Template for Pharmacist Letter: CYP2D6 Pharmacogenetic Testing Results
Essential Header Information
To: [Pharmacist Name/Pharmacy Name]
From: [Prescriber Name, Credentials]
Date: [Current Date]
Re: CYP2D6 Pharmacogenetic Testing Results for [Patient Name, DOB]
Patient Genetic Information
Include the following mandatory elements in your letter:
CYP2D6 Diplotype (Genotype): State the specific star allele combination detected (e.g., CYP2D6*1/*4, CYP2D6*2×2/*4), using standardized PharmVar nomenclature with the multiplication sign and number of gene copies for duplications 1
Predicted Metabolizer Phenotype: Clearly state whether the patient is a Poor Metabolizer (PM), Intermediate Metabolizer (IM), Extensive/Normal Metabolizer (EM), or Ultrarapid Metabolizer (UM) 1
Functional Interpretation: Explain what this means for drug metabolism—PMs have little to no enzyme activity (5-8% of Caucasians), IMs have reduced activity, EMs have normal activity, and UMs have increased activity (1-7% of Caucasians) 1
Clinical Implications Section
For Poor Metabolizers, include these specific warnings:
Fluoxetine: Single 20mg dose produces 3.9-fold higher drug exposure; 60mg produces 11.5-fold higher exposure for S-fluoxetine; recommend 50% dose reduction and caution regarding QT prolongation risk and potential sudden cardiac death 2
Paroxetine: Single 30mg dose produces 7-fold higher drug exposure in PMs; recommend 50% dose reduction 2
Venlafaxine: Dramatically altered drug ratios with substantial parent compound accumulation; start at 50% of standard dose; documented fatalities at 4.5 mg/kg blood concentration in PMs 2
Cardiac Safety Alert: Increased risk for QT prolongation, cardiac arrhythmias, and serotonin syndrome with CYP2D6 substrate medications 2
For Ultrarapid Metabolizers, include:
- Higher doses may be required for fluoxetine, paroxetine, and venlafaxine due to rapid drug clearance, or consider alternative agents not metabolized by CYP2D6 3
Medication-Specific Recommendations
List current and potential future medications affected by CYP2D6:
Approximately 20-25% of all clinically used drugs are metabolized by CYP2D6, including many psychiatric medications, pain medications (codeine, tramadol), cardiovascular drugs, and oncology agents 4, 5
For each relevant medication the patient is taking or may receive, provide specific dosing guidance based on Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines 1
Note that some medications like fluoxetine act as potent CYP2D6 inhibitors, converting 43% of extensive metabolizers to phenocopy poor metabolizers at 20mg/day chronic dosing 2
Testing Methodology and Limitations
Include transparency about the test performed:
Specify which CYP2D6 variants were tested—whether single nucleotide polymorphisms (SNVs), copy number variants (CNVs including deletions/duplications), or comprehensive sequencing was performed 1
State that CYP2D6*1 assignment indicates none of the tested variants were detected, but residual risk exists for rare non-*1 genotypes depending on test comprehensiveness 1
Note that structural variants (gene deletions, duplications, multiplications, CYP2D6/CYP2D7 hybrid genes) significantly affect function and should be included in comprehensive testing 1
Clarify any phasing ambiguities—when variants like c.506-1G>A and c.100C>T are detected as heterozygous without phasing data, report the most likely genotype based on population frequencies (e.g., CYP2D6*1/*4 rather than CYP2D6*4/*10) 1
Monitoring Recommendations
Provide specific follow-up instructions:
Therapeutic drug monitoring (TDM) is mandatory for all poor metabolizers and ultrarapid metabolizers on fluoxetine, paroxetine, venlafaxine, and tricyclic antidepressants 3
Baseline ECG is recommended before initiating CYP2D6-substrate medications in known poor metabolizers 2
Monitor for signs of drug accumulation in PMs (excessive sedation, orthostatic hypotension, cardiac symptoms) or treatment failure in UMs 1
Drug Interaction Alerts
Highlight critical interactions:
Avoid combining multiple CYP2D6 substrate medications or adding strong CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) in poor metabolizers 2
Consider that environmental factors including diet, smoking, and concomitant medications significantly affect drug metabolism independent of genotype 3
Contact Information
Provide clear follow-up pathway:
- Include prescriber contact information for questions about medication adjustments
- Reference to genetic counseling services if available for patient questions 1
- Laboratory contact information for technical questions about the test methodology 1
Supporting Documentation
Attach the following: