Omez D kaps. it is firm. No. 30

Structure and form of release

Structure

Active ingredients: omeprazolum and domperidon;

1 capsule contains omeprazolum 10 mg of a domperidon of 10 mg;

Excipients: microcrystalline cellulose, starch sodium (type A); silicon dioxide colloidal is attracted (E 421) by sucrose; sodium phosphate; sodium lauryl sulfate; magnesium stearate talc lactose monohydrate, calcium carbonate; gipromelloza; propylene glycol, methacrylate copolymer (type C) polysorbates, diethyl phthalate; sodium hydroxide, cetyl alcohol, starch corn.

release Form

solid capsules.

Pharmacological properties

Pharmacodynamics. omeprazolum — anti-secretory antiulcerous means, reduces spontaneous and stimulated gastric secretion owing to inhibition of N + / to +-atfazy (a proton pomp), necessary for transport of hydrogen ions. suppresses a final phase of basal and stimulated discharge of hydrochloric acid irrespective of the irritant nature.

Domperidon — the antagonist of receptors of dopamine, a prokinetic. Practically does not get through GEB. Increases duration of peristaltic reductions of antral department of a stomach and duodenum, speed of release of a stomach, raises a tone of the lower esophageal sphincter. Does not influence digestive secretion. Has antiemetichesky effect which is a combination of gastrokinetichesky action and antagonism to dopamine receptors in the trigger zone of chemoceptors which is out of GEB.

Pharmacokinetics

Omeprazolum. Omeprazolum is quickly soaked up. The C _max is reached in 1–2 h after oral administration of medicine. Absorption of omeprazolum happens in a small intestine and usually comes to the end during 3–6 h. The concomitant use of food does not affect bioavailability of omeprazolum. The bioavailability of a single oral dose of medicine is about 40%. At repeated application in the mode of 1 times a day the bioavailability increases up to 60%.

distribution Volume at healthy volunteers is about 0.3 l/kg of body weight. Omeprazolum contacts proteins of blood plasma for 97%.

Omeprazolum is completely metabolized by the system of P450 (CYP) cytochrome, generally with participation of CYP 2C19 which is responsible for formation of hydroxyomeprazolum as the main metabolite of omeprazolum in blood plasma. Sulfonic derivative omeprazolum it is formed with participation of other isoform, namely — CYP 3A4. Thanks to high affinity of omeprazolum to CYP 2C19 perhaps competitive inhibition of a metabolization of other substrates this isoform. At the same time affinity of omeprazolum to CYP 3A4 low therefore omeprazolum cannot inhibit a metabolization of other CYP substrates 3A4. However omeprazolum is not inhibited the main enzymes of a system of P450 cytochrome.

T _½ omeprazolum from blood plasma both at single, and at repeated dispensing — 1 h. Omeprazolum is completely removed from blood plasma during the period between receptions of the next doses. At application of 1 times in day of a tendency to accumulation of medicine it is noted. About 80% of the dose of omeprazolum which came to an organism are removed with urine in the form of metabolites. The rest is removed with a stake due to secretion with bile.

At repeated application of AUC for omeprazolum increases. This dose-dependent increase, and dependence is not linear. The dependence on time and a dose is a consequence of decrease in presistemny metabolism and system clearance probably at the expense of inhibition of CYP 2C19 omeprazolum and/or its metabolites (for example sulphone). Metabolites of omeprazolum do not influence secretion of acid in a stomach.

Domperidon. After oral administration on an empty stomach domperidon it is quickly soaked up. The C _max in blood plasma is reached in 30–60 min. The low absolute bioavailability of a domperidon (about 15%) after oral administration is caused by considerable presistemny metabolism in a wall of intestines and liver. Though the bioavailability of a domperidon increases at healthy volunteers at its reception with food, patients with complaints from a GIT should take the medicament in 15–30 min. prior to meal. The lowered acidity of gastric contents breaks absorption of a domperidon. The bioavailability after oral administration decreases at the previous intake of Cimetidinum and sodium bicarbonate. If domperidon to apply after meal, time of the maximum absorption is late a little, and AUC increases.

