Meta Information
ID:ipriflavone
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:
/biomarker/complete-blood-count
Target name:
Complete Blood Count (CBC)
Severity:
major
Interaction type:
requirement
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone can cause a significant and potentially dangerous drop in lymphocyte counts (lymphocytopenia), a type of white blood cell, which increases the risk of serious infections.
Actionable advice:
A baseline CBC test is required before starting, with regular monitoring (e.g., every 3-6 months) during therapy.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
a number of women developed lymphocytopenia after daily intake of 600 mg ipriflavone for three years
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC1481570/
Action type:
monitor
Target id:
/condition/immunocompromised
Target name:
Immunocompromised State
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Due to the significant risk of causing low white blood cell counts (lymphocytopenia), ipriflavone is contraindicated in individuals with pre-existing conditions that compromise the immune system.
Actionable advice:
This should be strictly avoided with a compromised immune system from a medical condition or medication.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lymphocyte concentrations decreased significantly (500/microL (0.5 x 10(9)/L]) in women treated with ipriflavone. Thirty-one women (13.2%) in the ipriflavone group developed subclinical lymphocytopenia, of whom 29 developed it during ipriflavone treatment.
Label source:
PubMed: JAMA (2001)
Source url:
Exact phrase from label:
Newer estrogenic-type supplements (eg, ipriflavone) appear interesting and have some preliminary data, but more research is desperately required to determine their actual impact and potential for adverse effects (such as lymphocytopenia from a recent trial).
Label source:
PubMed: Urology (2002)
Source url:
Exact phrase from label:
there are some concerns as to whether soy isoflavones, similar to ipriflavone, a synthetic isoflavone, cause lymphocytopenia in postmenopausal women.
Label source:
PubMed: Nutrition journal (2006)
Action type:
avoid
Target id:
/class/cyp2c9-substrates
Target name:
Drugs Metabolized by CYP2C9 (e.g., Warfarin, Phenytoin)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone is a potent inhibitor of the CYP2C9 enzyme, which can dangerously increase blood levels of medications cleared by this pathway, raising the risk of toxicity or severe side effects (e.g., bleeding with warfarin).
Actionable advice:
Co-administration should be avoided; if essential, it requires intensive medical monitoring and dose adjustments.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
On the other hand, our in vitro findings predict some more interaction with CYP2C9.
Label source:
PubMed: British journal of pharmacology (1998)
Source url:
Exact phrase from label:
Ipriflavone and 7-hydroxy-isoflavone competitively inhibited phenacetin O-deethylase and tolbutamide hydroxylase activity. The parent compound and its dealkylated metabolite were strong inhibitors exhibiting Ki values around 10-20 microM, while 7-(1-carboxy-ethoxy)-isoflavone had no effect on the cytochrome P450 activities investigated.
Label source:
PubMed: British journal of pharmacology (1998)
Source url:
Exact phrase from label:
large doses of IPR may affect the CYP3A4-catalyzed biotransformation of some drugs.
Label source:
PubMed: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (2018)
Action type:
avoid
Target id:
/intervention/theophylline
Target name:
Theophylline
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone inhibits CYP1A2, the primary enzyme that metabolizes theophylline. This can lead to toxic accumulation of theophylline, which has a narrow therapeutic window and can cause seizures or cardiac arrhythmias.
Actionable advice:
This combination should be avoided completely.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipriflavone may be due to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy-isoflavone with CYP1A2.
Label source:
PubMed: Ipriflavone as an inhibitor of human cytochrome P450 enzymes. (PMID 9517377)
Action type:
informational_none
Target id:
/condition/hepatic-impairment
Target name:
Liver Disease or Impairment
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone is metabolized in the liver and has been linked to cases of liver injury. Its use is contraindicated in individuals with pre-existing liver disease.
Actionable advice:
This should not be used with any form of liver disease or impaired liver function.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
Administer the drug with special caution to patients with severe liver or kidney damage and hematological troubles
Label source:
Primary literature: https://betterbones.com/wp-content/uploads/2016/11/ipriflavone.pdf
Action type:
avoid
Target id:
/condition/pregnancy
Target name:
Pregnancy
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The safety of ipriflavone during pregnancy is unknown. Due to its isoflavone structure and potential hormonal effects, it poses a theoretical risk to fetal development.
