Class: Proton-pump Inhibitors
Chemical Name: 2-[(R)-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]sulfinyl]-1H-benzimidazole
Molecular Formula: C16H14F3N3O2S
CAS Number: 138530-94-6
Brands: Dexilant (formerly Kapidex)
Uses for Dexlansoprazole
Gastroesophageal Reflux (GERD)
Crohn’s Disease-associated Ulcers
Some evidence for use of proton-pump inhibitors (e.g., omeprazole) for gastric acid suppressive therapy as an adjunct in the management of upper GI Crohn’s disease†, including esophageal, gastroduodenal, and jejunoileal disease.14 15 16 17 18 19 20
Dexlansoprazole Dosage and Administration
Administer orally once daily.1
Administer without regard to food; however, if symptoms after a meal do not respond adequately to postprandial administration, consider preprandial administration (because the effect on gastric pH during the initial 4 hours after a dose may be decreased slightly when dexlansoprazole is taken after a meal).1 13
Swallow capsules whole; alternatively, open capsule and sprinkle contents on a tablespoonful of applesauce and swallow immediately without chewing.1
Chronic, lifelong therapy with a proton-pump inhibitor is appropriate for many GERD patients.6
Treatment of Erosive EsophagitisOral
60 mg once daily for up to 8 weeks.1
Maintenance of Healing of Erosive EsophagitisOral
GERD without Erosive EsophagitisOral
30 mg once daily for 4 weeks.1
No dosage adjustment necessary in mild hepatic impairment (Child-Pugh class A).1 Consider maximum dosage of 30 mg daily in moderate hepatic impairment (Child-Pugh class B).1 Not studied in severe hepatic impairment (Child-Pugh class C).1
No dosage adjustment necessary.1
No dosage adjustment necessary.1
Cautions for Dexlansoprazole
Known hypersensitivity to dexlansoprazole or any ingredient in the formulation.1
Hypersensitivity reactions (e.g., anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome) reported.1
Response to dexlansoprazole therapy does not preclude presence of occult gastric neoplasm.1
Clostridium difficile Infection
Proton-pump inhibitors associated with possible increased (1.4–2.75 times) risk of Clostridium difficile infection, including C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis).335 336 339 340 Many patients also had other risk factors for CDAD.335 May be severe; colectomy and, rarely, death reported.335
Use the lowest effective dosage and shortest duration of therapy appropriate for the patient's clinical condition.335
Consider CDAD if persistent diarrhea develops and manage accordingly; initiate supportive therapy (e.g., fluid and electrolyte management), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.335 336
Several observational studies suggest that use of proton-pump inhibitors, particularly in high dosages (i.e., multiple daily doses) and/or for prolonged periods of time (i.e., ≥1 year), may be associated with increased risk of osteoporosis-related fractures of the hip, wrist, or spine.1 9 300 301 302 303 304 305 Magnitude of risk is unclear;9 300 301 302 303 304 305 310 causality not established.305 FDA is continuing to evaluate this safety concern.305
Individuals at risk for osteoporosis-related fractures should receive an adequate intake of calcium and vitamin D; assess and manage these patients’ bone health according to current standards of care.1 9 303 305 307
Hypomagnesemia, symptomatic and asymptomatic, reported rarely in patients receiving long-term therapy (≥3 months or, in most cases, >1 year) with proton-pump inhibitors, including dexlansoprazole.1 317 318 319 320 321 322 323 324 325 326 327 328 329 330 Serious adverse effects include tetany, seizures, tremors, carpopedal spasm, arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia), and abnormal QT interval.1 318 319 321 322 323 325 327 328 329 Paresthesia, muscle weakness, muscle cramps, lethargy, fatigue, and unsteadiness may occur.319 320 321 325 330 Most patients required magnesium replacement and discontinuance of the proton-pump inhibitor.1 317 319 321 322 323 324 325 326 327 330 Hypomagnesemia resolved within 1 week (median) following discontinuance and recurred within 2 weeks (median) of rechallenge.327
In patients expected to receive long-term proton-pump inhibitor therapy or in patients currently receiving digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), consider measuring serum magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 319 326 327 328 330
Possible Prescribing and Dispensing Errors
Ensure accuracy of prescription; similarity in spelling of Kapidex (former trade name for dexlansoprazole) and Casodex (trade name for bicalutamide, a nonsteroidal antiandrogenic antineoplastic agent220 ) or Kadian (a trade name for morphine sulfate, an opiate agonist analgesic221 ) may result in errors.217 218 219 223 In April 2010, manufacturer changed trade name for dexlansoprazole from Kapidex to Dexilant to avoid future errors.1 217
Also be aware of potential for Kapidex to be confused with Capadex (fixed-combination propoxyphene/acetaminophen preparation that is available via the Internet and is marketed in certain other countries [e.g., Australia]).216 219
Safety and efficacy not established in children <18 years of age.1
No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.1
Systemic exposure to dexlansoprazole is increased approximately twofold in individuals with moderate hepatic impairment.1 Not studied in severe hepatic impairment.1 (See Hepatic Impairment under Dosage and Administration.)
