TruthNexus
Drug-Drug Interactions · Medical

Interaction checking with mechanistic depth

Drug-drug interactions cause 30% of all adverse drug events. A patient on 8 medications has 28 interaction pairs to evaluate. Skippy DDI checks all of them in one call — explains the CYP mechanism, scores panel risk, and returns verified alternatives.

POST /api/check · 200 OK
Warfarin + Aspirin
COX-1 + VKORC1 synergy
MAJOR
Clinical Effect

Additive anticoagulation and antiplatelet effect. Concurrent use significantly increases GI and intracranial bleeding risk.

Confidence
0.94
Recommendation:Avoid concurrent use if possible. If clinically necessary, lowest effective aspirin dose (≤81mg/day) with close INR monitoring and GI protection.
panel_risk: highscore: 6pairs: 3
Evidence: DDInter · OpenFDA · PharmGKB
30%
Of adverse drug events are DDI-related
28 pairs
Interaction checks for an 8-drug regimen — one call
<100ms
Full panel analysis latency
4 enzymes
CYP2D6, CYP2C9, CYP2C19, CYP3A4 — mechanistic depth
Live Demo

Try Skippy DDI

Interaction checking and CYP pathway analysis — same API shape as production.

POST /api/checksimulation
Medication Panel
WarfarinAspirinOmeprazole
HIGH RISK· Risk score: 6 · 3 pairs evaluated
1 major1 moderate1 minor
Risk hub: Warfarin — involved in 2 interactions · Top enzyme: CYP2C9
Warfarin + Aspirin
MAJOR
COX-1 inhibition + anticoagulation synergy

Additive anticoagulation and antiplatelet effect. Concurrent use significantly increases GI and intracranial bleeding risk.

Avoid concurrent use if possible. If clinically necessary, use lowest effective aspirin dose (≤81mg/day) with close INR monitoring and GI protection.

94% conf.
Omeprazole + Warfarin
MODERATE
CYP2C9 competitive inhibition

Omeprazole reduces CYP2C9-mediated warfarin clearance, increasing warfarin plasma levels and INR.

CYP2C9

Monitor INR closely when initiating or discontinuing omeprazole. Pantoprazole has lower CYP2C9 interaction potential if PPI is required.

82% conf.
Omeprazole + Aspirin
MINOR
Pharmacodynamic gastroprotection

Omeprazole provides gastroprotective benefit against aspirin-induced GI irritation. Low clinical risk.

Favorable combination — PPI co-prescription reduces aspirin-related GI risk. No dose adjustment needed.

71% conf.
What It Does

Six endpoints. One API.

Interaction checking, pathway analysis, alternatives, drug profiles, panel risk, and PGx dosing — all callable from a single integration.

POST /api/check
Multi-drug interaction check

Evaluates all N×(N-1)/2 drug pairs in a single call. Returns severity, mechanism, CYP conflicts, confidence score, and recommendation for every pair — with panel risk score and risk hub identification.

POST /api/alternatives
Alternative recommendations

Given a MAJOR interaction, returns ranked alternatives verified against the full medication panel. The replacement is checked for new conflicts before being recommended.

GET /v1/ddi/cyp-pathway
CYP pathway analysis

Per-drug enzyme role breakdown (substrate, inhibitor, inducer) with cross-drug conflict detection across CYP2D6, CYP2C9, CYP2C19, and CYP3A4.

POST /api/profile
Drug profile

Full drug profile: mechanism of action, CYP metabolism, target bioactivities from DrugCentral, contraindications, and indications.

GET /api/panel-risk
Panel risk scoring

Aggregate risk score for a medication panel (MAJOR×3 + MODERATE×2 + MINOR×1), with risk hub — the drug involved in the most interactions — and top enzyme identified.

GET /v1/pgx/dosing/{drug}/{diplotype}
PGx genotype-aware dosing

CPIC-grounded dosing recommendations for drug + diplotype pairs. Pharmacogenomics meets interaction checking in the same API — when a co-medication also has a PGx implication.

