Dexlansoprazole
Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Healing of all grades of erosive esophagitis (EE) | ≥12 years | Monotherapy | FDA Approved |
| Maintenance of healed EE and relief of heartburn | ≥12 years | Monotherapy | FDA Approved |
| Symptomatic non-erosive GERD | ≥12 years | Monotherapy | FDA Approved |
Dexlansoprazole is the R-enantiomer of lansoprazole, formulated in a unique dual delayed-release technology that produces two distinct plasma peaks. Its FDA-approved indications are focused exclusively on GERD-spectrum conditions — erosive esophagitis healing and maintenance, and symptomatic non-erosive GERD. Unlike its racemic parent lansoprazole, dexlansoprazole does not carry indications for peptic ulcer disease, H. pylori eradication, NSAID-associated ulcers, or Zollinger-Ellison syndrome. Its key clinical advantage is the ability to be taken without regard to meal timing, a flexibility enabled by the dual-release pharmacokinetic profile.
Eosinophilic oesophagitis (EoE) — Evidence quality: Moderate. PPI-responsive EoE is a recognised entity, and PPIs including dexlansoprazole are used as initial therapy per gastroenterology guidelines, though the specific evidence base is predominantly with omeprazole and esomeprazole.
Non-variceal upper GI bleeding prophylaxis — Evidence quality: Low. Used empirically in some settings though data specific to dexlansoprazole is lacking; no IV formulation available.
Dosing
Dosing by Clinical Scenario (Patients ≥12 Years)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Erosive esophagitis — healing (all grades) | 60 mg once daily | 60 mg once daily | 60 mg/day | Up to 8 weeks Can be taken with or without food; swallow whole or sprinkle on applesauce |
| Healed EE — maintenance and heartburn relief | 30 mg once daily | 30 mg once daily | 30 mg/day | Controlled studies: up to 6 months in adults, up to 16 weeks in patients 12–17 years |
| Symptomatic non-erosive GERD — heartburn | 30 mg once daily | 30 mg once daily | 30 mg/day | 4 weeks |
Hepatic Impairment
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| EE healing — moderate hepatic impairment (Child-Pugh B) | 30 mg once daily | 30 mg once daily | 30 mg/day | Up to 8 weeks; dose reduced from 60 mg due to increased exposure |
| Severe hepatic impairment (Child-Pugh C) | Not recommended | |||
Dexlansoprazole’s dual delayed-release formulation allows dosing without regard to meal timing — a meaningful practical advantage over lansoprazole, omeprazole, and esomeprazole, which must be taken before meals for optimal absorption. In food-effect studies, Cmax increased 12–55% and AUC increased 9–37% with food, but these changes did not affect clinical efficacy, supporting the flexible dosing instruction. Capsules can be opened and sprinkled on applesauce, or given via oral syringe or nasogastric tube (≥16 French) with water.
Pharmacology
Mechanism of Action
Dexlansoprazole is the R-enantiomer of lansoprazole, a substituted benzimidazole that suppresses gastric acid secretion by irreversibly inhibiting the H+/K+-ATPase proton pump at the secretory surface of gastric parietal cells. Like its racemic parent, dexlansoprazole is a prodrug that accumulates in the acidic canalicular compartment of active parietal cells, where it undergoes acid-catalysed conversion to a reactive sulfenamide that covalently binds cysteine residues on the proton pump. The unique pharmacological feature of dexlansoprazole is its dual delayed-release formulation, which contains two types of enteric-coated granules with different pH-dependent dissolution profiles. This produces two distinct plasma peaks — the first at approximately 1–2 hours and the second at 4–5 hours post-dose — resulting in a prolonged plasma concentration profile and extended duration of acid suppression compared to conventional single-release PPIs.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Dual delayed-release: two plasma peaks at 1–2 h and 4–5 h; food increases Cmax by 12–55% and AUC by 9–37% but does not affect efficacy; highly variable PK (CV% >25%) | Can be taken with or without food; dual peaks extend the period of effective plasma concentration |
| Distribution | 96–99% plasma protein bound (concentration-independent over 0.01–20 mcg/mL); concentrates in parietal cell canaliculi | Extensively protein bound; not expected to be removed by haemodialysis |
| Metabolism | Extensive hepatic metabolism by oxidation, reduction, and conjugation (sulfate, glucuronide, glutathione); CYP2C19 (hydroxylation, major) and CYP3A4 (sulfone) are the primary enzymatic pathways; metabolites inactive | CYP2C19 poor metabolisers have higher exposure; dose reduction for moderate hepatic impairment (Child-Pugh B); not recommended in severe impairment (Child-Pugh C) |
| Elimination | t½ ~1–2 h; no clinically meaningful accumulation with daily dosing (AUC <10% higher on day 5 vs day 1) | Despite short half-life, dual-release design extends acid suppression; no renal dose adjustment needed |
Side Effects
No individual adverse reaction exceeded 10% incidence in controlled adult trials. Safety was evaluated in 4,548 adults across controlled and single-arm studies, with 863 treated for ≥6 months and 203 for ≥1 year.