Domperidon after intake does not collect and does not induce own metabolism. The C _max in blood plasma in 90 min. after application in a dose of 30 mg daily during 2 weeks practically same, as well as after reception of the first dose (21 ng/ml in comparison with 18 ng/ml). Domperidon contacts proteins of blood plasma for 91–93%.

Domperidon is quickly and extensively metabolized by

in a liver by hydroxylation and N-dealkylation.

by

With urine and a stake removes 31 and 66% of the dose accepted orally. An insignificant part of medicine is removed in not changed look (10% with a stake and 1% with urine). The t _½ after a single dose at healthy volunteers makes 7–9 h of blood plasma. This period is extended at patients with a heavy renal failure.

Indication

Functional dyspepsia, the slowed-down evacuation of contents of a stomach and gastroparez, a reflux esophagitis, a peptic ulcer of a stomach and duodenum; in schemes of an eradikation helicobacter pylori in the presence of a gastroesophageal reflux.

Use

Capsule to accept

inside whole, without opening and without chewing. the recommended dose depends on a course of the disease and is established individually. the average recommended dose for adults and children is aged more senior than 12 years — on 1 capsule 2–3 times a day in 30 min. prior to food, washing down with a glass of water. if necessary the dose can be raised by the doctor to 2 capsules 2 times a day. a course of treatment — 4–8 weeks

In schemes of an eradikation on 2 capsules 2 times a day in a combination with antibacterial agents.

Contraindication

Hypersensitivity to a domperidon, omeprazolum or other components of medicine. prolactin - a secretory tumor of a hypophysis (prolaktinom). gastrointestinal bleedings, mechanical intestinal impassability, perforation of a stomach or intestines. heavy or moderate abnormal liver functions and/or kidneys. simultaneous application of a ketokonazol, erythromycin or other strong CYP inhibitors 3a4, the medicines extending an interval of q-t such, as flukonazol, vorikonazol, klaritromitsin, Amiodaronum, telitromitsin (see special instructions, interaction). a concomitant use with atazanaviry.

Special instructions

Antiacid or anti-secretory medicaments at the combined reception with domperidony should be taken after a meal, but they should not be accepted along with medicine domperidon. patients at whom the feeling of discomfort after a meal does not pass and which should accept constantly domperidon during 2 weeks should see a doctor. patients at whom nausea and vomiting proceed 48 h need to see a doctor.

In interaction researches with an oral form of a ketokonazol noted lengthening of an interval of Q-T. Though the value of this research accurately is not established, it is necessary to choose alternative treatment if antifungal therapy ketokonazoly is shown.

Domperidon should be applied with care at patients with risk factors of prolongation of an interval of Q-T, including a hypopotassemia, a heavy hypomagnesiemia, organic heart diseases, and to patients with slight abnormal liver functions and/or kidneys.

If the ulcer exists or there is a suspicion on it, or one of such symptoms as considerable degrowth of a body which cannot be explained, vomiting, a dysphagy, vomiting with impurity of blood or a melena, it is necessary to exclude malignant process as treatment by omeprazolum can mask its symptoms and delay definition of the diagnosis.

Drug contains lactose, sucrose therefore medicament should not be used at patients with a lactose intolerance, a galactosemia and malabsorption of a glucose/galactose, fructose, sucrose-isomaltose.

Domperidon can lead

to increase in level of prolactin that causes a galactorrhoea in women and a gynecomastia in men.

At patients with a pheochromocytoma at application of a domperidon the developing of hypertensive crisis is possible

.

should inform

Patients that medicine is not recommended as antinaupathic drug.