Known High-Risk Combinations

Common dangerous pairs

Frequently co-prescribed combinations with established clinical interaction evidence.

Warfarin + Aspirin
MAJOR

Additive anticoagulation + antiplatelet effect — major GI and intracranial bleeding risk

Simvastatin + Clarithromycin
MAJOR

CYP3A4 inhibition → simvastatin plasma levels elevated → myopathy and rhabdomyolysis risk

SSRI + MAOI
MAJOR

Serotonin syndrome — potentially fatal. Washout period required before switching

Metformin + IV Contrast
MAJOR

Lactic acidosis risk — hold metformin 48h before and after contrast administration

Warfarin + Fluconazole
MAJOR

CYP2C9 inhibition by fluconazole markedly elevates warfarin levels — INR monitoring required

Atorvastatin + Amlodipine
MINOR

Modest CYP3A4 overlap — atorvastatin levels modestly increased. Low clinical risk at standard doses

The polypharmacy problem

Interaction pairs scale as N×(N-1)/2. A patient on 8 medications has 28 pairsto evaluate — manually, that means 28 separate lookups. At 12 drugs, it's 66. Skippy DDI evaluates the entire panel in a single call, returns a panel risk score, and identifies the risk hub — the drug involved in the most interactions.

2 drugs=1 pair
4 drugs=6 pairs
8 drugs=28 pairs
12 drugs=66 pairs
Severity Framework

Panel risk scoring

Every interaction pair carries a severity rating. Panel risk score = MAJOR×3 + MODERATE×2 + MINOR×1. The drug with the most interactions in the panel is flagged as the risk hub.

MAJOR3 pts

Contraindicated or strongly discouraged. Life-threatening outcome possible. Requires alternative selection or clinical escalation.

MODERATE2 pts

Use with caution and close monitoring. Dose adjustment, enhanced monitoring, or an alternative may be warranted.

MINOR1 pt

Low clinical risk at standard doses. Document for awareness. Routine monitoring is typically sufficient.

Mechanistic Depth

CYP enzyme pathway analysis

DDI doesn't return severity flags — it returns the mechanism. CYP substrate, inhibitor, and inducer relationships for each drug in your panel, with conflict detection across enzymes.

CYP2D6
CodeineTamoxifenTricyclicsMetoprolol

Major substrate for ~25% of marketed drugs. PM phenotype increases toxicity risk with codeine and TCAs.

CYP2C9
WarfarinPhenytoinNSAIDsLosartan

Narrow therapeutic index substrates dominate this enzyme. Inhibitors cause clinically significant INR changes.

CYP2C19
ClopidogrelPPIsSSRIsVoriconazole

Genetic variation and drug inhibition both affect this pathway — PGx overlap is highest here.

CYP3A4
StatinsMacrolidesCa-channel blockersImmunosuppressants

Responsible for ~50% of drug metabolism. Broad inhibitor/inducer landscape makes this the highest-traffic enzyme.

Known preventable events

Simvastatin + clarithromycin leading to rhabdomyolysis. SSRI + MAOI causing serotonin syndrome. Warfarin + NSAID resulting in fatal GI bleeding.

These are well-documented, preventable events — not edge cases. They happen when clinicians lack the mechanism-level detail to act on an alert. Skippy DDI surfaces not just the severity, but the CYP pathway, the clinical effect, and a verified alternative — at the moment of prescribing.

The alert fatigue problem
“69% of drug-drug interaction alerts are overridden by clinicians. The system isn't failing to generate alerts — it's failing to generate actionable ones.”

Published literature on DDI alert override rates in EHR systems

Static databases flag everything. Skippy DDI explains the mechanism, scores the risk, and offers a next step — so clinicians can act on an alert rather than dismiss it. Finding the interaction is step one. Knowing what to prescribe instead is what prescribing workflows actually need.