Common Adverse Effects
Interactions for Dexlansoprazole
Metabolized by CYP2C19 and CYP3A4.1
Unlikely to inhibit CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A: Pharmacokinetic interaction unlikely.1
Drugs that Cause Hypomagnesemia
Potential pharmacologic interaction (possible increased risk of hypomagnesemia).327 Consider monitoring magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.1 327 (See Hypomagnesemia under Cautions.)
Manufacturer of dexlansoprazole states that concomitant administration with atazanavir is not recommended1
Antiretroviral treatment-naive patients: If a proton-pump inhibitor is used concomitantly with atazanavir, administer ritonavir-boosted atazanavir (atazanavir 300 mg and ritonavir 100 mg once daily with food);11 administer the proton-pump inhibitor approximately 12 hours before ritonavir-boosted atazanavir10 11
Certain CYP2C19 inhibitors (e.g., omeprazole, esomeprazole) reduce exposure to clopidogrel’s active metabolite and decrease platelet inhibitory effect; potentially may reduce clopidogrel’s clinical efficacy30 31 40 41 42 224 225 228 229 230 235 236 237 238 240 311
Manufacturer of dexlansoprazole states clopidogrel dosage adjustment not required if used with recommended dexlansoprazole dosages1
American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that GI bleeding risk reduction with concomitant proton-pump inhibitor in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or NSAIAs; H. pylori infection) may outweigh potential reduction in cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction.311 In patients without such risk factors, ACCF/ACG/AHA states that risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor.311
If concomitant therapy with a proton-pump inhibitor and clopidogrel is deemed necessary, consider using an agent with little or no CYP2C19-inhibitory activity;30 31 46 224 230 350 alternatively, consider using a histamine H2-receptor antagonist (ranitidine, famotidine, nizatidine)30 31 230 but not cimetidine (also a potent CYP2C19 inhibitor)232 233
See table entry for gastric pH-dependent drugs
Diuretics (i.e., loop or thiazide diuretics)
Possible increased risk of hypomagnesemia327
Use of esomeprazole with fosamprenavir (with or without ritonavir) did not substantially affect concentrations of amprenavir (active metabolite of fosamprenavir)345
Gastric pH-dependent drugs (e.g., ampicillin esters, digoxin, iron salts, ketoconazole)
Dexlansoprazole may alter drug absorption1
No dosage adjustment required when proton-pump inhibitors used with lopinavir/ritonavir10
Manufacturer of dexlansoprazole recommends considering temporary discontinuance of proton-pump inhibitor therapy in some patients receiving high-dose methotrexate1
Some clinicians recommend withholding the proton-pump inhibitor for several days before and after administration of either high-dose or low-dose methotrexate or, alternatively, substituting a histamine H2-receptor antagonist for the proton-pump inhibitor333 334
Possible increase in whole blood tacrolimus concentrations, particularly in transplant patients with intermediate or poor metabolizer phenotypes for CYPC191
No change in warfarin pharmacokinetics or INR observed in healthy individuals given warfarin 25 mg on day 6 of an 11-day course of dexlansoprazole 90 mg once daily;1 12 however, increased PT and INR reported in patients receiving warfarin concomitantly with proton-pump inhibitors1
May need to monitor PT and INR1
Commercially available capsules contain 2 types of enteric-coated granules that dissolve at different pH values.1 Following oral administration, an initial (smaller) peak plasma concentration occurs at 1–2 hours followed by a second (larger) peak concentration at 4–5 hours.1 25
Following once-daily administration for 5 days, gastric pH is >4 for 17 hours per day with dexlansoprazole 60 mg versus 14 hours per day with lansoprazole 30 mg.1
Administration in fed versus fasted state not associated with significant difference in mean gastric pH; however, effect on gastric pH during initial 4 hours after a dose may be decreased slightly when dexlansoprazole is taken after a meal.1 13 (See Oral Administration under Dosage and Administration.)