Should consider the following information on risk of development of complications of the cardiovascular diseases caused by the medicines containing domperidon:

— some epidemiological researches showed that domperidon can be associated with the increased risk of serious ventricular arrhythmias or a sudden cardiac death;

— the risk of serious ventricular arrhythmias or a sudden cardiac death can be aged more senior above at patients than 60 years or at oral administration of medicine in doses Domperidon should appoint higher than 30 mg/days

by

adults and children in minimum effective dose.

Ratio of risk and advantage of a domperidon remains to

favorable.

Omeprazolum can reduce digestion of cyanocobalamine. It should be meant at long prescribing of medicine the patient with the reduced content of _{12 vitamin B} in an organism or at violation of absorption of _{12 vitamin B} in a GIT.

to Drivers

during medicament treatment needs to observe extra care at control of vehicles and/or during the work with potentially dangerous mechanisms.

Use during pregnancy and feeding by a breast

pregnant women Cannot apply

. In need of prescribing of medicine the feeding by a breast should be stopped.

Children

use Drug for treatment of children aged from 12 years and with a body weight not less than 35 kg.

Overdose

Overdose caused by action of a domperidon. symptoms: agitation, violation of consciousness, spasm, disorientation, drowsiness, extrapyramidal frustration.

Treatment: gastric lavage, intake of activated carbon, blockers of holinoretseptor for elimination of extrapyramidal frustration. In case of extrapyramidal reactions use anticholinergic medicaments and means for treatment of parkinsonism.

Overdose caused by effect of omeprazolum. Symptoms: nausea, vomiting, dizziness, abdominal cavity pain, meteorism, diarrhea, headache, tachycardia, apathy, depression, confusion of consciousness. All symptoms are tranzitorny. Clearance rate remains invariable irrespective of a dose (primary kinetics).

Treatment: symptomatic.

Side effects

Side reactions, data on which are given below, classified by bodies and systems and for emergence frequency: very often (≥1/10), it is frequent (≥1/100 and 1/10), infrequently (≥1/1000 and 1/100), is rare (≥1/10,000 and 1/1000), is very rare (1/10,000) and frequency is unknown (frequency cannot be determined on the available data).

• from the immune system: seldom — a Quincke's disease; reactions of hypersensitivity, including an anaphylaxis, an acute anaphylaxis; fever; very seldom — Stephens's syndrome — Johnson, a toxic epidermal necrolysis.
• from skin and its appendages: infrequently — skin rash, an itch, dermatitis, a small tortoiseshell; seldom — an alopecia, a photosensitization; very seldom — a multiformny erythema.
• Mental disorders: infrequently — uneasiness; seldom — excitement, confusion of consciousness, a depression; very seldom — aggression, hallucinations; frequency is unknown — nervousness.
• from nervous system: infrequently — a headache, dizziness, paresthesias, drowsiness, insomnia; frequency is unknown — spasms, extrapyramidal reactions, irritability, agitation, an akathisia, vertigo.
• from a cardiovascular system: very seldom — ventricular arrhythmias; frequency is unknown — lengthening of an interval of Q-T, peripheral hypostases, heartbeat, violation of frequency and a rhythm of warm reductions.
• from an organ of sight: seldom — illegibility of sight; frequency is unknown — okulogirny crisis.
• from a respiratory system: seldom — a bronchospasm.
• from a digestive tract: often — an abdominal pain, constipations, diarrhea, a meteorism; seldom — dryness in a mouth, stomatitis, GIT candidiasis, a food faddism; frequency is unknown — intestinal colic, regurgitation, change of appetite, change of taste, nausea, vomiting, heartburn, colitis, thirst.
• from the musculoskeletal system: seldom — arthralgia, myalgia; very seldom — muscle weakness; frequency is unknown — an onychalgia.
• from a gepatobiliarny system: seldom — hepatitis with jaundice or without it; very seldom — a liver failure, encephalopathy at patients with already available liver diseases.
• from an urinary system: seldom — interstitial nephrite; frequency is unknown — an ischuria, a dysuria, frequent urination.
• from a reproductive system: infrequently — a galactorrhoea, pain in mammary glands; frequency is unknown — a gynecomastia, an amenorrhea, increase in level of prolactin, decrease or lack of a libido, an irregular menstrual cycle, hypostasis of mammary glands, violation of a lactation.
• Metabolic violations: seldom — a hyponatremia; very seldom — a hypomagnesiemia.
• from blood: seldom — a leukopenia, thrombocytopenia; very seldom — the Agranulocytosis, a pancytopenia.
• Laboratory indicators: frequency is unknown — increase in the AlAT, AsAT and XC level, increase in content of prolactin in blood serum.
• Other violations: infrequently — an adynamy, an indisposition, peripheral hypostases; seldom — the increased sweating; frequency is unknown — conjunctivitis, slackness.

