Dexlansoprazole

Limits on what this shows

• Key null findings: The adipocyte result runs opposite to inhibition [19]. No human electron-transport, membrane-potential or biogenesis data found.
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the Dexilant label passes read [1].

Population evidence

CLASS EXTRAPOLATION (racemic parent), no human cohort. [17]: lansoprazole kills intracellular M. tuberculosis by targeting cytochrome bc1 through intracellular sulfoxide reduction to lansoprazole sulfide, and "spares the human H(+)K(+)-ATPase"; the abstract gives no data on human mitochondrial bc1. [18]: lansoprazole and the derivative AG-1789 inhibited respiration dose-dependently in H. pylori, a rotenone-like substrate pattern. [19]: in mice, lansoprazole increased energy expenditure and thermogenic gene expression and mitochondrial respiration in primary adipocytes, with PHOSPHO1 inhibition as the stated mechanism. No dexlansoprazole-specific mitochondrial study was retrieved (a PubMed listing for dexlansoprazole with mitochondria returned a 404 page; see Ungraded section for channels).

Mechanism

Named in microbes (cytochrome bc1 / complex III after sulfoxide reduction). Whether dexlansoprazole undergoes the same reduction was not tested in any source opened. Absent for human mitochondria: no study opened tests human cells or tissue for bc1 inhibition.

Cohort test

All three studies used racemic lansoprazole; dexlansoprazole (the R-enantiomer, present in the racemate) was not isolated, so activity cannot be assigned to R or S. Tier C, capped at yellow.

Counter-evidence held on record

Microbial targets reached through metabolite-dependent activation do not establish a human effect; [19] points the other way for mammalian respiration, and its dose is not stated in the abstract. Do not present this as human mitochondrial toxicity by dexlansoprazole, and do not present the mouse result as a metabolic benefit.

Limits on what this shows

• Key null findings: [21] is a near-null for lansoprazole in a chemical assay; [20] and [21] disagree in direction for the racemic parent, so the finding is unresolved.
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the Dexilant label passes read [1].

Population evidence

CLASS EXTRAPOLATION (racemic parent). Tier B-type in vitro, not this drug. [20]: lansoprazole increased HO-1 mRNA and ferritin protein in endothelial cells and macrophages and decreased NADPH-mediated ROS formation; the radical-scavenging effect diminished with a heme-oxygenase inhibitor; the authors link gastric protection to a pathway blocked by LY294002. [21]: DPPH assay of omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole (dexlansoprazole not tested); omeprazole and esomeprazole scavenged most, and the text says lansoprazole, pantoprazole and rabeprazole "might be having no role".

Mechanism

Named for the protective effect in cells (HO-1 induction) [20]. The dexlansoprazole AhR/CYP1A1 finding [13] makes no statement on oxidative stress. No systemic antioxidant-capacity or lipid-peroxidation data in dexlansoprazole users were found.

Cohort test

Dexlansoprazole not tested in either study; racemate only [20], absent from [21]. Tier C, capped at yellow.

Counter-evidence held on record

The racemate's chemistry appears mildly protective in vitro; no source shows depletion of antioxidants. Cell-culture concentrations are not related to plasma exposure in the abstracts read. This is not evidence that dexlansoprazole is an antioxidant therapy, and no antioxidant supplementation is implied.

Limits on what this shows

• Key null findings: No ferritin difference by PPI type or duration in [14]. No dexlansoprazole iron study was retrieved; the PubMed listing for dexlansoprazole with iron returned only two general PPI reviews, one with a null abstract [24][33].
• At-risk subgroups: People relying on non-haem iron or iron salts (label pH-dependence). In haemochromatosis the effect lowered phlebotomy need [11].

Regulatory status

Label section 7 lists iron salts among drugs dependent on gastric pH for absorption [1]. Direction: the drug changes iron absorption (drug-affects-nutrient, Hard Rule 4). No separation interval was found in the label passes read.

