More info
Active ingredients
Rabeprazole
Release form
Pills
Composition
Active ingredient: Rabeprazole (Rabeprazole) Active ingredient concentration (mg): 10mg
Pharmacological effect
The drug is characterized by anti-ulcer effect.
Pharmacokinetics
AbsorptionRabeprazole is rapidly absorbed from the intestine, and its peak plasma concentrations are reached approximately 3.5 hours after a 20 mg dose. Changes in peak plasma concentrations (Cmax) and the area under the concentration-time curve (AUC) of rabeprazole are linear in the dose range from 10 to 40 mg. Absolute bioavailability after oral administration of 20 mg (compared with intravenous administration) is about 52%. In addition, the bioavailability does not change with repeated use of rabeprazole. In healthy volunteers, T1 / 2 from plasma is about 1 hour (ranging from 0.7 to 1.5 hours), and the total clearance is 3.8 ml / min / kg. In patients with chronic liver damage, AUC is doubled compared with healthy volunteers, indicating a decrease in first-pass metabolism, and T1 / 2 from plasma increased by 2-3 times. Neither the time of the drug intake during the day, nor antacids affect the absorption of rabeprazole. Taking the drug with fatty foods slows down the absorption of rabeprazole for 4 hours or more, however, neither Cmax nor the degree of absorption changes. Distribution In humans, the degree of binding of rabeprazole with plasma proteins is about 97%. Metabolism and elimination rabeprazole sodium unchanged drug in the urine was not found. About 90% of rabeprazole is excreted in the urine mainly as two metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), and also in the form of two unknown metabolites detected during toxicological analysis. The remaining part of the administered rabeprazole sodium is eliminated with feces. The total elimination is 99.8%. These data indicate a small excretion of metabolites of rabeprazole sodium with bile. The main metabolite is thioether (M1). The only active metabolite is desmethyl (M3), however, it was observed in low concentration in only one study participant after taking 80 mg of rabeprazole. /1.73m2), removal of rabeprazole sodium is similar to that for healthy volunteers.AUC and Cmax in these patients were approximately 35% lower than in healthy volunteers. On average, T1 / 2 of 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 kidney disease in need of hemodialysis was approximately two times higher than in healthy volunteers. Chronic compensated cirrhosis. Patients with chronic compensated liver cirrhosis tolerate rabeprazole sodium at a dose of 20 mg 1 time per day, although AUC is doubled and Cmax is increased 50% compared with healthy volunteers of the appropriate sex. Elderly patients In elderly patients, the elimination of rabeprazole is somewhat slower. After 7 days of taking rabeprazole, 20 mg per day in elderly people had approximately twice the AUC, and Cmax increased by 60% compared with young healthy volunteers. However, there were no signs of rabeprazole cumulation. CYP2C19 polymorphism In patients with a slow CYP2C19 metabolism after 7 days of taking rabeprazole at a dose of 20 mg per day, the AUC increases 1.9 times and T1 / 2 1.6 times compared with the same parameters in “fast metabolisers” , while it increases by 40%.
Indications
Peptic ulcer in the acute stage and ulcer anastomosis; peptic ulcer of the duodenum in the acute stage; erosive gastroesophageal reflux disease or reflux esophagitis; maintenance therapy of gastroesophageal reflux disease; non-erosive gastroesophageal reflux disease; Zollinger-Ellison syndrome and other conditions characterized by pathological hypersecretion; in combination with appropriate antibiotic therapy for the eradication of Helicobacter pylori in patients with peptic ulcer.
Contraindications
Pregnancy; lactation period; children up to 12 years; hypersensitivity to rabeprazole, substituted benzimidazoles or to the auxiliary components of the drug. To use with caution in patients with severe severe renal insufficiency, in children.
Precautionary measures
Use with caution in patients with severe renal insufficiency.
