Is Ultram affected by genetics?

Yes — the active ingredient is metabolized by a gene known to vary between individuals.

Relevant genes: CYP2D6

Ultram is affected by pharmacogenetics through the CYP2D6 gene. Your genotype for this gene can change how your body processes Ultram, which can affect both how well it works and how well you tolerate it. The strongest evidence level on this page is Strong, based on CPIC or FDA guidelines.

What's in Ultram

tramadol affected by CYP2D6

Affected by CYP2D6 · CPIC, FDA · Strong evidence

Read the full tramadol genetics guide →

Tramadol phenotype recommendations

Published guidance from CPIC and FDA on how tramadol should be dosed or substituted based on your CYP2D6 phenotype.

Phenotype	What it means	Recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Your body converts tramadol to its active form too quickly, raising the risk of serious side effects or overdose.	CPIC Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid. FDA Avoid use. Use an alternative analgesic that is not metabolized by CYP2D6. Contraindicated in children under 12 and adolescents following tonsillectomy/adenoidectomy. Breastfeeding is not recommended.	Strong
Normal Metabolizer CYP2D6	Your body processes tramadol normally; you can follow the usual recommended dose.	CPIC Use tramadol label recommended age- or weight-specific dosing. FDA Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Your body processes tramadol somewhat slowly, but you can usually use standard doses. If it doesn't work well, you might need a different pain medication.	CPIC Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid. FDA Initiate therapy with recommended starting dose.	Optional
Poor Metabolizer CYP2D6	Your body doesn’t effectively convert tramadol into its active pain-relieving form, so it’s unlikely to work well for you.	CPIC Avoid tramadol use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-codeine opioid. FDA Initiate therapy with recommended starting dose.	Strong
Indeterminate CYP2D6	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	—
Not available CYP2D6	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	—

Sources: CPIC, FDA

The gene behind the guidance

CYP2D6 Cytochrome P450 2D6

CYP2D6 is the most clinically important pharmacogene. It metabolizes around a quarter of all prescription drugs, including many antidepressants, opioids, and stimulants. The gene is unusually variable: roughly 7 percent of people are poor metabolizers (they barely activate CYP2D6), and another 1 to 3 percent are ultrarapid metabolizers (their enzyme is overactive).

For most CYP2D6 drugs, poor metabolizers feel stronger effects and more side effects at standard doses, while ultrarapid metabolizers may feel almost nothing. For prodrugs like codeine, the relationship flips: poor metabolizers feel less effect because they can't activate the drug.

See all drugs affected by CYP2D6 →

Browse the full drug-class: Pain medications.

Related medications

Find out how your genetics affect Ultram

This page describes the general pharmacogenetics. A Gene2Rx report analyzes your own DNA to tell you which metabolizer group you fall into, across every medication.

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Informational only — not medical advice. Pharmacogenetic guidance describes population-level patterns; your individual response depends on many factors. Never start, stop, or change a medication without talking to your prescribing clinician.