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MyDeficiencies

Pasireotide

somatostatin and analogues

Also sold as Signifor, Signifor LAR.

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Findings for this medication

Research about this medication, graded for how strongly each finding can be attributed to it. Nothing here describes your own levels.

Pasireotide is a cyclohexapeptide somatostatin analog that is metabolically stable in human liver and kidney microsomes: the unchanged parent drug is the predominant species recovered in plasma, urine, and feces, it is not itself a significant CYP450 substrate, and it does not induce or inhibit CYP450 enzymes as its own clearance route (it may, like other somatostatin analogs, indirectly reduce the metabolic clearance of co-administered CYP450-substrate drugs via growth-hormone suppression, a drug-drug rather than nutrient interaction). Elimination is primarily hepatic/biliary, with roughly 48% of a dose recovered unchanged in feces and under 8% in urine over the first 10 days; renal impairment of any severity requires no dose adjustment, while moderate-to-severe hepatic impairment does. Like octreotide and lanreotide, pasireotide has no classical enzyme-induction or renal-electrolyte-wasting depletion machinery of its own. What sets it apart from both earlier-generation analogs is its receptor-binding profile: pasireotide binds SSTR1, SSTR2, SSTR3, and SSTR5 with clinically meaningful affinity (negligible only at SSTR4), most potently at SSTR5 (IC50 0.16 nmol/L), versus octreotide's predominantly SSTR2-restricted profile. Because SSTR5 is highly expressed on pancreatic beta cells and only weakly suppresses glucagon, this broader, SSTR5-weighted profile is the direct, named mechanism behind pasireotide's single most consequential labeled effect: hyperglycemia, reported in 40% of patients in the pivotal Cushing's disease trial and in 60-90% of acromegaly patients across the broader treated literature, driven by suppressed insulin secretion together with suppressed incretin hormones (GLP-1 and GIP). This is the drug's own intended-target pharmacologic action extended into an adverse metabolic effect, not a nutrient deficiency, and it is covered thoroughly in the pharmacokinetic basis and monitoring panel below rather than graded as a nutrient entry, per this protocol's rule against filing a drug's own pharmacologic effect as a nutrient-deficiency claim.

somatostatin and analogues · ATC H01CB05 · also sold as Signifor and Signifor LAR and pasireotide diaspartate/pamoate · reviewed 2026-09-26. This describes research about the medication. It does not say anything about your own levels or health.

How to read the evidence grades

These colours describe how strongly a finding can be attributed to the medication in the research. They are not a severity score and they say nothing about your own health.

Grades describe how strongly a finding can be attributed to Pasireotide in the research — not how common it is, how serious it would be, and not anything about you personally.

Red — Severe
severe. ≥2 independent Tier A sources with this drug in the cohort, the nutrient directly measured, consistent direction, clinically meaningful magnitude, a named mechanism, no substantial contradicting Tier A evidence.
Orange — Moderate
moderate. ≥1 Tier A source with this drug in the cohort showing a real deficit, but bounded by exposure window, subgroup, frequency, or a functional (not circulating) marker.
Yellow — Low
low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings.
Not graded — disclosed evidence gap
Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result.Source definition: evidence gap. No Tier B/C evidence to support even yellow, and no circulating claim to rebut as white. A disclosed absence of evidence, not a finding of safety.

What the research found

Potassium and magnesium

Orange — Moderate

See study details

Pasireotide therapy is associated with hypokalemia and hypomagnesemia clinically significant enough that the FDA label requires correcting both before starting treatment and monitoring periodically thereafter, though the incidence data are limited to a single bounded trial figure and the mechanism has not been isolated from pasireotide's own high rates of diarrhea and hyperglycemia.

Full detail and limits

What the grade means here: moderate. ≥1 Tier A source with this drug in the cohort showing a real deficit, but bounded by exposure window, subgroup, frequency, or a functional (not circulating) marker. Orange

Limits on what this shows

  • Null findings: None identified testing whether correcting diarrhea or glycemic control independently normalizes potassium or magnesium in pasireotide-treated patients specifically; a genuine gap in the mechanistic literature.
  • At-risk subgroups: Patients on concomitant QT-prolonging drugs (the label's own stated reason for mandatory pre-treatment correction); patients with pre-existing diarrhea or poorly controlled hyperglycemia on therapy.

Regulatory status

FDA label (Signifor injection, Section 5.4): "Hypokalemia and hypomagnesemia must be corrected prior to SIGNIFOR administration and should be monitored periodically during therapy." The Signifor LAR label separately requires baseline potassium and magnesium levels before the first dose. Both are tied explicitly to mitigating pasireotide's separate, dose-dependent QT-prolongation risk, not framed as a standalone nutritional warning.

Population evidence

Signifor (immediate-release) Phase III trial, n=162 Cushing's disease patients: hypokalemia reported in 6% of patients. No separate published incidence percentage for hypomagnesemia distinct from the "must be corrected" directive was located in the label sections reviewed.

Mechanism

Not characterized in the label as a specific receptor-mediated renal or GI effect. Two plausible contributing pathways, neither isolated or quantified specifically for pasireotide: (1) GI loss — pasireotide's own labeled diarrhea incidence is high (58% in the Phase III Cushing's disease trial), and chronic diarrhea is an established general mechanism of magnesium and potassium loss (general GI physiology, Tier B); (2) possible osmotic renal loss compounding from pasireotide's own well-documented, high-incidence hyperglycemia (see headline finding and pharmacokinetic basis), an established general mechanism in poorly controlled hyperglycemia of any cause (general endocrine physiology, Tier B, not pasireotide-specific).

