brand dexilant dr 30 mg capsule

Uses

Gastroesophageal Reflux

Dexlansoprazole is used for short-term (up to 8 weeks) treatment of all grades of erosive esophagitis, as maintenance therapy (for up to 6 months) following healing of erosive esophagitis to reduce recurrence of the disease, and for short-term (up to 4 weeks) management of symptoms (e.g., heartburn) of gastroesophageal reflux disease (GERD) in patients without erosive esophagitis.

Suppression of gastric acid secretion is considered by the American College of Gastroenterology (ACG) to be the mainstay of treatment for GERD, and a proton-pump inhibitor or histamine H₂-receptor antagonist is used to achieve acid suppression, control symptoms, and prevent complications of the disease. Because GERD is a chronic condition, the ACG states that continuous therapy to control symptoms and prevent complications is appropriate, and chronic, even lifelong, use of a proton-pump inhibitor is effective and appropriate as maintenance therapy in many patients with GERD. The ACG states that proton-pump inhibitors are more effective (i.e., provide more frequent and more rapid symptomatic relief and healing of esophagitis) than histamine H₂-receptor antagonists in the treatment of GERD. Proton-pump inhibitors also provide greater control of acid reflux than do prokinetic agents (e.g., cisapride [no longer commercially available in the US], metoclopramide) without the risk of severe adverse effects associated with these agents.

Efficacy of dexlansoprazole in the treatment of endoscopically diagnosed erosive esophagitis was established in 2 controlled studies in patients receiving dexlansoprazole 60 or 90 mg daily or lansoprazole 30 mg daily for 8 weeks. Healing rates at 4 weeks were similar for dexlansoprazole 60 mg daily and lansoprazole 30 mg daily (66-70 and 65%, respectively). Findings of one study showed higher rates of healing (85 versus 79%) for dexlansoprazole 60 mg daily versus lansoprazole 30 mg daily at 8 weeks; however, in the other study, healing rates at 8 weeks for these 2 regimens did not differ significantly (87 versus 85%, respectively). No additional benefit of the 90-mg dosage over the 60-mg dosage of dexlansoprazole was reported.

Efficacy of dexlansoprazole as maintenance therapy following healing of erosive esophagitis was established in a controlled study in patients with endoscopically confirmed healing of erosive esophagitis who received dexlansoprazole 30 or 60 mg daily or placebo for 6 months. Healing was maintained in 66% of patients receiving dexlansoprazole 30 mg daily compared with 14% of patients receiving placebo. In addition, patients receiving dexlansoprazole 30 mg daily reported a higher percentage of heartburn-free 24-hour periods over 6 months of maintenance therapy than did patients receiving placebo. Most patients receiving placebo discontinued such treatment between months 2 and 6 because of recurrent erosive esophagitis. No additional clinical benefit of the 60-mg dosage over the 30-mg dosage was reported.

Efficacy in patients with symptomatic nonerosive GERD was established in a controlled study in patients with a 6-month or longer history of heartburn episodes, no endoscopic evidence of erosive esophagitis, and heartburn for at least 4 of the 7 days immediately prior to randomization; patients received dexlansoprazole 30 or 60 mg daily or placebo for 4 weeks. The median percentage of days (24-hour periods) without heartburn was 55 or 19% during 4 weeks of therapy with dexlansoprazole or placebo, respectively; no additional benefit of the 60-mg dosage over the 30-mg dosage was reported.

For further information on the treatment of GERD,

Crohn's Disease-associated Ulcers

Although evidence currently is limited, proton-pump inhibitors have been used for gastric acid-suppressive therapy as an adjunct in the symptomatic treatment of upper GI Crohn's disease, including esophageal, gastroduodenal, and jejunoileal disease. Most evidence of efficacy to date has been from case studies in patients with Crohn's-associated peptic ulcer disease unresponsive to other therapies (e.g., histamine H₂-receptor antagonists, cytoprotective agents, antacids, and/or sucralfate).

For further information on the management of Crohn's disease,

Dosage and Administration

Administration

Dexlansoprazole is administered orally once daily. The drug may be taken without regard to food; however, 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, patients with postprandial symptoms that do not respond adequately to postprandial administration may benefit from preprandial administration of the drug. Dexlansoprazole capsules should be swallowed whole; alternatively, the contents of a capsule may be sprinkled on a tablespoonful of applesauce and swallowed immediately without chewing.

