Dexilant, 60 mg 28 pcs.

Pharmacotherapeutic group:Gastric gland secretion reducing agent – proton pump inhibitor

ATX code: A02BC06

Pharmacological properties

Pharmacodynamics

Dexlansoprazole is a proton pump inhibitor, inhibiting gastric juice secretion by inhibiting H⁺/K⁺-ATPase in gastric parietal cells. It blocks the final stage of hydrochloric acid secretion.

The use of antisecretory drugs increases serum gastrin levels in response to decreased gastric juice secretion. There is also an increase in chromogranin A (CgA) levels as a result of decreased gastric acidity. Elevated CgA levels may interfere with the diagnosis of neuroendocrine tumors.

Published data suggest that proton pump inhibitors (PPIs) should be stopped 5-14 days before determining CgA levels, allowing false elevated CgA concentrations that occur after proton pump inhibitor administration to return to normal.

The Dexylant^® capsule disintegrates in the stomach and contains two types of enteric-coated pellets that release the active ingredient depending on pH in different areas of the small intestine. This combination helps to prolong the action of dexlansoprazole and helps to reduce gastric juice secretion over a long period of time.

Pharmacokinetics

absorption

Dexlansoprazole is well absorbed when taken orally. Its bioavailability is 76% or more.

The two-component composition of Dexilant® causes absorption in two pH-dependent phases. The first peak of active substance concentration occurs 1 to 2 hours after oral intake (1st phase of active substance release) and 4 to 5 hours (2nd phase of active substance release), respectively. After 5 days of administration of dexlansoprazole in doses of 30 mg and 60 mg, the maximum plasma concentration (C_max) is 658 ng/mL and 1397 ng/mL, respectively.

The area under the concentration-time curve (AUC) is 3275 ng h/mL and 6529 ng h/mL after 5 days of dexlansoprazole doses of 30 mg and 60 mg, respectively. Distribution

The binding of dexlansoprazole to plasma proteins is 96.1 – 98.8%.

Metabolism

Dexlansoprazole is extensively metabolized in the liver to inactive metabolites by the processes of oxidation, reduction and subsequent formation of sulfate, glucoronide and glutathione compounds. Oxidation is carried out by the cytochrome P450 enzyme system, which is involved in both the hydroxylation process (primarily CYP2C19 isoenzyme) and the oxidation process (CYP3A4 isoenzyme) . The CYP2C19 isoenzyme is a polymorphic hepatic isoenzyme that exists in 3 fractions that exhibit different properties in substrate metabolism: fast, moderate, and slow metabolizers. Dexlansoprazole is a major constituent in plasma regardless of the type of metabolizer by CYP2C19 isoenzyme. In case of medium and strong metabolizers by CYP2C19 isoenzyme, 5-hydroxydexlansoprazole and its glucuronic compound are the main metabolites in blood plasma. With weak metabolites by CYP2C19 isoenzyme – dexlansoprazole sulfone.

Elimation

The half-life of the drug is 1-2 h.

The clearance after 5 days of dexlansoprazole is 11.4 and 11.6 L/h for 30 mg and 60 mg doses, respectively.

The drug is excreted through the kidneys (about 51%) and 48% is excreted through the intestine.

Since the drug is extensively metabolized in the liver, no dose reduction is required when using dexlansoprazole in patients with impaired renal function. As in patients with normal renal function, no change in pharmacokinetics is expected.

Indications

Gastritis, Heartburn, Nausea, Sour belching, Subscapular pain, Reflux esophagitis

Dexilant® is indicated for use in adults and adolescents aged 12 years and older for the following indications:

– treatment of erosive esophagitis of any severity;

– maintenance therapy after treatment of erosive esophagitis and relief of heartburn;

-symptomatic treatment of gastroesophageal reflux disease GERD (i.e.NERD – non-erosive reflux disease);

Active ingredient

Dexlansoprazole

Composition

Composition per 1 capsule 60 mg

Active ingredient: dexalansoprazole 60 mg

Associates: sugar grits¹ (500 µm to 710 µm) 40.0 mg, magnesium carbonate 16.0 mg, sucrose 39.52 mg, low-substituted hyprolose 12.0 mg, hyprolose 0.48 mg, hypromellose 2910 10.5067 mg, talc 29.68 mg, titanium dioxide 6.9933 mg, copolymer methacrylic acid dispersion² 7.02 mg, macrogol-8000 0.7 mg, polysorbate-80 0.32 mg, colloidal silica 0.13 mg, methacrylic acid and methyl methacrylate copolymer [1:2] 35.09 mg, methacrylic acid and methyl methacrylate copolymer [1:1] 11.70 mg, triethyl citrate 4.664 mg.

Capsule shell

Cap:carrageenan, potassium chloride, titanium dioxide, dye FD &C blue #2 aluminum varnish, purified water, hypromellose, purified gray ink for labeling³.

Corpus:carrageenan, potassium chloride, titanium dioxide, dye FD&C blue #2 aluminum varnish, purified water, hypromellose, gray purified ink for labeling³.

¹Composition of the sugar cube: sucrose, corn starch.

²Composition of methacrylic acid copolymer dispersion: methacrylic acid, ethyl acrylate, sodium lauryl sulfate, polysorbate-80.

³The purified gray ink for marking consists of iron oxide red dye, iron oxide yellow dye, dye FD & C blue #2 aluminum varnish, carnauba wax, shellac, glyceryl monooleate.

How to take, the dosage

Over the mouth: The capsule is taken whole regardless of meals. It is also possible to open the capsule, pour the granules from it into a tablespoon and mix them with apple puree; then immediately, without chewing, swallow.

Treatment of erosive esophagitis of any severity.