Population evidence

CLASS EXTRAPOLATION. Tier C [11]: in 7 haemochromatosis patients PPIs reduced phlebotomy requirements (p<0.001) and 7 days of PPI suppressed non-haem iron absorption (all p<0.01); the PPI used is not named in the abstract read. Tier C [10]: case-control, 77,046 iron-deficiency cases versus 389,314 controls, 2 or more years of PPI supply adjusted OR 2.49 (95% CI 2.35-2.64), strongest at over 1.5 pills/day for 10 years or more (OR 4.27, 2.53-7.21), decreasing after discontinuation; no individual PPI named. [14]: no significant difference in ferritin below 30 ng/mL by PPI type or duration; dexlansoprazole not in cohort. [22]: 37 long-term PPI users versus 30 unmatched controls, PPIs not named. Tier B but not this drug [12]: omeprazole raised hepcidin through AhR in HepG2 cells and mice; its FDA adverse-event analysis covered omeprazole, lansoprazole, rabeprazole and pantoprazole, and dexlansoprazole was not tested. Tier B for this drug [13]: dexlansoprazole is an AhR agonist that induces CYP1A1 at 2 micromolar in human and mouse cells.

Mechanism

Present, class A (pH-dependent solubilization of non-haem iron). A second hypothesis joins [12] (omeprazole's hepcidin rise needed AhR) to [13] (dexlansoprazole activates AhR). That link is this dossier's inference from two separate papers; no source tests dexlansoprazole on hepcidin, ferroportin or iron status, and [13] makes no statement on iron.

Cohort test

[10], [11], [22] do not name dexlansoprazole; [12] excluded it; [14] lacks it. Class extrapolation, capped at yellow.

Counter-evidence held on record

Reduced absorption is not an iron deficiency, and anemia is an outcome (Hard Rule 2). Confounding by indication (bleeding lesions, esophagitis) is presumed in [10]. In iron overload the PPI effect was the beneficial direction [11]. Do not read this as a reason to take iron: supplementation could be the hazard in iron-overload states. No dose is given. Surfaces only as a monitoring prompt.

Limits on what this shows

• Key null findings: No copper deficit measured in a PPI cohort in sources opened; the measurement found points upward.
• At-risk subgroups: None identified.

Regulatory status

Copper is not mentioned in the Dexilant label passes read [1].

Population evidence

CLASS EXTRAPOLATION. Tier C [22]: 37 long-term PPI users versus 30 unmatched controls: serum zinc and copper higher in PPI users; numbers are not in the abstract read and PPIs are not named. A 2015 J Neurol Sci article titled "PPIs as possible risk factor for copper deficiency myelopathy" exists, but its abstract is null in the record opened and its text was not read, so it is not relied on [30].

Mechanism

None named in any source opened. A consumer page suggests raised gastric pH "could theoretically impair copper uptake" without a cited mechanism [29].

Cohort test

Dexlansoprazole not shown in [22]. Tier C, capped at yellow. Kept independent of Iron (Hard Rule 7).

Counter-evidence held on record

The one measurement opposes a depletion claim; its design (unmatched controls, class-level, unnamed PPIs) limits it. Revisit-flagged because the myelopathy report could not be read. Higher serum copper is not an excess-risk claim either. Neither copper supplementation nor restriction is implied.

Limits on what this shows

• Key null findings: None retrieved for dexlansoprazole. A PubMed listing for dexlansoprazole with microbiota returned only [16] (no microbiota outcome) [33].
• At-risk subgroups: Hospitalized patients for C. difficile, per label.

Regulatory status

Label 5.3: PPI therapy "may be associated with an increased risk of Clostridium difficile-associated diarrhea" [1]. That is an infection outcome, not a measurement of microbiome composition.

Population evidence

CLASS EXTRAPOLATION. Tier C [15]: three Dutch cohorts, 1,815 individuals, 211 PPI users; significant decrease in Shannon diversity, 20% of taxa altered, Rothia p=9.8x10^-38; increases in Enterococcus, Streptococcus, Staphylococcus and Escherichia coli. The methods (read through a summarizing fetch tool) score PPI use if participants took "omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole or rabeprazole" and give no per-drug counts or per-drug analysis. [16]: dexlansoprazole 60 mg was in both arms of a 248-patient H. pylori regimen trial with clarithromycin, amoxicillin and metronidazole; it did not measure gut microbiota, and antibiotics would dominate any shift.

