Use of the drug "Pepsan-R" in the treatment of gastroesophageal reflux disease

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Dimethicone – has the property of reducing gas and foaming in the intestines. Thus, gas formation in the intestines is reduced and bloating is eliminated, as well as pain caused by stretching of the intestinal walls. The drug has an enveloping and absorbent effect, protecting the gastric mucosa. At the same time, complaints about discomfort caused by increased production of hydrochloric acid decrease.

Guiazulene – has pronounced antioxidant, regenerating anti-inflammatory effects.

Pepsan-R reduces the secretory activity of the gastrointestinal tract by suppressing the process of histamine release from mucosal cells.

Pharmacokinetics

No data.

Pepsan-R and its action

The drug Pepsan-R belongs to the group of antacids that reduce flatulence and have an anti-inflammatory effect. Thanks to its complex composition, it gives a combined effect. Do not confuse the drug with Pepsin tablets - this is a completely different drug. Pepsan-R is available in two forms:

• gel for internal use 10 g;
• capsules.

The gel is packaged in single dose sachets, it is bluish in color and has a pleasant mint aroma. The main active ingredients are dimethicone and guaiazulene. Excipients in the gel are sodium cyclamate, sorbitol, carrageenan, water, mint oil, preservative.

Capsules include the same active ingredients, as well as gelatin, glycerol, titanium dioxide, and sorbitol.

Both forms contain 3 g of dimethicone, 4 g of guaiazulene (a derivative of chamomile extract). Due to the presence of the first substance, the drug is classified as a carminative. It is indicated in therapy and for symptomatic use for various gastrointestinal diseases. Pepsan-R has the following effects:

• decrease in the secretion of hydrochloric acid in the upper gastrointestinal tract (up to 3-4 pH);

• enveloping the mucous membrane, creating a reliable protective layer in the stomach;
• preventing the appearance of erosions, microcracks, ulcers, areas of inflammation;
• removal of an existing inflammatory process;
• cessation of pain;
• reducing the intensity of allergic reactions from the gastrointestinal tract;
• antioxidant effect;

• enhancing the regeneration of damaged tissues.

Dimethicone eliminates increased gas formation, which appears as a result of diseases of the digestive system or against the background of eating disorders. This is achieved by enveloping and removing gas bubbles from the intestines.

Indications for use

In the symptomatic treatment of patients with complaints of pain in the stomach and esophagus caused by increased production of hydrochloric acid : pain in the stomach; disorders of the gastrointestinal tract with complaints of belching , heartburn , flatulence , nausea, stool disorders ( diarrhea / constipation ); preparing the patient for examination of the gastrointestinal tract.

Prohibitions on use and negative effects on the body

There are few contraindications to treatment with this drug. The gel is intended only for the treatment of adults; children under 18 years of age are not allowed to take it. Capsules can be taken by adolescents from 14 years of age; treatment is not prohibited. Also, a ban on therapy will be intolerance to the main or auxiliary components, which is rare. Side effects in rare cases include the following:

• abdominal pain
  , increased symptoms of dyspepsia (occurs as a reaction to intolerance to the components);
• bloating
  (occurs very rarely, mainly when the course of therapy is too long and the indicated dosage is exceeded);

• skin rash
  , redness, spots (allergic reaction to the components of the product).

Due to the presence of sorbitol in both dosage forms, the drug should be taken with great caution by people with certain hereditary diseases. These include deficiency of sucrase (an enzyme that breaks down sucrose), isomaltase, fructose intolerance, and glucose-galactose malabsorption syndrome.

Instructions for use Pepsan-R

One sachet/capsule orally three times a day, without chewing, before meals, with 0.5 glasses of drinking water or when pain occurs. The duration of taking the drug is determined by a specialist.

When preparing a patient for gastrointestinal examinations, take Pepsan on the eve of the examination, one capsule/sachet three times a day and one capsule/sachet in the morning on the day of the hardware examination.

Instructions for use of Pepsan-R indicate the possibility of prescribing the drug during lactation and pregnancy.