Actionable advice:
This should not be used during pregnancy, when planning to become pregnant, or without effective contraception.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Action type:
avoid
Target id:
/condition/lactation
Target name:
Breastfeeding (Lactation)
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
It is not known whether ipriflavone or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in the nursing infant, it is contraindicated.
Actionable advice:
This should not be used while breastfeeding.
Validation status:
anecdotal
Evidence tier:
tier_d
Evidence basis:
anecdotal_summary
Evidence anchors:
Exact phrase from label:
There isn't enough reliable information to know if ipriflavone is safe to use when pregnant or breast-feeding. Stay on the safe side and avoid use.
Label source:
Anecdotal: WebMD
Action type:
avoid
Target id:
/class/cyp1a2-substrates
Target name:
Drugs Metabolized by CYP1A2
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone inhibits the CYP1A2 enzyme, which can increase the concentration and effects of other drugs metabolized by this pathway, such as some antidepressants and antipsychotics.
Actionable advice:
This is best used with caution, and it is a good idea to monitor for increased side effects of the co-administered drug.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipriflavone may be due to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy-isoflavone with CYP1A2.
Label source:
PubMed: British journal of pharmacology (1998)
Source url:
Exact phrase from label:
Ipriflavone and/or its five metabolites were found to inhibit potently the metabolism of CYPs 1A2, 2C8, 2C9 and 2C19 substrates.
Label source:
PubMed: Xenobiotica; the fate of foreign compounds in biological systems (2007)
Source url:
Exact phrase from label:
Results indicate that the reduction of theophylline clearance by concomitant ipriflavone administration observed by Takahashi et al. [Takahashi J., Kawakatsu K., Wakayama T., Sawaoka H. (1992): Elevation of serum theophylline levels by ipriflavone in a patient with chronic obstructive pulmonary disease. Eur. J. Clin. Pharmacol., 43, 207-208] is primarily due to an interaction of the inhibitory ipriflavone and/or its metabolites with cytochrome P450 enzyme(s) that mediate N-demethylation of theophylline.
Label source:
PubMed: European journal of drug metabolism and pharmacokinetics (1996)
Action type:
monitor
Target id:
/class/hepatotoxic-agents
Target name:
Other Liver-Affecting Agents
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Combining ipriflavone with other drugs, supplements, or substances known to be potentially harmful to the liver (e.g., excessive alcohol, high-dose acetaminophen) may additively increase the risk of liver injury. [class-derived from: class_pharmacology]
Actionable advice:
Minimize or avoid concurrent use of other potentially hepatotoxic substances, including alcohol.
Validation status:
validated_via_expert_review
Evidence tier:
tier_c
Evidence basis:
expert_review_verbatim
Evidence anchors:
Exact phrase from label:
Occasionally increases in SGOT, SGPT and bilirubinemia can be observed
Label source:
Expert review: Ipriflavone inhibits CYP1A2 and CYP2C9 enzymes (WebMD monograph; https://www.webmd.com/vitamins/ai/ingredientmono-310/ipriflavone), and occasional increases in SGOT, SGPT, and bilirubinemia have been documented. Combining with other hepatotoxic agents (alcohol, high-dose acetaminophen) is a standard additive hepatotoxicity class inference.
Action type:
avoid
Target id:
/class/estrogens
Target name:
Estrogens (Hormonal Therapy)
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone may enhance the bone-protective effects of estrogen. However, this combination has not been well-studied for long-term safety and should only be used under strict medical supervision.
Actionable advice:
This combination is best used only if prescribed and closely monitored by a physician.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The increase of bone density obtained with the combination of conjugated estrogens with ipriflavone demonstrates that this combination improves the effects of low estrogen doses on bone mass representing a satisfactory approach in the prevention and treatment of all symptoms related to the climacteric syndrome.
Label source:
PubMed: Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. (PMID 1422321)
Action type:
monitor
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
requirement
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Taking ipriflavone with food is recommended to improve its absorption and reduce the likelihood of gastrointestinal discomfort.
