Aciphex (Rabeprazole) 20 mg

Pharmacology Aciphex 20 mg

Pharmacological action – antiulcer.

Aciphex Is a prodrug – in the acidic environment of parietal cells is converted into an active form sulfenamidnuyu interacting with the cysteine-H +-K +-ATPase (proton pump). Inhibits (partly reversibly) H +-K +-ATPase of gastric parietal cells and dose-dependently inhibits basal and stimulated secretion of hydrochloric acid. Antisecretory effect occurs within 1 h after ingestion of 20 mg. The maximum reduction in gastric pH recorded 2-4 hours after administration of the first dose. On the first day reduces the acidity of the daily average of 61% (this represents approximately 88% reduction in the secretion, achieved on day 8 of treatment). The average pH value for 24 hours is 3.4, while the time during which the pH is maintained at a 3 – 55.8%. Partial dissociation of the complex with H +-K +-ATPase leads to less than that of the irreversible proton pump inhibitors duration of action. The duration of inhibition of basal and stimulated secretion of up to 48 hours, stable antisecretory effect develops after 3 days of treatment. Cancellation is not accompanied by the phenomenon of rebound, restoration of secretory activity occurs within 2-3 days as the synthesis of new enzyme molecules.

H. pylori possesses activity: MIC 4-16 mg / ml. Accelerates the manifestation of H. pylori activity of several antibiotics. During triple eradication therapy (rabeprazole 20 mg 2 times a day in combination with clarithromycin and amoxicillin), 90% eradication of Helicobacter pylori is achieved within 4 days. Helikobaktera eradication at the end of the 7-day course of therapy, respectively, indicated at 100, 95, 90 and 63% in the treatment of rabeprazole in combination with clarithromycin + metronidazole, clarithromycin + amoxicillin, amoxicillin + metronidazole only with clarithromycin. When erosive or ulcerative gastroesophageal reflux disease on the first day of treatment (10-20 mg) reduces heartburn by day and at night. Effective with the 8-week treatment of erosive reflux esophagitis in 84% of patients. The efficiency of pathological hypersecretory conditions, including Zollinger-Ellison syndrome. In the first 8.2 weeks of long-term use temporarily increases the concentration of gastrin in serum (histologically not observed to increase the number of ECL-cell metaplasia frequency of intestinal colonization of H. pylori).

If ingestion absorption begins in the small intestine (because of the pill acid enteric-shell) and is carried out quickly and completely. The absolute bioavailability – 52% (expressed as the effect of “first pass” through the liver). The food and the reception did not alter the bioavailability. Cmax achieved within 2-5 h (mean 3.5 hours) after receiving a dose of 20 mg. Observed linear dependence of Cmax and AUC of the dose in the range of 10 to 40 mg. T1 / 2 0.7-1.5 h, the total Cl – 283 ml / min. Against the background of hepatocellular failure effect “first pass” through the liver is not expressed, AUC increased 2-fold (after a single dose) and 1.5-fold (after 7 days of treatment), T1 / 2 reaches 12.3 h. It is metabolized in liver with the participation of cytochrome P450 isozymes (CYP2C19 and CYP3A) to form inactive metabolites and demetiltioefira having a weak antisecretory activity. In the case of slow biotransformation after 7 days of receiving a dose of 20 mg / d T 1 / 2 up to 1-2 hours (on average, 1.6 h), Cmax increased by 40%. Appears mainly in the urine as metabolites (mercapturic conjugates and carboxylic acids). In old age, elimination of slow, Cmax increased by 60%, AUC – 2 times. Even at the stage of terminal renal failure in patients on dialysis, the pharmacokinetic parameters vary slightly – Cmax and AUC decreased by 35%, T1 / 2 during hemodialysis is 0.95 hours, after – 3.6 hours

Application of Aciphex 20 mg

Peptic ulcer and duodenal ulcer in the acute stage, gastroesophageal reflux disease, condition, characterized by pathological hypersecretion, including Zollinger-Ellison syndrome. In combination with antibacterial agents – eradication of Helicobacter pylori in patients with gastric ulcer or chronic gastritis, treatment and prevention of recurrence of ulcers in patients with peptic ulcer disease associated with Helicobacter pylori.