Mechanism

The abstract names none; the pattern is oral bacteria over-represented in stool [15]. Not tested in a dexlansoprazole-only cohort in sources opened.

Cohort test

Dexlansoprazole is named in the exposure definition but the number of its users is not reported and could be zero; inclusion cannot be verified. Tier C class extrapolation, capped at yellow.

Counter-evidence held on record

Cross-sectional association; confounding by indication, age and co-medication is not excluded; no nutrient consequence has been shown. Not a nutrient-deficiency claim; probiotics or other products are not recommended by this dossier.

Limits on what this shows

• Key null findings: None retrieved.
• At-risk subgroups: None defined; the event appears idiosyncratic.

Regulatory status

Label 6.2, Blood and Lymphatic System Disorders: "autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura" [1]. One extraction pass also reported "anemia" among section 6.1 terms; a second pass listing section 6.1 laboratory terms did not show it, so that point is unresolved and is not relied on.

Population evidence

CLASS EXTRAPOLATION (racemic parent) for the case report. [23]: a man treated only with lansoprazole developed jaundice, fatigue and dark urine; hemoglobin 14.0 g/dL on admission, 3.3 g/dL three days later; direct Coombs test positive; IgG antibody to lansoprazole detected; recovered within three weeks after transfusion and corticosteroids (1996, abstract; antibiotics were started five days after symptoms began). Tier C [22]: 37 long-term PPI users versus 30 unmatched healthy controls (mean age 57.1 versus 39.3 years): red cell count 4.24 versus 4.7 x10^6/ul and hemoglobin 12.5 versus 14.3 g/dl (both p<0.001); PPIs not named. Whether the lansoprazole antibody cross-reacts with dexlansoprazole is not addressed in any source opened.

Mechanism

For the label term and [23], immune-mediated hemolysis (not nutritional). For [22], none shown; the authors suggest iron deficiency without demonstrating it. No arterial oxygenation, red-cell mass or tissue oxygen-delivery data for dexlansoprazole were found.

Cohort test

[22] does not name dexlansoprazole; [23] is the racemate. The label term is drug-specific but spontaneous, with no denominator. Capped at yellow.

Counter-evidence held on record

Controls in [22] were about 18 years younger and unmatched, and anemia is an outcome (Hard Rule 2). One case cannot give a frequency. This entry is a mechanism clarification: an immune adverse event is not an oxygen-delivery deficiency. Anemia in a dexlansoprazole user is not evidence of iron or B12 deficiency without direct measurement. Sudden jaundice or dark urine is a prescriber-level issue, not a nutrient issue.

Limits on what this shows

• Key null findings: No human or mammalian ATP, phosphocreatine or energy-charge data found. No dexlansoprazole ATP study found (PubMed listing for dexlansoprazole with oxygen, reactive oxygen species or ATP returned three unrelated items) [33].
• At-risk subgroups: None identified.

Regulatory status

Not addressed in the Dexilant label passes read [1].

Population evidence

CLASS EXTRAPOLATION (racemic parent). [18]: lansoprazole and AG-1789 "dose-dependently inhibited cellular respiration by an endogenous substrate and decreased the ATP level in Helicobacter pylori cells"; 50% inhibitory concentrations for respiration were close to growth MICs. The mouse adipocyte study [19] reports increased mitochondrial respiration, with no ATP result in the abstract.

Mechanism

Present in bacteria (respiratory-chain inhibition); absent for human cells and for dexlansoprazole in sources opened.

Cohort test

Racemic lansoprazole in H. pylori; dexlansoprazole not tested alone. Tier C, capped at yellow. Shares its only evidence with Mitochondrial burden (see Overlap map).

Counter-evidence held on record

Bacterial finding; the mammalian result [19] points the other way. Fatigue from B12 or magnesium status is a separate question handled in those entries. Not a statement that dexlansoprazole lowers energy output in people.