Dexilant^® (Capsules) Instructions for Use

Marketing Authorization Holder

Takeda Pharmaceuticals U.S.A., Inc. (USA)

Manufactured By

Takeda GmbH (Germany)

Packaging and Quality Control Release

DELPHARM NOVARA, S.r.l. (Italy)

ATC Code

A02BC06 (Dexlansoprazole)

Active Substance

Dexlansoprazole (Rec.INN WHO registered)

Dosage Forms

	Dexilant®	Modified-release capsules 30 mg: 14 or 28 pcs.
		Modified-release capsules 60 mg: 14 or 28 pcs.

Dosage Form, Packaging, and Composition

Modified-release capsules with an opaque blue cap and an opaque gray body; the cap is imprinted with the logo “TAP” in dark gray ink, the body is imprinted with “30”. The capsule contents are a mixture of granules from white to light brown in color.

Excipients: sugar spheres* (from 500 µm to 710 µm) – 28.8 mg, magnesium carbonate – 11.5 mg, sucrose – 41.5 mg, low-substituted hypromellose – 8.64 mg, hypromellose – 0.34 mg, hypromellose 2910 – 7.54 mg, talc – 17.7 mg, titanium dioxide – 5.5 mg, methacrylic acid copolymer dispersion** – 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 compositioncap carrageenan, potassium chloride, titanium dioxide, dye FD&C Blue No. 2 aluminum lake, purified water, hypromellose, purified gray marking ink***;
body carrageenan, potassium chloride, titanium dioxide, black iron oxide, purified water, hypromellose, purified gray marking ink^***.

* Sugar spheres composition sucrose, corn starch.
** Methacrylic acid copolymer dispersion composition methacrylic acid, ethyl acrylate, sodium lauryl sulfate, polysorbate-80.
*** Purified gray marking ink consists of red iron oxide, yellow iron oxide, FD&C Blue No.2 aluminum lake, carnauba wax, shellac, glyceryl monooleate.

14 pcs. – blisters (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Modified-release capsules with opaque blue cap and body; the cap is imprinted with the logo “TAP” in dark gray ink, the body is imprinted with “60”. The capsule contents are a mixture of granules from white to light brown in color.

Excipients: sugar spheres^× (from 500 µm to 710 µm) – 40 mg, magnesium carbonate – 16 mg, sucrose – 39.52 mg, low-substituted hypromellose – 12 mg, hypromellose – 0.48 mg, hypromellose 2910 – 10.507 mg, talc – 29.68 mg, titanium dioxide – 6.993 mg, methacrylic acid copolymer dispersion^×× – 7.02 mg, macrogol 8000 – 0.7 mg, polysorbate 80 – 0.32 mg, colloidal silicon dioxide – 0.13 mg, methacrylic acid and methyl methacrylate copolymer [1:2] – 35.09 mg, methacrylic acid and methyl methacrylate copolymer [1:1] – 11.7 mg, triethyl citrate – 4.664 mg.

Capsule shell composition:
Cap: carrageenan, potassium chloride, titanium dioxide, dye FD&C Blue No. 2 aluminum lake, purified water, hypromellose, purified gray marking ink***;
body: carrageenan, potassium chloride, titanium dioxide, black iron oxide, purified water, hypromellose, purified gray marking ink^***.

* Sugar spheres composition: sucrose, corn starch.
** Methacrylic acid copolymer dispersion composition: methacrylic acid, ethyl acrylate, sodium lauryl sulfate, polysorbate-80.
*** Purified gray marking ink consists of red iron oxide, yellow iron oxide, FD&C Blue No.2 aluminum lake, carnauba wax, shellac, glyceryl monooleate.

14 pcs. – blisters (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

A drug that reduces the secretion of gastric glands. Proton pump inhibitor

Pharmacotherapeutic Group

Gastric secretion reducing agent – proton pump inhibitor

Pharmacological Action

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

When using antisecretory drugs, the serum gastrin level increases in response to reduced gastric acid secretion. There is also an increase in the level of chromogranin A (CgA) due to decreased gastric acidity. Elevated CgA levels may interfere with the diagnosis of neuroendocrine tumors.

Published data suggest that proton pump inhibitor (PPI) use should be discontinued 5-14 days before CgA level measurement to allow the falsely elevated CgA concentration that occurs after PPI use to return to normal.

