Ontimes - instructions for use, doses, side effects, contraindications

In 1 tablet, covered with enteric-coated shell, contains active substance: rabeprazole sodium 10.00 mg or 20.00 mg; Excipients: Mannitol 11.50 mg or 23.00 mg; giprolose low-substituted 13.15 mg or 26.30 mg; magnesium oxide 30.00 mg or 60.00 mg; giprolose 2.75 mg or 5.50 mg; magnesium stearate 0.60 mg or 1.20 mg; shell: Sepiafilim LP-761 white: hypromellose-2910 15cP (E 464) 2.530 mg or 5.060 mg; cellulose microcrystalline 0.550 mg or 1.100 mg; stearic acid 0.960 mg or 1.920 mg; titanium dioxide (E171) 0.960 mg or 1.920 mg; enteric membrane: hypromellose phthalate (HP-55) 12.70 mg or 19.00 mg; triethyl citrate 1.30 mg or 2.00 mg; shell of Opadrai II 31F24127 pink (for a dosage of 10 mg): lactose monohydrate 0.360 mg; hypromellose-2910 15sP (E464) 0.280 mg; titanium dioxide (E171) 0.230 mg; Macrogol-4000 0.100 mg; iron oxide oxide yellow 0.013 mg; ferric oxide red oxide 0.017 mg; shell of Opadrai II31F32870 yellow (for a dosage of 20 mg): lactose monohydrate 0.720 mg; hypromellose-2910 15sP (E464) 0.560 mg; titanium dioxide (E171) 0.463 mg; macrogol-4000 0.200 mg; ferric oxide yellow oxide 0.056 mg; ferric oxide red oxide 0.001 mg; ferric oxide black oxide 0.001 mg.

Description:

Dosage of 10 mg: round biconvex tablets with a weak specific odor, covered with a pink shell with a brown tinge, with a black inscription "N" and "10" on the one hand.

Dosage of 20 mg: round biconvex tablets with a weak specific odor, coated with a yellow coating, with a black "93" and "64" on one side.

Pharmacotherapeutic group:a means of reducing the secretion of the glands of the stomach - the proton pump inhibitor.

ATX: & nbsp

A.02.B.C Proton pump inhibitors

A.02.B.C.04 Rabeprazole

Pharmacodynamics:

Mechanism of action. Rabetrazole belongs to the class of antisecretory compounds, which are chemically substituted benzimidazoles.The drug does not possess anticholinergic activity and is not a blocker of the H2 receptor of the stomach wall, but suppresses the synthesis of hydrochloric acid by specific inhibition of the activity of the enzyme H + -K + -ATPase (acid or proton pump). This effect is dose-dependent and leads to inhibition of both basal and stimulated secretion of hydrochloric acid regardless of the stimulus. As a weak foundation rabeprazole in any doses is rapidly absorbed and concentrated in the acidic environment of parietal cells and, when converted to an active sulfenamide group, sequentially interacts with the cysteines of the proton pump.

Antisecretory activity. After oral administration of 20 mg of rabeprazole, the antisecretory effect occurs within 1 hour and reaches a maximum after 2-4 hours. The oppression of basal and food-stimulated acid secretion at 23 hours after the first dose of rabeprazole was 62 and 82%, respectively, and the duration of this action reached 48 h. The inhibitory effect of rabeprazole on the secretion of hydrochloric acid is gradually increased as a result of the daily intake of 1 tablet,the maximum level of oppression of secretion is reached in 3 days after the beginning of taking the drug. After discontinuing reception of rabeprazole secretory activity is restored after 2-3 days. Effect on the concentration of gastrin in the blood serum. In clinical trials, patients received 10 mg or 20 mg of rabeprazole 1 time / day with a treatment duration of up to 43 months. In the first 2-8 weeks of rabeprazole therapy, the serum gastrin concentration increased as a result of its inhibitory effect on the secretion of hydrochloric acid and returned to baseline, usually within 1-2 weeks after discontinuation of treatment.

