Drug Interaction Checker

Overview

Pull all active medications for a patient, cross-reference each pair against known major drug-drug interaction databases, classify by severity (contraindicated, major, moderate, minor), identify CYP450 pathway conflicts, and suggest therapeutic alternatives when significant interactions are detected.

FHIR Resources Used

Instructions

Step 1: Verify Patient and Retrieve Demographics

Tool: fhir_read
resourceType: "Patient"
id: "[patient-id]"

Extract age, gender, weight if available. Age and organ function affect CYP450 metabolism rates.

Step 2: Pull All Active Medications

2a: Prescribed medications

Tool: fhir_search
resourceType: "MedicationRequest"
queryParams: "patient=[patient-id]&status=active&_count=100"

2b: Patient-reported medications (includes OTC, supplements)

Tool: fhir_search
resourceType: "MedicationStatement"
queryParams: "patient=[patient-id]&status=active&_count=100"

Merge both lists. Deduplicate by RxNorm code (system: http://www.nlm.nih.gov/research/umls/rxnorm).

Step 3: Pull Renal and Hepatic Function

Tool: fhir_search
resourceType: "Observation"
queryParams: "patient=[patient-id]&code=33914-3,48642-3,69405-9,77147-7&_sort=-date&_count=4"

LOINC codes:

• •33914-3: eGFR (CKD-EPI)
• •48642-3: eGFR for African American
• •69405-9: Glomerular filtration rate
• •77147-7: eGFR (CKD-EPI 2021)

Impaired renal/hepatic function reduces drug clearance and increases interaction risk.

Step 4: Build Medication Pair Matrix

For N active medications, evaluate N*(N-1)/2 unique pairs. For each pair, check against the interaction reference (see references/major-drug-interactions.md) in the following order:

1. •Contraindicated combinations - Never co-prescribe
2. •Major interactions - Significant clinical risk, avoid or monitor closely
3. •Moderate interactions - Clinical significance in certain patients
4. •Minor interactions - Limited clinical significance

Step 5: Evaluate CYP450 Pathway Conflicts

For each medication, identify its CYP450 profile (see references/cyp450-pathways.md):

• •Is it a substrate (metabolized by the enzyme)?
• •Is it an inhibitor (blocks the enzyme, increasing substrate levels)?
• •Is it an inducer (accelerates the enzyme, decreasing substrate levels)?

Flag when:

• •A strong inhibitor of CYP3A4 is combined with a CYP3A4 substrate with a narrow therapeutic index
• •A strong inducer is combined with a substrate where reduced levels cause treatment failure
• •Multiple inhibitors of the same pathway are present (additive inhibition)

Step 6: Classify and Report Interactions

For each identified interaction, report:

Step 7: Generate Interaction Summary

Structure output:

1. •Contraindicated Pairs (if any) - RED flag, require immediate prescriber attention
2. •Major Interactions - ORANGE flag, require monitoring plan or alternative
3. •Moderate Interactions - YELLOW flag, clinical judgment needed
4. •Minor Interactions - Informational only
5. •CYP450 Summary - Table of which enzymes are affected by current regimen
6. •Recommended Actions - Prioritized list of changes

Step 8: Document Interaction Check (if requested)

Tool: fhir_create
resourceType: "DetectedIssue"
resource: {
  "resourceType": "DetectedIssue",
  "status": "preliminary",
  "code": {
    "coding": [{
      "system": "http://terminology.hl7.org/CodeSystem/v3-ActCode",
      "code": "DRG",
      "display": "Drug Interaction Alert"
    }]
  },
  "severity": "high",
  "patient": {"reference": "Patient/[patient-id]"},
  "identifiedDateTime": "[current-datetime]",
  "implicated": [
    {"reference": "MedicationRequest/[drug-a-id]"},
    {"reference": "MedicationRequest/[drug-b-id]"}
  ],
  "detail": "[interaction description]",
  "mitigation": [{
    "action": {"text": "[recommended action]"},
    "date": "[date]"
  }]
}

Examples

Example 1: Checking Interactions for a New Prescription

User says: "Check drug interactions for patient 67890 - about to start amiodarone."

Actions:

1. •Read Patient 67890.
2. •Pull active MedicationRequests: finds warfarin 5mg daily, simvastatin 40mg daily, metformin 1000mg BID, lisinopril 20mg daily.
3. •Pull renal function: eGFR 55 mL/min (Stage 3a CKD).
4. •Cross-reference amiodarone against each active medication.
5. •Check CYP450: amiodarone is a strong inhibitor of CYP3A4, CYP2C9, CYP2D6, and P-glycoprotein.