Counter-evidence held on record

No contradicting Tier A evidence was found; no study was located isolating diarrhea or glycemic control as the dominant contributing pathway over the other. Framing caution: this is a mandatory pre-treatment safety gate tied to cardiac (QT-prolongation) risk, not a general wellness depletion syndrome. Potassium and magnesium repletion must be physician-directed and lab-confirmed; self-directed supplementation is inappropriate given that both hypokalemia and drug-induced electrolyte shifts in either direction carry cardiac risk in this specific population, and no over-the-counter dose is recommended here.

Sodium

Orange — Moderate

See study details

Pasireotide's on-target suppression of ACTH can lower cortisol enough to produce hypocortisolism, of which hyponatremia is a named, directly measured symptom in a bounded 3-9% subgroup of treated patients, not a universal drug effect.

Full detail and limits

What the grade means here: moderate. ≥1 Tier A source with this drug in the cohort showing a real deficit, but bounded by exposure window, subgroup, frequency, or a functional (not circulating) marker. Orange

Limits on what this shows

  • Null findings: None found isolating serum sodium specifically outside the hypocortisolism-symptom context; no dedicated study measuring sodium trajectories in the majority of pasireotide-treated patients who do not develop hypocortisolism was located.
  • At-risk subgroups: Patients who develop clinically apparent hypocortisolism/adrenal insufficiency on therapy; plausibly more relevant in Cushing's disease (where ACTH suppression is the intended therapeutic effect) than in acromegaly (where it is an off-target effect), though the label reports adrenal insufficiency incidence in both populations.

Regulatory status

FDA label (Signifor injection, Section 5.2, Hypocortisolism): incidence 6% (9/162) in the pivotal Cushing's disease trial; named symptoms include "weakness, fatigue, anorexia, nausea, vomiting, hypotension, hyponatremia, or hypoglycemia." Signifor LAR label: adrenal insufficiency incidence 3-7% across acromegaly and Cushing's disease trials.

Population evidence

As above; both figures are Tier A, drug-specific, and bounded to the hypocortisolism-affected subgroup (3-9% of treated patients depending on formulation and indication), not the full treated population.

Mechanism

Named. ACTH suppression, pasireotide's intended on-target action in Cushing's disease, lowers circulating cortisol; cortisol has a permissive role in renal free-water clearance, so hypocortisolism can produce dilutional hyponatremia (hormonal-disturbance mechanism, Tier B for the general cortisol-sodium/water physiology, Tier A for pasireotide's own ACTH-suppression and hyponatremia-as-symptom statement).

Counter-evidence held on record

None found contradicting the bounded, subgroup-specific nature of this finding. Framing caution, per the excess/disturbance distinction: this is a dilutional, hormonally mediated effect, not a dietary sodium deficiency. Sodium or salt supplementation is not the remedy; the label-specified management is glucocorticoid replacement therapy and/or temporary dose reduction or interruption of pasireotide itself, under prescriber direction. Never present this as "pasireotide depletes sodium."

Vitamin B12

Yellow — Low

See study details

Pasireotide shares, and via its broader receptor profile arguably exceeds, octreotide's pancreatic-protease-suppressing mechanism that depresses vitamin B12 in octreotide-treated patients, but no pasireotide-specific study or regulatory statement documents an actual B12 deficit.

Full detail and limits

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None found either direction for pasireotide specifically; a true data gap rather than a tested-and-refuted claim.
  • At-risk subgroups: Not established by direct evidence. By analogy to the octreotide precedent, long-duration continuous Signifor LAR depot use would be the plausible highest-risk subgroup if the mechanism holds for pasireotide as well.

Regulatory status

Neither the Signifor nor the Signifor LAR FDA label mentions vitamin B12, cobalamin, or the Schilling test anywhere, confirmed by direct full-document review of both labels during this session. This contrasts with octreotide's FDA label (Sandostatin injection, independently reviewed in this same session), which states verbatim: "Depressed vitamin B12 levels and abnormal Schilling's tests have been observed in some patients receiving Sandostatin Injection therapy, and monitoring of vitamin B12 levels is recommended."

Population evidence

None found. PubMed searches for "pasireotide B12" and "pasireotide AND B12" both returned zero results (accessed 2026-09-26).

Mechanism

Tier C, class extrapolation. Octreotide's own label documents the mechanism: suppressed pancreatic protease secretion impairs the normal R-protein-to-intrinsic-factor handoff of B12 in the duodenum. Pasireotide's own label independently confirms the same upstream pancreatic-enzyme and bile-acid suppression (Section 5.7, see Fat-soluble vitamins entry below), and pasireotide's receptor-binding profile is, if anything, broader than octreotide's (SSTR1/2/3/5 versus predominantly SSTR2), so the mechanism is at least as plausible for pasireotide as for octreotide. This keeps the entry at yellow rather than white.

Counter-evidence held on record

The absence of any B12 statement in pasireotide's own label, despite the FDA having required this exact statement for octreotide and pasireotide's receptor profile being at least as broad, is itself a weak counter-signal that the two drugs may not behave identically here; it is not proof of absence. Do not present this as an established pasireotide deficiency by extension from octreotide. It is a plausible, unconfirmed, class-level hypothesis only.

Vitamin A, D, E, and K

Yellow — Low

See study details

Pasireotide's own label documents the same pancreatic-enzyme and bile-acid suppression that causes steatorrhea in the wider somatostatin-analog class, but no pasireotide-specific study of vitamin A, D, E, or K status was located.

Full detail and limits

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None found either way for A, D, E, or K — a true data gap, not a tested-and-refuted claim. (This differs from octreotide and lanreotide, for which at least one drug-adjacent vitamin D study exists in the wider literature; no equivalent was independently verified for pasireotide in this review.)
  • At-risk subgroups: Patients with clinically apparent (more than mild/transient) steatorrhea; long-duration continuous Signifor LAR therapy; pre-existing pancreatic exocrine insufficiency as a plausible but unconfirmed compounding group.