In special clinical studies, it has been proven that the use of rabeprazole for 36 months does not lead to histological changes in enterochromafin-like cells of the biopsy specimens of the bottom and antrum of the stomach, does not affect the incidence of atrophic gastritis, intestinal metaplasia, and limits the prevalence of infection Helicobacter pylori.

Other effects. Currently, there is no evidence that rabeprazole causes systemic effects from the central nervous system, cardiovascular and respiratory systems. Rabeprazole in a daily dose of 20 mg for 2 weeks does not affect the function of the thyroid gland, the metabolism of carbohydrates, as well as the blood levels of parathyroid hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating hormone, luteinizing hormone, renin , aldosterone and growth hormone.

Pharmacokinetics:

Suction. Rabeprazole is cleaved under the action of hydrochloric acid, therefore it is used in a special intestinal-soluble drug form. Rabeprazole quickly absorbed from the intestine. After taking 20 mg, the maximum concentration CmaxRabeprazole in plasma is achieved after about 3.5 hours. Changes in C_max and AUC are linear in the dose range of 10 to 40 mg. Absolute bioavailability after ingestion of 20 mg (compared with intravenous administration) is approximately 52% due to the effect of "first passage" through the liver. Bioavailability does not change with re-administration of rabeprazole. The intake of food and the time of taking the drug within a day have no effect on the absorption of rabeprazole.

Distribution. 97% of rabeprazole is in plasma in a protein-related condition.

Metabolism. Rabeprazole metabolized in the liver by the cytochrome P 450 system (CYP450). Biotransformiruetsya with the participation of enzymes CYP2C19 and CYP3A4 with the formation of active metabolites - thioether (M1) and carboxylic acid (M6), as well as secondary metabolites present in low concentrations - sulfone (M2), dimethyl thioester (M4) and mercapturic acid conjugate (M5). Only dimethyl metabolite (M3) has an insignificant antisecret activity, but it has not been detected in plasma. In studies in vitro Rabeprazole does not induce or inhibit isoenzyme metabolism CYP3A4, thus, any interaction of rabeprazole and cyclosporine can be ruled out.

Excretion. In healthy volunteers T1 / 2 is about 1 hour (0.7-1.5 h), the total clearance is 283 ± 98 ml / min.

After a single dose of 20 mg of labeled ¹⁴With rabeprazole, excretion of the active substance in unchanged form does not occur. Approximately 90% of this dose is excreted in the urine mainly in the form of two metabolites: a conjugate of mercapturic acid (M5) and carboxylic acid (MB). The rest of the drug is excreted with feces.

Pharmacokinetics in special clinical cases

Sex differences. After a single dose of rabeprazole at a dose of 20 mg with similar body weight and growth, no significant differences in pharmacokinetic parameters are observed with gender.

Impaired renal function. In patients at the terminal stage of renal failure requiring hemodialysis (creatinine clearance less than 5ml / min / 1,732), the distribution of rabeprazole was very similar to that of healthy volunteers. Area under the curve "concentration - time" AUC and C_max in these patients were approximately 35% lower than in healthy volunteers. On the average, T 1/2 rabeprazole was 0.82 h in healthy volunteers, 0.95 h in patients during hemodialysis and 3.6 h after hemodialysis. The clearance of the drug in patients with diseases of the kidneys in need of hemodialysis was approximately 2 times higher than in healthy volunteers.

Violation of the function of the liver. After a single dose of rabeprazole at a dose of 20 mg in patients with moderate chronic liver failure AUC increased by 2 times and T1 / 2 increased by 2-3 times in comparison with healthy volunteers. However, after taking rabeprazole 20 mg / day for 7 days AUC increased only 1.5 times, and Cmax - in 1,2 times. T1 / 2 in patients with hepatic insufficiency was 12.3 hours compared with 2.1 hours in healthy volunteers. The pharmacodynamic response (pH control in the stomach) in both groups was clinically comparable.

Older people. Older patients removing rabeprazole somewhat slowed down. 7 days after taking rabeprazole 20 mg / day in this category of patients AUC was about 2 times greater, and Cmax - 60% higher compared to young healthy volunteers. However, there were no signs of cumulation of rabeprazole.

