Geerdine

Geerdin is a proton pump inhibitor drug.

Indications Geerdine

Rabeprazole in the form of a lyophilisate for injection solutions is used when it is impossible to use this substance in oral form:

• an aggravated ulcer in the duodenum or stomach, accompanied by severe erosions and bleeding;
• short-term therapy for GERD with ulcers and erosions;
• to prevent aspiration of acidic gastric juice;
• with gastrinoma.

Release form

Released in the form of a lyophilisate for injection solutions, in a 10 ml vial (with 20 mg of rabeprazole inside). A separate pack contains 1 vial.

Pharmacodynamics

A drug that inhibits the H ⁺ -K ⁺ -ATPase element. Inhibition of this enzyme's activity inside the parietal cells of the stomach helps block the final stage of hydrochloric acid formation. This effect depends on the dosage and can cause suppression of stimulated and basal secretion of hydrochloric acid (the type of irritant is not important).

Rabeprazole is synthesized by covalent binding to the proton pump of parietal cells. This process results in an irreversible decrease in the amount of secreted acid. Its secretion can only be carried out with the participation of the newly formed proton pump. This allows us to conclude that the plasma pharmacokinetics of the substance rabeprazole does not have a decisive effect on the antisecretory effect. The time of bioactivity of the active component significantly exceeds its half-life. The half-life of the proton pump (20-24 hours) is considered more important than the half-life of rabeprazole.

The peak rate of secretion reduction can develop when rabeprazole reaches the parietal cell precisely at the moment when it is activated. This effect can be achieved by intravenous infusion of the drug. As a result, the proton pump activated under the influence of circadian rhythms (the substance acetylcholine) or after eating (the substance gastrin with histamine) is immediately synthesized with the molecule of the active component of the drug, thereby stopping the production of hydrochloric acid.

The active component of the drug quickly accumulates inside the acidic environment of the gastric parietal cells, transforming there into an active form - by attaching to it a category of sulfamides. It interacts with the cysteine of the proton pump.

The use of the drug in a daily dosage of 20 mg for a period of 2 weeks does not affect the functioning of the thyroid gland, carbohydrate metabolism, and in addition, the blood levels of such substances as cortisol, parathyroid hormone, LH and FSH, testosterone with estrogens, as well as cholecystokinin, prolactin, renin with glucagon and STH with aldosterone and secretin.

Pharmacokinetics

The drug begins to act 1 hour after injection, reaching its maximum after 2-4 hours. The average clearance rate after an intravenous injection of 20 ml is 283+/-98 ml/minute. The half-life of this dosage is approximately 1.02+/-0.63 hours. The excretory activity of the stomach is restored after 2-3 days after the drug is discontinued.

The absolute bioavailability index after intravenous injection of 20 mg is approximately 100% (all molecules of the substance enter the parietal cells). This index does not change after repeated administration. Synthesis with plasma protein is 97%. With repeated administration of the drug, the pharmacokinetic characteristics remain linear (the level of distribution volume, clearance and half-life do not depend on the dose).

It undergoes hepatic metabolism, which results in the formation of the main breakdown products, carbonic acid with thioether. Other breakdown products, such as dimethylthioether with sulfone and mercapturic acid conjugate, have a low concentration.

The serum half-life is approximately 1 hour. About 90% of the dose is excreted in the urine, mainly as 2 breakdown products: a carboxylic acid with a mercaptopuric acid conjugate. A small portion of the breakdown products is excreted in the faeces.

Dosing and administration

Geerdin injections by the intravenous method should be performed only in situations where it is impossible to take the drug orally. If it becomes possible to take the drug orally, its intravenous administration must be immediately discontinued.

The recommended daily dose is a single use of 20 mg. The solution is administered exclusively by intravenous method.

Before injection, it is necessary to dissolve the lyophilisate in a special solvent (5 ml). For this, you can use injection water or sodium chloride solution (0.9%). The injection procedure is performed slowly - about 5-15 minutes.

When using the drug in the form of an infusion, the lyophilisate is also dissolved - first in injection water (5 ml), and then the resulting solution is transferred to a container with sodium chloride (0.9% solution; 100 ml) or glucose solution (5%; 100 ml). Before starting the infusion, a visual assessment of the dissolution of the powder is required to exclude the presence of sediment and a change in the color of the liquid, as well as its transparency. The drug (in the amount of 100 ml) is administered over a period of 15-30 minutes and used for 4 hours.

It is prohibited to save the prepared solution that is not used during the procedure.

Use Geerdine during pregnancy

There have been no studies conducted on the safety of Geerdin in pregnant women, therefore its use is prohibited during this period.

There is no information on the penetration of the active component into breast milk. The corresponding tests have not been conducted either, so the drug is not prescribed during lactation either.

Contraindications

Among the contraindications:

• intolerance to rabeprazole, as well as substituted benzimidazoles or other components of the drug;
• Do not combine with atazanavir;
• Since there is insufficient experience with the use of drugs in children, use in this age category is contraindicated.

