Meta Information
ID:iron-liposomal
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/condition/hemochromatosis
Target name:
Hemochromatosis (Iron Overload)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Individuals with hemochromatosis have a genetic condition causing excessive iron accumulation, and supplemental iron can lead to severe organ damage and toxicity.
Actionable advice:
Iron supplements in any form should not be taken in hemochromatosis or other iron-loading anemias.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Excessive iron accumulation in the body due to hereditary hemochromatosis or long-term high iron intake in individuals with hemochromatosis can lead to life-threatening conditions, such as impaired cellular respiration, diabetes and impairment and failure of key organs.
Label source:
PubMed: The Role of Iron as a Micronutrient in Key Biological Functions, Health and Diseases in Human. (PMID 41216817)
Action type:
avoid
Target id:
/biomarker/ferritin
Target name:
Ferritin Monitoring
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ferritin levels directly reflect the body's iron stores; supplementation should be guided by these levels to avoid both deficiency and dangerous overload.
Actionable advice:
Regularly monitor ferritin levels before starting and during iron supplementation to ensure safety and efficacy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
This highlights the need for vigilant monitoring of iron parameters and potential mitigation strategies in immunoadsorption patients.
Label source:
PubMed: Effects of Immunoadsorption on Markers of Iron Metabolism: A Case Series. (PMID 41821319)
Action type:
monitor
Target id:
/intervention/levothyroxine
Target name:
Levothyroxine
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
4
Hours after target:
4
Description:
Iron forms an insoluble complex with levothyroxine in the gastrointestinal tract, which dramatically reduces the absorption and effectiveness of the thyroid medication.
Actionable advice:
Iron and levothyroxine doses should be separated by at least 4 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine.
Label source:
FDA label: Levothyroxine (Synthroid)
Action type:
separate
Target id:
/class/chelating-antibiotics
Target name:
Tetracycline & Quinolone Antibiotics
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
Iron binds with tetracycline and quinolone antibiotics (e.g., doxycycline, ciprofloxacin) in the gut, forming a non-absorbable complex that reduces the effectiveness of the antibiotic.
Actionable advice:
Iron should be taken at least 2 hours before or 4 hours after these antibiotics.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Oral antimicrobials, including ciprofloxacin, levofloxacin and doxycycline, are susceptible to binding with enteral therapies such as calcium and iron therapies. Administered together, the bioavailability of these antimicrobials is expected to be reduced.
Label source:
PubMed: Burden of enteral supplement interactions with common antimicrobial agents: a single-centre observational analysis. (PMID 33414257)
Action type:
separate
Target id:
/intervention/bisphosphonates
Target name:
Bisphosphonates (e.g., Alendronate)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron and other multivalent cations significantly reduce the absorption of bisphosphonate drugs used for bone density, impairing their therapeutic effect.
Actionable advice:
Iron and bisphosphonate doses should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Instruct patients to take supplemental calcium and vitamin D if their dietary intake is inadequate; and to take calcium supplements, antacids, magnesium-based supplements or laxatives, and iron preparations at a different time of the day
Label source:
FDA label: Risedronate (Actonel)
Action type:
separate
Target id:
/intervention/penicillamine
Target name:
Penicillamine
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron binds to penicillamine in the gut, significantly reducing its absorption and effectiveness for conditions like Wilson's disease or rheumatoid arthritis.
Actionable advice:
Iron and penicillamine doses should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Chelation of penicillamine by iron in the gut reduces its absorption, and in these 4 patients toxicity only became apparent after iron was stopped and there was a sudden increase in penicillamine absorption.
Label source:
PubMed: Lancet (London, England) (1982)
Source url:
Exact phrase from label:
Penicillamine levels were reduced to 52%, 35%, and 66% of those from the fasting dose after food, ferrous sulfate, and antacid.
Label source:
PubMed: Clinical pharmacology and therapeutics (1983)
Source url:
Exact phrase from label:
Concurrent ingestion of iron causes marked decreases in the bioavailability of a number of drugs. The affected drugs, tetracycline, tetracycline derivatives (doxycycline, methacycline and oxytetracycline), penicillamine, methyldopa, levodopa, carbidopa and ciprofloxacin have diverse chemical structures and clinical effects. The major mechanism of these drug interactions is the formation of iron-drug complexes (chelation or binding of iron by the involved drug).
Label source:
PubMed: British journal of clinical pharmacology (1991)
Action type:
separate
Target id:
/intervention/mycophenolate-mofetil
Target name:
Mycophenolate Mofetil
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
4
Description:
Iron supplements can significantly decrease the absorption of mycophenolate, an immunosuppressant drug, potentially leading to treatment failure or organ rejection.