Result:

DRUG INTERACTION CHECK - Patient 67890
New medication: Amiodarone

CONTRAINDICATED: None

MAJOR INTERACTIONS:
1. Amiodarone + Warfarin [MAJOR]
   Mechanism: Amiodarone inhibits CYP2C9, reducing warfarin metabolism
   Effect: INR increase of 50-70%, bleeding risk
   Management: Reduce warfarin dose by 30-50%. Check INR within 3-5 days, then weekly x4.

2. Amiodarone + Simvastatin [MAJOR]
   Mechanism: Amiodarone inhibits CYP3A4, increasing simvastatin levels
   Effect: Rhabdomyolysis risk. Simvastatin max dose with amiodarone is 20mg.
   Alternative: Switch to pravastatin 40mg (not CYP3A4 metabolized) or rosuvastatin 10mg.

MODERATE INTERACTIONS:
3. Amiodarone + Metformin [MODERATE]
   Mechanism: Amiodarone may increase metformin levels via OCT transporter inhibition
   Effect: Increased metformin exposure, lactic acidosis risk (especially with eGFR 55)
   Management: Monitor renal function closely. Consider metformin dose reduction.

CYP450 IMPACT:
- CYP3A4: STRONGLY INHIBITED by amiodarone (affects simvastatin)
- CYP2C9: STRONGLY INHIBITED by amiodarone (affects warfarin)
- CYP2D6: INHIBITED by amiodarone (no current substrates affected)

RECOMMENDED ACTIONS:
1. [URGENT] Reduce warfarin dose 30-50% before starting amiodarone
2. [URGENT] Switch simvastatin to pravastatin or reduce to 20mg max
3. [MONITOR] Renal function and metformin tolerance
4. [SCHEDULE] INR check 3-5 days after amiodarone start

Example 2: Routine Polypharmacy Interaction Screen

User says: "Screen all drug interactions for patient Jane Doe, DOB 1940-07-22."

Actions:

1. •Search Patient by name and DOB. Confirm identity. Age 85.
2. •Pull 14 active medications (polypharmacy).
3. •Evaluate 91 unique pairs (14 choose 2).
4. •Identify 3 major, 5 moderate, 2 minor interactions.
5. •Note elderly patient - flag CYP450 metabolism decline with age.

Result:

DRUG INTERACTION SCREEN - Jane Doe (Age 85)
Total active medications: 14
Pairs evaluated: 91

MAJOR INTERACTIONS: 3
1. Clopidogrel + Omeprazole [MAJOR]
   Mechanism: Omeprazole inhibits CYP2C19, reducing clopidogrel activation
   Alternative: Switch to pantoprazole (weaker CYP2C19 inhibitor)

2. Methotrexate + Trimethoprim [MAJOR]
   Mechanism: Both cause folate depletion, additive bone marrow suppression
   Management: Avoid combination. If unavoidable, supplement with leucovorin.

3. Fluoxetine + Tramadol [MAJOR]
   Mechanism: Serotonin syndrome risk (both serotonergic). Fluoxetine inhibits CYP2D6, reducing tramadol conversion to active metabolite.
   Alternative: Switch tramadol to acetaminophen or non-serotonergic analgesic.

MODERATE INTERACTIONS: 5
[... listed with management ...]

AGE-RELATED CONSIDERATIONS:
- CYP450 activity reduced ~30% at age 85
- Renal clearance likely reduced (check eGFR)
- Polypharmacy (14 meds) increases interaction probability
- Recommend comprehensive prescription appropriateness review

Troubleshooting

Medication codes are not in RxNorm

• •Use medicationCodeableConcept.text for name-based matching against interaction tables.
• •If medication is a contained reference, resolve via fhir_read on the referenced Medication resource.
• •Note in output that coded interaction checking was not possible for unrecognized medications.

Patient has very large medication list (>20 medications)

• •Prioritize pairs involving high-alert medications (anticoagulants, antiarrhythmics, opioids, immunosuppressants).
• •Focus on contraindicated and major interactions first.
• •Present interactions grouped by severity rather than listing all 190+ pairs.

Interaction found but clinical significance is unclear

• •Report the interaction with its evidence level (Established/Probable/Suspected/Possible).
• •Include the mechanism so the clinician can assess applicability.
• •Note patient-specific factors that modify risk (renal function, age, duration of concurrent use).

Related Skills

• •medication-reconciliation - Reconcile medication list before running interaction check
• •prescription-appropriateness-review - Broader appropriateness review beyond interactions
• •opioid-risk-assessment - Focused assessment when opioid interactions detected
• •problem-list-review - Review conditions that affect interaction severity