Dexilant, 30 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 the parietal cells of the stomach. 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 intended for use in adults and adolescents over the age of 12 years 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);

Pharmacological effect

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

ATX code: A02BC06

Pharmacological properties

Pharmacodynamics

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

When antisecretory drugs are used, the level of gastrin in the blood serum increases in response to a decrease in the secretion of gastric juice. There is also an increase in chromogranin A (CgA) levels as a result of decreased acidity in the stomach. Elevated CgA levels may interfere with the diagnosis of neuroendocrine tumors.

Published data suggest that use of proton pump inhibitors (PPIs) should be discontinued 5 to 14 days before CgA levels are determined to normalize the falsely elevated CgA concentrations that occur after proton pump inhibitors.

The Dexilant® capsule disintegrates in the stomach and contains two types of enteric-coated granules that release the active substance depending on the pH in different areas of the small intestine. This combination helps prolong the effect of dexlansoprazole and helps reduce gastric acid secretion over a long period of time.

Pharmacokinetics

Suction

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

The two-component composition of the drug Dexilant® causes absorption in the form of two pH-dependent phases. The first peak concentration of the active substance occurs in the range from 1 to 2 hours after oral administration (phase 1 of the release of the active substance) and from 4 to 5 hours (phase 2 of the release of the active substance), respectively. After 5 days of taking dexlansoprazole at dosages of 30 mg and 60 mg, the maximum plasma concentration (Cmax) is 658 ng/ml and 1397 ng/ml, respectively.

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

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

Metabolism

Dexlansoprazole is intensively metabolized in the liver to inactive metabolites as a result of oxidation, reduction and subsequent formation of sulfate, glucuronide and glutathione compounds. Oxidation is carried out using the cytochrome P450 enzyme system, which is involved in both the hydroxylation process (mainly the 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 the metabolism of substrates: rapid, moderate and slow metabolizers. Dexlansoprazole is the main component in the blood plasma, regardless of the type of metabolizer by the CYP2C19 isoenzyme. In the case of moderate and strong metabolizers by the CYP2C19 isoenzyme, the main metabolite in the blood plasma is 5-hydroxydexlansoprazole and its glucuronic compound. For weak metabolizers by the CYP2C19 isoenzyme, dexlansoprazole sulfone.

Removal

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

Clearance after 5 days of dexlansoprazole is 11.4 and 11.6 l/h for dosages of 30 mg and 60 mg, respectively.

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

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 changes in pharmacokinetics are expected.

Special instructions

Before starting treatment with dexlansoprazole, the possibility of malignancy should be excluded, since the drug may mask symptoms and delay the correct diagnosis.

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

When taking proton pump inhibitors, which include dexlansoprazole, the risk of gastrointestinal infections accompanied by diarrhea caused by bacteria of the genus Clostridium difficile increases, especially in hospitalized patients. This must be taken into account if the patient’s condition does not improve with treatment of diarrhea.

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

In patients receiving high doses of the drug, or with long-term 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 acid secretion, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account when treating patients with reduced reserves of this vitamin in the body or during long-term treatment of patients with risk factors for developing vitamin B12 deficiency, as well as when observing corresponding clinical symptoms.

In rare cases, patients have experienced symptomatic and asymptomatic hypomagnesemia when taking PPI drugs for at least three months, and in most cases when taking PPI drugs for a year. Symptoms of hypomagnesemia include tetany, arrhythmia, and seizures. Treatment is magnesium replacement and discontinuation of PPI medications. In patients who require long-term treatment or who are concomitantly taking PPI drugs with digoxin or other drugs that can cause hypomagnesemia (for example, 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 (SCLE). If a focus of the disease appears, especially on areas of the skin exposed to sunlight, and if there is pain in the joints, the patient should immediately consult a doctor, and it is recommended to stop using Dexilant®. It should be noted that in the case of development of PCLE after treatment with a proton pump inhibitor, the risk of developing PCLE may subsequently increase with the use of other PPIs.

It must be taken into account that elevated levels of chromogranin A (CgA) may interfere with the diagnosis of neuroendocrine tumors. In order to exclude such an effect, the use of Dexilant® should be discontinued at least 5 days before determining the CgA level. If CgA and gastrin levels do not return to normal after the first determination, the test should be repeated 14 days after stopping the proton pump inhibitors.

Impact on the ability to drive vehicles/machines.

Due to the likelihood of dizziness and visual impairment, you should refrain from driving vehicles and other mechanisms that require increased attention.