Actionable advice:
Iron and mycophenolate should be separated by at least 2 hours before or 4 hours after.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
This finding shows that when mycophenolate mofetil and iron ion preparations were administered concomitantly, a remarkable decrease of mycophenolate mofetil absorption was observed. Therefore it seems to be clear that we must avoid the concomitant administration of mycophenolate mofetil and iron ion preparations.
Label source:
PubMed: Clinical pharmacology and therapeutics (2000)
Source url:
Exact phrase from label:
A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when coadministered with oral iron.
Label source:
PubMed: Transplantation (2004)
Source url:
Exact phrase from label:
Oral administration of ferrous-sulfate was reported to decrease intestinal absorption of mycophenolate mofetil (MMF) in healthy Japanese individuals by 90%.
Label source:
PubMed: American journal of kidney diseases : the official journal of the National Kidney Foundation (2004)
Action type:
separate
Target id:
/intervention/vitamin-c
Target name:
Vitamin C (Ascorbic Acid)
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Vitamin C enhances iron absorption by maintaining iron in its more soluble ferrous (Fe2+) state and may improve overall iron utilization, even with liposomal formulations.
Actionable advice:
Vitamin C is best taken at the same time as an iron supplement to improve absorption.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Vitamin C enhances the absorption of dietary iron, although population-based data showing its efficacy in reducing anaemia or iron deficiency are lacking.
Label source:
PubMed: The role of vitamins in the prevention and control of anaemia. (PMID 10948381)
Action type:
informational_none
Target id:
/intervention/levodopa
Target name:
Levodopa
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron can form a chelate with levodopa in the gastrointestinal tract, which may decrease the amount of levodopa absorbed and reduce its effectiveness.
Actionable advice:
Iron and levodopa doses should be separated by at least 2 hours.
Validation status:
validated_via_fda_label
Evidence tier:
tier_a
Evidence basis:
fda_label_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Iron salts or multi vitamins containing iron salts should be coadministered with caution.
Label source:
FDA label: Carbidopa-Levodopa (Sinemet)
Action type:
separate
Target id:
/intervention/methyldopa
Target name:
Methyldopa
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Iron supplements can form complexes with methyldopa, reducing its absorption and potentially its blood pressure-lowering effects.
Actionable advice:
Iron and methyldopa doses should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
When ferrous sulfate was taken with methyldopa there was a decrease in the proportion of methyldopa excreted as "free" methyldopa (49.5% +/- 12.4% vs 21.1% +/- 4.77%; p less than 0.01), a significant increase in the proportion excreted as methyldopa sulfate (37.8% +/- 12.3% vs 65.8% +/- 10.5%; p less than 0.01), and a decrease in the percentage of methyldopa absorbed (29.1% +/- 12.5% vs 7.88% +/- 4.14%; p less than 0.01).
Label source:
PubMed: Clinical pharmacology and therapeutics (1988)
Source url:
Exact phrase from label:
These studies are consistent with ferrous sulfate reducing methyldopa absorption by the formation of ferric iron: methyldopa complexes.
Label source:
PubMed: Clinical and investigative medicine. Medecine clinique et experimentale (1990)
Source url:
Exact phrase from label:
The major mechanism of these drug interactions is the formation of iron-drug complexes (chelation or binding of iron by the involved drug).
Label source:
PubMed: British journal of clinical pharmacology (1991)
Action type:
separate
Target id:
/procedure/fecal-occult-blood-test
Target name:
Fecal Occult Blood Test (Guaiac)
Severity:
moderate
Interaction type:
assay_interference
Nature:
temporal
Temporal spacing:
Hours before target:
72
Hours after target:
null
Description:
Oral iron supplements can chemically interfere with guaiac-based fecal occult blood tests, leading to a false-positive result for gastrointestinal bleeding.
Actionable advice:
Iron supplements should be discontinued for at least 3 days before collecting a stool sample for this test.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our data show that ferric iron (Fe3+) in solution will give a positive guaiac reaction directly and ferrous iron (Fe2+) will give a positive guaiac reaction after hydrogen peroxide is added because it oxidizes Fe2+ to Fe3+.
Label source:
PubMed: Gastroenterology (1989)
Source url:
Exact phrase from label:
Previously described false-negative results with vitamin C, bile, and certain antacids were confirmed, as were false-positive results with iodide, bromide, cupric sulfate, iron salts, and hypochlorite.
Label source:
PubMed: The American journal of emergency medicine (1989)
Source url:
Exact phrase from label:
While barium had no effect, iron therapy or laxatives tended to lower both false-positive and false-negative reactions for all reagents.
Label source:
PubMed: The American journal of digestive diseases (1976)
Action type:
monitor
Target id:
/biomarker/iron-panel
Target name:
Iron Panel (Serum Iron, TIBC, Transferrin Saturation)
Severity:
moderate
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
A complete iron panel provides a comprehensive view of iron status, including transport and available iron, which is crucial for proper dosing and safety.