Regulatory status

FDA label (Signifor injection, Section 5.7): "Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss," with instruction to evaluate for pancreatic exocrine insufficiency if steatorrhea is new or worsening. The label does not name vitamin A, D, E, or K specifically.

Population evidence

None located specific to pasireotide and any of the four vitamins. A PubMed search using "pasireotide 25-hydroxyvitamin" (as a proxy for vitamin D, the most commonly tested class member in the wider somatostatin-analog literature) returned zero results. A consumer drug-reference check (Drugs.com) found no mention of any fat-soluble vitamin for this drug.

Mechanism

The upstream step (steatorrhea from pancreatic enzyme/bile suppression) is Tier A and drug-specific, directly confirmed in pasireotide's own label. The downstream step (that this drug's steatorrhea measurably lowers A, D, E, or K status) is inferred from general GI physiology, not from pasireotide-specific data.

Counter-evidence held on record

None found in either direction specific to pasireotide. Grouped as one entry because the evidence for A, D, E, and K is identical and entirely mechanism-only for pasireotide specifically. Do not read this as four independently confirmed findings.

The five body-system areas

Each finding is counted once, in a single area. Where a study is mentioned in a second area it is context only.

Mitochondrial Burden

Each finding below is counted once, in this area only.

Mitochondrial burden

Yellow — Low

See study details

In human pituitary tumor cells tested head-to-head against octreotide, pasireotide measurably decreased mitochondrial oxygen consumption rate, most effectively in cells carrying a genetic variant associated with higher baseline mitochondrial respiration; this is a real, drug-specific, tumor-tissue antiproliferative finding, not a systemic mitochondrial-burden signal.

Full detail, limits and 1 references

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None identified within this study; it is a single-source finding not independently replicated elsewhere in this review.
  • At-risk subgroups: Not applicable in the depletion sense: this is a tumor-tissue, genotype-dependent, intended-therapeutic finding, not a risk to normal tissue. FGFR4-G388 (the more common isoform) cells showed a smaller drug effect.

Regulatory status

Not addressed in the FDA label.

Population evidence

Ezzat S, Wang R, Pintilie M, Asa SL, 2017, Oncotarget, 8(2):3481-3494, PMID 27966451, independently opened and verified for this review (full abstract and results retrieved directly). Human pituitary tumor cells genotyped for the FGFR4-Gly388Arg polymorphism were tested with both pasireotide and octreotide in parallel. FGFR4-R388-variant cells showed higher baseline mitochondrial oxygen consumption rate (OCR) than the more common FGFR4-G388 isoform. Pasireotide was significantly more effective than octreotide at reducing OCR in FGFR4-R388-variant cells (p=0.019 and p=0.004 reported across two comparisons), with parallel superiority in colony-formation reduction (p=0.0003 and p=0.004).

Mechanism

Named. FGFR4-R388-expressing cells show elevated mitochondrial STAT3 serine phosphorylation driving basal and maximal OCR; pasireotide, via its broader and higher-affinity somatostatin-receptor engagement, suppresses this more effectively than octreotide, consistent with its intended antiproliferative action on GH- or ACTH-secreting pituitary tumor cells.

Counter-evidence held on record

None found; this is a single in vitro/ex-vivo study and should not be over-weighted. This is the drug's intended antitumor mechanism in target pituitary tumor tissue, not evidence of systemic mitochondrial harm, and must never be marketed either as "pasireotide damages your mitochondria" (wrong tissue and direction for a consumer nutrient claim) or as a general cellular-energy benefit (also wrong; this is genotype-dependent, tumor-suppressive action, not a wellness effect). See Overlap map regarding ATP production below.

  • Ezzat S, Wang R, Pintilie M, Asa SL. FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors. — Oncotarget 2017;8(2):3481-3494. In vitro/ex-vivo human pituitary tumor cell study, pasireotide and octreotide both directly tested. PMID 27966451, DOI 10.18632/oncotarget.13843. Full abstract and results independently opened and read via the publisher's site.

Oxidative Stress

Each finding below is counted once, in this area only.

Oxidative stress

Yellow — Low

See study details

No pasireotide-specific oxidative-stress study was located, but real, independently verified animal studies directly testing octreotide and lanreotide, both close class relatives, consistently show these somatostatin analogs reduce tissue oxidative-stress markers rather than increase them, keeping this a class-extrapolated, reverse-direction yellow rather than an ungraded gap.

Full detail, limits and 3 references

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None identified within either source study for the treated octreotide or lanreotide arms.
  • At-risk subgroups: Not applicable in the depletion sense: this is a protective-direction, disease-model finding for class relatives, not a systemic risk signal, and has not been tested for pasireotide itself.

Regulatory status

Not addressed in either the Signifor or Signifor LAR FDA label.

Population evidence

No pasireotide-specific study was located. Two class-level animal studies were independently opened and verified in this revision: (1) Wang YL, Liu JY, Jing YL, Zhang YB, Sun N, Wang XJ, 2011, Journal of Sichuan University (Medical Science Edition), PMID 21355297: rat severe acute pancreatitis model, octreotide (sandostatin) directly in the treated arm, measured malondialdehyde (lipid peroxidation marker) and superoxide dismutase (antioxidant enzyme) activity alongside Na+/K+/Ca2+/Mg2+-ATPase activity, reporting improved, protective values in octreotide-treated animals versus untreated pancreatitis controls; verified via OpenAlex abstract reconstruction. (2) Kalyoncu Ucar A, et al, 2020, Journal of Obstetrics and Gynaecology Research, PMID 32748523: rat ovarian ischemia-reperfusion (torsion-detorsion) model testing both octreotide and lanreotide directly in the treated arms, reporting significantly decreased total oxidant status, oxidative stress index, and peroxynitrite in treated groups versus injury controls; verified via direct PubMed article-page fetch.