Dispensing and Administration Precautions

Dispensing errors have occurred because of similarity in spelling between Kapidex (the former trade name for dexlansoprazole) and Casodex (the trade name for bicalutamide, a nonsteroidal antiandrogenic antineoplastic agent) or Kadian (a trade name for an extended-release capsule preparation of morphine sulfate, an opiate agonist analgesic). Therefore, in April 2010, the manufacturer of Kapidex changed the trade name for dexlansoprazole from Kapidex to Dexilant to avoid future dispensing errors.(See Dispensing and Administration Precautions under Cautions: Warnings/Precautions.)

Dosage

Gastroesophageal Reflux

For short-term treatment of erosive esophagitis, the recommended adult dosage of dexlansoprazole is 60 mg once daily for up to 8 weeks. For maintenance therapy following healing of erosive esophagitis, the recommended adult dosage of dexlansoprazole is 30 mg once daily for up to 6 months. The manufacturer states that controlled studies of dexlansoprazole maintenance therapy beyond 6 months have not been performed. For short-term management of symptomatic gastroesophageal reflux disease (GERD) in patients without erosive esophagitis, the recommended adult dosage of dexlansoprazole is 30 mg once daily for 4 weeks. However, the American College of Gastroenterology (ACG) states that chronic, even lifelong, therapy with a proton-pump inhibitor is appropriate in many patients with GERD.

Special Populations

No adjustment of dexlansoprazole dosage is necessary in geriatric patients, patients with renal impairment, or patients with mild hepatic impairment (Child-Pugh class A). The manufacturer states that a maximum dosage of 30 mg daily should be considered in patients with moderate hepatic impairment (Child-Pugh class B). The drug has not been studied in patients with severe hepatic impairment (Child-Pugh class C).

Cautions

Contraindications

Known hypersensitivity to dexlansoprazole or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome) have been reported with dexlansoprazole.

Gastric Malignancy

Symptomatic response to therapy with dexlansoprazole does not preclude the presence of gastric malignancy.

Clostridium difficile Infection

Available data suggest a possible association between use of proton-pump inhibitors and risk of Clostridium difficile infection, including C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis). In most observational studies to date, the risk of C. difficile infection in patients exposed to proton-pump inhibitors has ranged from 1.4-2.75 times that in patients not exposed to proton-pump inhibitors; however, some observational studies have found no increase in risk. Although many of the cases occurred in patients who had other risk factors for CDAD, including advanced age, comorbid conditions, and/or use of broad-spectrum anti-infectives, the US Food and Drug Administration (FDA) concluded that a contributory role for proton-pump inhibitors could not be definitively ruled out. The mechanism by which proton-pump inhibitors might increase the risk of CDAD has not been elucidated. Although it has been suggested that reduction of gastric acidity by gastric antisecretory agents might facilitate colonization with C. difficile, some studies have raised questions about this proposed mechanism or have suggested that the observed association is the result of confounding with other risk factors for CDAD. FDA also is reviewing the risk of CDAD in patients exposed to histamine H₂-receptor antagonists.

CDAD can be serious in patients who have one or more risk factors for C. difficile infection and are receiving concomitant therapy with a proton-pump inhibitor; colectomy and, rarely, death have been reported. FDA recommends that patients receive proton-pump inhibitors at the lowest effective dosage and for the shortest possible time appropriate for their clinical condition. Patients experiencing persistent diarrhea should be evaluated for CDAD and should be managed with appropriate 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.

Musculoskeletal Effects

Findings from several observational studies suggest that therapy with proton-pump inhibitors, particularly in high dosages (i.e., multiple daily doses) and/or for prolonged periods of time (i.e., one year or longer), may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The magnitude of risk is unclear; causality has not been established. FDA is continuing to evaluate this safety concern. Although controlled studies are required to confirm these findings, patients should receive proton-pump inhibitors at the lowest effective dosage and for the shortest possible time appropriate for their clinical condition. Individuals who are at risk for osteoporosis-related fractures should receive an adequate intake of calcium and vitamin D and should have their bone health assessed and managed according to current standards of care.

