Precision Medicine Therapeutics

Clinical Use Cases

• Antidepressant selection: A psychiatrist orders pharmacogenomic testing for a patient with treatment-resistant depression. The skill interprets CYP2D6 and CYP2C19 results and recommends escitalopram dose reduction for ultra-rapid CYP2C19 metabolizers or suggests switching to a non-CYP2D6-dependent agent
• Oncology targeted therapy: A medical oncologist receives next-generation sequencing results showing an ALK rearrangement in a non-small cell lung cancer patient. The skill maps the variant to FDA-approved ALK inhibitors (crizotinib, alectinib, lorlatinib) with tier-level evidence annotations
• Cardiology: Clopidogrel response: A cardiologist considering dual antiplatelet therapy post-PCI uses the skill to check CYP2C19 loss-of-function allele status and recommends prasugrel or ticagrelor for intermediate/poor metabolizers per CPIC guidelines
• Pain management pharmacogenomics: Guides opioid selection by interpreting CYP2D6 status; flags codeine as contraindicated in ultra-rapid metabolizers due to rapid morphine conversion risk

Safety & Evidence

• Safety Classification: Caution — Genomic interpretation directly influences prescribing decisions. All recommendations must be validated by a qualified clinician before implementation. The skill flags variants of uncertain significance (VUS) distinctly from pathogenic/likely pathogenic findings and does not recommend treatment changes based on VUS alone.
• Evidence Level: High — Recommendations are grounded in CPIC guidelines (peer-reviewed, evidence-based), PharmGKB curated annotations, ClinVar submissions from expert clinical laboratories, and FDA pharmacogenomic labeling.

Example Usage

Pharmacogenomic dose adjustment:

Patient genotype: CYP2D6 *4/*4 (poor metabolizer)
Current medication: codeine 30mg Q4H PRN for pain
Recommend adjustment.

Result: CYP2D6 poor metabolizer status results in negligible conversion of codeine to its active metabolite morphine. Codeine will be ineffective for analgesia. CPIC guideline recommendation: avoid codeine entirely. Consider morphine, oxycodone (partially CYP2D6-dependent but has direct analgesic activity), or non-opioid alternatives based on pain severity.

Tumor variant therapy matching:

NGS results: BRAF V600E mutation detected in metastatic melanoma
No prior targeted therapy exposure
Recommend treatment options.

Result: BRAF V600E is an FDA-approved companion diagnostic biomarker. Recommended regimens: (1) Encorafenib + binimetinib (COLUMBUS trial, PFS 14.9 months); (2) Dabrafenib + trametinib (COMBI-d trial, PFS 11.0 months); (3) Vemurafenib + cobimetinib (coBRIM trial, PFS 12.3 months). Single-agent BRAF inhibitor monotherapy is not recommended due to inferior outcomes and rapid resistance via MAPK pathway reactivation.

Technical Details

• Category: Treatment
• Author: OMS Contributors
• License: MIT
• Version: 1.0.0
• Specialty: Medical Genetics, Oncology, Pharmacology

References

• Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines — cpicpgx.org
• PharmGKB: Pharmacogenomics Knowledge Base — pharmgkb.org
• ClinVar database (NCBI) — ncbi.nlm.nih.gov/clinvar/
• Relling MV, Klein TE. "CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network." Clin Pharmacol Ther. 2011;89(3):464-467.
• NCCN Clinical Practice Guidelines in Oncology (current edition)
• FDA Table of Pharmacogenomic Biomarkers in Drug Labeling

This skill is part of Open Medical Skills, a curated marketplace of medical AI skills maintained by physicians for physicians and the healthcare industry.