Side effects Geerdine

The drug often causes moderate to mild side effects that disappear fairly quickly:

• invasive and infectious diseases: the occurrence of infectious processes or the development of interstitial pneumonia;
• reactions of the lymph and systemic blood flow: development of neutro-, pancyto-, thrombocyto-, leukopenia, lymphopenia and erythrocytopenia, as well as leukocytosis, anemia (this includes the hemolytic form) and agranulocytosis;
• immune disorders: dry mouth mucous membranes, rashes, hypersensitivity reactions (including shock), anaphylactoid symptoms, facial swelling, urticaria, shortness of breath and decreased blood pressure. General manifestations of acute allergies are also noted, which usually disappear after discontinuation of the drug;
• metabolic disorders: development of hyponatremia or hypomagnesemia, as well as anorexia;
• mental reactions: a feeling of excitement, drowsiness, confusion and nervousness, as well as insomnia, delirium, depression and coma;
• manifestations from the nervous system: dizziness, asthenia, feeling of disorientation, headaches, feeling of weakness in the limbs and numbness, as well as hypoesthesia, speech disorder and weakening of the grip strength;
• disorders of the visual organs: problems with vision and increased intraocular pressure;
• vascular dysfunction: increased pressure, appearance of peripheral edema and palpitations;
• reactions of the respiratory system: bronchitis and pharyngitis with glossitis and sinusitis, as well as a runny nose with a cough, bronchial spasms and Quincke's edema;
• gastrointestinal disorders: nausea, constipation, abdominal pain, bloating, vomiting, diarrhea, belching and dyspeptic symptoms. In addition, dry mouth mucous membranes and rash in the mouth, stomatitis, candidiasis, gastritis, esophagitis with enteritis, heartburn and cheilosis develop. There is a feeling of heaviness and fullness in the stomach, taste bud disorders and hemorrhoids;
• problems with the liver, as well as the biliary system: development of hepatitis (also its fulminant form), jaundice and hepatic encephalopathy (rarely it occurs in people with liver cirrhosis), in addition, functional liver disorder;
• manifestations from the subcutaneous layer and skin: the appearance of erythema (also polyform type), rashes, itching, TEN and Stevens-Johnson syndrome, as well as hyperhidrosis, acute general manifestations of allergy and bullous reactions;
• reactions of the muscles and bone structure: development of rhabdomyolysis, arthralgia or myalgia, as well as cramps in the legs, pain in the back or non-specific pain;
• disorders of the urinary and renal organs: tubulointerstitial nephritis, infectious diseases of the urinary tract and acute renal failure;
• disorders in the functioning of the reproductive organs: increased erection and gynecomastia are observed;
• local manifestations and systemic disorders: the appearance of pain in the sternum and back, a feeling of weakness, malaise, fever, thirst and heat, as well as asthenia, hyperhidrosis, chills, alopecia and flu-like syndrome, as well as reactions at the injection site;
• laboratory test data: increased AST and ALT (liver enzymes), GGT, total cholesterol and bilirubin, as well as alkaline phosphatase, triglycerides, CPK, TSH and urea nitrogen with uric acid. In addition, hyperammonemia, proteinuria, and along with this, an increase in weight and glucose levels in the urine are observed.

Interactions with other drugs

Rabeprazole is metabolized by the CYP-450 liver enzyme system, including CYP2C19 and CYP3A4. The substance does not have significant drug or pharmacokinetic interactions with phenytoin, diazepam, warfarin, or theophylline (all of which are metabolized by the CYP-450 system).

Interactions caused by inhibition of gastric acid secretion processes.

Sodium rabeprazole promotes a long-term and powerful reduction in the production of hydrochloric acid. As a result, the substance may interact with drugs whose absorption depends on the level of gastric pH. When combining Geerdin with itraconazole or ketoconazole, a decrease in the plasma values of the latter is possible, and when combined with digoxin, on the contrary, an increase in the latter is observed. Therefore, those individuals who combine the above drugs with rabeprazole require constant monitoring during treatment - in order to adjust the dosage sizes in time.

The combination of atazanavir (300 mg)/ritonavir (100 mg) with omeprazole (40 mg once daily) or atazanavir (400 mg) with lansoprazole (60 mg once daily) significantly reduces the AUC of atazanavir. The absorption of this component is pH dependent. Similar results can be expected with other proton pump inhibitors. Therefore, they (including rabeprazole) should not be used together with atazanavir.

When combined with food containing a small amount of fat, the absorption of rabeprazole does not change. When used together with fatty dishes, absorption may slow down by 4+ hours, but its degree, as well as the peak concentration of the substance, do not change.

In vitro studies have shown that rabeprazole slows down the metabolism of cyclosporine. The inhibition rate in this case is similar to the level of inhibition by omeprazole.

Medicines that are prohibited to combine with the component rabeprazole: atazanavir sulfate - as its medicinal effect may be weakened. The antisecretory properties of rabeprazole increase the gastric acidity index and reduce the solubility of atazanavir sulfate, as a result of which its plasma level also decreases.

Medicines to be used with caution:

• digoxin and methyldigoxin - their levels in the blood may increase. The antisecretory effect of Geerdin contributes to an increase in the gastric pH, which accelerates the absorption of the above substances;
• gefitinib and itraconazole - a decrease in the levels of these components in the blood is possible. The increased pH level in the stomach leads to the fact that the absorption of these elements is slowed down;
• aluminum- and magnesium-containing antacid drugs - when rabeprazole is combined with antacid drugs, a decrease in the levels of this substance is observed.

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Storage conditions

Geerdin should be stored out of the reach of small children. Temperature level – maximum 25°C.

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Shelf life

Geerdin can be used for a period of 2 years from the date of release of the drug.