Generic Name

Dexilant

Mechanism

• Dexilant (dexlansoprazole) is a proton pump inhibitor (PPI) that irreversibly binds to the hydrogen‑potassium ATPase (H⁺/K⁺‑ATPase) on the parietal cell membrane.
• This blockage prevents the final step of acid secretion, leading to sustained gastric pH elevation.
• Unlike conventional PPIs, dexlansoprazole is formulated in a dual‑release capsule: an enteric‑coated core that releases drug in the duodenum and a supplementary coating that releases gradually in the ileum.
• Result: twice‑longer, more stable acid suppression and an extended therapeutic window.

Pharmacokinetics

• Bioavailability: 52 % (≈75 % in CYP2C19 poor metabolizers).
• Onset of action: ~30 min after oral dose.
• Peak plasma concentration (Tₘₐₓ): 1–2 h.
• Half‑life: 0.8–1.0 h for the drug; effect lasts ~24 h due to irreversible pump binding.
• Metabolism: Primarily via CYP2C19 and CYP3A4; CYP2C19 polymorphism significantly influences plasma levels.
• Excretion: Mostly metabolized; <2 % excreted unchanged in urine.
• Drug interactions: Strong CYP3A4 inhibitors/inducers alter exposure; avoid concomitant use with ketoconazole or rifampin without dose adjustment.

Indications

• GERD maintenance therapy (symptom control after initial flare).
• Erosive esophagitis: healing and symptom remission (Phase I‑II and III trials).
• Non‑erosive reflux disease (NERD) refractory to low‑dose PPIs.
• Helicobacter pylori eradication regimens (as an adjunct to clarithromycin or amoxicillin).
• Peptic ulcer disease (short‑course adjunct in duodenal ulcers).
• Maintenance of cicatrising esophagitis following partial or complete healing.

Contraindications

• Hypersensitivity to dexlansoprazole or any excipient.
• Severe hepatic impairment (baseline ALT/AST >5× ULN).
• Caution in patients with congestive heart failure (monitor for fluid retention).
• Waning of esophageal protection if administered >5 h after a meal.
• Pregnancy/Lactation: Category C; use only if benefits outweigh risks.
• Drug interactions:
• CYP3A4 inhibitors increase plasma concentration → risk of toxicity.
• Ketoconazole: avoid co‑administration.
• Dihydrofolate reductase inhibitors: decreased dexlansoprazole exposure.

Dosing

*Administer capsule whole, with head‑up position for ≤5 min to facilitate enteric coating.*

Adverse Effects

• Common (≤5 %)
• Headache, abdominal pain, flatulence, dyspepsia, diarrhea or constipation.
• Nasopharyngitis, sore throat.
• Mild hypomagnesemia.
• Serious (>1 %)
• Clostridioides difficile colitis (≥3 days of diarrhea).
• Hypomagnesemia → tetany, seizures.
• Vitamin B12 deficiency with long‑term use (>12 mo).
• Bone fracture risk (≥5 yrs).
• Severe hypersensitivity (angioedema, rash).
• Drug interaction‑mediated QT prolongation when combined with certain antimicrobials.

Monitoring

• Baseline: CBC, CMP, magnesium, calcium, vitamin B12 (if >12 mo therapy).
• During therapy:
• Monitor serum Mg²⁺ quarterly (especially if on diuretics or proton pump inhibitor >12 mo).
• Liver enzymes in patients with pre‑existing liver disease or concomitant hepatotoxic drugs.
• Watch for symptomatic improvement; if persists after 4–6 weeks, consider doubling dose or evaluating for refractory GERD.
• Long‑term (>12 mo):
• Vitamin B12 monthly if risk factors present.
• Dual‑energy X‑ray absorptiometry (DEXA) for patients >70 y or on steroids.

Clinical Pearls

• Dual‑release design allows fast onset (≤30 min) and a second release phase at ~6 h—ideal for 24‑h acid control, especially in nocturnal reflux.
• CYP2C19 polymorphism: Poor metabolizers reach ~3× higher plasma levels; dose reduction to 30 mg may suffice.
• Drug‑drug interaction check is mandatory—CYP3A4 inducers (rifampin, phenytoin) can reduce efficacy by 90 %.
• Take with head up for at least 5 min post‑dose to avoid mucosal contact of capsule before dissolution.
• When switching from other PPIs, maintain the same dose if symptom control achieved; if not, increase to 60 mg once daily.
• Nutritional deficiencies: Patients on >12 mo therapy should have their vitamin B12 and magnesium levels rebilled every 6 mo.
• Patient counseling: Advise them to report persistent loose stools (>3 days) promptly for possible C. difficile evaluation.

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• Keywords: Dexilant, dexlansoprazole, proton pump inhibitor, GERD therapy, esophagitis healing, dual‑release capsule, CYP2C19 polymorphism, hypomagnesemia, drug interactions, long‑term PPI safety.