Who It's For

Prescribers, pharmacists, and platform builders

EHR Vendors
Embed DDI checking at medication order entry with evidence citations and verified alternatives surfaced at the point of prescribing.
PBMs & Pharmacy Systems
Prioritize high-risk combinations for pharmacist review at scale — evidence-grounded analysis, not static flagging rules.
Medication Therapy Management
Automate comprehensive medication reviews with mechanistic depth and panel risk scoring that static databases cannot provide.
Telehealth Platforms
Safety checks at point of prescription, with calibrated confidence and full audit trail for every prescribing decision.
Regulatory

FHIR-native, Joint Commission aligned

DDI findings are returned as FHIR R4 Observation resources with LOINC code 89378-2 (Drug-drug interaction check) and calibrated confidence extensions — ready for certified EHR integration.

ECE-calibrated confidence scores (ECE = 0.07, Gate 1 confirmed) meet FDA SaMD AI/ML guidance requirements. Every interaction check generates an immutable audit record for Joint Commission medication safety documentation. HIPAA-ready with BAA available.

HIPAA ReadyFHIR R4 LOINC 89378-2SMART on FHIRJoint CommissionCPIC Level A/B510(k) Pathway Planned
Differentiation

Not a static lookup table.

Drug interaction databases return a severity flag from a static rule table. Skippy DDI returns a verified finding from evidence — with mechanism, confidence, source lineage, and alternatives already evaluated.

Mechanism, not just severity

Returns the CYP enzyme involved, the type of conflict (inhibition, induction, substrate competition), and the clinical effect — not just MAJOR/MODERATE/MINOR.

Polypharmacy-native

N×(N-1)/2 pairs evaluated in a single API call with a panel risk score and risk hub identification. Designed for real prescribing complexity.

Alternatives already verified

Recommended substitutes are checked against the full medication panel before being returned. The replacement won&apos;t create a new conflict.

Calibrated confidence, not flags

Every interaction carries a calibrated confidence score from real evidence — not a binary flag. Contested findings are surfaced explicitly, not silently dropped.

EHR Delivery

Built for the prescribing workflow

DDI alerts that interrupt workflow get dismissed. DDI that surfaces at the right moment with actionable detail gets used.

medication-prescribe

Fires when a new medication order is placed — surfaces interactions before the order is signed.

patient-view

Panel risk summary on the patient chart — high-risk flag before any new prescribing session begins.

order-review

Full interaction report during pharmacist order review — detailed mechanism and alternative recommendations.

DDI findings are returned as FHIR R4 Observation resources (LOINC 89378-2) with structured severity, mechanism, and confidence extensions. Compatible with any FHIR-capable EHR or clinical decision support platform.
FHIR R4
Native output format
< 90 days
Agreement to live in Epic
REST API
Direct integration available
Evidence Sources

Five authoritative databases.

Every interaction finding is traceable to its source database — not a proprietary black box. Confidence scores reflect actual evidence quantity and quality across all five sources.

DDInter

Primary DDI database — curated interaction pairs with severity, mechanism, and clinical evidence. ~1.2M catalogued interaction pairs from peer-reviewed literature.

OpenFDA

FDA Drug Label database — brand-name resolution, prescribing information, contraindications, and FDA-reviewed interaction warnings from 15,000+ drug labels.

DrugCentral

University of New Mexico bioactivity database — IC50/Ki binding assay data for CYP enzyme inhibitor classification and target conflict analysis.

DGIdb

Drug-Gene Interaction Database — drug-gene associations used for shared molecular target analysis and novel interaction inference via gene pathway overlap.

PharmGKB

Stanford Pharmacogenomics Knowledgebase — PGx variant-drug annotations with level-of-evidence grades for gene-drug interactions and CPIC dosing guidelines.

Clinical Decision Support · Not a Substitute for Clinical Judgment. Skippy DDI is an evidence-grounded clinical decision support tool. All interaction findings, severity ratings, and alternative recommendations are intended to support — not replace — the judgment of qualified prescribers and pharmacists. Recommendations should be evaluated in the context of the individual patient's clinical history, comorbidities, and therapeutic goals.

See DDI in your prescribing workflow

We work with EHR vendors, PBMs, and medication safety teams. Let's talk about your drug interaction problem.