Pharmacokinetics

Dexlansoprazole is well absorbed after oral administration. Its bioavailability is 76% or more. After 5 days of dexlansoprazole administration at doses of 30 mg and 60 mg, the C_max in plasma is 658 ng/ml and 1397 ng/ml, respectively. The AUC is 3275 ng×h/ml and 6529 ng×h/ml after 5 days of dexlansoprazole administration at doses of 30 mg and 60 mg, respectively. The plasma protein binding of dexlansoprazole is 96.1-98.8%. Dexlansoprazole is extensively metabolized in the liver to inactive metabolites via oxidation, reduction, and subsequent formation of sulfate, glucuronide, and glutathione conjugates. Oxidation is mediated by the cytochrome P450 enzyme system, which is involved in both the hydroxylation process (primarily the CYP2C19 isoenzyme) and the oxidation process (CYP3A4 isoenzyme). The CYP2C19 isoenzyme is a polymorphic hepatic isoenzyme that exists in 3 fractions exhibiting different substrate metabolism properties: rapid, intermediate, and poor metabolizers. Dexlansoprazole is the main component in plasma regardless of the CYP2C19 metabolizer type. In intermediate and extensive CYP2C19 metabolizers, the main metabolite in plasma is 5-hydroxydexlansoprazole and its glucuronide conjugate. In poor CYP2C19 metabolizers, it is dexlansoprazole sulfone.T_1/2 is 1-2 h. The clearance after 5 days of dexlansoprazole administration is 11.4 and 11.6 L/h for the 30 mg and 60 mg doses, respectively. The drug is excreted by the kidneys (about 51%) and 48% is excreted via 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

Treatment of erosive esophagitis of any severity; maintenance therapy after treatment of erosive esophagitis and relief of heartburn symptoms; symptomatic treatment of gastroesophageal reflux disease GERD (i.e., NERD – non-erosive reflux disease).

ICD codes

Dosage Regimen

Administer orally, swallowed whole. Do not crush or chew capsules.

Take once daily, at any time, with or without food.

For healing of erosive esophagitis, the recommended dosage is 60 mg for up to 8 weeks.

For maintenance of healed erosive esophagitis and relief of heartburn, the recommended dosage is 30 mg.

For symptomatic treatment of non-erosive gastroesophageal reflux disease (GERD), the recommended dosage is 30 mg for 4 weeks.

For adolescents 12 to 17 years of age, the dosage for all indications is 30 mg for up to 8 weeks.

In patients with moderate hepatic impairment (Child-Pugh Class B), the maximum recommended dosage is 30 mg.

No dosage adjustment is necessary for patients with renal impairment or mild hepatic impairment (Child-Pugh Class A).

Use the lowest effective dose for the shortest duration appropriate to the condition being treated.

Adverse Reactions

Immune system disorders: frequency unknown – hypersensitivity (including anaphylactic reactions), exfoliative dermatitis, anaphylactic shock.

Metabolism and nutrition disorders: frequency unknown – hypomagnesemia, hyponatremia.

Gastrointestinal disorders: common – diarrhea, abdominal discomfort and pain, constipation, flatulence, nausea; uncommon – dry mouth, vomiting; rare – oral candidiasis; frequency unknown – oral mucosal edema, pancreatitis.

Renal and urinary disorders: frequency unknown – acute renal failure.

Hepatobiliary disorders: uncommon – changes in liver function tests; frequency unknown – drug-induced hepatitis.

Skin and subcutaneous tissue disorders: uncommon – rash, urticaria, pruritus; frequency unknown – leukocytoclastic vasculitis, generalized rash, subacute cutaneous lupus erythematosus, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis.

Respiratory, thoracic and mediastinal disorders: common – upper respiratory tract infections; uncommon – cough; frequency unknown – laryngeal edema, throat tightness.

Blood and lymphatic system disorders: frequency unknown – autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura.

Musculoskeletal and connective tissue disorders: uncommon – fracture of the femur, wrist bones, or spine.

Cardiac disorders: uncommon – hot flush, increased blood pressure.

Nervous system disorders: common – headache; uncommon – dizziness, dysgeusia; rare – paresthesia, convulsions; frequency unknown – stroke, transient ischemic attack.

Eye disorders: rare – visual impairment; frequency unknown – blurred vision.