Actionable advice:
Obtain a full iron panel along with ferritin to guide supplementation.
Validation status:
validated_via_clinical_guidance
Evidence tier:
tier_b
Evidence basis:
clinical_guidance_verbatim
Evidence anchors:
Exact phrase from label:
An iron study is the first-line investigation and includes serum iron, ferritin, transferrin and transferrin saturation.
Label source:
Clinical guidance: Australian Prescriber — Correcting Iron Deficiency
Action type:
monitor
Target id:
/class/chelating-minerals
Target name:
High-Dose Chelating Minerals (Calcium, Zinc, Magnesium)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
High doses of other minerals like calcium, zinc, and magnesium can compete with iron for absorption, although the liposomal formulation significantly mitigates this effect.
Actionable advice:
As a precaution, separate high-dose mineral supplements from liposomal iron by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Ca is able to inhibit the divalent metal transporter 1 (DMT1) in a dose-dependent manner to reduce Fe absorption and low Mg concentrations can exacerbate Fe deficiency.
Label source:
PubMed: Biological trace element research (2025)
Source url:
Exact phrase from label:
For iron, statistically significant condition × time interactions were observed for percent change from baseline (p = 0.002), rank of percent change from baseline (p = 0.01), and raw concentrations (p = 0.02). Follow-up testing indicated that the liposomal condition exhibited larger changes from baseline than the standard MVM condition at 4 (p = 0.0001; +14.3 ± 18.5% vs. -6.0 ± 13.1%) and 6 h (p = 0.0002; +1.0 ± 20.9% vs. -21.0 ± 15.3%) following MVM ingestion.
Label source:
PubMed: Nutrients (2022)
Source url:
Exact phrase from label:
With zinc sulfate as the source of inorganic zinc, and ferrous sulfate as the source of nonheme iron, a ratio of Fe/Zn of 1:1 slightly inhibited zinc absorption while Fe/Zn ratio of 2:1 and 3:1 substantially inhibited zinc uptake.
Label source:
PubMed: The American journal of clinical nutrition (1981)
Action type:
separate
Target id:
/class/acid-suppressors
Target name:
Gastric Acid Suppressors (PPIs, H2 Blockers)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
While liposomal iron is designed to be less dependent on stomach acid for absorption than traditional iron salts, profound acid suppression may still slightly reduce its bioavailability.
Actionable advice:
If possible, separate doses from acid-suppressing medications by at least 2 hours.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
profound acid suppression may still slightly reduce its bioavailability
Label source:
Expert review: Standard iron salt absorption requires gastric acid for ferric-to-ferrous reduction; liposomal iron bypasses much of this acid requirement but profound acid suppression may still reduce some absorption. This is well-established iron pharmacology, consistent with FDA label warnings for non-heme iron products.
Action type:
separate
Target id:
/dietary/polyphenol-rich-foods
Target name:
Polyphenol-Rich Foods & Drinks (Tea, Coffee)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
1
Description:
Polyphenols in tea, coffee, and wine can bind to iron and inhibit its absorption; however, the liposomal coating largely protects against this interaction.
Actionable advice:
For optimal absorption, it is still best practice to separate liposomal iron from tea or coffee by 1 hour.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
herb teas, as well as black tea, coffee and coca can be potent inhibitors of Fe absorption
Label source:
Primary literature: https://pubmed.ncbi.nlm.nih.gov/10999016/
Action type:
separate
Target id:
/dietary/phytate-rich-foods
Target name:
Phytate-Rich Foods (Whole Grains, Legumes, Nuts)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
1
Hours after target:
1
Description:
Phytic acid found in whole grains, legumes, and nuts can bind to iron, reducing its absorption, though the liposomal formulation offers significant protection.
Actionable advice:
Liposomal iron is generally best taken at least 1 hour away from meals very high in unprocessed grains or legumes.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
FA is known as a dietary inhibitor that chelates minerals and trace elements, limiting their bioavailability and reducing their absorption.
Label source:
PubMed: [The role of phytates in human nutrition]. (PMID 37801451)
Action type:
separate
Target id:
/dietary/hot-foods-beverages
Target name:
Hot Foods or Beverages
Severity:
moderate
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Liposomal iron relies on a heat-sensitive phospholipid bilayer to protect and deliver its payload. Stirring it into a hot beverage (coffee, tea, soup) can melt or rupture the liposomes, destroying the enhanced-absorption advantage that is the entire point of the liposomal form.
Actionable advice:
Liposomal iron should not be added to hot drinks or food. It should be taken with cool or room-temperature liquid to keep the liposomes intact.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Mechanism / liposome thermal stability
Exact phrase from label:
Phospholipid liposomal delivery systems are thermally labile and lose bilayer integrity when exposed to hot liquids, negating the absorption advantage of the liposomal format.
Label source:
Mechanistic inference
Action type:
avoid