Analogues and important data

Among the analogues we can name a number of drugs with the same effect, which are widely used in gastroenterology:

Do not take the drug simultaneously with other antacids - they reduce the effectiveness of treatment. The effect of dimethicone is enhanced by simultaneous intake of digestive enzymes. No interactions with other drugs have been established. Pepsan-R does not affect the ability to drive vehicles or operate machinery.

Analogs

Level 4 ATC code matches: Disflatil
Mint tablets

Kuplaton

Espumisan

Espumisan Baby

Espumisan L

Espumisan 40

Bobotik

Dill water

Sub Simplex

Infacol

Plantex

Bebinos

Dicetel

Meteospasmil

Romazulan

Espumisan , Meteospazmil , Simikol , Gascon , Drop , Unienzim with MPS, Pepfiz , Relzer , Softovak and others.

Pepsan-R price, where to buy

The price of Pepsan-R in capsules No. 30 ranges from 279 to 316 rubles; gel - No. 30 sachets from 343 to 395 rubles. You can purchase Pepsan-R in most pharmacies in Moscow.

• Online pharmacies in RussiaRussia

ZdravCity

• Pepsan-R gel for oral administration sachet 10g 14 pcs.Rosa-Phytopharm
  RUB 387.order

Use of the drug "Pepsan-R" in the treatment of gastroesophageal reflux disease

O. Minushkin, Doctor of Medical Sciences, Professor, I. Loranskaya, Doctor of Medical Sciences, Professor, I. Zverkov, Doctor of Medical Sciences, Professor, L. Rakitskaya, Candidate of Medical Sciences, L. Mamedova, Candidate of Medical Sciences, V. Vishnevskaya, Candidate of Medical Sciences, L. Maslovsky, Doctor of Medical Sciences,

Department of Gastroenterology, MC UD of the President of the Russian Federation,

The anti-inflammatory effect of the drug “Pepsan-R”, new to the Russian Federation, was assessed, treatment of which was received by 50 patients with gastroesophageal reflux disease (GERD) grades 0–1. Treatment was carried out in monotherapy mode. The drug contains 2 active ingredients: guaiazulene and dimethicone. Its mechanism of action is to suppress the degranulation of mast cells and create a protective layer on the mucous membrane of the esophagus and stomach. The effectiveness of the drug has been clinically demonstrated in 100% of patients (10% of them required an increase in the dose of the drug). Morphoendoscopically positive dynamics over 4 weeks were noted in 50% of patients. No side effects have been reported. Key words : gastroesophageal reflux disease, treatment, Pepsan-R.

* The drug underwent pre-registration studies at 2 centers: the Department of Gastroenterology of the MC UD of the President of the Russian Federation and the Department of Gastroenterology of the Russian Medical Academy of Postgraduate Education.

Reflux is the reflux of contents from the underlying sections of the gastrointestinal tract to the overlying ones in places of physiological narrowings (sphincters) separating physiologically and anatomically different sections of the digestive tract; reflux leads to irritation, inflammation and structural changes in the areas of reflux with the formation of certain clinical manifestations (our definition, 1986).

In clinical practice, they distinguish: gastroesophageal, duodenal-gastric reflux and reflux from the large intestine to the small intestine through the ileocecal valve.

The true incidence of reflux and its clinical significance are unknown. Maximum importance is attached to gastroesophageal reflux, which is most likely due to the most studied clinical manifestations and diagnostic approaches.

The Genval Conference (1999) stated: “The term “gastroesophageal reflux disease” can be used to encompass all individuals who are at risk of physical complications from gastroesophageal reflux or who experience clinically significant impairment of well-being (quality of life) due to reflux-related symptoms after adequate confirmation of the benign nature of these symptoms." Finally, the Montreal Congress of Gastroenterology (2006) defines gastroesophageal reflux disease (GERD) “as a condition that occurs when reflux of stomach contents causes distressing symptoms and/or complications.”

From the definitions it is clear that ideas about GERD are dynamic. This dynamism continues to this day, which is determined by unsatisfactory treatment results.