Plasma Protein Binding
Major circulating metabolite varies depending on CYP2C19 phenotype, but dexlansoprazole is the major circulating form of the drug regardless of CYP2C19 phenotype.1
Eliminated in urine (51%) and feces (48%); unchanged drug is not recovered in urine.1
Approximately 1–2 hours.1
Intermediate or poor metabolizers of CYP2C19 substrates: Systemic exposure to dexlansoprazole generally is increased.1 In Japanese men, AUC increased twofold in intermediate metabolizers and up to 12-fold in poor metabolizers compared with extensive metabolizers.1
Moderate hepatic impairment: Twofold increase in AUC.1
Renal impairment: Pharmacokinetic alterations not expected.1
Geriatric individuals: Half-life of 2.2 hours (versus 1.5 hours in younger individuals); not considered clinically important.1
25°C (may be exposed to 15–30°C).1
For information on systemic interactions resulting from concomitant use, see Interactions.
Immediately use extemporaneous mixtures of capsule contents and applesauce.1
Dexlansoprazole is the R-isomer of lansoprazole (a racemic mixture of R- and S-isomers).1 5 22 Both isomers inhibit hydrogen-potassium ATPase, but plasma clearance of dexlansoprazole is slower than that of S-lansoprazole.25 32
Proton-pump inhibitors inhibit basal and stimulated gastric acid secretion.24
Dexlansoprazole binds to and inactivates hydrogen-potassium ATPase (proton, hydrogen, or acid pump) in gastric parietal cells, blocking the final step in secretion of hydrochloric acid; results in potent, long-lasting inhibition of gastric acid secretion.1 22
Advice to Patients
Importance of swallowing capsule whole or, alternatively, of opening capsule and sprinkling contents on a tablespoonful of applesauce and swallowing immediately without chewing.1 Dexlansoprazole may be administered without regard to food (see Oral Administration under Dosage and Administration).1
Importance of continuing therapy for the entire treatment course, unless directed otherwise.1
Risk of hypomagnesemia; importance of immediately reporting and seeking care for any cardiovascular or neurologic manifestations (e.g., palpitations, dizziness, seizures, tetany).1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1
Possible increased risk of Clostridium difficile infection; importance of contacting a clinician if persistent watery stools, abdominal pain, and fever occur.335
Importance of informing clinicians of any symptoms suggestive of an allergic reaction (e.g., facial swelling, rash).1
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of informing patients of other important precautionary information.1 (See Cautions.)
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Capsules, delayed-release (containing enteric-coated granules)
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Dexilant 30MG Delayed-release Capsules (TAKEDA PHARMACEUTICALS): 30/$153.45 or 90/$420.39
Dexilant 60MG Delayed-release Capsules (TAKEDA PHARMACEUTICALS): 30/$149.99 or 90/$420.44
AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions February 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
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