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

Rabeprazole is a proton pump inhibitor (H⁺/TO⁺ATPase) is metabolized in parietal cells of the stomach to active sulfonamide derivatives that inactivate the sulfhydryl groups of H⁺/TO⁺ATPase.It blocks the final stage of hydrochloric acid secretion, reducing the content of basal and stimulated secretion irrespective of the nature of the stimulus. It has high lipophilicity, easily penetrates into the parietal cells of the stomach and concentrates in them, providing a cytoprotective effect and increasing the secretion of bicarbonate. The median inhibitory effect of rabeprazole on gastric secretion to 24 hours after the administration of the first dose is 88% of the maximum. After the end of the injection, the secretory activity is normalized within 2-3 days. Rabeprazole in a dose of 20 mg inhibits basal and food-stimulated secretion by 86% and 95%, respectively. In the first 2-8 weeks of therapy, the concentration of gastrin in the serum increases and Returns to the original levels within 1-2 weeks after cancellation.

Pharmacokinetics:

Bioavailability with intravenous injection - 100%. Pharmacokinetics (maximum concentration and area under the concentration-time curve (AUC)) Rabeprazole is linear in the dose range of 10 to 40 mg; pharmacokinetic parameters do not change with repeated administration. The half-life (T1 / 2) of plasma is 1-2 hours.The connection with plasma proteins is 96.3%. Extensively metabolized. The thioether and sulfone derivative are the primary metabolites found in plasma. Both metabolites do not have significant antisecretory activity. Research in vitro showed that rabeprazole metabolized in the liver with the participation of cytochrome P450 isoenzymes CYP3A to the sulfonic derivative and CYP2C19 to desmethylrabeprazole. The thioether is formed by non-enzymatic conversion of rabeprazole. It is known that CYP2C19 has genetic polymorphism due to its deficiency in some subpopulations (3-5% for the European race, 17-20% for the Mongoloid race). Metabolism of rabeprazole in these patients is slowed. Clearance - 283 ± 98 ml / min. It is excreted by the kidneys - 90% mainly in the form of thioester of carboxylic acid, as well as in conjugates and metabolites of mercapturic acid; the remainder is excreted through the intestine.

In patients with hepatic insufficiency AUC increases by 2 times, the maximum concentration (Сmах) - by 60%.

Indications:

Rabeprazole for intravenous administration is indicated as an alternative for those patients for whom oral therapy is not possible or not indicated:

- Acute duodenal ulcer with bleeding or severe erosive lesion;

- Acute stomach ulcer with bleeding or severe erosive lesion; - Short-term therapy of gastroesophageal reflux disease (GERD) with erosive or ulcerative lesions;

-prophylaxis of aspiration with acidic stomach contents;

-stress-induced lesion of the mucous membrane of the gastrointestinal tract in critical states;

-pathological hypersecretory conditions, including Zollinger-Ellison syndrome;

-step transition (stepwise therapy) with oral administration of rabeprazole in case the patient was previously treated with oral rabeprazole and temporarily can not take oral medication for any reason.

Contraindications:

Hypersensitivity to rabeprazole, incl. substituted benzimidazoles, or any other component of the drug, pregnancy, lactation, children under 18 years of age (efficacy and safety not established).

Carefully:

Severe hepatic insufficiency.

Dosing and Administration:

For intravenous administration only. Intravenous administration is indicated only in cases when oral therapy is not possible; as soon as oral therapy can be carried out,intravenous administration is discontinued.

The recommended adult dose is 20 mg once daily.

Intravenous injection: the contents of the vial are dissolved in 5 ml of water for injection, which is administered for 5-15 minutes.

Intravenous infusion: the intravenous injection solution prepared above should be diluted in a sufficient amount of a compatible infusion solution and administered by short-term infusion for 15-30 minutes.

Compatibility with solutions for infusion: rabeprazole compatible with sterile water for injection and 0.9% solution of sodium chloride. No other fluids and solutions should be used for the intravenous administration of rabeprazole.

Side effects:

In clinical studies with a frequency> 2% and with a frequency exceeding placebo, the following adverse reactions were reported: pain (without clarification of localization), pharyngitis, flatulence, infection, constipation. For the following undesirable reactions observed in clinical studies, a causal relationship with the use of rabeprazole has not been established: headache, abdominal pain, diarrhea, dry mouth, dizziness, peripheral edema,increased activity of "hepatic" enzymes, hepatitis, hepatic encephalopathy, myalgia, arthralgia. Postmarketing experience: fractures of bones.