Mechanism

Not molecularly dissected beyond the reported enzyme-activity and oxidant-marker readouts in either source study. Plausible for pasireotide given its shared somatostatin-receptor pharmacology, broader and higher-affinity than octreotide's per the pharmacokinetic basis above, but this is Tier C class extrapolation, not pasireotide-specific evidence, since neither study administered pasireotide itself.

Counter-evidence held on record

No pasireotide-specific study confirms or refutes this class-level pattern for pasireotide directly. Direct pasireotide searches remain constrained in this revision: PubMed "pasireotide oxidative stress" again returned a bot-verification challenge page on repeated, separately timed attempts, not a confirmed zero; "pasireotide reactive oxygen species" returned a clean, confirmed zero-result PubMed search; a Crossref bibliographic search for "pasireotide oxidative stress reactive oxygen species" returned only general oxidative-stress literature with no pasireotide-specific hits; Europe PMC, Semantic Scholar, and OpenAlex search endpoints all returned HTTP 429 rate-limit responses for the same terms. This is a reverse-direction, class-extrapolated finding, not pasireotide-specific evidence, and shares the Wang 2011 source with the ATP production entry below (see Overlap map). Do not present this as an established "pasireotide reduces oxidative stress" claim, and never market it as a consumer antioxidant benefit.

  • Wang YL, Liu JY, Jing YL, Zhang YB, Sun N, Wang XJ. [Study on the protective effects of octreotide and Gardenia jasminoides Ellis on pancreatic mitochondria in rats with severe acute pancreatitis]. — Journal of Sichuan University (Medical Science Edition) 2011. PMID 21355297. Rat severe-acute-pancreatitis model, octreotide (sandostatin) directly in the treated arm, not pasireotide. Reported improved malondialdehyde and superoxide dismutase levels and preserved Na+/K+/Ca2+/Mg2+-ATPase activity versus untreated pancreatitis controls. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cohort: octreotide, not pasireotide; used only as Tier C class-level context for the Oxidative stress and ATP production entries, never as pasireotide-specific evidence.Cohort excluded pasireotide; Tier C class-level context only.
  • Kalyoncu Ucar A, et al. Octreotide and lanreotide decrease ovarian ischemia-reperfusion injury in rats by improving oxidative and nitrosative stress. — Journal of Obstetrics and Gynaecology Research 2020. PMID 32748523. Rat ovarian torsion-detorsion ischemia-reperfusion model, both octreotide and lanreotide directly in treated arms, not pasireotide. Reported significantly decreased total oxidant status, oxidative stress index, and peroxynitrite versus injury controls. Added in this revision; independently opened and verified via direct PubMed article-page fetch (this individual article page was reachable even while PubMed's search-listing pages returned bot-verification challenges). Cohort: octreotide and lanreotide, not pasireotide; used only as Tier C class-level context for the Oxidative stress entry, never as pasireotide-specific evidence.Cohort excluded pasireotide; Tier C class-level context only.
  • PubMed search-listings, access-blocked attempts (tooling limitation, not a confirmed result either way). — "pasireotide oxidative stress," "pasireotide AND \"reactive oxygen species\"" (search-listing page only; the term-specific zero-result variant above did succeed), "pasireotide AND vitamin D," and "pasireotide AND erythropoietin" each returned a bot-verification ("checking your browser") challenge page on multiple separately timed attempts across both the original review and this revision rather than a clean result. Individual PubMed article pages (e.g. PMID 32748523) remained reachable even while search-listing pages were blocked.Disclosed tooling limitation, reconfirmed in this revision; Oxygen delivery/utilization and Copper remain the only entries this constraint leaves genuinely ungraded (Oxidative stress and ATP production were resolved to yellow via independently verified class-level sources instead).

Copper and Iron Balance

Copper and iron are assessed separately. Nothing here is counted twice.

Iron

Yellow — Low

See study details

Pasireotide's own label documents transient, mild reduction of gastric acidity, a mechanistic pathway toward reduced non-heme iron absorption, but a randomized controlled trial shows pasireotide-LAR also reduces transfusion requirements in refractory gastrointestinal bleeding, a real, drug-specific finding pulling in the opposite direction; net effect on iron status is unresolved.

Full detail, limits and 1 references

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None found isolating serum iron, ferritin, or hemoglobin as a measured endpoint in either study; the ANGIOPAS trial's primary and only reported endpoint is transfused pRBC units, not a direct iron or hemoglobin measurement.
  • At-risk subgroups: For the theoretical absorption pathway: unclear, theoretically long-term continuous high-dose therapy without a confounding GI condition. Conversely, patients using pasireotide-LAR specifically for refractory gastrointestinal angiodysplasia bleeding, the ANGIOPAS trial's bounded population, would be expected to have reduced iron losses from chronic blood loss rather than an absorption-driven deficit.

Regulatory status

FDA label (Signifor LAR, Section 12.2): pasireotide "produces transient, mild...reduced gastric acidity" as part of its pharmacodynamic profile; no iron-specific warning appears anywhere in either label.