Use during pregnancy and lactation
There are no data on the safety of rabeprazole during pregnancy. Reproduction studies in rats and rabbits showed no signs of impaired fertility or fetal developmental defects due to rabeprazole; however, in rats in small quantities, the drug penetrates the placental barrier.Pariet should not be used during pregnancy unless the expected positive effect on the mother exceeds the possible harm to the fetus. It is not known whether rabeprazole is excreted in breast milk. Relevant studies in nursing women have not been conducted. At the same time, rabeprazole was found in the milk of activating rats, and therefore Pariet should not be given to lactating women.
Dosage and administration
Tablets of the drug Pariet should be swallowed whole, not chewed or crushed. It was established that neither the time of day nor food intake affect the activity of rabeprazole sodium.
Side effects
Acute systemic allergic reactions; thrombocytopenia, neutropenia, leukopenia; hypomagnesemia; increased liver enzymes, hepatitis, jaundice, hepatic encephalopathy; interstitial nephritis; bullous rash, urticaria, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome. Myalgia, arthralgia, gynecomastia.
Overdose
Symptoms: data on intentional or accidental overdose is minimal. No cases of a severe overdose with rabeprazole were noted. Treatment: symptomatic and supportive therapy. The specific antidote is unknown. Rabeprazole binds well to plasma proteins, so it is poorly excreted by dialysis.
Interaction with other drugs
Rabeprazole sodium, like other proton pump inhibitors (PPIs), is metabolized with the participation of the cytochrome P450 (CYP450) system in the liver. Studies on human liver microsomes showed that rabeprazole sodium is metabolized by CYP2C19 and CYP3A4 isoenzymes. Studies on healthy volunteers showed that rabeprazole sodium does not have pharmacokinetic or clinically significant interactions with drugs that are metabolized by the cytochrome P450 system — a patient, a patient, and a patient, receive a physiological rate test. diazepam (regardless of whether patients metabolize diazepam heavily or weakly). A combination therapy with antibacterial was studied alnymi drugs. This quadrilateral crossover study involved 16 healthy volunteers who received 20 mg of rabeprazole, 1000 mg of amoxicillin, 500 mg of clarithromycin, or a combination of these three drugs (RAK - rabeprazole, amoxicillin, clarithromycin).AUC and Cmax for clarithromycin and amoxicillin were similar when comparing combination therapy with monotherapy. AUC and Cmax for rabeprazole increased by 11% and 34%, respectively, and for 14-hydroxy-clarithromycin (the active metabolite of clarithromycin), AUC and Cmax increased by 42% and 46%, respectively, for combination therapy compared to monotherapy. This increase in exposure indicators for rabeprazole and clarithromycin was not recognized as clinically significant. Interactions due to inhibition of gastric secretion Rabareprazole sodium provides sustained and prolonged suppression of the secretion of gastric juice. Thus, there may be interaction with substances for which absorption is pH dependent. When taken simultaneously with sodium rabeprazole, ketoconazole absorption is reduced by 30% and digoxin absorption increases by 22%. Therefore, some patients should be monitored to address6 the need to adjust the dose while taking rabeprazole sodium with ketoconazole, digoxin or other drugs for which absorption is pH dependent. Atazanavir 300 mg / ritonavir 100 mg with omeprazole (40 mg once a day) or with atazanavir 400 mg with lansoprazole (60 mg once a day), healthy volunteers showed a significant decrease in the effects of atazanavir. Absorption of atazanavir is pH dependent. Although co-administration with rabeprazole has not been studied, similar results are expected for other proton pump inhibitors. Thus, simultaneous administration of atazanavir with proton pump inhibitors, including rabeprazole, is not recommended. Antacid agents In clinical studies, antacid agents were used together with rabeprazole sodium. Clinically significant interactions of rabeprazole sodium with aluminum hydroxide gel or magnesium hydroxide were not observed. Food intake In a clinical study, there were no clinically significant interactions during the administration of sodium rabeprazole with a fat-poor food. Intake of rabeprazole sodium at the same time as food enriched with fats can slow down the absorption of rabeprazole up to 4 hours or more, however, Cmax and AUC do not change. concentration, 50 times higher than Cmax for healthy volunteers after 20 days of taking 20 mg of rabeprazole.The degree of inhibition is similar to that of omeprazole for equivalent concentrations. Metotrexate According to the data on adverse events, data from published pharmacokinetic studies and data from a retrospective analysis, it can be assumed that simultaneous administration of IPP and methotrexate (primarily in high doses) can lead to an increase in methotrexate concentration and / or its metabolite hydroxymetotrexate and increase T1 / 2. However, special studies of drug interaction of methotrexate with PPI have not been conducted.