Hypomagnesemia

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients receiving long-term therapy (for at least 3 months or, in most cases, for longer than one year) with proton-pump inhibitors, including dexlansoprazole. Clinically serious adverse effects associated with hypomagnesemia, which are similar to manifestations of hypocalcemia, include tetany, seizures, tremors, carpopedal spasm, arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia), and abnormal QT interval. Other reported adverse effects include paresthesia, muscle weakness, muscle cramps, lethargy, fatigue, and unsteadiness. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuance of the proton-pump inhibitor. Following discontinuance of the proton-pump inhibitor, hypomagnesemia resolved within a median of one week; upon rechallenge, hypomagnesemia recurred within a median of 2 weeks.

In patients expected to receive long-term therapy with a proton-pump inhibitor or in those receiving a proton-pump inhibitor concomitantly with digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), clinicians should consider measurement of serum magnesium concentrations prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter. (.)

Respiratory Effects

Administration of proton-pump inhibitors has been associated with an increased risk for developing certain infections (e.g., community-acquired pneumonia). For further precautionary information about this adverse effect,

Dispensing and Administration Precautions

Because of similarity in spelling between Kapidex (the former trade name for dexlansoprazole) and Casodex (the trade name for bicalutamide, a nonsteroidal antiandrogenic antineoplastic agent) or Kadian (a trade name for morphine sulfate, an opiate agonist), dispensing errors have been reported. Therefore, in April 2010, the manufacturer of Kapidex changed the trade name for dexlansoprazole from Kapidex to Dexilant to avoid future dispensing errors. The potential exists for serious adverse effects to occur if patients receive the incorrect drug. Bicalutamide may cause fetal harm if used during pregnancy, and use of this drug is contraindicated in women. Kadian is an extended-release morphine sulfate preparation intended for use in managing moderate to severe pain when a continuous around-the-clock opiate analgesic is needed for an extended period of time; ingestion of 100- or 200-mg Kadian capsules by patients who are not opiate tolerant can cause fatal respiratory depression. In addition, there is a potential for the trade name Kapidex to be confused with Capadex (a trade name for a fixed-combination preparation containing propoxyphene and acetaminophen that is available via the Internet and marketed in certain other countries [e.g., Australia]). Some experts recommend that pharmacists assess measures of avoiding dispensing errors and implement them as appropriate (e.g., by using computerized name alerts, matching the prescribed drug with the patient's medical history, verifying orders for these drugs) and that clinicians consider including the intended use of the drug on the prescription.

Specific Populations

Pregnancy

Category B.

Lactation

It is unknown whether dexlansoprazole is distributed into milk. However, lansoprazole and its metabolites are distributed into milk in rats; the manufacturer states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Pediatric Use

Safety and efficacy have not been established in pediatric patients younger than 18 years of age.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity of some older patients cannot be ruled out.

Hepatic Impairment

Systemic exposure to dexlansoprazole is increased approximately twofold in individuals with moderate hepatic impairment. The drug has not been studied in severe hepatic impairment.(See Dosage and Administration: Special Populations.)

Renal Impairment

Because dexlansoprazole is extensively metabolized in the liver to inactive metabolites, and unchanged drug is not recovered in urine following administration of an oral dose, renal impairment is not expected to affect the pharmacokinetics of the drug.

Common Adverse Effects

Adverse effects reported in 2% or more of patients receiving dexlansoprazole and more frequently than with placebo include diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence.

Drug Interactions

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Dexlansoprazole is metabolized by cytochrome P-450 (CYP) isoenzymes 2C19 and 3A4. In vitro studies indicate that dexlansoprazole is unlikely to inhibit CYP isoenzymes 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4; therefore, interactions with drugs metabolized by these isoenzymes are considered unlikely. Dexlansoprazole did not alter the pharmacokinetics of diazepam (a CYP2C19 substrate) in healthy individuals (mainly extensive or intermediate metabolizers of CYP2C19 substrates), nor did dexlansoprazole alter the pharmacokinetics of phenytoin (a CYP2C9 substrate) or theophylline (a CYP1A2 substrate) in healthy individuals; CYP1A2 genotypes were not determined.

Drugs that Cause Hypomagnesemia

Potential pharmacologic interaction (possible increased risk of hypomagnesemia). In patients receiving diuretics (i.e., loop or thiazide diuretics) or other drugs that may cause hypomagnesemia, monitoring of magnesium concentrations should be considered prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.(See Hypomagnesemia under Warnings/Precautions: General Precautions, in Cautions.)

