Introduction
Dexilant (dexlansoprazole) is a proton pump inhibitor (PPI) approved by the FDA in 2009 for the treatment of gastroesophageal reflux disease (GERD) and related conditions. It is the R-enantiomer of lansoprazole and features a novel dual delayed-release formulation that provides two separate releases of medication for prolonged acid suppression.
Mechanism of Action
Dexlansoprazole is a proton pump inhibitor that suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. This enzyme system is regarded as the acid (proton) pump within the gastric mucosa, making dexlansoprazole a potent inhibitor of both basal and stimulated acid secretion. The drug is administered as a prodrug that undergoes activation in the acidic environment of the parietal cell canaliculi.
Indications
- Healing of all grades of erosive esophagitis (EE)
- Maintenance of healed erosive esophagitis
- Treatment of symptomatic non-erosive gastroesophageal reflux disease (GERD)
- Relief of heartburn associated with symptomatic GERD
Dosage and Administration
Adults:- Healing of erosive esophagitis: 60 mg once daily for up to 8 weeks
- Maintenance of healed EE: 30 mg once daily
- Symptomatic GERD: 30 mg once daily for 4 weeks
- Should be taken without regard to food
- Swallow capsules whole; do not crush or chew
- For patients with difficulty swallowing, capsules may be opened and sprinkled on one tablespoon of applesauce
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Consider dose reduction in patients with severe hepatic impairment
- Geriatric patients: No dosage adjustment necessary
Pharmacokinetics
Absorption: Dual delayed-release formulation results in two distinct peak plasma concentrations (1-2 hours and 4-5 hours post-dose). Bioavailability is approximately 76-90%. Distribution: Protein binding is 96-99%, primarily to albumin. Volume of distribution is approximately 40L. Metabolism: Extensively metabolized in the liver via cytochrome P450 system (CYP2C19 and CYP3A4). Elimination: Half-life is 1-2 hours. Excretion is primarily urinary (51%) with some fecal elimination (48%).Contraindications
- Known hypersensitivity to dexlansoprazole or any component of the formulation
- Patients taking rilpivirine-containing products
Warnings and Precautions
- Gastric malignancy: Symptomatic response does not preclude presence of gastric malignancy
- Acute interstitial nephritis: Has been observed with PPIs; monitor for changes in renal function
- Clostridium difficile-associated diarrhea: Increased risk with PPI use
- Bone fracture: Long-term therapy may be associated with increased risk of osteoporosis-related fractures
- Hypomagnesemia: Reported with prolonged PPI use; monitor magnesium levels
- Cutaneous and systemic lupus erythematosus: New onset or exacerbation may occur
Drug Interactions
- Clopidogrel: Reduced antiplatelet effect due to CYP2C19 inhibition
- Methotrexate: May increase methotrexate levels
- Warfarin: Increased INR and prothrombin time
- Digoxin: Increased digoxin absorption
- Ketoconazole, iron salts, erlotinib: Reduced absorption due to increased gastric pH
- CYP2C19 substrates: May alter metabolism of drugs such as phenytoin, diazepam
Adverse Effects
Common (≥2%):- Diarrhea (4.8%)
- Abdominal pain (4.0%)
- Nausea (3.2%)
- Upper respiratory infection (2.8%)
- Vomiting (2.6%)
- Flatulence (2.3%)
- Acute interstitial nephritis
- Clostridium difficile-associated diarrhea
- Vitamin B12 deficiency (with long-term use)
- Hypomagnesemia
- Bone fracture
Monitoring Parameters
- Symptom improvement and resolution
- Renal function (BUN, creatinine)
- Magnesium levels (with prolonged use)
- Vitamin B12 levels (with long-term therapy)
- Bone density (with long-term use in high-risk patients)
- Signs of gastrointestinal bleeding
Patient Education
- Take medication as directed, usually once daily
- Report any signs of allergic reaction (rash, itching, swelling)
- Inform healthcare provider of all medications being taken
- Report persistent diarrhea, abdominal pain, or bloody stools
- Long-term use may require monitoring of vitamin B12 and magnesium levels
- Do not stop medication abruptly without consulting healthcare provider
- Report any new or worsening symptoms of joint pain or fractures
References
1. Dexilant [package insert]. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2021. 2. Fass R, Shapiro M, Dekel R, et al. Systematic review: proton-pump inhibitor failure in gastroesophageal reflux disease—where next? Aliment Pharmacol Ther. 2015;42(10):1187-1201. 3. Vakil N, van Zanten SV, Kahrilas P, et al. The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol. 2006;101(8):1900-1920. 4. Strand DS, Kim D, Peura DA. 25 years of proton pump inhibitors: a comprehensive review. Gut Liver. 2017;11(1):27-37. 5. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitors. US Food and Drug Administration. 2011. 6. Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-691.