Interaction

Domperidon. anticholinergic medicines can neutralize anti-dispeptic action of a domperidon.

should not take the antiacid and anti-secretory medicaments along with domperidony as they reduce its bioavailability after intake.

Main way of metabolic transformations of a domperidon occurs with the participation of an isoenzyme of CYP 3A4 of the system of P450 cytochrome therefore at the simultaneous application of a domperidon and medicines considerably inhibiting this isoenzyme the increase in level of a domperidon in blood plasma is possible.

Simultaneous application with ketokonazoly, erythromycin or other potential CYP inhibitors 3A4 can lead to lengthening of an interval of Q-T.

At simultaneous application of a domperidon in a dose of 10 mg 4 times a day and a ketokonazol in a dose of 200 mg 2 times a day note lengthening of an interval of Q-T on average on 9.8 ms (from 1.2 to 17.5 ms are individual). At simultaneous application of a domperidon in a dose of 10 mg 4 times a day and erythromycin in a dose of 500 mg 3 times a day note lengthening of an interval of Q-T on average on 9.9 ms (from 1.6 to 14.3 ms are individual). In an equilibrium state in such interaction of the C _max and AUC for a domperidon increases approximately by 3 times. In the specified researches the monotherapy domperidony in a dose of 10 mg 4 times a day led to increase in an interval of Q-T by 1.6 ms (an interaction research with ketokonazoly) and on 2.5 ms (an interaction research with erythromycin). Monotherapy ketokonazoly (200 mg 2 times a day) led to increase in an interval of Q-T by 3.8 ms, and monotherapy by erythromycin (500 mg 3 times a day) — on 4.9 ms.

Strong CYP inhibitors 3A4 with which it is not recommended to apply domperidon: azolny antifungal medicines, such, as flukonazol ^* , itrakonazol ^* and vorikonazol ^* ; makrolidny antibiotics, such, as klaritromitsin ^* and erythromycin; HIV protease inhibitors, such, as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir and sakvinavir; antagonists of calcium, such as diltiazem and verapamil; ^{Amiodaronum *} ; amrepitant; nefazodon; telitromitsin ^* ( ^* prolong Q-Ts interval). Domperidon it is possible to combine with neuroleptics which action he strengthens; dofaminergichesky agonists (Bromocriptinum, L-finish singing), which undesirable peripheral effects — digestion violation, nausea, vomiting — he suppresses without neutralization of the main properties.

Omeprazolum. Decrease in acidity in a stomach during use of omeprazolum can change absorption of medicines for which this process is rn-dependent. At simultaneous use of omeprazolum with nelfinaviry, atazanaviry concentration of the last in blood plasma decreases. The combined use of omeprazolum with nelfinaviry is contraindicated. Use of omeprazolum in a dose of 40 mg of 1 times a day reduces the maintenance of a nelfinavir on average by 40%, and it pharmacological an active metabolite of M8 — for 75–90%. Other mechanism of interaction is possible through CYP 2C19.