Gastric pH-dependent Drugs

Pharmacokinetic interaction is possible when dexlansoprazole is used concomitantly with gastric pH-dependent drugs (e.g., ketoconazole, iron salts, digoxin, ampicillin esters); altered absorption at increased gastric pH values.

Antiretroviral Agents

Atazanavir

Potential pharmacokinetic interaction with atazanavir (possible altered oral absorption of atazanavir at increased gastric pH, resulting in decreased plasma atazanavir concentrations). Concomitant use of omeprazole 40 mg once daily and atazanavir (with or without low-dose ritonavir) results in a substantial decrease in plasma concentrations of atazanavir and possible loss of the therapeutic effect of the antiretroviral agent. The manufacturer of dexlansoprazole states that concomitant administration with atazanavir is not recommended. If atazanavir is administered in a treatment-naive patient receiving a proton-pump inhibitor, a ritonavir-boosted regimen of 300 mg of atazanavir once daily with ritonavir 100 mg once daily with food is recommended. The dose of the proton-pump inhibitor should be administered approximately 12 hours before ritonavir-boosted atazanavir; the dose of the proton-pump inhibitor should not exceed omeprazole 20 mg daily (or equivalent). Concomitant use of proton-pump inhibitors with atazanavir is not recommended in treatment-experienced patients.

Fosamprenavir

Concomitant use of esomeprazole with fosamprenavir (with or without ritonavir) did not substantially affect concentrations of amprenavir (active metabolite of fosamprenavir). No dosage adjustment is required when proton-pump inhibitors are used concomitantly with fosamprenavir (with or without ritonavir).

Lopinavir

Concomitant use of omeprazole with the fixed combination of lopinavir and ritonavir (lopinavir/ritonavir) did not have a clinically important effect on plasma concentrations or area under the concentration-time curve (AUC) of lopinavir. No dosage adjustment is required when proton-pump inhibitors are used concomitantly with lopinavir/ritonavir.

Raltegravir

Pharmacokinetic interaction with omeprazole (substantially increased peak plasma concentration and AUC of raltegravir); however, no dosage adjustment is recommended when proton-pump inhibitors are used concomitantly with raltegravir.

Rilpivirine

Pharmacokinetic interaction with omeprazole (decreased plasma concentrations and AUC of rilpivirine). Concomitant use of other proton-pump inhibitors also may result in decreased plasma concentrations of rilpivirine. Concomitant use of rilpivirine and proton-pump inhibitors is contraindicated.

Saquinavir

Potential pharmacokinetic interaction (increased peak plasma concentration and AUC of saquinavir). Concomitant use of omeprazole 40 mg once daily and ritonavir-boosted saquinavir (saquinavir 1 g twice daily and ritonavir 100 mg twice daily) increased the peak plasma concentration and AUC of saquinavir by 75 and 82%, respectively. Caution is advised if proton-pump inhibitors are used concomitantly with ritonavir-boosted saquinavir, and patients should be monitored for saquinavir toxicity.

Clopidogrel

Potential pharmacokinetic interaction (decreased plasma concentration of the active metabolite of clopidogrel) and pharmacodynamic interaction (reduced antiplatelet effects) between proton-pump inhibitors and clopidogrel. Clopidogrel is metabolized to its active metabolite by CYP2C19. Concurrent use of omeprazole or esomeprazole, which inhibit CYP2C19, with clopidogrel reduces exposure to the active metabolite of clopidogrel and decreases platelet inhibitory effects. Although the clinical importance has not been fully elucidated, a reduction in the effectiveness of clopidogrel in preventing cardiovascular events is possible. Proton-pump inhibitors vary in their potency for inhibiting CYP2C19. The change in inhibition of adenosine diphosphate (ADP)-induced platelet aggregation associated with concomitant use of proton-pump inhibitors is related to the change in exposure to the active metabolite of clopidogrel. In pharmacokinetic and pharmacodynamic studies in healthy individuals, concomitant use of dexlansoprazole, lansoprazole, or pantoprazole had less effect on the antiplatelet activity of clopidogrel than did concomitant use of omeprazole or esomeprazole. In individuals who were extensive metabolizers of CYP2C19 substrates, use of dexlansoprazole (60 mg once daily) concomitantly with clopidogrel (75 mg once daily) for 9 days reduced exposure to the active metabolite of clopidogrel by about 9% compared with use of clopidogrel alone. The observed effects of dexlansoprazole on metabolite exposure and clopidogrel-induced platelet inhibition were not considered clinically important, and the manufacturer of dexlansoprazole states that no adjustment of clopidogrel dosage is necessary if clopidogrel is used concomitantly with recommended dosages of dexlansoprazole.