Contraindications Aciphex 20 mg

Hypersensitivity, including to substituted benzimidazole, pregnancy, breast-feeding.

Restrictions apply Aciphex 20 mg

Severe hepatic failure, children’s age (not enough experience with).

Pregnancy and breastfeeding Aciphex 20 mg

Rabeprazole should not be administered to pregnant women (data on the safety of rabeprazole during pregnancy is not). In reproduction studies in rats and rabbits revealed no signs of impaired fertility or fetal development defects caused by rabeprazole, but the rats small amounts of the drug crosses the placental barrier.

Category of the fetus by FDA – B.

At the time of treatment should stop breastfeeding. It is not known whether rabeprazole released in breast milk. Relevant studies in lactating women has not been conducted. However, rabeprazole is detected in the milk of lactating rats.

Side effects Aciphex 20 mg

From the digestive tract: diarrhea, nausea, vomiting, abdominal pain, constipation, flatulence, elevated liver enzymes, dryness of the oral mucosa, rarely – loss of appetite, stomatitis.

Since the nervous system and sense organs: headache, dizziness, drowsiness, fatigue, rarely – depression, impaired vision or taste.

Cardio-vascular system and blood (blood, hemostasis): thrombocytopenia, leukopenia.

On the part of the musculoskeletal system: myalgia, leg cramps, arthralgia.

The respiratory system: pharyngitis, rhinitis, rarely – cough, sinusitis.

Allergic reactions: skin rash.

Other: back pain, flu-like symptoms, fever, rarely – weight gain, increased sweating.

Interaction Aciphex 20 mg

Rabeprazole is metabolized by microsomal liver isoenzymes of cytochrome P450. Studies in healthy volunteers have shown that rabeprazole does not enter into a clinically significant interaction with amoxicillin and other drugs that are metabolized by this enzyme system (warfarin, phenytoin, theophylline, diazepam). Due to the fact that rabeprazole causes marked and prolonged decline in the production of hydrochloric acid, there was interaction when taken with drugs whose absorption is dependent on the acidity of gastric contents. In healthy volunteers receiving rabeprazole caused a decrease in the concentration of ketoconazole in plasma by 33% and increase the minimum concentration of digoxin by 22% (while taking necessary to adjust the dose of ketoconazole or digoxin).

The concentrations of rabeprazole and clarithromycin active metabolite in plasma at the same time taking increased by 24 and 50% respectively. This increases the effectiveness of this combination in the eradication of Helicobacter pylori. The study found no interaction rabeprazole with liquid antacids. There were no clinically significant interactions of rabeprazole with food.

Studies in vitro in human liver microsomes have shown that rabeprazole is metabolized by CYP2C19 and isoenzymes of CYP3A. Found that at concentrations expected in plasma rabeprazole does not have any stimulatory or inhibitory effect on CYP3A4. These studies also give reason to believe that rabeprazole does not affect the metabolism of cyclosporine.

Overdose Aciphex 20 mg

The symptoms were not reported.

Treatment: If overdose is suspected, recommended maintenance and symptomatic therapy. Specific antidote is known. Dialysis is ineffective (rabeprazole well bound to plasma proteins).

Dosage and administration Aciphex 20 mg

Inside, in the morning, before eating, not chewing or crushing of 20 mg 1 time a day for stomach ulcers and duodenal ulcers in the acute stage – for 4-6 weeks, if necessary – up to 12 weeks, with reflux esophagitis – 4-8 weeks, further possible maintenance therapy: 10-20 mg 1 time per day, with Zollinger-Ellison syndrome the dose selected individually. Infection H. pylori eradication therapy in the use of appropriate combinations of antibiotics for 7 days.

Precautions Aciphex 20 mg

Before treatment is necessary to exclude gastric malignancy (symptomatic improvement during treatment with rabeprazole may hamper timely diagnosis.) We recommend caution in the first appointment of rabeprazole in patients with severely impaired liver function. In the case of sleepiness should give up driving and other activities requiring your full attention. Patients receiving rabeprazole simultaneously with ketoconazole or digoxin, need further follow-up (may require dose adjustment of these drugs).