Dexylant® (Dexilant®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceDexlensoprazoleDexlensoprazole
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  • Dexylant®
    capsules inwards 
    Takeda Pharmaceuticals USA, Inc.     USA
    • Dosage form: & nbspmodified release capsules
    Composition:

    Composition per 1 capsule 30 mg

    Active substance: dexlensoprazole 30 mg

    Excipients: sugar loaf1 (from 500 μm to 710 μm) 28.8 mg, magnesium carbonate 11.5 mg, sucrose 41.5 mg, giprolose low-substituted 8.64 mg, giprolose 0.34 mg, hypromellose 2910 7.54 mg, talc 16.64 mg, titanium dioxide 5.5 mg, dispersion of methacrylic acid copolymer2 9.66 mg, macrogol-8000 0.96 mg, polysorbate-80 0.44 mg, silicon colloidal dioxide 0.09 mg, methacrylic acid and methyl methacrylate copolymer [1: 2] 15.95 mg, methacrylic acid and methyl methacrylate copolymer [ 1: 1] 5.32 mg, triethyl citrate 2.12 mg;

    Capsule shell: carrageenan 0,192-0,624 mg, potassium chloride 0,144-0,48 mg, titanium dioxide 2,4768 mg, dye FD & C blue # 2 aluminum varnish 0.3456 mg, iron oxide dye oxide 0.0576 mg black, hypromellose q.s. up to 48 mg, gray ink cleaned for labeling3 trace amounts.

    1 The composition of sugar grits: sucrose 18-26.352 mg, corn starch 2.448-10.8 mg;

    2 The composition of the dispersion of methacrylic acid copolymer: methacrylic acid 4.4436 mg, ethyl acrylate 4.2504 mg, sodium lauryl sulfate 0.2254 mg, polysorbate-80 0.7406 mg;

    Composition per 1 capsule 60 mg

    Active substance: dexlansoprazole 60 mg

    Excipients: sugar loaf1 (from 500 μm to 710 μm) 40.0 mg, magnesium carbonate 16.0 mg, sucrose 39.52 mg, low-substituted giprolose 12.0 mg, giprolose 0.48 mg, hypromellose 2910 10.5067 mg, talc 27.5499 mg, titanium dioxide 6.9933 mg, dispersion of methacrylic acid copolymer2 7.02 mg, macrogol-8000 0.7 mg, polysorbate-80 0.32 mg, silicon dioxide colloidal 0.13 mg, methacrylic acid and methyl methacrylate copolymer [1: 2] 31.9 mg, methacrylic acid and methyl methacrylate copolymer [ 1: 1] 10.64 mg, triethyl citrate 4.24 mg.

    Capsule shell: carrageenan 0,24-0,78 mg, potassium chloride 0,18-0,6 mg, titanium dioxide 2,52 mg, dye FD & With blue №2 aluminum varnish 1,08 mg, hypromellose q.s. up to 60 mg, gray ink cleaned for labeling3 trace amounts.

    1 Ingredients of sugar grits: sucrose 25-36,6 mg, corn starch 3,4-15 mg;

    2 The composition of the dispersion of methacrylic acid copolymer: methacrylic acid 3.292 kg, ethylacrylate 3.0888 mg, sodium lauryl sulfate 0.1638 mg, polysorbate-80 0.5382 mg;

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

    Description:

    Dosage of 30 mg

    Capsules with an opaque blue lid and an opaque gray body.The cap is marked with a dark gray ink on the logo "TAR", on the body - the inscription "30". The contents of capsules are granules from white to almost white.

    Dosage of 60 mg

    Capsules with opaque blue lid and body. On the cap with dark gray ink the "TAR" logo is printed, on the body - the inscription "60". The contents of capsules are granules from white to almost white.

    Pharmacotherapeutic group:The iron of the stomach secretion is a reducing agent - a proton pump inhibitor
    ATX: & nbsp

    A.02.B.C   Proton pump inhibitors

    A.02.B.C.06   Dexlensoprazole

    Pharmacodynamics:

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

    The capsule of Dexilant® disintegrates in the stomach and contains two types of enteric coated beads that release the active substance depending on the pH in various areas of the small intestine. This combination helps prolong the effect of dexlansoprazole and helps reduce gastric juice secretion for a long time.

    Pharmacokinetics:

    Suction

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

    The two-component formulation of the Dexylant® prepares absorption in the form of two pH-dependent phases. The first peak of the concentration of the active substance occurs between 1 and 2 hours after ingestion (1 phase of release of the active substance) and 4 to 5 hours (2-phase release of the active substance), respectively. After 5 days of taking dexlansoprazole in doses of 30 mg and 60 mg, the maximum concentration in the blood plasma (CmOh) is 658 ng / ml and 1397 ng / ml, respectively.