| Adverse Effect | Incidence (Total) | Clinical Note |
|---|---|---|
| Diarrhoea | 4.8% (vs 2.9% placebo; 30 mg: 5.1%, 60 mg: 4.7%) | Most common adverse reaction overall; led to discontinuation in 0.7% of patients |
| Abdominal pain | 4.0% (vs 3.5% placebo) | Similar to placebo at the 30 mg dose (3.5%); slightly higher at 60 mg (4.0%) |
| Nausea | 2.9% (vs 2.6% placebo) | Marginally above placebo; 30 mg: 3.3%, 60 mg: 2.8% |
| Upper respiratory tract infection | 1.9% (vs 0.8% placebo; 30 mg: 2.9%) | Higher at the 30 mg dose (2.9%) than the 60 mg dose (1.7%) |
| Vomiting | 1.6% (vs 0.8% placebo; 30 mg: 2.2%) | More common at 30 mg than 60 mg |
| Flatulence | 1.6% (vs 0.6% placebo; 30 mg: 2.6%) | More common at 30 mg than 60 mg |
In adolescents (12–17 years, N=166), the most common adverse reactions (≥5%) were headache, abdominal pain, diarrhoea, nasopharyngitis, and oropharyngeal pain. The profile was consistent with that observed in adults.
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Clostridioides difficile-associated diarrhoea | Rare | Days to months | Stool testing; discontinue PPI; targeted antibiotic therapy |
| Acute tubulointerstitial nephritis | Rare | Any point during therapy | Discontinue dexlansoprazole; evaluate renal function |
| Severe cutaneous reactions (SJS, TEN, DRESS, AGEP) | Very rare; some fatal | Days to weeks | Immediate discontinuation; emergency dermatological care |
| Hypomagnesaemia | Rare | Usually after ≥3 months; most after ≥1 year | Check magnesium; supplement; consider PPI discontinuation |
| Osteoporosis-related fractures | Rare; increased with long-term use | After ≥1 year | Use lowest dose/shortest duration; manage per guidelines |
| Cutaneous and systemic lupus erythematosus | Very rare | Weeks to years | Discontinue PPI; refer to specialist; most resolve in 4–12 weeks |
| Vitamin B12 deficiency | Rare; with use >3 years | After years of continuous use | Monitor B12; supplement if deficient |
| Fundic gland polyps | Uncommon; risk increases >1 year | Months to years | Usually asymptomatic; use shortest PPI duration |
| Anaphylactic shock | Very rare (post-marketing) | Any time | Emergency care; permanent discontinuation |
| Drug-induced hepatitis | Very rare (post-marketing) | Variable | Monitor liver function; discontinue if suspected |
Diarrhoea occurred in 4.8% of dexlansoprazole-treated adults (vs 2.9% placebo) and was the most common cause of treatment discontinuation (0.7%). Rates were similar between the 30 mg and 60 mg doses. In most cases, diarrhoea was mild and self-limiting. Persistent or severe diarrhoea warrants evaluation for C. difficile, especially in hospitalised patients or those concurrently receiving antibiotics.
Drug Interactions
Dexlansoprazole is metabolised primarily by CYP2C19 and CYP3A4. In vitro studies show it is unlikely to inhibit CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2D6, 2E1, or 3A4. In vivo studies confirmed no impact on the pharmacokinetics of phenytoin (CYP2C9 substrate) or theophylline (CYP1A2 substrate). Although dexlansoprazole has the potential to inhibit CYP2C19 in vitro, an in vivo study in CYP2C19 extensive and intermediate metabolisers showed no clinically relevant effect on diazepam pharmacokinetics.
Monitoring
- MagnesiumBaseline and periodically if use >3 months
RoutineSerum magnesium prior to initiation and periodically during prolonged use. Also monitor calcium in patients with pre-existing hypocalcaemia risk. Supplement as needed; consider PPI discontinuation if hypocalcaemia is refractory. - Vitamin B12Consider after ≥3 years
Trigger-basedMonitor if symptoms of B12 deficiency develop. Long-term acid suppression impairs B12 absorption. - Renal FunctionIf signs of nephritis
Trigger-basedMonitor creatinine if unexplained renal decline. Acute TIN can occur at any point during therapy. - Bone DensityPer guidelines
Trigger-basedConsider DXA for patients on long-term high-dose PPI therapy with fracture risk factors. - Chromogranin AHold PPI ≥14 days before testing
Trigger-basedPPI-induced hypergastrinaemia elevates CgA and ECL cell hyperplasia; causes false positives in neuroendocrine tumour workups. - Symptom Response4–8 weeks
RoutineAssess symptom resolution at end of treatment course. Suboptimal response does not exclude gastric malignancy — consider endoscopy in older adults.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to any component of the formulation (reactions include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute TIN, urticaria)
- Concomitant use with rilpivirine-containing products
Relative Contraindications (Specialist Input Recommended)
- Severe hepatic impairment (Child-Pugh C) — dexlansoprazole is not recommended; no clinical data in this population
- Concurrent high-dose methotrexate — consider temporary PPI withdrawal
Use with Caution
- Moderate hepatic impairment (Child-Pugh B) — reduce EE healing dose to 30 mg once daily
- Long-term use (>1 year) — increased risks of hypomagnesaemia, B12 deficiency, bone fractures, fundic gland polyps
- Paediatric patients <2 years — not recommended due to risk of heart valve thickening demonstrated in juvenile rat studies with lansoprazole
- Pregnancy — animal data suggest possible adverse effects on fetal bone growth; use only if clearly needed
- Hospitalised patients or those on antibiotics — increased C. difficile risk
The FDA has issued safety communications regarding class-wide PPI risks, including C. difficile-associated diarrhoea, bone fractures, hypomagnesaemia, vitamin B12 deficiency, cutaneous and systemic lupus erythematosus, fundic gland polyps, and severe cutaneous adverse reactions (SJS, TEN, DRESS, AGEP). Use the lowest effective dose for the shortest clinically appropriate duration.