Overdose:

No cases of an overdose of rabeprazole have been reported. The specific antidote for rabeprazole is unknown. Due to the fact that rabeprazole is highly bound to blood proteins, it is not excreted through dialysis. When

overdose symptomatic and supportive treatment.

Interaction:

Drugs metabolized by cytochrome isoenzymes CYP4S0

Rabeprazole is metabolized by the cytochrome P450 enzyme system. Studies in healthy volunteers have shown that rabeprazole did not have a clinically significant interaction with other drugs metabolized by cytochrome P450 isoenzymes, such as warfarin and theophylline with a single oral administration, diazepam with a single intravenous injection, phenytoin with a single intravenous administration (with an additional oral intake).

Warfarin

There are reports of lengthening of the international normalized relationship (INR) andprothrombin time (PI) in patients who simultaneously received proton pump inhibitors, including rabeprazole, and warfarin. Elongation of MNO and PV may lead to an increased risk of bleeding.

Cyclosporin

In studies in vitro with human liver microsomes it was shown that rabeprazole inhibits the metabolism of cyclosporin with an inhibitory concentration of 50-62 μmol, which is more than 50 times higher than the maximum concentration in healthy volunteers after 20 mg of rabeprazole. This degree of inhibition was similar to that of omeprazole at equivalent concentrations.

Medicines, the absorption of which depends on the pH of the stomach The interaction of drugs, whose absorption depends on the pH of the stomach, can occur due to significant inhibition of hydrochloric acid secretion with rabeprazole. For example, in healthy volunteers, simultaneous use of 20 mg of rabeprazole resulted in a 30% reduction in the bioavailability of ketoconazole and a decrease AUC and Stax digoxin by 19% and 29%, respectively; It is necessary to monitor patients with simultaneous use of rabeprazole and such medications.

The simultaneous use of rabeprazole and antacids leads to clinically significant changes in the plasma concentration of rabeprazole.

With the simultaneous use of atazanavir with proton pump inhibitors, a significant decrease in the concentration of atazanavir is expected, which leads to a decrease its therapeutic effect, so the simultaneous use of atazanavir with proton pump inhibitors (including rabeprazole) Not recommended.

Medicines, metabolites from the isoenzyme CYP2C19

In a clinical study in Japan evaluating rabeprazole in patients depending on the genotype CYP2C19 (n = 6 in each genotype category), acid suppression was higher in slow metabolizers than in fast metabolites, which may be due to a higher concentration of rabeprazole in slow metabolizers. Differences between slow and fast metabolizers when interacting with other drugs metabolized with participation CYP2C19, not investigated.

Special instructions:

Before and after treatment it is recommended to carry out endoscopic control to exclude malignant neoplasm.treatment can mask symptoms and delay correct diagnosis.

Several published observational studies have reported a possible association of treatment with proton pump inhibitors with an increased risk of developing osteoporosis-associated fractures of the hip bone, wrist, spine. The risk of fractures was increased in patients who received high doses or who were treated for a long time (1 year or more). It is necessary to use the lowest effective dose and the minimum course of treatment, depending on the indications for which proton pump inhibitors are used.

Studies of the effect of the drug on the ability to drive vehicles and work with complex mechanisms have not been carried out.

In case of development of such undesirable reactions as dizziness, it is recommended to refrain from driving and other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Lyophilizate for the preparation of a solution for intravenous administration of 20 mg.

Packaging:For 95 mg of the drug (corresponding to 20 mg of rabeprazole sodium) in a bottle of neutral glass type I (USP), corked with bromobutyl stopper, crimped aluminum cap with lid type "Flip off". Each vial with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years.

Do not use after the expiry date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001200

Date of registration:11.11.2011

The owner of the registration certificate:Cadil Pharmaceuticals Co., Ltd.Cadil Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

CADILA PHARMACEUTICALS, Ltd. India

Representation: & nbspCADILA PHARMACEUTICALS LTD. CADILA PHARMACEUTICALS LTD. India

Information update date: & nbsp11.11.2011

Illustrated instructions

Instructions

Rabelok® (Rabeloc®)