Domrid suspension

General characteristics. Structure:

Active ingredient: domperidone; 1 ml of suspension contains a domperidon of 1 mg.

Auxiliary a veshchestva:sakharoza, polysorbate 80, silicon dioxide colloid anhydrous, sodium carboxymethylcellulose, sodium chloride, propylene glycol, glycerin, methylparahydroxybenzoate (Е 218), пропилпарагидроксибензоат (Е 216), Ponso 4R (Е 124), flavoring additive the strawberry, water purified.

Pharmacological properties:

Pharmacodynamics. Domperidon is the antagonist of receptors of a dopamine, a prokinetic. Antiemetic action is caused by a combination of peripheral (gastrokinetichny) 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 a stomach excrement. Practically does not influence gastric secretion.

Pharmacokinetics. Domperidon is quickly absorbed from intestines after oral administration on an empty stomach with achievement of the maximum levels in a blood plasma in 30–60 min. Reduced acidity of a stomach reduces absorption of a domperidon.
Bioavailability makes about 15%. Food substantially reduces bioavailability of a domperidon.
Linkng with blood proteins makes 91–93%.
Drug is metabolized in a liver by a hydroxylation and N-dealkylation. At a research of metabolism of the drug in vitro using diagnostic inhibitors it was established that the isoenzyme 3A4 is the main isoenzyme of system of P450 cytochrome which takes part in process of N-dealkylation of a domperidon whereas isoenzymes of CYP3A4, CYP1A2, CYP2E1 take part in process of an aromatic hydroxylation of a domperidon. Drug is exposed to extensive primary metabolism in a wall of intestines and in a liver that causes its low bioavailability.
It is removed by kidneys (31%) and with excrements (66%). In not changed state only the insignificant percent of drug is removed (10% – with excrements and about 1% – kidneys).
The elimination half-life of a domperidon after reception of a single dose makes 7–9 hours of a blood plasma.
Domperidon practically does not get through a blood-brain barrier.

Indications to use:

Adults:
- Nausea and vomiting;
- feeling of overflow in epigastriums;
- pain in an upper part of a stomach;
- heartburn with throwing of contents of a stomach in a mouth or without throwing.
Children:
- Weakening of symptoms of nausea and vomiting.

Route of administration and doses:

Drug is recommended to be accepted to food. At administration of drug after food absorption is a little slowed down.
Dosing and term of treatment are defined by the doctor depending on a clinical situation and character of a course of a disease.
Dosing for adults and children is more senior than 12 years with the body weight of 35 kg and more. Appoint 10–20 mg (10–20 ml of syrup) 3–4 times in days in 15–30 min. prior to food and, in case of need, before going to bed.
The maximum daily dose of drug – 80 mg (80 ml of suspension).
Dosing for children age till 1 year. Appoint on 0,25 mg (0,25 ml of suspension) to 1 kg of body weight of the child 3–4 times in days.

Dosing for children age from 1 year to 12 years. Appoint on 0,25–0,5 mg (0,25-0,5 ml of suspension) to 1 kg of body weight of the child 3–4 times in days.
The maximum daily dose – 2,4 mg (2,4 ml of suspension) on 1 kg of body weight of the child, but is no more than 80 mg in days.
Duration of primary treatment – 4 weeks. The doctor defines need of further use of drug.
At a renal failure it is necessary to reduce the frequency of administration of drug; at a liver failure it is not necessary to appoint drug (see the section "Features of Use").
It is necessary to pay attention that the measured spoon is intended for measurement of 2,5 or 5 ml of suspension, i.e. for dosing to children with body weight from 4 kg. Children with body weight to 4 kg less than 1 ml can use the plastic one-time syringe without needle with a capacity of 2 ml to dosage measurement.

Features of use:

Domrid's use together with ketokonazoly, erythromycin or other potential CYP3A4 inhibitors can lead to lengthening of an interval of QT. Домрид® patients need to apply with care with risk factors of prolongation of an interval of QT, including a hypopotassemia, a heavy hypomagnesiemia, organic heart diseases, a concomitant use of medicines which extend 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. As the insignificant percent of drug is removed by kidneys in not changed look, the single dose of drug can not be subject to correction. But at long use of a domperidon by the patient with a renal failure it is necessary to reduce the frequency of inclusion to 1–2 times in days, depending on weight of renal failures. For such patients it is necessary to establish regular medical control.
Important information on drug use to children of the first year of life.
Because processes of metabolism and function of a blood-brain barrier in the first months of life are developed not completely, children of chest age should appoint drug with care and under strict medical supervision. It is necessary to define very attentively and accurately a single dose of drug. Strengthening of side reactions from a nervous system is possible, in particular in the form of disturbances of activity of extrapyramidal system (see the section "Side reactions").
Домрид® contains sucrose that needs to be considered at appointment as its sick diabetes mellitus.