Thus, until 1995, GERD was associated with erosive reflux esophagitis, the treatment of which was a course of treatment. In 1995, it became clear that the effect of treatment was temporary, and the question arose about prolonged treatment, albeit for certain groups of patients. By 1999, the final point of view had emerged: treatment should be permanent or should begin in the early period of the disease. At the same time, the early stage of GERD was identified - non-erosive reflux disease. Did this solve all the problems? No! But new ones have been born, the solution of which is being addressed by modern gastroenterology.

It has been established that the main mechanism for the development of GERD is a dysfunction of the antireflux barrier, in which the leading role belongs to a decrease in the tone of the lower esophageal sphincter, insufficiency of the obturator mechanism of the cardia, a decrease in esophageal clearance (chemical and peristaltic) and a decrease in the resistance of the esophageal mucosa.

Increased intragastric and intra-abdominal pressure and destruction of the lower esophageal sphincter are considered factors contributing to the development of GERD; consumption of certain foods (coffee, chocolate, citrus fruits, fats) and taking medications (nitrates, antispasmodics, β-blockers, etc.). Under these conditions, reflux of gastric or duodenal contents with damaging agents takes on a decisive role. Gastric juice contains hydrochloric acid and pepsin, which, when they enter the esophageal mucosa, weaken intercellular contacts, widen intercellular spaces, disrupt intercellular interaction, which leads to damage to the esophagus. A protective reaction is the arrival of polymorphonuclear leukocytes to the site of damage, which cannot cope with the protective function, since the aggression factor is not eliminated, lipid peroxidation (LPO) products and free radicals appear, which contribute to aggression [4]. Acid aggression in the esophagus promotes the activation of fat cells, then an increase in their number and degranulation with the release of inflammatory mediators, primarily histamine [2], and, finally, a decrease in the pH of the environment triggers the mechanism of reverse diffusion of hydrogen ions. The consequence of the triggering of the damage mechanism is necrosis of the esophagus with the formation of erosions, and subsequently ulcers of the esophageal mucosa.

In some patients with GERD, it is not the acid that is released, but the alkaline content. In this case, the damaging agents are bile acids and pancreatic enzymes, which are activated in an alkaline environment, and with prolonged exposure lead to the destruction of protective mucus, damage to the epithelium, activation of inflammation, cell damage, the formation of erosive and ulcerative changes, and at later stages - to intestinal metaplasia, dysplasia, neoplasia.

Treatment of GERD primarily involves: avoiding foods that reduce the tone of the lower esophageal sphincter or have an irritating effect (fats, chocolate, mint, spices, onions, coffee, alcohol, orange and tomato juices); a recommendation to avoid a horizontal body position for 3–4 hours after eating; raising the head end of the bed; smoking cessation; loss of body weight if it is excess; refusal to wear tight clothing; if possible, stop taking medications that reduce the tone of the lower esophageal sphincter (antispasmodics, β-blockers, nitrates, anticholinergic drugs, calcium antagonists, theophylline, etc.).

Drug therapy is prescribed in case of ineffectiveness of lifestyle modification measures in the negative form of GERD and immediately in the erosive form of GERD and Barrett's esophagus. Antisecretory drugs are used as basic therapy: H2 receptor blockers or proton pump inhibitors; prokinetics are of auxiliary value. Having achieved a clinical or clinical-endoscopic effect, the patient is transferred to long-term maintenance treatment (minimum effective doses). At the same time, according to the Maastricht III recommendations, in the presence of persistent Helicobacter pylori (Hp) infection, it is necessary to carry out eradication therapy to prevent the migration of Hp, the development of infectious gastritis of the gastric body and the acceleration of mucosal atrophy.

We studied the clinical effectiveness of the drug "Pepsan-R" in the uncomplicated form of GERD (grades 0–1).

The objectives of the study included assessment of clinical and economic indicators during treatment with the drug, drug safety, and development of effective treatment regimens.

The drug "Pepsan-R" contains 2 active ingredients: guaiazulene (an azulene derivative) and dimethicone. Available in gel form or capsules for oral administration. Guiazulen is a chamomile extract. Currently, it is obtained by clinical synthesis. The mechanism of its action is represented by the suppression of degranulation of fat cells, a decrease in the level of histaminase and histamine at the tissue level, which is manifested by its anti-inflammatory effect, and at the level of smooth muscle fibers - by their relaxation. These effects are shown in the works of M. Akagi [1]. According to studies by A. Kouzounakis [3], in vitro, guaiazulene has an antioxidant effect on the membranes of liver microsomes, suppressing lipid peroxidation, which also contributes to the development of inflammation.

