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Dexlansoprazole

Pronunciation: DEX-lan-SOE-pra-zole
Class: Proton pump inhibitor

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Trade Names

Dexilant
- Capsules, delayed-release, oral 30 mg
- Capsules, delayed-release, oral 60 mg

Pharmacology

Suppresses gastric acid secretion via inhibition of the proton pump in the gastric parietal cell, which blocks the final step of acid production.

Pharmacokinetics

Absorption

Mean C _max and AUC values increase approximately dose-proportionally. The dual delayed-release formulation results in 2 distinct peaks: the first is at 1 to 2 h postdose and the second is at 4 to 5 h. C _max increased 12% to 55%, AUC increased 9% to 37%, and T _max varied from a decrease of 0.7 h to an increase of 3 h under fed conditions. Mean intragastric pH did not differ significantly, but the percentage of time intragastric pH exceeded 4 throughout the 24-h dosing interval decreased slightly when administered after a meal.

Distribution

Protein binding ranges from 96.1% to 98.8%. Apparent Vd is 40.3 L.

Metabolism

Extensively metabolized in the liver by oxidation, reduction, and subsequent formation of sulfate, glucuronide, and glutathione conjugates to inactive metabolites. Oxidative metabolites are formed by CYP enzyme systems, including hydroxylation primarily by CYP2C19, and oxidation to sulfones by CYP3A4.

Elimination

No unchanged drug is excreted in the urine. Approximately 50.7% is excreted in the urine and 47.6% in the feces. Apparent Cl is 11.5 L/h. Half-life is approximately 1 to 2 h.

Special Populations

Renal Function Impairment

No parent drug is excreted in the urine; therefore, pharmacokinetics are not expected to be altered and no dosage adjustment is needed in patients with renal impairment.

Hepatic Function Impairment

Plasma exposure to the drug is approximately 2 times greater in patients with moderate hepatic impairment compared with subjects with healthy hepatic function.

Elderly

Elimination half-life and AUC are increased in elderly subjects; however, no dosage adjustment is needed.

Children

Pharmacokinetics have not been studied.

Gender

Systemic exposure is higher in women than men; however, no dosage adjustment is needed.

CYP2C19 polymorphism

Systemic exposure is generally higher in intermediate and poor metabolizers.

Indications and Usage

Healing of all grades of erosive esophagitis; maintaining healing of erosive esophagitis; treatment of heartburn associated with nonerosive gastroesophageal reflux disease (GERD).

Contraindications

Hypersensitivity to dexlansoprazole or any component of the formulation.

Dosage and Administration

Healing of Erosive Esophagitis
Adults

PO 60 mg once daily for up to 8 wk.

Maintenance of Healing of Erosive Esophagitis
Adults

PO 30 mg once daily.

Symptomatic Nonerosive GERD
Adults

PO 30 mg once daily for 4 wk.

Hepatic Function Impairment
Adults Moderate hepatic impairment

PO Max of 30 mg once daily.

General Advice

May be taken without regard to meals. Some patients may benefit from administering the dose prior to a meal if postmeal symptoms do not resolve under postfed conditions.
Capsules should be taken whole; alternatively, capsule granules may be sprinkled intact on 1 Tbsp of applesauce and swallowed immediately. Granules should not be chewed.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Atazanavir, indinavir

Absorption may be decreased, resulting in loss of therapeutic effect of atazanavir and development of HIV resistance. Do not coadminister dexlansoprazole and atazanavir.

Clarithromycin, fluvoxamine

Dexlansoprazole plasma concentrations may be elevated, increasing the risk of adverse reactions. Monitor for an increase in adverse reactions.

Clopidogrel

Clopidogrel antiplatelet activity may be decreased. If concurrent use of dexlansoprazole and clopidogrel is clearly warranted, use with caution and closely monitor the clinical response.

Digoxin

Digoxin absorption may be increased, leading to elevated levels and increased risk of toxicity. Monitor digoxin concentrations and observe the patient for signs of digoxin toxicity. Adjust the digoxin dose as needed.

Drugs affected by gastric pH (eg, ampicillin esters, calcium salts, dasatinib, erlotinib, iron salts, nilotinib)

Bioavailability may be altered. Monitor the clinical response and adjust treatment as needed.

Itraconazole, ketoconazole

Itraconazole and ketoconazole absorption may be reduced, decreasing the pharmacologic effects. If possible, avoid this combination. It may be necessary for patients to take itraconazole and ketoconazole with an acidic beverage (eg, Coca-Cola ) to help increase azole antifungal absorption.

Mycophenolate

Mycophenolate plasma concentrations and pharmacologic effects may be decreased. Larger mycophenolate doses may be needed during coadministration of dexlansoprazole. Monitor the clinical response and adjust the mycophenolate dose as needed.

Salicylates, enteric-coated (eg, enteric-coated aspirin)

Monitor for increased gastric adverse effects. Advise patients who are at risk of serious gastric disorders to avoid concurrent use because of the release of salicylates in the stomach.