Population evidence

No study directly measuring non-heme iron absorption or serum iron/ferritin status in pasireotide-treated patients was located; PubMed search "pasireotide AND iron deficiency" returned zero results, reconfirmed in this revision. A real, drug-specific Tier A trial exists in the opposite direction: Benamouzig R, Benallaoua M, Saurin JC, et al, 2018, Therapeutic Advances in Gastroenterology, PMID 29479375 (the ANGIOPAS study), a phase II multicenter, double-blinded, randomized, noncomparative trial in 22 patients with refractory gastrointestinal angiodysplasia bleeding requiring 6 or more units of packed red blood cells (pRBC) monthly (10 pasireotide-LAR 60mg, 12 placebo, every 28 days for 6 months). Median transfusion requirement fell from 13 to 3 pRBC units in the pasireotide arm versus 9.5 to 11.5 units in placebo; a 30% or greater reduction in transfused units ("success") was reached in 50% of patients by intent-to-treat analysis and 83% by per-protocol analysis. Independently opened and verified in this revision via OpenAlex abstract reconstruction (DOI 10.1177/1756283x18756260), not taken on trust from title metadata alone.

Mechanism

Named for the absorption-interference pathway: gastric acid suppression reduces reduction/solubilization of non-heme dietary iron (Tier A for pasireotide's own gastric-acidity fact; Tier B/general-physiology for the downstream iron-absorption inference). The ANGIOPAS trial's own mechanism for reducing angiodysplasia bleeding is not fully characterized in the reconstructed abstract available in this review; it is presumed to be pasireotide's intended broad anti-secretory and antiangiogenic somatostatin-receptor action on the vascular lesion itself, not an iron-absorption mechanism.

Counter-evidence held on record

A real, drug-specific, Tier A randomized controlled trial (ANGIOPAS) demonstrates pasireotide's own intended pharmacologic effect substantially reduces transfusion requirements in a bounded refractory-bleeding population, pulling toward reduced iron loss, not depletion. This is the drug's intended therapeutic action on the underlying vascular lesion, not an iron-absorption finding, and is filed here as context per the outcome-versus-mechanism distinction (Hard Rule 2), not as depletion evidence. The same trial is cross-referenced, not re-cited as independent evidence, under Oxygen delivery/utilization below; see Overlap map. Two opposite-direction pathways exist (theoretical acid-mediated absorption impairment versus a real, RCT-confirmed hemostatic transfusion-reduction effect in a narrow refractory-bleeding population); neither has been quantified for net effect on iron status in the wider treated population, and the label carries no iron-specific warning. Do not present pasireotide as uniformly "depleting" or "protecting" iron status.

  • Benamouzig R, Benallaoua M, Saurin JC, Boubaya M, Cellier C, Laugier R, et al. Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study. — Therapeutic Advances in Gastroenterology 2018. PMID 29479375, DOI 10.1177/1756283x18756260. Phase II, double-blinded, randomized, noncomparative trial, n=22 (10 pasireotide-LAR, 12 placebo), pasireotide directly in the treated arm. Reported median transfusion requirement falling from 13 to 3 packed-red-blood-cell units in the treatment arm versus 9.5 to 11.5 in placebo, with 3 cases of glycemic impairment including one new diabetes diagnosis. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cited under Iron and cross-referenced under Oxygen delivery/utilization; measured transfused units, not hemoglobin or iron levels directly.

Copper

Not graded — disclosed evidence gap

See study details

No mechanism, no drug-specific data, and no circulating consumer claim were found linking pasireotide to copper status; this is a confirmed, high-confidence zero-result search rather than a tooling-blocked one.

Full detail and limits

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: The mechanism screen identified no plausible pathway: pasireotide does not chelate copper, does not induce or inhibit any copper-dependent enzyme system named in its label, and is not renally wasting. PubMed search "pasireotide AND copper" returned a clean, confirmed zero-result search (the page explicitly stated "No results were found," not a bot-verification block) both in the original review and again on reconfirmation in this revision, a genuine, high-confidence gap.

Circulating-claim check

No claim about pasireotide and copper was found in the consumer drug-reference check completed (Drugs.com).

Disclosure

This matches the same ungraded finding independently reached for both octreotide and lanreotide in this same dossier series, though each drug's copper entry was researched and confirmed independently rather than assumed from class pattern. This revision re-ran the search from scratch (not carried forward from the prior pass) and reached the same clean zero-result outcome.

Gut Microbiome Risk

Each finding below is counted once, in this area only.

Gut microbiome risk

Yellow — Low

See study details

Pasireotide's own label documents reduced gallbladder motility and broad anti-secretory pharmacology consistent with the mechanism implicated in altered small-bowel bacterial counts elsewhere in this drug class, but no pasireotide-specific microbiome or bacterial-overgrowth study was located.

Full detail and limits

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None found either way for pasireotide specifically; a true data gap.
  • At-risk subgroups: Not established by direct evidence; by general physiologic reasoning, continuous higher-dose depot regimens would plausibly carry more motility suppression than intermittent dosing, though this is untested for pasireotide.

Regulatory status

FDA label documents "reduces gallbladder motility" (Section 12.2) and steatorrhea/loose stools (Section 5.7) as recognized pharmacologic and GI effects; no explicit "bacterial overgrowth/dysbiosis" language appears in either label.

Population evidence

None found specific to pasireotide. PubMed searches for "pasireotide AND microbiota" and "pasireotide AND microbiome" both returned zero results (the latter after an initial bot-verification block was cleared on retry).

Mechanism

Tier A for pasireotide's own anti-secretory and motility-suppressing pharmacology, independently confirmed in its own label; Tier C for the downstream inference that this alters gut microbial composition, which draws on general GI/microbiome physiology rather than pasireotide-specific or even class-specific outcome data independently verified in this review.

Counter-evidence held on record

None found in either direction for pasireotide specifically. Direction is entirely unconfirmed for this drug. Do not present this as a demonstrated "pasireotide harms the gut microbiome" claim.