The second component of the drug is dimethicone, which is a hydrophobic polymer substance with low surface tension, which reduces gas formation (destroys the shell of gas bubbles and enhances gas removal), i.e. influences bloating and associated clinical manifestations.

All effects of Pepsan-R can be summarized as follows:

• reduces the level of histaminase and histamine;
• suppresses mast cell degranulation;
• has anti-inflammatory and anti-edema effects;
• reduces the aggressive properties of refluxate (reducing the acid-producing function of the stomach);
• shortens the exposure time of refluxate in the esophagus;
• reduces irritation and inflammation of the esophageal mucosa by binding free radicals;
• forms a protective layer on the mucous membrane of the esophagus and stomach;
• eliminates flatulence and reduces the number of gastroesophageal refluxes;
• acts throughout the entire “intestinal tube”.

The study included 50 patients, divided into 2 groups of 25 patients each, with an average age of 46.1±5.2 years.

Concomitant diseases were in remission, without signs of decompensation, and no additional prescriptions were required. Patients of group 1 received the drug in the form of a gel, 1 sachet after each meal; if necessary, they could take an additional sachet if the heartburn did not stop, but not earlier than 15 minutes after the 1st dose.

Patients of the 2nd group received capsules (1 after each meal; they could take an additional capsule if the effect did not occur). In 1 day, no more than 6 capsules or gel packets were allowed. The treatment lasted 28 days.

Endoscopic monitoring was carried out initially, on the 14th and 28th days of treatment. Clinical symptoms were assessed initially and over time using a 5-point Likert scale with calculation of average scores (on days 1, 14, 28 of the study):

• 1 point – no symptoms;
• 2 points – low intensity (you can’t notice it if you don’t think about it);
• 3 points – moderate severity of symptoms (cannot be ignored, but do not interfere with daytime activity or sleep);
• 4 points – severe intensity (symptoms interfere with daytime activity or sleep);
• 5 points – very strong intensity (daytime activity or sleep is impossible).

Endoscopic pH-metry was performed initially.

Statistical processing of the results included calculating the arithmetic mean and standard deviation, applying the Student's test, and determining the significance of differences between groups.

Patients kept daily diaries with an assessment of the main symptoms: heartburn, burning sensation in the chest, belching.

In the 1st group of patients who took Pepsan-R in the form of a gel, GERD was manifested by heartburn (3.5±0.17 points), belching (2.9±0.18 points), burning sensation in the sternum (2.2± 0.2 points). In group 2 (taking Pepsan-R capsules), the average Likert scale score before treatment was: for heartburn - 3.2±0.21, for belching - 2.4±0.34, for burning sensation in the chest - 1 .7±0.26. There were no significant differences between the groups in these indicators; The pH in the lower third of the esophagus in both groups was >5.

According to endoscopy, the patients were divided approximately equally (negative forms, catarrhal esophagitis; erosive esophagitis was recorded in 6 patients - single erosions).

The average dose of the drug was 3.6 capsules and 3.7 sachets per day; 6 patients received 6 sachets or 6 capsules per day (about 10% of patients).

The dynamics of clinical symptoms during treatment with Pepsan-R are presented in the table.

Assessment of clinical symptoms during treatment with Pepsan-R (M±m)

As can be seen from the table, on the 14th day of treatment in the 1st group of patients receiving the gel, heartburn was assessed at 3.0±0.21 points, belching – at 2.5±0.22 points, burning sensation in the sternum – at 2.0±0.37 points (differences with indicators before treatment are significant only for heartburn; p=0.0149).

In group 2 (Pepsan-R capsules), heartburn was rated at 2.5±0.25 points, belching – at 2.1±0.28 points, burning sensation behind the sternum – at 1.4±0.22 points ( the differences are significant only for heartburn before treatment and on the 14th day of treatment; p = 0.0031).