Ear and labyrinth disorders: rare – vertigo; frequency unknown – hearing loss.

Psychiatric disorders: uncommon – insomnia, depression; rare – auditory hallucinations; frequency unknown – visual hallucinations.

General disorders and administration site conditions: uncommon – asthenia, appetite changes; frequency unknown – facial edema.

Contraindications

Hypersensitivity to dexlansoprazole, concomitant use with HIV protease inhibitors whose absorption depends on gastric pH (such as atazanavir, nelfinavir) due to a significant decrease in their bioavailability; age under 12 years; pregnancy, breastfeeding period.

With caution

Patients taking tacrolimus, CYP2C19 isoenzyme inhibitors (such as fluvoxamine), warfarin (with monitoring of prothrombin time and INR), methotrexate.

Use in Pregnancy and Lactation

Use during pregnancy and breastfeeding is contraindicated.

Use in Hepatic Impairment

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

Clinical data on use in patients with severe impairment (Child-Pugh class C) are not available.

No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A).

Use in Renal Impairment

No dose adjustment is required in patients with impaired renal function.

Special Precautions

Before starting treatment with dexlansoprazole, the possibility of a malignant neoplasm should be excluded, as this agent may mask symptoms and delay the correct diagnosis.

If symptoms persist despite adequate treatment, further investigation should be conducted.

When taking PPIs, 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 should be taken into account if the patient’s condition does not improve during treatment for diarrhea.

In this case, patients 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 PPI therapy for a year or more, the risk of osteoporotic fractures of the hip, wrist, and spine increases. Patients at risk of osteoporotic fractures should adhere to the recommended doses.

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 considered when treating patients with reduced body stores of this vitamin or during long-term treatment of patients with risk factors for vitamin B₁₂ deficiency, as well as when observing relevant clinical symptoms.

In rare cases, symptomatic and asymptomatic hypomagnesemia has been observed in patients taking PPI drugs for at least 3 months, and in most cases – for a year. Symptoms of hypomagnesemia include tetany, arrhythmia, and seizures. Treatment involves magnesium replenishment and discontinuation of PPI intake. In patients requiring long-term treatment or taking PPIs concomitantly with digoxin or other drugs that can cause hypomagnesemia (e.g., diuretics), serum magnesium levels should be monitored before starting and during treatment.

The use of proton pump inhibitors may be associated with very rare cases of subacute cutaneous lupus erythematosus (SCLE). If a lesion appears, especially on sun-exposed skin areas, and if there is joint pain, the patient should immediately consult a doctor, and it is recommended to discontinue dexlansoprazole. It should be noted that in case of SCLE development after treatment with a proton pump inhibitor, the risk of SCLE development with the use of other PPIs may be increased in the future.

It must be taken into account that elevated CgA levels may interfere with the diagnosis of neuroendocrine tumors. To exclude such influence, dexlansoprazole use should be discontinued at least 5 days before CgA level measurement. If CgA and gastrin levels do not return to normal after the first measurement, the test should be repeated 14 days after discontinuation of proton pump inhibitors.

Effect on ability to drive vehicles and operate machinery

Due to the possibility of dizziness and visual impairment, patients should refrain from driving vehicles and operating other machinery requiring increased attention during treatment.

Drug Interactions

Dexlansoprazole can be used without risk of drug interaction in patients taking clopidogrel. In case of concomitant use, no adjustment of the clopidogrel dose is required.

No clinically significant drug interactions with phenytoin, theophylline, and diazepam have also been noted.

Concomitant use of dexlansoprazole may affect the absorption of drugs whose bioavailability depends on gastric pH (e.g., ampicillin esters, digoxin, iron salts, ketoconazole, erlotinib).

Concomitant administration with tacrolimus may lead to an increase in tacrolimus plasma concentration, especially in transplant patients who are intermediate or poor metabolizers for the CYP2C19 isoenzyme.

When taken concomitantly with fluvoxamine, there is a possibility of increased systemic exposure to dexlansoprazole.

Concomitant administration of dexlansoprazole and methotrexate may lead to an increase and persistence of high serum concentrations of methotrexate and/or its metabolite, which may accordingly lead to the development of methotrexate toxicity. If high doses of methotrexate are necessary, temporary discontinuation of dexlansoprazole is recommended.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.