The decision to use a proton-pump inhibitor concomitantly with clopidogrel should be based on the assessed risks and benefits in individual patients. The American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) states that the reduction in GI bleeding risk with proton-pump inhibitors is substantial in patients with risk factors for GI bleeding (e.g., advanced age; concomitant use of warfarin, corticosteroids, or nonsteroidal anti-inflammatory agents [NSAIAs]; H. pylori infection) and may outweigh any potential reduction in the cardiovascular efficacy of antiplatelet treatment associated with a drug-drug interaction. In contrast, ACCF/ACG/AHA states that patients without such risk factors receive little if any absolute risk reduction from proton-pump inhibitor therapy, and the risk/benefit balance may favor use of antiplatelet therapy without a proton-pump inhibitor in these patients.

If concomitant therapy with a proton-pump inhibitor and clopidogrel is considered necessary, use of an agent with little or no CYP2C19-inhibitory activity should be considered. Alternatively, treatment with a histamine H₂-receptor antagonist (ranitidine, famotidine, nizatidine) may be considered, although such agents may not be as effective as a proton-pump inhibitor in providing gastric protection; cimetidine should not be used since it also is a potent CYP2C19 inhibitor. There currently is no evidence that histamine H₂-receptor antagonists (other than cimetidine) or other drugs that reduce gastric acid (e.g., antacids) interfere with the antiplatelet effects of clopidogrel. For further information on interactions between proton-pump inhibitors and clopidogrel, .

Digoxin

Hypomagnesemia (e.g., resulting from long-term use of proton-pump inhibitors) sensitizes the myocardium to digoxin and, thus, may increase the risk of digoxin-induced cardiotoxic effects. In patients receiving digoxin, monitoring of magnesium concentrations should be considered prior to initiation of prescription proton-pump inhibitor therapy and periodically thereafter.

Methotrexate

Potential pharmacokinetic interaction (increased serum methotrexate concentrations, possibly resulting in toxicity) when proton-pump inhibitors, including dexlansoprazole, are used concomitantly with methotrexate. Increased serum concentrations and delayed clearance of methotrexate and/or its metabolite hydroxymethotrexate, with or without symptoms of methotrexate toxicity, have been reported in patients receiving methotrexate (usually at doses of 300 mg/m to 12 g/m) concomitantly with a proton-pump inhibitor. Although most of the reported cases occurred in patients receiving high doses of methotrexate, toxicity also has been reported in patients receiving low dosages of methotrexate (e.g., 15 mg per week) concomitantly with a proton-pump inhibitor. No formal studies of interactions between high-dose methotrexate and proton-pump inhibitors have been conducted to date.

The manufacturer of dexlansoprazole states that temporary discontinuance of proton-pump inhibitor therapy may be considered in some patients receiving high-dose methotrexate therapy. Some clinicians recommend either withholding proton-pump inhibitor therapy for several days before and after methotrexate administration or substituting a histamine H₂-receptor antagonist for the proton-pump inhibitor when acid suppressive therapy is indicated during methotrexate therapy. Pending further evaluation, some clinicians state that these recommendations should extend to patients receiving low-dose methotrexate.

Tacrolimus

Potential pharmacokinetic interaction (increased whole blood concentrations of tacrolimus, particularly in transplant patients who are intermediate or poor metabolizers of CYP2C19 substrates).

Warfarin

When warfarin 25 mg was administered orally on day 6 of an 11-day course of dexlansoprazole 90 mg once daily in healthy individuals, the pharmacokinetics of warfarin and the international normalized ratio (INR) were not altered; however, increased INR and prothrombin time have been reported in patients receiving warfarin concomitantly with proton-pump inhibitors. The INR and prothrombin time may need to be monitored when dexlansoprazole is used concomitantly with warfarin.