Martín Fernando Gómez

In acute coronary syndrome or angioplasty, consider an alternative antiplatelet agent (prasugrel or ticagrelor) if there is no contraindication: clopidogrel activation is reduced.

Increased risk of myopathy with high-dose simvastatin. Prefer doses ≤ 20 mg, or an alternative statin (rosuvastatin, pravastatin).

Combined with CYP2C9 *1/*1, it predicts a lower-than-standard initial dose requirement. Use a pharmacogenetic dosing algorithm if coumarin anticoagulation is started.

Standard dosing per the package insert.

CYP4F2 regulates vitamin K availability: people who carry *3 need somewhat MORE warfarin than VKORC1 and CYP2C9 alone predict. That is not your case, so there is nothing to offset the increased sensitivity of your VKORC1 — the lower initial dose stands.

CYP3A4 and CYP3A5 metabolize many of the same drugs, so they are read together. With normal CYP3A4 activity and a non-expresser CYP3A5, your elimination profile is the one package inserts assume: standard dosing. Carriers of *22 eliminate more slowly and may accumulate tacrolimus or statins at usual doses.

This genotype used to predict how likely a person was to respond to interferon treatment for hepatitis C. It is among the best-measured items on the panel: the position the guideline interrogates is covered. But direct-acting antivirals replaced interferon-based regimens and cure more than 95% regardless of this genotype, so today the datum barely changes a decision. It is reported for completeness and with that caveat, not because it will guide a treatment.

CFTR modulators are indicated for people WITH cystic fibrosis, and which one applies depends on what variants are present in BOTH copies of the gene. You have one copy with F508del and one normal copy: you are a healthy carrier, not a patient, so none of these drugs apply to you. It appears here because the same gene reads differently depending on the question — for what the finding does mean for you, see the Carriers section.

You acetylate isoniazid more slowly than average, so at standard doses you reach higher and more sustained concentrations. That increases the risk of hepatotoxicity, the adverse effect that cuts tuberculosis treatments short. It does not mean not using it: it means that liver function monitoring at the start of treatment is not optional in your case, and that if transaminases rise there is a pharmacogenetic explanation on top of the usual ones. About half of people of European ancestry are slow acetylators.

No risk variants detected. Standard fluoropyrimidine dosing.

Standard thiopurine dosing as far as TPMT is concerned. The other half of the recommendation depends on NUDT15, which the chip covers much worse — see the next row.

No risk variants detected, but this is one of the worst-covered genes on the panel: 17 of 20 positions are left out and 18 alleles are indistinguishable. In people of Asian or Indigenous American ancestry —where NUDT15 variants are more frequent— a negative here carries little weight, and in the face of myelosuppression with thiopurines, genotyping by a targeted method is warranted.

No dose adjustment in heterozygotes. It may be associated with mild hyperbilirubinemia (Gilbert syndrome) with no pathological significance.

Very low risk of hypersensitivity. It matters to understand where this result comes from: the array does not type HLA directly, it infers it from neighboring markers that usually travel with the allele. The inference is good but it is not a typing, and the reaction to abacavir can be severe, so before prescribing it the validated HLA-B*57:01 test is still called for.

ABCG2 moves rosuvastatin out of the cell. With decreased function it accumulates and the risk of myopathy rises, which is why CPIC caps the dose. Your function is normal, so rosuvastatin can be prescribed without that cap — which makes it a solid alternative to simvastatin, which your SLCO1B1 genotype does compromise.

CPIC interrogates a short list of variants in this gene and none is present. But this does NOT allow you to be considered not susceptible to malignant hyperthermia: most of the risk lives in RYR1, which this test cannot rule out. See the row below.

The variants that cause malignant hyperthermia are spread across an enormous gene and are mostly private to each family. An array measures fixed positions and cannot sequence the gene, so a negative result here means nothing. If there is a personal or family history of an anesthetic complication, referral for specific testing (RYR1 sequencing and, depending on the case, an in vitro contracture test) is warranted, and the anesthesiologist should be told regardless.

Efavirenz is eliminated more slowly, which increases exposure and with it the neuropsychiatric adverse effects —vivid dreams, dizziness, insomnia— that are the most frequent cause of treatment discontinuation. CPIC recommends considering 400 mg daily instead of 600 in intermediate metabolizers.

No deficiency among the variants evaluated. Watch the coverage: the chip measures 63 of the 171 positions the guideline interrogates, so a negative lowers the probability but does not rule it out. Faced with an indication for rasburicase —where the deficiency can cause severe hemolysis— measuring enzyme activity is warranted; it is the reference method and it is inexpensive.

Most people of European ancestry do not express CYP3A5 and metabolize tacrolimus more slowly. For this genotype CPIC recommends starting at the standard dose; it is the expressers who need between 1.5 and 2 times more. Relevant when a transplant is involved: it shortens the time to reach therapeutic levels.

The array does not reliably resolve duplications, deletions, or CYP2D6/CYP2D7 hybrids. If the CYP2D6 phenotype is needed, it requires a targeted assay (CNV + sequencing).