Oxygen and ATP Output

Oxygen delivery and ATP production are assessed separately. Nothing here is counted twice.

ATP production

Yellow — Low

See study details

No pasireotide-specific ATP or ATPase study was located, but octreotide, a close class relative, has real Tier B rat pancreatitis data showing preserved membrane-transport ATPase activity, keeping this a class-extrapolated yellow rather than an ungraded gap.

Full detail, limits and 1 references

What the grade means here: low/theoretical. Mechanistic plausibility only (Tier B), or class extrapolation (Tier C) where at least one class member has real data but this drug does not; also used for context flags and reverse-direction/protective findings. Yellow

Limits on what this shows

  • Null findings: None identified in the octreotide-treated arm of the source study.
  • At-risk subgroups: Not applicable; disease-model (acute pancreatitis) finding in a class relative, not a routine-dosing risk signal for pasireotide.

Regulatory status

Not addressed in either FDA label.

Population evidence

No pasireotide-specific study was located. PubMed search "pasireotide AND \"ATP production\"" returned a clean, confirmed zero-result search, reconfirmed in this revision. The class-level lead is the same Wang YL et al 2011 rat severe-acute-pancreatitis study cited under Oxidative stress above (PMID 21355297, independently verified via OpenAlex): the study reported preserved Na+/K+/Ca2+/Mg2+-ATPase activity, a functional marker of energy-dependent membrane transport, in octreotide-treated animals versus untreated pancreatitis controls.

Mechanism

Not molecularly dissected beyond the ATPase-activity readout. Membrane-transport ATPase activity is an energy-dependent process but is a distinct endpoint from mitochondrial ATP synthesis itself, so this is treated as suggestive, Tier C class-extrapolated evidence, not a direct ATP-production measurement even for the class member studied.

Counter-evidence held on record

The one pasireotide-specific energy-metabolism-adjacent finding located in this review, Ezzat 2017's mitochondrial oxygen consumption rate data in pituitary tumor cells filed under Mitochondrial burden above, measured oxygen consumption, not ATP synthesis or ATP levels, so it does not independently support this entry; see Overlap map. No pasireotide-specific ATPase or ATP-synthesis study was located despite Crossref, Europe PMC, Semantic Scholar, and OpenAlex search-endpoint attempts in this revision (the latter three rate-limited). This is a class-extrapolated, Tier C finding resting on a single class-relative (octreotide) source shared with the Oxidative stress entry above; see Overlap map. It is not pasireotide-specific evidence and should never be presented as a confirmed "pasireotide supports cellular energy" claim.

  • Wang YL, Liu JY, Jing YL, Zhang YB, Sun N, Wang XJ. [Study on the protective effects of octreotide and Gardenia jasminoides Ellis on pancreatic mitochondria in rats with severe acute pancreatitis]. — Journal of Sichuan University (Medical Science Edition) 2011. PMID 21355297. Rat severe-acute-pancreatitis model, octreotide (sandostatin) directly in the treated arm, not pasireotide. Reported improved malondialdehyde and superoxide dismutase levels and preserved Na+/K+/Ca2+/Mg2+-ATPase activity versus untreated pancreatitis controls. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cohort: octreotide, not pasireotide; used only as Tier C class-level context for the Oxidative stress and ATP production entries, never as pasireotide-specific evidence.Cohort excluded pasireotide; Tier C class-level context only.

Oxygen delivery/utilization

Not graded — disclosed evidence gap

See study details

No mechanism was found by which pasireotide directly affects hemoglobin synthesis, erythropoietin, red-cell mass, or arterial oxygenation, and the one real pasireotide-specific trial touching this domain measured transfused blood units rather than a hemoglobin or oxygen-delivery parameter directly.

Full detail, limits and 1 references

What the grade means here: Nothing has been measured here, so this finding cannot be graded. That does not establish either safety or harm, and it is not the same as a White result. Ungraded

Limits on what this shows

  • Why no grade: The mechanism screen found no pathway for a direct pasireotide effect on oxygen-carrying capacity. PubMed search "pasireotide AND hemoglobin" returned 26 results, but every one reviewed concerned glycemic biomarkers (HbA1c as a diabetes-monitoring marker in the context of pasireotide-induced hyperglycemia) rather than oxygen-carrying capacity, a false-positive keyword match, not oxygen-delivery evidence. A separate search, "pasireotide AND erythropoietin," was blocked by a PubMed bot-verification challenge on repeated, separately timed attempts across both the original review and this revision and could not be completed as a clean search. In this revision, Europe PMC, Semantic Scholar, and OpenAlex search endpoints for pasireotide combined with hemoglobin, erythropoietin, hematocrit, or oxygen terms all returned HTTP 429 rate-limit responses, and a Crossref bibliographic search for the same terms returned only general erythropoietin/hemoglobin literature with no pasireotide-specific hits. A real, drug-specific Tier A randomized trial does exist, the ANGIOPAS study (Benamouzig et al 2018, PMID 29479375, cited in full under Iron above and independently verified via OpenAlex in this revision), showing pasireotide-LAR reduces transfusion requirements in refractory gastrointestinal angiodysplasia bleeding. Per Hard Rule 2, a reduction in transfused blood-product units is the drug's own intended hemostatic clinical outcome on an underlying vascular lesion, not a direct measurement of hemoglobin, hematocrit, red-cell mass, or arterial oxygenation, so it is cross-referenced as context under Iron rather than used to grade this category (see Overlap map).

Framing note

Pasireotide's labeled bradycardia (6% incidence in the Phase III trial) is a cardiac electrophysiologic adverse effect, named and graded nowhere in this dossier as an oxygen-delivery finding, per the caution against mistaking a drug's cardiac effect for a hematologic or oxygen-delivery deficiency.

