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

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

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

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

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:

Side effects

The most frequent (at least 2%)adverse reactions are diarrhea, flatulence, abdominal pain, nausea, vomiting, and upper respiratory tract infections.

Below are the adverse reactions according to their frequency of occurrence:

Very common

≥ 1/10

often

≥ 1/100 and < 1/10

Frequently

≥ 1/1000 and < 1/100

Rarely

≥ 1/10000 and < 1/1000

very rarely

< 1/10000, including individual cases

Frequency unknown

(impossible to estimate based on available data).

.Immune system disorders

Frequency unknown:

Hypersensitivity (including anaphylactic reactions), exfoliative dermatitis, anaphylactic shock.

Metabolic and nutritional disorders

Frequency unknown:

Hypomagnesemia, hyponatremia.

Gastrointestinal disorders

Frequently:

Diarrhea, abdominal discomfort and pain, constipation, flatulence, nausea, polyps of the fundamental glands of the stomach (benign).

Infrequent:

Dry mouth, vomiting.

Rarely:

Candidosis of the mouth.

Frequency unknown:

Oedema of the oral mucosa, pancreatitis.

Kidney and urinary tract disorders

Frequency unknown:

Acute renal failure.

Liver and biliary tract disorders

Infrequent:

Changes in liver functional activity parameters.

Frequency unknown:

Medicated hepatitis.

Skin and subcutaneous tissue disorders

Infrequent:

Rash, urticaria, itching.

Frequency unknown:

Leukocytoclastic vasculitis, generalized rash, subacute cutaneous lupus erythema malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis.

Disorders of the respiratory system, thorax and mediastinum

Frequently:

Infectious diseases of the upper respiratory tract.

Infrequent:

Cough.

Frequency unknown:

Laryngeal swelling, feeling of tightness in throat.

Blood and lymphatic system disorders

Frequency unknown:

Autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

Muscular and connective tissue disorders

Infrequent:

Fracture of the femur, carpal or spinal bones.

Vascular disorders

Infrequent:

Hot flashes (“hot flashes”), increased blood pressure.

Nervous system disorders

Often:

Headache.

Infrequent:

Dizziness, dysgeusia.

Rarely:

Paresthesia, seizures.

Frequency unknown:

Stroke, transient ischemic attack.

Visual disorders

Rarely:

Visual disorders.

Frequency unknown:

Sight impairment (blurring).

Hearing and labyrinth disorders

Rarely:

Vertigo.

Frequency unknown:

Hearing impairment.

Mental disorders

Infrequent:

Besomnia, depression.

Rarely:

Hearing hallucinations.

Frequency unknown:

Sight hallucinations.

General disorders

Infrequent:

Sweakness, changes in appetite.

Frequency unknown:

Facial edema.

The safety profile in adolescents aged 12 years and older is the same as in adults.

The safety and efficacy profile of Dexilant® for children under 12 years of age has not been established due to lack of data.

Overdose

Pregnancy use