular arrhythmias.
Digestive tract: rarely - gastrointestinal disorders, including abdominal pain, diarrhea, regurgitation, appetite changes, nausea, heartburn, constipation; very rarely – short-time intestinal spasms.
Skin: rarely - itching, rash.
Reproductive system and mammary glands: rarely – galactorrhea, gynecomastia, amenorrhea, decrease or feeling of libido.
Urinary system: rarely - repeated urination, dysuria.
Musculoskeletal system: rarely – leg pain, asthenia.
Others: rarely – conjunctivitis, stomatitis.
Laboratory findings: increasing of ALT, AST levels and cholesterol.
Since the pituitary gland is located outside the blood-brain barrier, domperidone may increase prolactin level. Rarely hyperprolactinemia may lead to neuroendocrine side effects such as galactorrhea, gynecomastia and amenorrhea.
Extrapyramidal effects were observed very rarely. These side effects disappeared spontaneously and completely right after treatment termination.
Symptoms: drowsiness, disorientation and extrapyramidaldisorders, impairment of consciousness, convulsions.
Treatment: there is no specific antidote. In case of overdose it is recommended gastric lavage, activated carbon administration, thorough medical supervision of patient and other supportive measures.
Anticholinergic agents, drugs used for the treatment of Parkinsonism or antihistaminic drugs with anticholinergic properties can be effective in extrapyramidal disorders appearance.
Pregnancy and lactation:
There are restrictions regarding the administration of domperidone in pregnant women. The potential risk for humans is unknown. Therefore Domrid® SR can be administered during pregnancy only if the expected benefit to the mother outweighs any potential risk to the fetus.
Domrid® SR is excreted into breast milk (primarily as metabolites). The concentration of domperidone in women breast milk range from 10 to 50% of concentration in blood plasma and is less than 10 ng/mL. At the present time it has not been established does it harm the newborn.
If it is necessary to administer the drug to nursing women, for the period of treatment breastfeeding should be stopped.
Children:The drug is administered in children in another pharmaceutical form.
It is not recommended to exceed the dose or prolong the course of treatment recommended by physician independently. In a case of appearance of any unusual reactions during the drug administration an additional medical consultation is necessary.
Peculiarities of use:
Domrid® SR administration combined with ketoconazole erythromycin or other potential inhibitors CYP3A4 may lead to the prolongation of the QT interval. Domrid® SRshould be carefully administrated to patients with risk factors of prolongation of the QT interval, including hypokalemia, Liddle syndrome, organic heart diseases, simultaneous administration of drugs which prolong the QT interval. In interaction studies with oral form of ketoconazole was registered the prolongation of QT interval. Although the significance of this study is not clearly established, choose an alternative treatment, if the fungicide ketoconazole therapy is administered (see “Drug interactions and other kinds of interactions”).
Administration in patients with hepatopathy: Considering the high level of metabolism of domperidone metabolism in liver, the drug should not be administered in patients with liver failure.
Administration in patients with kidney diseases: in patients with severe renal insufficiency (serum creatinine > 6 mg/100 mL, i.e.> 0.6 mmol/L) the half-life of domperidone is increasing from 7.4 to 20.8, but the drug levels in blood plasma are lower than in healthy volunteers.
In long-term therapy patients should undergo a regular medical surveillance.
Due to the fact that the drug contains lactose, patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome should not administer the drug.
Effects on ability to drive and operate machinery:
Considering the fact that drug administration in sensitive patients may cause side effects (drowsiness, extrapyramidal side effects), during drug administration these patients should avoid driving and other work requiring a high attention concentration.
Drug interactions and other kinds of interactions:
Anticholinergic drugs can neutralize anti-dyspepsic action of Domrid® SR.
Simultaneous application of Domrid® SR and cimetidine or sodium bicarbonate cause the reduction of Domrid® SR bioavailability.
It is not recommended to administrate simultaneously antacids and antisecretory agents with Domrid® SR because they reduce its bioavailability after oral administration.
The results of in vitro studies indicate that the simultaneous application of domperidone and other medicines that greatly inhibit isoenzyme CYP3A4 may increase domperidone levels in blood plasma. Examples of drugs that inhibit this isoenzyme may be azole antifungals (ketoconazole, fluconazole, itraconazole, voriconazole), macrolide antibiotics (erythromycin, clarithromycin), HIV protease inhibitors (ritonavir, amprenavir, atazanavir, fosamprenavir, indinavir, saquinavir), Antidepressants (nefazodone), sodium antagonists (diltiazem, verapamil), amiodarone, apreрitant, telithromycin.
Simultaneous application of Domrid® SR with m-cholinolytics and narcotic analgesics cause the reducing of domperidone effect on the motor-evacuation function of stomach and intestine.
Administration with ketoconazole. During in vitro study of domperidone and ketoconazole interaction it was indicated that ketoconazole inhibits CYP3A4-dependent primary metabolism of domperidone, resulting approximately threefold increasing of area under curve "concentration-time" (AUC) and peak concentration (Cmax) of domperidone in plasma. If it is necessary to administrate simultaneously ketoconazole with Domrid® SR one should monitor the dynamics of changes in ECG parameters and, if necessary, conduct an appropriate adjustment of dose regime of both drugs, or decide if the combination therapy is reasonable. A medical surveillance of the patient’s cardiovascular system should be established.
Simultaneous administration of domperidone in patients that receive paracetamol and/or digoxin did not influence on the level of these drugs in blood.
Domrid® SRcan be also combined with:
- neuroleptics, which action it intensifies;
- dopaminergic agonists (bromkriptine, levodopa), the unwanted peripheral actions (indigestion, nausea, vomiting) it inhibits without neutralizing their basic properties.
Pharmacodynamics. Domperidone is dopamine antagonist, prokinetic. Antiemetic action is resulted from the combination of peripheral (gastrokinetic) action and antagonism to dopamine receptors (D2) in chemoreceptor trigger zone. Domperidone increases tone in the lower esophagus, improves the mobility of the antrum and duodenum and accelerates antroduodenalnu gastric ejection. Domperidone virtually does not influence on gastric secretion.
Domperidone is absorbed quickly in oral administration on an empty stomach with maximal plasma levels reaching after 30–60 minutes. Reduced gastric acidity reduces absorption of domperidone.
Pharmacokinetics. Domperidone bioavailability is about 15%. Food is largely reduces the bioavailability of domperidone.
Binding with blood proteins is 91–93%.
The drug is metabolized in liver via hydroxylation and N-dealkylation. In in vitro studies of the drug metabolism with the usage of diagnostic inhibitors it was determined that CYP 3A4 isoenzyme is the main of P450 cytochrome system, which takes part in Domperidone N-dealkylation process, whereas CYP3A4, CYP1A2 and CYP2Е1 isoenzymes take part in Domperidone aromatic hydroxylation process. The drug undergoes extensive primary metabolism in gut wall and in liver, which determines its low bioavailability.
It is excreted by the kidneys (31%) and with feces (66%). Only a little part of the drug is excreted in unchanged form (10% – with feces and 1% – by the kidneys).
Basic physical and chemical properties: white-yellow color, double-layer, round, flat tablets having chamfered edges and logo "K" on a yellow layer of tablet.
Store below 25°С in a dark and dry place. Keep it out of reach of children.
10 tablets in blister. 1 or 3 blisters in a carton box.
Conditions of supply:
“KUSUM PHARM” LTD.
54, Skryabina Str., Sumy, 40030, Ukraine.