On the 28th day of treatment in group 1, the average score for heartburn was 2.4±0.22, for belching - 2.1±0.28, for burning sensation in the chest - 1.7±0.30. Only the heartburn indicator was significantly different from that on the 1st day (before treatment) and on the 14th day of treatment (p = 0.0051). For belching, a significant difference was observed only between the 1st and 28th days of treatment (p = 0.02236) and the same for burning behind the sternum (p = 0.0149).

In group 2 (capsules), after completion of treatment, the average score for heartburn was 1.6±0.27, for belching - 1.7±0.21, for burning sensation in the chest - 1.1±0.10. For heartburn, this indicator was significantly different from that on day 1 (p = 0.00075). For belching, there was a significant difference between the initial position and the 14th day of treatment (p = 0.0367), for a burning sensation in the chest - between the initial position and the 28th day of treatment (p = 0.0239).

The assessment of the therapeutic effectiveness of Pepsan-R on a Likert scale is presented in Fig. 1 and 2. The figures show that a significant decrease in the intensity of all clinical symptoms was recorded during treatment with Pepsan-R (gel, capsules).

Rice. 1. Assessment of therapeutic effectiveness on the Likert scale of the drug “Pepsan-R” (gel)

Rice. 2. Assessment of therapeutic effectiveness on the Likert scale of the drug “Pepsan-R” (capsules)

When comparing the effectiveness of treatment in groups 1 and 2 on the 28th day of treatment, a significant difference was found only for heartburn. For other indicators, no significant difference was obtained (p=0.276 and p=0.0738).

Lack of clinical effect was noted in 2 patients; In 1 patient, treatment could not be completed due to the development of urticaria (on the 25th day of treatment).

A control endoscopic study recorded positive dynamics (endoscopic signs of catarrhal esophagitis disappeared in half of the patients).

GERD today is not only the most common gastroenterological pathology, but also the most difficult in therapeutic terms. Due to the instability of the effect of a course of treatment, a permanent treatment option has been adopted as the main one, which is typical for diseases whose nature is not completely clear.

For GERD, secretion blockers are used, which reduce the aggressiveness of reflux, and agents that regulate the tone and motility of the esophagus and sphincters, reducing reflux into the esophagus. These two links are very important for the initiation and formation of the disease, but its inflammatory morphological substrate remains without direct influence.

Clinical and morpho-endoscopic data from the study allow us to hope that the drug "Pepsan-R" can take its rightful place in the complex therapy of GERD, since, thanks to its mechanism of action, it reduces the content of the inflammatory mediator - histamine, blocking the degranulation of mast cells.

The results of the study allow us to draw the following conclusions:

1. Pepsan-R reduces and relieves symptoms in the vast majority of patients with GERD stage 0–I. 10% of patients need to increase the standard dose: 3 capsules (sachets) per day to 6 capsules (sachets).
2. Positive endoscopic dynamics over 28 days of treatment were observed in 50% of patients.
3. The drug was well tolerated; adverse reactions (urticaria) were noted in 1 (2%) patient.
4. The drug can and should be used in complex therapy of GERD and in maintenance treatment.

Literature

1. Akagi M., Matsui N., Mochizuki S. et al. Inhibitory 1. effect of egualen sodium: a new stable derivative of azulen on histamine release from mast cell – like cells in the stomach // Pharmacology. – 2001; 63(4):203–209.
2. Barclay RL, Dinda PK, Morris GP et al. Morphological evidence of mast cell degranulation in an animal model of acid-induced esophageal mucosal injuri // Dig Dis Sci. – 1995; 40(8):1651–1658.
3. Kourounakis AP, Rekka EA, Kourounakis PN Antioxidant activity of guaiazulene and protection against paracetamol hepatoxicity in rats // J. Pharm. Pharmacol. – 1997; 49(9):938–942.
4. Oh TY, Lee JS, Ahn BO et al. Oxidative damages are critical in the pathogenesis of reflux esophagitis: implication of antioxodants in its treatment // Free Radic Biol Med. – 2001; 30(8):905–915.