Is Tofranil affected by genetics?

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

Relevant genes: CYP2C19, CYP2D6

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Tofranil is affected by pharmacogenetics through the CYP2C19 and CYP2D6 genes. Your genotype for these genes can change how your body processes Tofranil, 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 Tofranil

imipramine affected by CYP2C19, CYP2D6

Affected by CYP2C19, CYP2D6 · CPIC · Strong evidence

Read the full imipramine genetics guide →

Imipramine phenotype recommendations

Published guidance from CPIC on how imipramine should be dosed or substituted based on your CYP2D6, CYP2C19 phenotype.

Phenotype	What it means	Recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Your body breaks down imipramine much faster than normal, which means the drug may not reach effective levels. A different antidepressant or a higher dose may be needed.	CPIC Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2D6	Your body processes imipramine at a normal rate. The standard dose should work as expected for you.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Your body breaks down imipramine more slowly than normal, which can lead to higher drug levels and a greater chance of side effects. A lower dose may be recommended.	CPIC Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Your body breaks down imipramine very slowly, causing the drug to build up to high levels and significantly increasing the risk of side effects. A different antidepressant is recommended.	CPIC Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Indeterminate CYP2D6	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	—
Not available CYP2D6	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	—
Ultrarapid Metabolizer CYP2C19	Your body converts imipramine into other compounds much faster than normal, which may reduce its effectiveness. A different type of antidepressant may work better for you.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid Metabolizer CYP2C19	Your body converts imipramine into other compounds faster than normal, which may reduce its effectiveness. A different type of antidepressant may work better for you.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2C19	Your body processes imipramine at a normal rate through this pathway. The standard dose should work as expected.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Your body processes imipramine somewhat more slowly than normal through this pathway, but the standard starting dose is still recommended.	CPIC Initiate therapy with recommended starting dose.	Moderate
Poor Metabolizer CYP2C19	Your body processes imipramine very slowly through this pathway, which can change how the drug works and increase the chance of side effects. A different antidepressant or a much lower dose is recommended.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Likely Intermediate Metabolizer CYP2C19	Your body likely processes imipramine somewhat more slowly than normal through this pathway, but the standard starting dose is still recommended.	CPIC Initiate therapy with recommended starting dose.	Moderate
Likely Poor Metabolizer CYP2C19	Your body likely processes imipramine very slowly through this pathway, which can change how the drug works and increase the chance of side effects. A different antidepressant or a much lower dose is recommended.	CPIC Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Indeterminate CYP2C19	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	—
Not available CYP2C19	The impact of your genotype on response to this drug is unknown	CPIC Initiate therapy with recommended starting dose.	—

Source: CPIC

The genes behind the guidance

CYP2C19 Cytochrome P450 2C19

CYP2C19 handles several SSRIs (citalopram, escitalopram, sertraline), proton pump inhibitors (omeprazole, esomeprazole), and the blood thinner clopidogrel. About 2 to 5 percent of people of European descent and 15 to 20 percent of people of East Asian descent are poor metabolizers. Another 30 percent carry a rapid-metabolizer variant.

Rapid metabolizers clear affected drugs before they reach therapeutic levels. Poor metabolizers accumulate the drug and feel stronger effects.

See all drugs affected by CYP2C19 →

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: Tricyclic antidepressants.

Related medications

Find out how your genetics affect Tofranil

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.