Circulating-claim check

No claim about pasireotide and oxygen delivery or hemoglobin was found in the consumer-reference check performed (Drugs.com).

  • Benamouzig R, Benallaoua M, Saurin JC, Boubaya M, Cellier C, Laugier R, et al. Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study. — Therapeutic Advances in Gastroenterology 2018. PMID 29479375, DOI 10.1177/1756283x18756260. Phase II, double-blinded, randomized, noncomparative trial, n=22 (10 pasireotide-LAR, 12 placebo), pasireotide directly in the treated arm. Reported median transfusion requirement falling from 13 to 3 packed-red-blood-cell units in the treatment arm versus 9.5 to 11.5 in placebo, with 3 cases of glycemic impairment including one new diabetes diagnosis. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cited under Iron and cross-referenced under Oxygen delivery/utilization; measured transfused units, not hemoglobin or iron levels directly.
All references used above
  1. FDA label / DailyMed, SIGNIFOR (pasireotide) injection, Recordati Rare Diseases, Inc. — Prescribing information, current revision. Opened directly for mechanism of action, pharmacokinetics, renal/hepatic impairment dosing, drug interactions, and Sections 5.2-5.7 warnings (hyperglycemia, QT prolongation, hypokalemia/hypomagnesemia, bradycardia, liver enzymes, cholelithiasis, hypocortisolism).
  2. FDA label / DailyMed, SIGNIFOR LAR (pasireotide long-acting release) kit, Recordati Rare Diseases, Inc. — Prescribing information, current revision. Opened directly for pharmacokinetics, hepatic impairment dosing, hyperglycemia incidence in acromegaly and Cushing's disease, QT prolongation, electrolyte monitoring, cholelithiasis, and adrenal insufficiency incidence.
  3. FDA label / DailyMed, SANDOSTATIN (octreotide acetate) injection, Novartis Pharmaceuticals Corporation. — Opened directly, independently in this session, to quote verbatim the vitamin B12/Schilling test statement and pancreatic enzyme/bile acid suppression mechanism used as class-context evidence for the Vitamin B12 and Fat-soluble vitamins entries above. Cohort: octreotide, not pasireotide; used only as Tier C class-level context, never as pasireotide-specific evidence.
  4. Ezzat S, Wang R, Pintilie M, Asa SL. FGFR4 polymorphic alleles modulate mitochondrial respiration: A novel target for somatostatin analog action in pituitary tumors. — Oncotarget 2017;8(2):3481-3494. In vitro/ex-vivo human pituitary tumor cell study, pasireotide and octreotide both directly tested. PMID 27966451, DOI 10.18632/oncotarget.13843. Full abstract and results independently opened and read via the publisher's site.
  5. Benamouzig R, Benallaoua M, Saurin JC, Boubaya M, Cellier C, Laugier R, et al. Efficacy and safety of pasireotide-LAR for the treatment of refractory bleeding due to gastrointestinal angiodysplasias: results of the ANGIOPAS multicenter phase II noncomparative prospective double-blinded randomized study. — Therapeutic Advances in Gastroenterology 2018. PMID 29479375, DOI 10.1177/1756283x18756260. Phase II, double-blinded, randomized, noncomparative trial, n=22 (10 pasireotide-LAR, 12 placebo), pasireotide directly in the treated arm. Reported median transfusion requirement falling from 13 to 3 packed-red-blood-cell units in the treatment arm versus 9.5 to 11.5 in placebo, with 3 cases of glycemic impairment including one new diabetes diagnosis. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cited under Iron and cross-referenced under Oxygen delivery/utilization; measured transfused units, not hemoglobin or iron levels directly.
  6. Wang YL, Liu JY, Jing YL, Zhang YB, Sun N, Wang XJ. [Study on the protective effects of octreotide and Gardenia jasminoides Ellis on pancreatic mitochondria in rats with severe acute pancreatitis]. — Journal of Sichuan University (Medical Science Edition) 2011. PMID 21355297. Rat severe-acute-pancreatitis model, octreotide (sandostatin) directly in the treated arm, not pasireotide. Reported improved malondialdehyde and superoxide dismutase levels and preserved Na+/K+/Ca2+/Mg2+-ATPase activity versus untreated pancreatitis controls. Added in this revision; independently opened and verified via OpenAlex abstract reconstruction after PubMed's article page returned a bot-verification challenge on repeated attempts. Cohort: octreotide, not pasireotide; used only as Tier C class-level context for the Oxidative stress and ATP production entries, never as pasireotide-specific evidence.Cohort excluded pasireotide; Tier C class-level context only.
  7. Kalyoncu Ucar A, et al. Octreotide and lanreotide decrease ovarian ischemia-reperfusion injury in rats by improving oxidative and nitrosative stress. — Journal of Obstetrics and Gynaecology Research 2020. PMID 32748523. Rat ovarian torsion-detorsion ischemia-reperfusion model, both octreotide and lanreotide directly in treated arms, not pasireotide. Reported significantly decreased total oxidant status, oxidative stress index, and peroxynitrite versus injury controls. Added in this revision; independently opened and verified via direct PubMed article-page fetch (this individual article page was reachable even while PubMed's search-listing pages returned bot-verification challenges). Cohort: octreotide and lanreotide, not pasireotide; used only as Tier C class-level context for the Oxidative stress entry, never as pasireotide-specific evidence.Cohort excluded pasireotide; Tier C class-level context only.
  8. Störmann S, et al. Management of pasireotide-induced hyperglycemia in patients with acromegaly: An experts' consensus statement. — Frontiers in Endocrinology 2024. Consensus statement drawing on primary pasireotide trial data; incidence, mechanism (SSTR5/insulin/incretin), risk factors, and reversibility independently opened and read in full text.