Tacrolimus

Tacrolimus whole blood levels may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Closely monitor tacrolimus plasma trough concentrations when dexlansoprazole is started or stopped. Clinical monitoring for signs and symptoms of toxicity is also warranted. Rabeprazole may be a potential alternative to dexlansoprazole.

Tolterodine ER

An increase in the release of tolterodine from the ER doseform may occur as a result of the increase in gastric pH associated with proton pump inhibitor administration. Plasma concentrations of tolterodine and its active metabolite may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Monitor the clinical response and for adverse reactions. Adjust the tolterodine dose as needed.

Voriconazole

Dexlansoprazole plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Close clinical monitoring is warranted. An initial reduction in the dexlansoprazole dose may be needed when voriconazole is added.

Warfarin

There have been reports of increased INR and PT in patients receiving proton pump inhibitors and warfarin concomitantly. Monitor patients for possible increases in INR and PT. Adjust the warfarin dose as needed.

Adverse Reactions

Cardiovascular

Angina, arrhythmia, bradycardia, chest pain, deep vein thrombosis, hot flush, hypertension, MI, palpitation, tachycardia (less than 2%).

CNS

Abnormal dreams, altered taste, anxiety, asthenia, convulsions, depression, dizziness, falls, feeling abnormal, headaches, insomnia, libido changes, memory impairment, migraine, paresthesia, psychomotor hyperactivity, tremor, trigeminal neuralgia (less than 2%).

Dermatologic

Acne, dermatitis, erythema, pruritus, rash, skin lesion, sunburn, urticaria (less than 2%).

EENT

Ear pain, eye irritation, eye swelling, nasopharyngitis, pharyngitis, sore throat, tinnitus, vertigo (less than 2%); auditory hallucination.

Endocrine

Goiter (less than 2%); hypothyroidism.

GI

Diarrhea (5%); abdominal pain (4%); flatulence, nausea (3%); vomiting (2%); abdominal discomfort, abdominal tenderness, abnormal bowel sounds, abnormal feces, anal discomfort, Barrett esophagus, bezoar, breath odor, colonic polyp, constipation, dry mouth, duodenitis, dyspepsia, dysphagia, enteritis, eructation, esophagitis, gastric polyp, gastritis, gastroenteritis, GERD, GI disorders, GI hypermotility, GI ulcers and perforation, hematemesis, hematochezia, hemorrhoids, impaired gastric emptying, irritable bowel syndrome, microscopic colitis, mucus stools, oral herpes, oral mucosal blistering, oral paresthesia, painful defecation, proctitis, rectal hemorrhage (less than 2%).

Genitourinary

Acute cholecystitis, dysmenorrhea, dyspareunia, dysuria, menorrhagia, menstrual disorder, micturition urgency, vulvovaginal infection (less than 2%); rectal tenesmus.

Hepatic

Biliary colic, cholelithiasis, hepatomegaly (less than 2%).

Hematologic-Lymphatic

Anemia, lymphadenopathy (less than 2%); decreased Hgb, decreased mean corpuscular Hgb concentration, epistaxis, increased neutrophils, neutropenia, thrombocythemia.

Hypersensitivity

Hypersensitivity (less than 2%); anaphylaxis.

Lab Tests

Abnormal LFTs, decreased and increased bilirubin, decreased platelet count, increased alkaline phosphatase, increased ALT and AST, increased blood creatinine, increased blood gastrin, increased blood glucose, increased blood potassium, increased total protein (less than 2%).

Metabolic-Nutritional

Appetite changes, edema, hypercalcemia, hypokalemia, weight increase (less than 2%); dehydration, diabetes mellitus, gout, hyperglycemia, hyperlipidemia.

Musculoskeletal

Arthralgia, arthritis, joint sprains, muscle cramps, musculoskeletal pain, myalgia (less than 2%).

Respiratory

Upper respiratory tract infection (3%); aspiration, asthma, bronchitis, cough, dyspnea, hiccups, hyperventilation, respiratory tract congestion, sinusitis (less than 2%).

Miscellaneous

Candida infections, chest pain, chills, inflammation, influenza, mucosal inflammation, nodule, overdosage, pain, procedural pain, pyrexia, viral infection (less than 2%); B-cell lymphoma.

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Greater sensitivity of some older individuals cannot be ruled out.

Hypersensitivity

Hypersensitivity and anaphylaxis have been reported.

Renal Function

No dosage adjustment is needed in patients with renal impairment.

Hepatic Function

Adjust dosage in patients with moderate hepatic impairment. Dosing in patients with severe hepatic impairment has not been studied.

Gastric malignancy

Symptomatic response does not preclude the presence of gastric malignancy.

Overdosage

Symptoms

Overdosage has not been reported.

Patient Information

Advise patients that product may be taken without regard to meals.
Advise patients to swallow capsules whole, or open capsule and sprinkle contents on 1 Tbsp of applesauce and swallow immediately.
Instruct patients to watch for signs of an allergic reaction because these could be serious and may require discontinuation of dexlansoprazole.
Advise patients to inform their health care provider if they are taking atazanavir, tacrolimus, warfarin, and drugs that are affected by gastric pH changes.
Advise patients to immediately report common cold, diarrhea, gas, stomach pain, and vomiting to health care provider.