Combined use of omeprazolum with atazanaviry is contraindicated to

. At simultaneous use of omeprazolum in a dose of 40 mg of 1 times a day and an atazanavir of 300 mg / ritonavira 100 mg at healthy volunteers the effect of an atazanavir decreases by 75%. Increase in a dose of an atazanavir to 400 mg does not compensate such influence of omeprazolum. At the combined use of omeprazolum in a dose of 20 mg of 1 times a day and an atazanavir of 400 mg / ritonavira 100 mg at healthy volunteers the effect of an atazanavir decreases approximately by 30%.

to

It was reported about increase in level in blood serum of other antiretroviral means, such as sakvinavir. There are also other antiretroviral medicines which levels in blood plasma at simultaneous application with omeprazolum remained invariable.

Combined use of omeprazolum in a dose of 20 mg of 1 times a day with digoxin at healthy volunteers increases bioavailability of digoxin by 10%. Though about toxic shows of digoxin in such cases it is not reported, it is necessary to be careful at use of omeprazolum in high doses with digoxin to elderly people.

In cross clinical trial at simultaneous application of a klopidogrel (load dose of 300 mg, and then 75 mg/days) with omeprazolum (80 mg at a concomitant use) during 5 days the effect of an active metabolite of a klopidogrel decreased by 46% (1st day) and for 42% (2nd day). Aggregation of platelets decreased by 47% in 24 h and for 30% — for the 5th day. In other clinical trial it is shown that reception of a klopidogrel and omeprazolum at different times does not prevent the specified interaction which is probably caused by the inhibition of CYP 2C19 caused by medicine.

omeprazolum Use significantly reduces absorption of a pozakonazol, erlotinib, ketokonazol and itrakonazol owing to what clinical performance of the specified medicines can decrease.

Omeprazolum suppresses CYP 2C19, the main omeprazolmetaboliziruyushchy enzyme. Thus, metabolism of the accompanying medicines, also metabolized CYP 2C19 — diazepam, Phenytoinum, warfarin (R-warfarin) or other antagonists of vitamin K and tsilostazol, can slow down. Monitoring of the patients accepting Phenytoinum also is recommended there can be a need for Phenytoinum dose decline. However simultaneous application of 20 mg of omeprazolum a day did not change concentration of Phenytoinum in blood plasma of patients, is long using this drug. Monitoring of the international normalized relation at patients who apply warfarin or other antagonists of vitamin K is recommended; the warfarin dose decline can be required (or other antagonist of vitamin K). Simultaneous application of 20 mg of omeprazolum a day, nevertheless, did not change coagulation time at patients, is long applying warfarin.

Omeprazolum is partially metabolized also by CYP 3A4, but does not suppress this enzyme. Thus, omeprazolum does not influence metabolism of medicines which are metabolized by CYP 3A4, such as cyclosporine, lidocaine, quinidine, oestradiol, erythromycin and budesonid. It was reported about increase in level of a methotrexate at some patients at a concomitant use with inhibitors of a proton pomp. In need of application of a methotrexate in high doses it is necessary to consider a question of temporary cancellation of omeprazolum.

Simultaneous use of omeprazolum with takrolimusy can lead

to increase in concentration of a takrolimus in blood plasma. At the beginning or after medicament treatment it is recommended to monitorirovat concentration of a takrolimus in blood plasma.

At simultaneous use of omeprazolum and CYP inhibitors 2C19 and CYP 3A4 (for example klaritromitsin and vorikonazol) increase in content of omeprazolum in blood plasma owing to decrease in metabolism of the last is possible

. The combined application of a vorikonazol and omeprazolum leads to strengthening of effects of the last twice. As such increase in content of omeprazolum is quite acceptable, usually dose adjustment is not required, except for patients with a heavy liver failure or in case of a long course of treatment.

Drugs inducing CYP 2C19, CYP 3A4 or both enzymes (for example rifampicin), can lead to decrease in level of omeprazolum in blood plasma by acceleration of his metabolism.

Storage conditions

B the dry, protected from light place at a temperature up to 25; °C.