  9. Witek P, et al. Pasireotide-induced hyperglycemia in Cushing's disease and Acromegaly: A clinical perspective and algorithms proposal. — Frontiers in Endocrinology 2024. Independently opened and read in full text for incidence figures, mechanism, time course/reversibility, and management algorithm (metformin, GLP-1 agonists, why DPP-4 inhibitors underperform given the incretin-suppression mechanism).
  10. Costanza F, Basile C, Chiloiro S, et al. Impact of pasireotide on lipid and glucose metabolism in patients with acromegaly: a systematic review and meta-analysis. — 2025. PMID 40622518. Title and journal identified via PubMed search-listing metadata only; full text was not opened in this review.Listing-level source only, not independently opened for its findings; cited in the headline narrative as corroborating context, not as a stand-alone graded citation.
  11. Biagetti B, Araujo-Castro M, Tebé C, et al. Real-world evidence of effectiveness and safety of pasireotide in the treatment of acromegaly: a systematic review and meta-analysis. — 2025. PMID 39527181. Title and journal identified via PubMed search-listing metadata only; full text was not opened in this review.Listing-level source only, not independently opened.
  12. Feldt-Rasmussen U, Bolanowski M, Zhang SL, et al. Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing's disease receiving pasireotide treatment. — 2024. PMID 38577574. Title and journal identified via PubMed search-listing metadata only; full text was not opened in this review.Listing-level source only, not independently opened.
  13. Samson SL. Management of Hyperglycemia in Patients With Acromegaly Treated With Pasireotide LAR. — Drugs 2016. PMID 27473537. Title identified via PubMed search-listing metadata only; full text was not opened in this review.Listing-level source only, not independently opened.
  14. Drugs.com, Signifor (pasireotide) consumer/professional drug information page. — Opened directly for the circulating-claim audit: checked for any mention of vitamin B12, cobalamin, vitamin A/D/E/K, iron, zinc, chromium, copper, magnesium, or potassium depletion claims. Found only magnesium/potassium monitoring language matching the label; no unsupported nutrient-depletion claim was present.
  15. WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index. — Opened directly to confirm pasireotide's ATC code (H01CB05) within the H01CB somatostatin-and-analogues subclass, alongside octreotide (H01CB02), lanreotide (H01CB03), vapreotide (H01CB04), and paltusotine (H01CB06).
  16. PubMed search-listings, confirmed zero-result searches (not blocked): "pasireotide B12" / "pasireotide AND B12"; "pasireotide AND copper"; "pasireotide AND microbiota"; "pasireotide AND chromium"; "pasireotide AND \"ATP production\""; "pasireotide AND iron deficiency"; "pasireotide 25-hydroxyvitamin"; "pasireotide reactive oxygen species". — Each returned PubMed's own "No results were found" / "processed without automatic term mapping because it retrieved zero results" message, a genuine negative result rather than a tooling block. Reconfirmed on fresh, separately timed attempts in this revision (session used to redo the Oxidative stress, Copper, Oxygen delivery/utilization, and ATP production entries).
  17. PubMed search-listings, access-blocked attempts (tooling limitation, not a confirmed result either way). — "pasireotide oxidative stress," "pasireotide AND \"reactive oxygen species\"" (search-listing page only; the term-specific zero-result variant above did succeed), "pasireotide AND vitamin D," and "pasireotide AND erythropoietin" each returned a bot-verification ("checking your browser") challenge page on multiple separately timed attempts across both the original review and this revision rather than a clean result. Individual PubMed article pages (e.g. PMID 32748523) remained reachable even while search-listing pages were blocked.Disclosed tooling limitation, reconfirmed in this revision; Oxygen delivery/utilization and Copper remain the only entries this constraint leaves genuinely ungraded (Oxidative stress and ATP production were resolved to yellow via independently verified class-level sources instead).
  18. Europe PMC REST API, Semantic Scholar Graph API, and OpenAlex Works/Search API endpoints. — Search endpoints queried for pasireotide combined with oxidative stress, reactive oxygen species, hemoglobin, erythropoietin, hematocrit, and oxygen terms.All three search endpoints returned repeated HTTP 429 rate-limit responses in this revision, consistent with the original review; no usable search results were obtained from any of the three hosts' search endpoints in either session. OpenAlex's per-work lookup endpoint (fetching a specific work by PMID rather than searching) was reachable in this revision and was used to independently verify the ANGIOPAS, Wang 2011, and Kalyoncu 2020 findings cited above.
  19. Crossref REST API (api.crossref.org), bibliographic relevance searches. — Used as a partial substitute where PubMed and Europe PMC were blocked: "pasireotide mitochondrial," "pasireotide oxidative stress," "pasireotide gut microbiome microbiota," "pasireotide copper iron trace element," "pasireotide gastric acid iron absorption," "pasireotide hemoglobin erythropoietin oxygen," "pasireotide hypomagnesemia hypokalemia electrolyte mechanism," "pasireotide induced hyperglycemia management mechanism incretin," "pasireotide oxidative stress reactive oxygen species antioxidant" (this revision), and "pasireotide erythropoietin hemoglobin hematocrit oxygen" (this revision). Yielded the FGFR4/Ezzat 2017 lead and the Störmann/Witek/Samson/Silverstein hyperglycemia titles; returned no pasireotide-specific hits for microbiome, copper/iron, electrolyte-mechanism, oxidative-stress, or hemoglobin/erythropoietin queries, consistent with (not identical to) the PubMed findings for those same categories.