Domrid SR

General characteristics. Structure:

Active ingredient: domperidone maleate; 1 tablet contains a domperidon of a maleate is equivalent a domperidona of 30 mg.

Auxiliary veshchestva:laktoza monohydrate, povidone, quinolinic yellow (Е 104), sodium of a kroskarmelloz, magnesium stearate, silicon dioxide colloid anhydrous, gidroksipropilmetiltsellyuloza, talc.

Pharmacological properties:

Pharmacodynamics. Domperidon is the antagonist of receptors of a dopamine, a prokinetic. Antiemetic action is caused by a combination of peripheral (gastrokinetichesky) action and antagonism to receptors of a dopamine (D2) in a trigger zone of chemoceptors. Domperidon raises a tone in a lower part of a gullet, improves antroduodenal mobility and accelerates gastric emptying. Practically does not influence gastric secretion.
Domperidon is quickly absorbed in intestines after intake on an empty stomach and reaches the maximum level in a blood plasma in 30-60 min. The lowered acidity of a stomach reduces absorption of a domperidon.

Pharmacokinetics. Bioavailability makes about 15%. The food considerably reduces bioavailability of a domperidon.
Linkng with proteins of plasma makes 91-93%.
Drug is metabolized in a liver by a hydroxylation and N-dealkylation. As a result of drug metabolism researches іп vitro using diagnostic inhibitors was established that the isoenzyme of ZA4 is the main isoenzyme of system of P450 cytochrome participating in process of N-dealkylation of a domperidon whereas isoenzymes of SURZA4, SUR1A2, SUR2E1 participate in process of an aromatic hydroxylation of a domperidon. Drug is exposed to extensive primary metabolism in a wall of intestines and liver that causes its low bioavailability.
It is removed by kidneys (31%) and with excrements (66%). In not changed look the insignificant percent of drug is removed (10% – with a stake and about 1% – kidneys).

Indications to use:

– Nausea and vomiting (for relief of symptoms),
– feeling of overflow of a stomach;
– swelling in epigastric area;
– heartburn with a reflux of contents of a stomach or without reflux which is observed after food.

Route of administration and doses:

Acute states (preferential nausea, vomiting).
Adults. 1 tablet of 1 times a day in 15-30 min. prior to food and if necessary 1 more tablet before going to bed.
The maximum duration of treatment makes 48 hours.
Chronicities (preferential dyspepsia).
Adults. 1 tablet of 1 times a day in 15-30 min. prior to food and if necessary 1 more tablet before going to bed.
The maximum duration of treatment makes 2 weeks.
The maximum daily dose of drug makes 60 mg.

Features of use:

Use of a domperidon together with ketokonazoly, erythromycin or other potential SURZA4 inhibitors can lead to lengthening of an interval of QT.  Домрид® SR should be applied with care to patients with risk factors of prolongation of an interval of QT, including a hypopotassemia, a heavy hypomagnesiemia, organic heart diseases, a concomitant use of the medicines extending QT interval. In interaction researches with a peroral form of a ketokonazol lengthening of an interval of QT was noted. Though value of this research accurately is not established, it is necessary to choose alternative treatment if antifungal therapy ketokonazoly is shown (see the section "Interaction with Other Medicines and Other Types of Interactions").
Use at liver diseases. Considering a high metabolic rate of a domperidon in a liver, it is not necessary to appoint drug sick with a liver failure.
Use at diseases of kidneys. At patients with a heavy renal failure (serumal creatinine> of 6 mg / 100 ml, i.e.> 0,6 mmol/l) the elimination half-life of a domperidon increases from 7,4 to 20,8 o'clock, but drug levels in a blood plasma remain lower, than with healthy volunteers.
At long therapy patients have to undergo regular medical control.
Drug contains lactose therefore patients with rare hereditary forms of intolerance of a galactose, insufficiency of lactase or a syndrome of glyukozo-galaktozny malabsorption should not use drug.

Ability to influence speed of response at control of motor transport or other mechanisms.
Considering that sensitive patients at use of drug can have side reactions (drowsiness, extrapyramidal side effects), for the period of administration of drug by this patient it is necessary to abstain from control of vehicles and performance of other works demanding the increased concentration of attention.

Use during pregnancy or feeding by a breast.
There are restrictions on use of a domperidon to pregnant women. The potential risk for the person is unknown. Therefore it is possible to appoint drug during pregnancy only when the expected advantage for mother exceeds potential risk for a fruit.
Домрид® SR is excreted in breast milk (generally in the form of metabolites). Concentration of a domperidon in breast milk of the woman makes from 10 to 50% of concentration in a blood plasma and does not exceed 10 mg/ml. Now it is not established, it causes damage to the newborn.
In case of need uses of drug during feeding by a breast for treatment it is necessary to stop feeding by a breast.

Children. To children drug is used in other dosage form.

Special precautionary measures.
It is not necessary to exceed the recommended dose or to independently prolong the therapy course recommended by the doctor. In case of any unusual reactions throughout use of drug it is necessary to consult in addition with the doctor.