Active ingredient

Dexlansoprazole

Composition

Composition per 1 capsule 30 mg

Active ingredient: dexlansoprazole 30 mg

Excipients: granulated sugar1 (from 500 microns to 710 microns) 28.8 mg, magnesium carbonate 11.5 mg, sucrose 41.5 mg, low-substituted hyprolose 8.64 mg, hyprolose 0.34 mg, hypromellose 2910 7.54 mg, talc 17.7 mg, titanium dioxide 5.5 mg, dispersion of methacrylic acid copolymer2 9.66 mg, macrogol-8000 0.96 mg, polysorbate-80 0.44 mg, colloidal silicon dioxide 0.09 mg, methacrylic acid and methyl methacrylate copolymer [1:2] 17.55 mg, methacrylic acid and methyl methacrylate copolymer [1:1] 5.85 mg, triethyl citrate 2.332 mg;

Capsule shell

Cap: carrageenan, potassium chloride, titanium dioxide, FD&C blue dye No. 2 aluminum varnish, purified water, hypromellose, purified gray ink for marking3.

Body: carrageenan, potassium chloride, titanium dioxide, black iron oxide dye, purified water, hypromellose, purified gray ink for marking3.

Pregnancy

The use of Dexilant® during pregnancy is contraindicated. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Contraindications

– hypersensitivity to any of the components of the drug.

– combined use with HIV protease inhibitors, the absorption of which depends on the pH of the stomach (such as atazanavir, nelfinavir), due to a significant decrease in their bioavailability.

– age up to 12 years.

– pregnancy, lactation period.

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

With caution, Dexilant® may be prescribed:

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

Side Effects

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

The following is information about adverse reactions depending on the frequency of their occurrence:

Very often

≥ 1/10

Often

≥ 1/100 and < 1/10

Uncommon

≥ 1/1000 and < 1/100

Rarely

≥ 1/10000 and < 1/1000

Very rarely

< 1/10000, including isolated cases

Frequency unknown

(cannot be estimated 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

Often:

Diarrhea, discomfort and pain in the abdomen, constipation, flatulence, nausea, polyps of the fundic glands of the stomach (benign).

Uncommon:

Dry mouth, vomiting.

Rarely:

Oral candidiasis.

Frequency unknown:

Swelling of the oral mucosa, pancreatitis.

Renal and urinary tract disorders

Frequency unknown:

Acute renal failure.

Disorders of the liver and biliary tract

Uncommon:

Changes in liver functional activity indicators.

Frequency unknown:

Drug-induced hepatitis.

Skin and subcutaneous tissue disorders

Uncommon:

Rash, hives, itching.

Frequency unknown:

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

Respiratory, thoracic and mediastinal disorders

Often:

Infectious diseases of the upper respiratory tract.

Uncommon:

Cough.

Frequency unknown:

Swelling of the larynx, a feeling of tightness in the throat.

Blood and lymphatic system disorders

Frequency unknown:

Autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

Musculoskeletal and connective tissue disorders

Uncommon:

Fracture of the femur, wrist or spine.

Vascular disorders

Uncommon:

Attack of heat (“hot flashes”), increased blood pressure.

Nervous system disorders

Often:

Headache.

Uncommon:

Dizziness, dysgeusia.

Rarely:

Paresthesia, convulsions.

Frequency unknown:

Stroke, transient ischemic attack.

Visual disorders

Rarely:

Visual impairment.

Frequency unknown:

Visual impairment (blurred).

Hearing and labyrinth disorders

Rarely:

Vertigo.

Frequency unknown:

Hearing loss.

Mental disorders

Uncommon:

Insomnia, depression.

Rarely:

Auditory hallucinations.

Frequency unknown:

Visual hallucinations.

General disorders

Uncommon:

Weakness, changes in appetite.

Frequency unknown:

Swelling of the face.

The safety profile in adolescents over 12 years of age is the same as in adults.

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

Interaction

Dexlansoprazole can be prescribed without the risk of drug interactions in patients taking clopidogrel. In case of co-administration, no dose adjustment of clopidogrel is required. There was 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 gastric pH (for example, ampicillin esters, digoxin, iron salts, ketoconazole, erlotinib).
Concomitant use with tacrolimus may lead to increased plasma concentrations of tacrolimus, especially in transplant patients who are moderate or slow metabolizers of the CYP2C19 isoenzyme.
When taken concomitantly with fluvoxamine, there is a possibility of increased systemic exposure to dexlansoprazole.
Concomitant use of dexlansoprazole and methotrexate can lead to an increase and maintenance of high concentrations of methotrexate and/or its metabolite in the blood serum, which, accordingly, can lead to the development of methotrexate toxicity. If it is necessary to take high doses of methotrexate, temporary discontinuation of dexlansoprazole is recommended.

Overdose

There have been no reports of significant cases of overdose resulting from the use of Dexilant®. Multiple doses of 120 mg and single doses of 300 mg did not cause severe side effects. A side effect was observed in the form of an increase in blood pressure above 140/90 mmHg. when taking Dexilant® 60 mg 2 times a day.
However, in case of overdose and only in the presence of clinical manifestations, symptomatic therapy is carried out.
Dexlansoprazole is not eliminated by hemodialysis.

Storage conditions

Store in original packaging at a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life

3 years

Manufacturer

Takeda GmbH, Germany