Dexlansoprazole

Uses

Healing of erosive esophagitis, maintenance of healed erosive esophagitis & symptomatic non-erosive GERD (NERD).

Dexlansoprazole is also used to associated treatment for these conditions: Erosive Esophagitis, Heartburn, Healed erosive esophagitis, Symptomatic non-erosive gastroesphageal reflux disease

How Dexlansoprazole works

Dexlansoprazole inhibits the H/K ATPase enzyme, which is involved in the secretion of hydrochloric acid, hydrolyzing ATP and exchanging H+ ions from the cytoplasm for K+ ions in the secretory canaliculus, which results in HCl secretion into the gastric lumen. Dexlansoprazole inhibits this effect of H/K ATPase by demonstrating a high degree of activation in the acidic environment. After passing through the liver and reaching the gastric parietal cells activated by a meal, PPIs undergo protonation in the acidic pH environment, followed by conversion to sulphenamide which represents the active form of the drug. Sulphenamide inhibits the activity of the proton pump and hence the transport of hydrogen ions into the gastric lumen via covalent binding to the SH groups of the cysteine residues of H/K ATPase . The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum (25% of total drug dose) and the second (75% of total drug dose) in the more distal small intestine. Dexlansoprazole reduces both basal and stimulated gastric acid secretion.

Dosage

Dexlansoprazole dosage

Healing of erosive esophagitis: 60 mg once daily for up to 8 week

Maintenance of healed erosive esophagitis & relief of heartburn: 30 mg once daily

Symptomatic non-erosive GERD (NERD): 30 mg once daily for 4 week

Side Effects

Diarrhea, abdominal pain, nausea, upper resp tract infection, vomiting, flatulence.

Toxicity

Oral LD50 value in mice, rats and dogs is > 5,000 mg/kg. Most commonly reported adverse reactions are diarrhea, abdominal pain, nausea, upper respiratory tract infection, vomiting, and flatulence. There are no reports of significant overdose but serious adverse events of hypertension have been reported in association with twice daily doses of DEXILANT 60 mg. Nonclicnial toxicology of dexlansopraole was assessed using lansoprazole studies. In two 24-month carcinogenicity studies involving rats, lansoprazole induced dose-related gastric ECL cell hyperplasia and ECL cell carcinoids and increased the incidence of intestinal metaplasia of the gastric epithelium in both sexes of rats. Dexlansoprazole is expected to have no effect on fertility and the reproductive system.

Precaution

Hepatic impairment. Gastric malignancy should be ruled out. Pregnancy and lactation. Not known whether distributed into breast milk; discontinue nursing or drug

Interaction

Drugs with pH-dependent absorption. Increased risk of hypomagnesaemia with diuretics and digoxin. May decrease plasma concentration of erlotinib, dasatinib and lapatinib. May decrease the bioavailability of itraconazole and ketoconazole. May increase plasma concentration of cilostazol and methotrexate. Reduced bioavailability with antacids and sucralfate.

Food Interaction

• Avoid St. John's Wort. This may induce the CYP3A4 metabolism of dexlansoprazole, which may cause reduced efficacy.
• Take with or without food. Dexlansoprazole's dual delayed release formulation allows it to be taken without regard to food in contrast to other PPIs.

Dexlansoprazole Drug Interaction

Moderate: levothyroxineMinor: aspirin, duloxetine, linaclotide, clopidogrel, cyanocobalaminUnknown: ubiquinone, rosuvastatin, cyclobenzaprine, fluticasone nasal, atorvastatin, metoprolol, metoprolol, omega-3 polyunsaturated fatty acids, bifidobacterium infantis / lactobacillus acidophilus, pantoprazole, acetaminophen, ascorbic acid, cholecalciferol, alprazolam

Dexlansoprazole Disease Interaction

Major: C. diffModerate: liver disease, bone fractures, hypomagnesemia

Volume of Distribution

The apparent volume of distribution after multiple doses in symptomatic GERD patients was 40.3 L .

Elimination Route

After oral administration, the peak plasma concentration increases approximately dose proportionally. The dual delayed release formulation achieves two plasma concentration peaks, where the first peak occurs one to two hours after administration, followed by a second peak within four to five hours. The delivery technology of dexlansoprazole MR is designed to release the drug in two separate pH-dependent phases, the first in the proximal duodenum (25% of total drug dose) and the second (75% of total drug dose) in the more distal small intestine. The median time (Tmax) to peak plasma concentrations (Cmax) of 30 mg dexlansoprazole was 4 hours and ranged from 1 to 6 hours with the Cmax value of 688 ng/mL. AUC was found to be 3275 (ng∙h/mL).

Half Life

Dexlansoprazole is eliminated with a half-life of approximately one to two hours in healthy subjects and in patients with symptomatic GERD.

Clearance

Apparent clearance (CL/F) in healthy subjects was 11.4 to 11.6 L/hour, respectively, after five days of 30 or 60 mg once daily administration.

Elimination Route

Dexlansoprazole is cleared from the body by either fecal excretion (50.7%) or renal excretion (47.6%) following oral ingestion, with no unchanged drug detected in the urine.

Pregnancy & Breastfeeding use

Pregnancy Category B. Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

Contraindication

Dexlansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation. Hypersensitivity reactions, including anaphylaxis have been reported. Acute interstitial nephritis (AIN) has been reported with other proton pump inhibitors (PPIs), including lansoprazole of which dexlansoprazole is the R-enantiomer. Dexlansoprazole isalso contraindicated with rilpivirine-containing products.

Innovators Monograph

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