Side effects:

Assessment of frequency of side reactions: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); seldom (> 1/10 000, <1/1000); very seldom (<1/10 000), including single cases.
- From immune system: very seldom – anaphylactic reactions, including an acute anaphylaxis, a Quincke's disease, a face edema, hands, shins or a foot, a small tortoiseshell, allergic reactions.
- From endocrine system: seldom – increase in level of prolactin in a blood plasma.
- Mental disorders: seldom – nervousness; very seldom – agitation.
- From a nervous system: often – dryness in a mouth, a headache; infrequently – sleeplessness, dizziness, thirst, slackness, irritability, hypererethism, it is rare – extrapyramidal frustration, is very rare – drowsiness, spasms.
- From cardiovascular system: seldom – hypostasis, a heart consciousness, disturbance of frequency and a rhythm of cordial reductions, lengthening of an interval of QT, ventricular arrhythmias.
- From a digestive tract: seldom – gastrointestinal frustration, including an abdominal pain, diarrhea, regurgitation, appetite change, nausea, heartburn, a lock, it is very rare – short-term intestinal spasms.
- From skin: seldom – an itch, rash.
- From reproductive system and mammary glands: seldom – a galactorrhoea, a gynecomastia, an amenorrhea, decrease or feeling of a libido.
- From an urinary system: seldom – a frequent urination, a dysuria.
- From a musculoskeletal system: seldom – an onychalgia, an adynamy.
- Other: seldom – conjunctivitis, stomatitis.
- Laboratory indicators: increase in the ALT, nuclear Heating Plant level and cholesterol.
As the hypophysis is out of a blood-brain barrier, домперидон can lead to increase in level of prolactin. Seldom the giperprolaktinemiya can result in neuroendocrinal side effects, such as a galactorrhoea, a gynecomastia and an amenorrhea.
The extrapyramidal phenomena were observed very seldom. These side reactions disappear spontaneously and completely right after the treatment termination.

Interaction with other medicines:

Anticholinergic drugs can neutralize anti-dispeptic effect of the drug Domrid® SR.
At simultaneous use with Cimetidinum or sodium bicarbonate bioavailability of Domridu® of SR decreases.
It is not necessary to accept antiacid and anti-secretory drugs along with Domridom® of SR as they reduce its bioavailability after intake.
Results of the researches in vitro demonstrate that at simultaneous use of a domperidon with medicines which considerably suppress SURZA4 isoenzyme the level of a domperidon in a blood plasma can increase. Antifungal drugs of an azolovy row (кетоконазол, флуконазол, итраконазол, вориконазол), antibiotics of group of macroleads (erythromycin, кларитромицин), HIV protease inhibitors (ритонавир, ампренавир, атазанавир, фозампренавир, индинавир, саквинавир), antidepressants (нефазодон), antagonists of calcium (diltiazem, verapamil), Amiodaronum, an aprepitant, телитромицин can be an example of the drugs inhibiting this isoenzyme.
At simultaneous use of the drug Domrid® SR with m cholinolytics and narcotic analgetics influence of a domperidon on a motor evakuatornuyu activity of a stomach and intestines decreases.

Use with ketokonazoly. During a research of interaction of a domperidon with ketokonazoly in vivo it is revealed that кетоконазол inhibits SURZA4-dependent primary metabolism of a domperidon therefore triple increase in the area under a curve "concentration time" (AUC) and peak concentration (Cmax) of a domperidon in a blood plasma is reached. In case of need simultaneous use of a ketokonazol with Domridom® of SR it is necessary to watch dynamics of change of indicators of an ECG and if it is necessary, to carry out the corresponding correction of the dose mode of both drugs or to resolve an issue of expediency of a combination therapy. It is necessary to conduct medical observation of a condition of cardiovascular system of the patient.
Simultaneous use of a domperidon by the patient which in parallel receive paracetamol and/or digoxin did not influence the level of these drugs in blood. Домрид® SR can be combined with:
- neuroleptics which action it strengthens;
- dopaminergic agonists (Bromocriptinum, a levodopa) which undesirable peripheral actions (digestion disturbance, nausea, vomiting) it suppresses without neutralization of their main properties.

Contraindications:

– Hypersensitivity to drug components.
– It is not necessary to use drug if stimulation of motive function of a stomach can be dangerous, for example, at gastrointestinal bleeding, mechanical impassability or perforation. 
– Prolaktinsekretorny tumor of a hypophysis (prolaktinom).
– Simultaneous use of a ketokonazol, erythromycin or other strong CYP3A4 inhibitors, medicines which extend an interval of QT, such as флуконазол, вориконазол, кларитромицин, Amiodaronum, телитромицин (see the section "Interaction with Other Medicines and Other Types of Interactions").
– Heavy or moderate abnormal liver functions and/or kidneys.

Overdose:

Symptoms: drowsiness, disorientation and extrapyramidal frustration, disturbance of consciousness, spasm.
Treatment: there is no specific antidote. In case of overdose the gastric lavage, reception of absorbent carbon, careful observation of the doctor of the patient and other supporting actions is recommended.
Anticholinergics, drugs for treatment of parkinsonism or antihistaminic drugs with anticholinergic properties can be effective for correction of extrapyramidal frustration.

Storage conditions:

To store at a temperature not above 25 °C in dry, protected from light and the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in the blister. On 1 or 3 blisters in cardboard packaging.