    Area under the curve "concentration-time" (AUC) was 3275 ng h / ml and 6529 ng h / ml after 5 days of dexlansoprazole at 30 mg and 60 mg, respectively.

    Distribution

    Binding dexlansoprazole to plasma proteins is 96.1 - 98.8%.

    Metabolism

    Dexlensoprazole is extensively 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 with the help of the cytochrome P450 enzyme system, which participates both in the hydroxylation process (mainly isoenzyme CYP2C19), and in the process of oxidation (isoenzyme CYP3A4) . Isozyme CYP2C19 is a polymorphic hepatic isoenzyme that exists in 3 fractions exhibiting different properties in the metabolism of substrates: fast, moderate and slow metabolizers.

    Dexlansoprazole is the main component in blood plasma regardless of the type of isobenzomim metabolizer CYP2C19. In the case of medium and strong isobenzomeric metabolizers CYP2C19 the main metabolite in the blood plasma is 5-hydroxydeclansoprazole and its glucuronic compound. With weak metabolizers by isoenzyme CYP2C19 dexlansoprazole sulfone.

    Excretion

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

    The clearance after 5 days of taking dexlansoprazole is 11.4 and 11.6 l / h for a dosage of 30 mg and 60 mg, 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, the use of dexlansoprazole in patients with impaired renal function is not required to reduce the dose. As in patients with normal renal function, a change in pharmacokinetics is not expected.

    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 (ie NERB - non-erosive reflux disease).

    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 environment (such as atazanavir, nelfinavir), due to a significant decrease in their bioavailability.

    - age to 18 years.

    - pregnancy, lactation.

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

    Carefully:

    Carefully Dexylant® can be prescribed:

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

    Pregnancy and lactation:

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

    Dosing and Administration:

    Inside: the capsule is taken entirely regardless of the food intake. Also, you can open the capsule, pour the granules out of it into a tablespoon and mix them with apple puree; then immediately, without chewing, swallow.

    Treatment of erosive esophagitis of any severity.

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

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

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

    Patients with erosive esophagitis of moderate and severe degree recommended dose is 60 mg once a day. In the studies, the course of treatment was up to 6 months.

    Symptomatic treatment of gastroesophageal reflux disease of GERD (ie NERB - non-erosive reflux disease).

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

    In patients with impaired liver function of moderate severity (class B by Child-Pugh), the daily dose should not exceed 30 mg of dexlansoprazole.

    Clinical data on the administration of the drug in patients with severe disorders (class C according to Child-Pugh) are absent.

    Dose adjustments in elderly patients, patients with impaired renal function and with mild liver function disorder (Child-Pugh class A) are not required.

    Side effects:

    The most frequent (not less than 2 %) undesirable side reactions are diarrhea, flatulence, abdominal pain, nausea, vomiting, upper respiratory tract infection.

    The following are data on undesirable side reactions depending on the frequency their occurrence:

    Very often ≥ 1/10

    Frequently ≥ 1/100 and <1/10

    Not infrequently ≥ 1/1000 and <1/100

    Rarely ≥1 / 10000 and <1/1000

    Very rarely <1/10000, including individual cases

    The frequency is unknown (can not be estimated from the available data).

    Immune system disorders:

    Frequency unknown:

    Hypersensitivity (including anaphylactic reactions), malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis, exfoliative dermatitis, anaphylactic shock.

    Disorders from the metabolism and nutrition:

    Frequency unknown:

    Hypomagnesemia, hyponatremia.

    Disorders from the gastrointestinal tract:

    Often:

    Diarrhea, discomfort and abdominal pain, constipation, flatulence, nausea, vomiting.

    Infrequently:

    Dry mouth

    Rarely:

    Candidiasis of the mouth

    Frequency unknown:

    Edema of the oral mucosa, pancreatitis.

    Disorders from the kidneys and urinary tract:

    Frequency unknown:

    Acute kidney failure.

    Disorders from the liver and bile ducts:

    Infrequently:

    Change in indicators of functional activity of the liver.

    Frequency unknown:

    Medicinal hepatitis.

    Disturbances from the skin and subcutaneous tissues:

    Infrequently:

    Rash, hives, itching

    Frequency unknown:

    Leukocytoclastic vasculitis, generalized rash.