Actionable advice:
The dose is best taken at the same time as a meal or snack.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A pilot study was conducted in healthy male volunteers that showed an 8- to 20-fold increase in the IP bioavailability after administration of Osteofix tablets in the fed state relative to the fasting state.
Label source:
PubMed: Pharmacokinetics of ipriflavone and metabolites after oral administration of a corn-oil suspension relative to the Osteofix tablet. (PMID 10423615)
Action type:
informational_none
Target id:
/intervention/calcium-citrate
Target name:
Calcium Supplements
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Ipriflavone's action to inhibit bone breakdown is most effective when the body has sufficient calcium, the primary mineral component of bone, to maintain or build new bone.
Actionable advice:
Meeting daily calcium requirements through diet or supplementation is a good idea as part of a bone health regimen.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
In rats fed on a more severe calcium restricted (0.03%), vitamin D deficient diet, the administration of ipriflavone (100 mg/kg BW/day) did not significantly affect the cortical thickness or calcium content.
Label source:
PubMed: Endocrinologia japonica (1986)
Source url:
Exact phrase from label:
It is concluded that even in hens fed on a low-calcium diet, the addition of 20 mg/kg IP exerted beneficial effects on histological structure and structural histomorphometric parameters of tibia, indicating an alleviation of caged layer osteoporosis (CLO).
Label source:
PubMed: British poultry science (2014)
Source url:
Exact phrase from label:
This protective effect of IP may be partly due to its ability to enhance calcium absorption.
Label source:
PubMed: Calcified tissue international (2000)
Action type:
informational_none
Target id:
/intervention/vitamin-d
Target name:
Vitamin D Supplements
Severity:
moderate
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Adequate vitamin D levels are crucial for the absorption of dietary calcium. Without sufficient vitamin D, the benefits of both calcium and ipriflavone on bone density are diminished.
Actionable advice:
Optimal vitamin D levels are best maintained through sun exposure or supplementation as recommended by a doctor.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
CONCLUSION: Vitamin D plus calcium is superior to no therapy or calcium alone in the management of corticosteroid-induced osteoporosis.
Label source:
PubMed: The role of vitamin D in corticosteroid-induced osteoporosis: a meta-analytic approach. (PMID 10446876)
Action type:
informational_none
Target id:
/condition/renal-impairment
Target name:
Kidney Disease or Impairment
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
The pharmacokinetics of ipriflavone in patients with kidney disease have not been well-studied. Caution is warranted as impaired renal function could potentially alter the drug's clearance.
Actionable advice:
It is important to talk to a physician before use with any degree of kidney impairment.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Plasma levels at steady-state of the unchanged drug, and its metabolites M1, M2 and M5 were higher in the patient group, with the presence of secondary peaks, which could be explained by the biliary excretion of the substances.
Label source:
PubMed: Steady-state pharmacokinetics of ipriflavone and its metabolites in patients with renal failure. (PMID 1813437)
Action type:
informational_none
Target id:
/intervention/caffeine
Target name:
Caffeine
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By inhibiting the CYP1A2 enzyme, ipriflavone can slow the metabolism of caffeine, potentially amplifying its effects such as jitteriness, increased heart rate, and difficulty sleeping.
Actionable advice:
Consider reducing your caffeine intake while taking ipriflavone to avoid potential overstimulation.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The results indicate that the decrease in theophylline metabolism observed in a patient treated with ipriflavone may be due to a competitive interaction of ipriflavone or its metabolite, 7-hydroxy-isoflavone with CYP1A2.
Label source:
PubMed: British journal of pharmacology (1998)
Source url:
Exact phrase from label:
Ipriflavone and/or its five metabolites were found to inhibit potently the metabolism of CYPs 1A2, 2C8, 2C9 and 2C19 substrates.
Label source:
PubMed: Xenobiotica; the fate of foreign compounds in biological systems (2007)
Source url:
Exact phrase from label:
The pharmacokinetics of caffeine are highly variable among individuals due to a polymorphism at the level of the CYP1A2 isoform of cytochrome P450, which metabolizes 95% of the caffeine ingested.
Label source:
PubMed: Pharmacological reviews (2018)
Action type:
avoid