Patient Counselling
Purpose of Therapy
Dexlansoprazole reduces stomach acid to heal damage caused by acid reflux and to relieve heartburn. It may be prescribed for a short course (4–8 weeks) or for ongoing maintenance to prevent reflux damage from returning.
How to Take
Dexlansoprazole can be taken at any time of day, with or without food. Swallow the capsule whole. If unable to swallow capsules, open the capsule and sprinkle the granules on one tablespoon of applesauce — swallow immediately without chewing. The granules can also be given through an oral syringe with water or via a nasogastric tube.
Sources
- DEXILANT (dexlansoprazole) delayed-release capsules prescribing information. Takeda Pharmaceuticals America, Inc. Revised 2/2025. DailyMed. dailymed.nlm.nih.govCurrent FDA-approved prescribing information — primary source for all indications, dosing, adverse reactions, drug interactions, and PK data including the dual-peak profile.
- DEXILANT (dexlansoprazole) prescribing information. FDA label 2020. accessdata.fda.govFDA label confirming clopidogrel interaction data (~9% reduction in active metabolite AUC), food-effect data, and paediatric dosing.
- FDA approval letter for DEXILANT (dexlansoprazole) supplemental NDA, July 2023. accessdata.fda.govMost recent supplemental approval incorporating updated safety labelling for severe cutaneous adverse reactions.
- Sharma P, Shaheen NJ, Perez MC, et al. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation — results from two randomized controlled studies. Aliment Pharmacol Ther. 2009;29(7):731-741. doi:10.1111/j.1365-2036.2009.03933.xPivotal Phase 3 trials establishing dexlansoprazole 60 mg non-inferiority to lansoprazole 30 mg for EE healing.
- Metz DC, Howden CW, Perez MC, et al. Clinical trial: dexlansoprazole MR, a proton pump inhibitor with dual delayed-release technology, effectively controls symptoms and prevents relapse in patients with healed erosive oesophagitis. Aliment Pharmacol Ther. 2009;29(7):742-754. doi:10.1111/j.1365-2036.2009.03954.xMaintenance study demonstrating dexlansoprazole 30 mg superiority over placebo for maintaining EE healing over 6 months.
- Katz PO, Dunbar KB, Schnoll-Sussman FH, et al. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022;117(1):27-56. doi:10.14309/ajg.0000000000001538Current GERD guideline supporting PPI use for EE healing and maintenance; addresses PPI step-down and long-term use considerations.
- Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis. Gastroenterology. 2018;155(4):1022-1033.e10. doi:10.1053/j.gastro.2018.07.009Consensus criteria removing the requirement for PPI non-response in EoE diagnosis; supports PPI trial as initial therapy.
- Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep. 2008;10(6):528-534. doi:10.1007/s11894-008-0098-4Comprehensive PPI pharmacology review covering activation chemistry and irreversible pump binding relevant to all PPIs including dexlansoprazole.
- Vakily M, Zhang W, Wu J, et al. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin. 2009;25(3):627-638. doi:10.1185/03007990802693696Key PK/PD analysis establishing the dual-peak plasma profile and demonstrating extended acid suppression compared to lansoprazole.
- Lee RD, Vakily M, Mulford D, et al. Clinical trial: the effect and timing of food on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR, a novel dual delayed release formulation of a proton pump inhibitor — evidence for dosing flexibility. Aliment Pharmacol Ther. 2009;29(8):824-833. doi:10.1111/j.1365-2036.2009.03898.xFood-effect study establishing that dexlansoprazole can be taken without regard to meal timing despite modest PK increases with food.
- Zhang W, Wu J, Atkinson S. Effects of dexlansoprazole MR, a novel dual delayed-release formulation of a proton pump inhibitor, on plasma gastrin levels in healthy subjects. J Clin Pharmacol. 2009;49(4):444-454. doi:10.1177/0091270008329547Characterises the gastrin response to dexlansoprazole; relevant to monitoring guidance and CgA interference.
- Wu J, Vakily M, Gipson A, et al. Effect of hepatic impairment on dexlansoprazole pharmacokinetics. Clin Pharmacol Ther. 2008;83(Suppl 1):S58. doi:10.1038/sj.clpt.6100434Data supporting dose reduction in moderate hepatic impairment and contraindicating use in severe hepatic impairment.