For use in adults and adolescents 12 years and older:

The recommended dose is 60 mg once daily. The course of treatment is 8 weeks.

Supportive therapy after treatment of erosive esophagitis and relief of heartburn.

Adults

The recommended dose is 30 mg once daily. In the conducted studies, the course of treatment was up to 6 months.

Patients with moderate to severe erosive esophagitis have a recommended dose of 60 mg once daily. In the studies conducted, the course of treatment was up to 6 months.

Adolescents from 12 years of age:

The recommended dose is 30 mg once daily. The duration of treatment is determined by the physician.

Symptomatic treatment of gastroesophageal reflux disease GERD (i.e. NERD – non-erosive reflux disease).

For use in adults and adolescents aged 12 years and older:

The recommended dose is 30 mg once daily. The course of treatment is 4 weeks.

In patients with moderate hepatic impairment (Child-Pugh class B), the daily dose should not exceed 30 mg of dexlansoprazole.

There are no clinical data on the use of the drug in patients with severe impairment (Child-Pugh class C).

Dose adjustment in elderly patients, patients with impaired renal function and patients with mild hepatic impairment (Child-Pugh class A) is not required.

Interaction

Dexlansoprazole can be administered without the risk of drug interaction in patients taking clopidogrel. In case of coadministration, no dose adjustment of clopidogrel is required. There is also no clinically significant drug interaction with phenytoin, theophylline and diazepam. Concomitant use of dexlansoprazole may affect the absorption of drugs whose bioavailability depends on the pH of the stomach (e.g., ampicillin esters, digoxin, iron salts, ketoconazole, erlotinib). Concomitant administration with tacrolimus may lead to increased plasma concentrations of tacrolimus, especially in post-transplant patients who are moderate or slow metabolizers by CYP2C19 isoenzyme. When concomitantly administered with fluvoxamine, there is a possibility of increasing the systemic effects of dexlansoprazole. Concomitant administration of dexlansoprazole and methotrexate may increase and maintain high concentrations of methotrexate and/or its metabolite in blood serum, which, accordingly, may lead to methotrexate toxicity. If high doses of methotrexate are required, temporary withdrawal of dexlansoprazole is recommended.

Special Instructions

Pre-treatment with dexlansoprazole should exclude the possibility of malignancy, as the drug may mask symptoms and delay correct diagnosis.

If symptoms persist despite adequate treatment, further evaluation should be performed.

The use of proton pump inhibitors, which include dexlansoprazole, increases the risk of gastrointestinal infections with diarrhea caused by bacteria of the genus Clostridium difficile, especially in hospitalized patients. This should be considered if the patient’s condition does not improve with treatment of diarrhea.

Patients in this case are recommended to take the lowest effective dose of dexlansoprazole with the shortest duration of treatment.

In patients receiving high doses of the drug, or with prolonged therapy with proton pump inhibitors (PPIs) for a year or more, the risk of osteoporotic fractures of the hips, hands and spine increases. Patients at risk of osteoporotic fractures should adhere to the recommended dosages (see section “Dosage and administration”).

Dexlansoprazole, like other drugs that block gastric juice secretion, may decrease absorption of vitamin B₁₂ (cyanocobalamin) due to hypo- or achlorhydria. This should be considered when treating patients with reduced stores of this vitamin in the body or when treating patients with risk factors for vitamin B₁₂ deficiency for a long time, as well as when observing corresponding clinical symptoms.

In rare cases, symptomatic and asymptomatic hypomagnesemia have been observed in patients when taking IPN drugs for at least three months, and in most cases when taking them for one year. Symptoms of hypomagnesemia are tetany, arrhythmia, and seizures. Treatment is magnesium supplementation and discontinuation of IPN medications. In patients who require prolonged treatment or who concomitantly take PPIs with digoxin or other drugs that may cause hypomagnesemia (e.g., diuretics), serum magnesium concentrations should be monitored before and during treatment.

The use of proton pump inhibitors may be associated with very rare cases of subacute cutaneous lupus erythematosus (SLE). If a flare-up occurs, especially in sun-exposed areas of the skin and if there is pain in the joints, the patient should immediately consult a physician and the use of Dexilant® is recommended to be discontinued. It should be noted that if PKCV develops after treatment with a proton pump inhibitor, the risk of PKCV with other PPIs may increase in the future.

It should be noted that elevated chromogranin A (CgA) levels may interfere with the diagnosis of neuroendocrine tumors. In order to eliminate this effect, the use of Dexilant^® should be discontinued at least 5 days prior to determining CgA levels. If CgA and gastrin levels do not return to normal values after the first determination, the analysis should be repeated 14 days after discontinuation of proton pump inhibitors.

Influence on driving ability/mechanisms.

Because of the possibility of dizziness and visual impairment, one should refrain from driving vehicles and other mechanisms requiring increased attention.

Synopsis

The capsules have an opaque blue cap and body. The lid has the “TAP” logo in dark gray ink, the body has the inscription “60”. The content of the capsules is a mixture of white to light brown granules.

Contraindications

– Hypersensitivity to any of the ingredients of the drug.

– Co-use with HIV protease inhibitors whose absorption depends on the pH of the stomach (such as atazanavir, nelfinavir), because of a significant decrease in their bioavailability.

– age less than 12 years.

Pregnancy, lactation.

The drug contains sucrose, so it is not recommended for patients with hereditary fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency.

With caution, Dexilant^® may be prescribed:

• patients taking tacrolimus.
• patients taking CYP2C19 isoenzyme inhibitors such as fluvoxamine
• patients taking warfarin, under control of prothrombin time and INR;
• patients taking methotrexate.

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