CYP2C19 polymorphism

In case of delayed metabolism CYP2CI9 after receiving rabeprazole 20 mg / day for 7 days AUC increases 1.9 times, and T1 / 2 - in 1,6 times in comparison with the same parameters at extensive metabolizers, while Сmax increases by 40%.

Indications:

peptic ulcer of the stomach and duodenum in the phase of exacerbation;
erosive or ulcerative gastroesophageal reflux disease (GERD);
long-term maintenance therapy GERD;
symptomatic treatment of GERD;
Zollinger-Ellison syndrome;
eradication Helicobacter pylori in combination with antibacterial agents.

Contraindications:

increased sensitivity to rabeprazole sodium or substituted benzimidazoles, as well as to any ingredient of this drug;
pregnancy and the period of breastfeeding.

Carefully:

abnormal liver function.

Pregnancy and lactation:

There were no special studies on the safety of Ontime on pregnant women. Therefore, the use of the drug during pregnancy is not recommended. Experimental studies of reproductive performance in rats and rabbits showed no signs of impaired fertility or fetal development defects caused by Ontime; However, in rats in small quantities, the drug penetrates the placental barrier.

It is not known whether Ontime is excreted in breast milk. Appropriate studies in lactating women were not conducted. However, Ontime is found in the milk of lactating rats, so the drug should not be given during breastfeeding.

Dosing and Administration:

Inside. If the drug is taken according to the indications required to take the drug 1 time per day, you should take the pill in the morning before eating. It is established that neither the time of day nor the intake of food does not affect the activity of the drug.But the recommended time of taking the tablets contributes to better adherence to the patient's treatment regimen. Tablets should be swallowed whole, without chewing or grinding.

Stomach ulcer and duodenal ulcer in the acute phase: it is recommended to take 20 mg 1 time / day in the morning for 4-6 weeks.

In most patients with duodenal ulcer, ulcer healing occurs within 4 weeks. It should be noted that some patients need to take Ontime for 4 weeks to heal ulcers.

In most patients with peptic ulcer disease, healing occurs within 6 weeks, but some patients may need an additional 6-week treatment with Ontimes for healing ulcers.

Erosive or ulcerative GERD: it is recommended to take 1 tab. (20 mg) 1 time / day for 4-8 weeks.

Long-term maintenance therapy GERD: it is recommended to take in a dose of 10 or 20 mg

1 time / day. The duration of treatment depends on the patient's well-being. Symptomatic treatment of GERD: patients without esophagitis should be taken at a dose of 10 mg 1 time / day for 4 weeks.If after 4 weeks of treatment the symptoms do not disappear, you should conduct an additional examination of the patient. If the symptoms of the disease are not permanent, it is recommended to take Ontime as needed in a dose of 10 mg 1 time per day.

Zollinger-Addison syndrome: the dose is selected individually. The initial dose is 60 mg / day, if necessary, the daily dose can be increased to 120 mg / day and divided into two doses: 60 mg 2 times / day. The maximum single dose, as a rule, is 100 mg. Treatment should continue until the clinical effect is achieved. Eradication Helicobacter pylori in combination with antibacterial agents: it is recommended to carry out a course of treatment of 7 days with the following combination of drugs:

preparation Ontime on 20 mg 2 times / day + clarithromycin 500 mg 2 times / day and amoxicillin 1 g 2 times / day.

Patients with impaired renal or hepatic function correction of the Ontime dose is not required.

Side effects:

Ontimes is usually well tolerated. Side effects, as a rule, are transient.

From the hematopoietic and lymphatic systems: with a frequency of not less than 1/10000, but less than 1/1000 - leukopenia, neutropenia, thrombocytopenia.

From the side of metabolism: with a frequency of not less than 1/10000, but less than 1/1000 - anorexia.

From the immune system: with a frequency of not less than 1/10000, but less than 1/1000 - allergic reactions.

From the nervous system: with a frequency of at least 1/100, but less than 1/10 - insomnia, headache, dizziness; with a frequency of at least 1/1000, less than 1/100 - irritability, drowsiness, with a frequency of at least 1/10000, but less than 1/1000 - depression.