special instructions
Tablets drug Pariet can not be chewed or crushed. Tablets should be swallowed whole. It has been established that neither time of day nor food intake affects the activity of rabeprazole sodium. In a special study in patients with mild or moderate liver dysfunction, there was no significant difference in the frequency of side effects of the drug Pariet from that in healthy individuals selected by sex and age but, despite this, caution is recommended at the first use of the drug Pariet in patients with severely impaired liver function. AUC of rabeprazole sodium in patients with severely impaired liver function is approximately two times higher than in healthy patients. Patients with impaired renal or hepatic function do not need to adjust the dose of Pariet drug. Hypomagnesia When treated with proton pump inhibitors for at least 3 months in rare cases there were cases of symptomatic or asymptomatic hypomagnesemia. In most cases, these messages were received one year after the treatment. Serious side effects were tetany, arrhythmia, and seizures. Most patients required treatment for hypomagnesemia, including magnesium replacement and discontinuation of proton pump inhibitor therapy. In patients who will receive long-term treatment or who are taking proton pump inhibitors with drugs such as digoxin or drugs that can cause hypomagnesemia (such as diuretics), medical professionals should monitor magnesium levels before starting treatment with proton pump inhibitors and during the treatment period. should not be taken simultaneously with the drug Pariet other agents that reduce acidity,for example, H2-receptor blockers or proton pump inhibitors. Bone fractures According to observational studies, it can be assumed that proton pump inhibitor (PPI) therapy may lead to an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The risk of fractures was increased in patients who received high doses of IPP for a long time (a year or more). Simultaneous use of rabeprazole with methotrexate. hydroxymetotrexate and increase T1 / 2, which can lead to the manifestation of toxicity of methotrexate. If high doses of methotrexate are needed, the possibility of temporarily stopping treatment with IPP may be considered. Clostridium difficile IPP therapy may lead to an increased risk of gastrointestinal infections, such as Clostridium difficile. Patients taking Pariet for short-term symptomatic treatment of GERD and NERD ) without a prescription, you should consult a doctor in the following cases: - use of remedies for relieving the symptoms of heartburn and digestive disorders for 4 weeks or more; - the emergence of new symptoms or change of previously observed symptoms in patients over 55 years old - cases of unintentional weight loss, anemia, gastrointestinal bleeding, dysphagia, pain when swallowing, constant vomiting or vomiting with blood and epigastric contents, cases of stomach ulcers or operations on the stomach and anamnesis, jaundice, etc. (including abnormal liver and kidney function). Patients suffering from recurrent symptoms of digestive disorders or heartburn for a long time should be regularly monitored by a doctor. Patients over 55 years old who take over-the-counter medicines for relieving heartburn symptoms and digestive disorders should inform their attending physician. Patients should not take other acidity reducing drugs, such as H2-receptor blockers or proton pump inhibitors, at the same time as Pariet. . When using other drugs, patients should consult with a pharmacist or doctor before starting treatment with Pariet over-the-counter medicine.Patients should inform the doctor before starting the use of Pariet over-the-counter if they are prescribed an endoscopic examination. Do not use Pariet before taking the urea breath test. symptomatic treatment of manifestations of GERD and NERD (for example, heartburn). The effect on the ability to drive motor vehicles and control mechanisms Aubin pharmacodynamics of rabeprazole and its profile of adverse effects, it is unlikely that Pariet affects the ability to drive and operate machinery. However, in the event of drowsiness, these activities should be avoided.