Ability to influence speed of response at control of motor transport or work with 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 keep from control of vehicles and performance of other works which demand the increased concentration of attention.

Use during pregnancy or feeding by a breast.
There are restrictions concerning use of a domperidon to pregnant women. The potential risk for the person is unknown. Therefore Domrid® can appoint during pregnancy only when the expected advantage for mother exceeds potential risk for a fruit.
Домрид® it 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 ng/ml. At present it is not established whether it does harm to the newborn.
In case of need drug uses the feeding women for treatment need to stop feeding by a breast.

Children. With care appoint to newborn and premature children.
At use newborn, especially premature, and babies should calculate very attentively appointed dose. At increase in the recommended dose there can be extrapyramidal frustration.

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 isolated 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 disturbances: seldom – nervousness; very seldom – agitation.
- From a nervous system: often – dryness in a mouth, a headache; infrequently – sleeplessness, dizziness, thirst, slackness, annoyance, the raised vozbuzhdayemost; seldom – extrapyramidal frustration; very seldom – 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 abdominal pain, diarrhea, a regirgutation, appetite change, nausea, heartburn, a lock; very seldom – short-term intestinal spasms.
- From skin: seldom – an itch, rashes.
- From reproductive system and mammary glands: seldom – a galactorrhoea, a gynecomastia, an amenorrhea.
- From an urinary system: seldom – a frequent urination, a dysuria.
- From a musculoskeletal system: seldom – an onychalgia, an adynamy.
- Others: 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 at newborns and babies, especially at adults. These side reactions disappear spontaneously and completely right after the treatment termination.
Other side effects connected with a nervous system – spasms, agitation and drowsiness were observed very seldom and preferential at babies and children.

Interaction with other medicines:

Anticholinergic drugs can neutralize anti-dispeptic effect of the drug Domrid®.
At simultaneous use of Domrid with Cimetidinum or sodium bicarbonate bioavailability of the drug Domrid® decreases.
It is not necessary to accept antiacid and anti-secretory drugs along with Domrid as they reduce its bioavailability after intake.
Results of the researches ip vitro demonstrate that at simultaneous use of a domperidon with medicines which substantially oppress CYP3A4 isoenzyme the level of a domperidon in a blood plasma can increase. Antifungal drugs of an azalovy 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 drugs which inhibit this isoenzyme.
At simultaneous use of Domrid with m cholinolytics and narcotic analgetika 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 CYP3A4 - dependent primary metabolism of a domperidon owing to what approximately triple increase in the area under a curve "concentration time" (AUC) and peak concentration (Cmax) in a blood plasma of a domperidon is reached. In a research of interaction of a domperidon and ketokonazol it is established that at combined use of a domperidon in a dose of 10 mg 4 times in days and a ketokonazol in a dose of 200 mg 2 times in days are observed lengthening of an interval of QT on an ECG on 10–20 ms. At monotherapy domperidony both in similar doses, and at reception of a daily dose of 160 mg (that exceeds the most admissible daily dose twice), it was not recorded clinically significant changes of an interval of QT.

In need of simultaneous use of a ketokonazol with the drug Domrid® it is necessary to watch dynamics of changes of indicators of an ECG and, if necessary, to carry out the corresponding correcting of the dose mode of both drugs or to resolve an issue of expediency of a combination therapy. It is necessary to establish medical observation of a condition of cardiovascular system of the patient.
Simultaneous use of Domrid to patients who in parallel receive paracetamol and/or digoxin did not influence the level of these drugs in blood.
Домрид® it is also possible to combine with:
- neuroleptics which action it strengthens;
- dofaminergichesky agonists (Bromocriptinum, a levodopa) which undesirable peripheral actions (digestion disturbance, nausea, vomiting) it oppresses 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.
Prolactin-secretory 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").

Overdose:

Symptoms: drowsiness, disorientation and extrapyramidal frustration.
Treatment: the specific antidote does not exist. In case of overdose the gastric lavage, use of absorbent carbon, careful observation of the doctor of the patient and other supporting measures 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 protected from light and the place, unavailable to children. After the first opening of a bottle to store drug no more than 4 weeks.

Issue conditions:

According to the recipe

Packaging:

On 60 ml or 100 ml in bottles. Each bottle in a cardboard box together with a measured spoon.