On the part of the organs of vision: with a frequency of not less than 1/10000, but less than 1/1000 - reduced visual acuity.

From the respiratory system: with a frequency of at least 1/100, but less than 1/10 - cough, rhinitis, pharyngitis; with a frequency of at least 1/1000, less than 1/100 - bronchitis, sinusitis.

From the digestive system: with a frequency of at least 1/100, but less than 1/10 - nausea, vomiting, diarrhea, increased gassing, abdominal pain, constipation; with a frequency of at least 1/1000, less than 1/100 - dyspepsia, belching, dryness of the oral mucosa; with a frequency of not less than 1/10000, but less than 1/1000 - gastritis, stomatitis, perversion of taste.

From the liver and bile ducts: with a frequency of at least 1/1000, less than 1/100 - an increase in the activity of transaminases in the blood plasma; with a frequency of not less than 1/10000, but less than 1/1000 - hepatitis, jaundice, hepatic encephalopathy.

From the skin and subcutaneous fat: with a frequency of at least 1/1000, less than 1/100

rash, erythema; with a frequency of not less than 1/10000, but less than 1/1000 - itching, excessive sweating, bullous reactions; with a frequency of less than 1/10000 - erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome.

From the side of the musculoskeletal system and connective tissue: with a frequency of at least 1/100, but less than 1/10 - nonspecific pain in the back; with a frequency of at least 1/1000, less than 1/100

Myalgia, arthralgia, leg cramps.

From the urinary system: with a frequency of at least 1/100, but less. 1/10 - pollakiuria, urine retention; with a frequency of at least 1/1000, less than 1/100 - interstitial nephritis.

Other: with a frequency of at least 1/100, but less than 1/10 - asthenia; with a frequency of at least 1/1000, less than 1/100 - chest pains, chills, fever.

Overdose:

Until now, there have been no reports of cases of deliberate overdose of Ontime. The maximum daily dose does not exceed, as a rule, 160 mg per day. The resulting side effects are usually little expressed and do not require additional therapy. In the event of an accidental overdose, symptomatic and supportive therapy should be given. There is no specific antidote. The Ontem drug extensively binds to plasma proteins, so it is practically not removed during dialysis.

Interaction:

The Ontime product causes a pronounced and prolonged decrease in the production of hydrochloric acid, increasing the pH of the contents of the stomach. Therefore, when used simultaneously with drugs, the absorption of which depends on the pH of the stomach contents, including ketoconazole and itraconazole, it is necessary to adjust their doses taking into account that the concentration of these drugs in the blood plasma decreases.

In special studies, no interaction of Ontime with liquid antacids was found.

Special instructions:

Before starting therapy with Ontime, the presence of a malignant neoplasm of the stomach should be excluded, since taking the drug can mask symptoms and delay the correct diagnosis.

Patients who are forced to take Ontime for a long time should be under constant medical supervision.

Pediatric use:

Ontime is not recommended for children, since there is currently no experience with its use in pediatric practice.

Application in special clinical cases:

In patients with mild or moderate hepatic impairment, there was no significant difference in the incidence of Ontimes' side effects from that ofmatched by the sex and age of healthy individuals, but in spite of this, it is recommended that care be taken with the first administration of the drug to patients with severe impairment of liver function.

Effect on the ability to drive transp. cf. and fur:

Based on the characteristics of pharmacodynamics and the profile of adverse reactions of rabeprazole, it is unlikely that Ontime has an effect on the ability to drive and other mechanisms. However, in the case of drowsiness and dizziness, these activities should be avoided.

Form release / dosage:

Tablets coated with enteric-coated 10 mg or 20 mg.

Packaging:

10 tablets in a blister of PVC / aluminum / polyamide and aluminum foil.

1, 2 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:PL-000831

Date of registration:07.10.2011

The owner of the registration certificate:TEVA, LLC TEVA, LLC Russia

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Information update date: & nbsp02.08.2013

Illustrated instructions

Instructions

Ontime® (Ontime®)