    Disorders from the respiratory system, chest mediastinum:

    Often:

    Infectious diseases of the upper respiratory tract

    Infrequently:

    Cough

    Frequency unknown:

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

    Violations from the blood and lymphatic system:

    Frequency unknown:

    Autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

    Disturbances from the musculoskeletal and connective tissue:

    Frequency unknown:

    Fractures

    Vascular disorders:

    Infrequently:

    A heat attack ("hot flashes"), an increase in blood pressure.

    Impaired nervous system:

    Often:

    Headache

    Infrequently:

    Dizziness, dysgeusia

    Rarely:

    Paresthesia, seizures

    Frequency unknown:

    Stroke, transient ischemic attack.

    Disorders from the side of the organ of vision:

    Rarely:

    Visual impairment

    Frequency unknown:

    Visual impairment (fogging).

    Hearing disorders and labyrinthine disturbances:

    Rarely:

    Vertigo

    Frequency unknown:

    Hearing loss.

    Disorders of the psyche:

    Infrequently:

    Insomnia, depression

    Rarely:

    Auditory hallucinations.

    General disorders:

    Infrequently:

    Weakness, changes in appetite

    Frequency unknown:

    Swelling of the face.

    Overdose:

    No significant cases of overdose were reported as a result of the use of Dexilant®. Multiple dose of 120 mg and a single dose of 300 mg did not cause serious side effects. There was a side effect in the form of an increase in blood pressure above 140/90 mm Hg. when taking Dexilant® 60 mg 2 times a day.

    However, in case of an overdose and only in the presence of clinical manifestations, symptomatic therapy is performed.

    Dexlansoprazole is not excreted by hemodialysis.

    Interaction:

    Dexlansoprazole may be prescribed without the risk of drug interactions to patients receiving clopidogrel. In the case of co-administration of dose adjustment, clopidogrel is not required. There was also a lack of clinically significant drug interaction with phenytoin, theophylline and diazepam. The simultaneous use of dexlansoprazole may affect the absorption of drugs whose bioavailability depends on the pH of the stomach (for example, ampicillin esters, digoxin, iron salts, ketoconazole, erlotinib).

    Simultaneous administration with tacrolimus can lead to an increase in tacrolimus concentration in the blood plasma, especially in patients after transplantation, which are moderate or slow isoenzyme metabolizers CYP2C19 With simultaneous administration with fluvoxamine, there is a possibility of increasing the systemic effect of dexlansoprazole.

    The simultaneous administration of dexlansoprazole and methotrexate may lead to an increase and retention of a high concentration of methotrexate and / or its metabolite in the serum, which, accordingly, may lead to the development of methotrexate toxicity.If it is necessary to take high doses of methotrexate, a temporary withdrawal of dexlansoprazole is recommended.

    Special instructions:

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

    If the symptoms persist despite adequate treatment, further examination should be carried out.

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

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

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

    In rare cases, symptomatic and asymptomatic hypomagnesemia was observed in patients receiving IPN drugs for at least three months, and in most cases, with admission during the year. Symptoms of hypomagnesemia are tetany, arrhythmia and convulsions. Treatment - the replacement of magnesium and the withdrawal of drugs IPN. In patients who require long-term treatment or who simultaneously take IPN medications with digoxin or other drugs that can cause hypomagnesemia (eg, diuretics), it is necessary to monitor the magnesium concentration in the serum prior to and during treatment.

    Effect on the ability to drive transp. cf. and fur:

    Due to the likelihood of dizziness and visual impairment, one should refrain from managing vehicles and other mechanisms requiring increased attention.

    Form release / dosage:

    Capsules with a modified release of 30 mg and 60 mg.

    Packaging:

    For 14 or 28 capsules with modified release into a vial of high-density polyethylene,sealed with aluminum foil and sealed with a screw cap made of polypropylene. The container contains a desiccant container containing silica gel.

    One bottle with instructions for use is placed in a cardboard box.

    For 14 capsules with modified release in AL / PVC blister.

    For 1 or 2 blisters with instructions for use are placed in a cardboard box.

    Storage conditions:

    Store in a dry place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    When packing in vials: 4 years.

    When packing in blisters: 3 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002477
    Date of registration:26.05.2014 / 04.08.2016
    Expiration Date:26.05.2019
    The owner of the registration certificate:Takeda Pharmaceuticals USA, Inc.Takeda Pharmaceuticals USA, Inc. USA
    Manufacturer: & nbsp
    Representation: & nbspTakeda Pharmaceuticals Ltd.Takeda Pharmaceuticals Ltd.
    Information update date: & nbsp22.03.2017
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