Is Sinequan affected by genetics?

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

Relevant genes: CYP2C19, CYP2D6

Considering GeneSight for Sinequan?

Gene2Rx covers this medication using the same CPIC and FDA guidelines GeneSight uses, costs $5-$49 instead of several hundred, and works with your existing 23andMe data.

See the comparison →

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

doxepin affected by CYP2C19, CYP2D6

Affected by CYP2C19, CYP2D6 · CPIC · Strong evidence

Read the full doxepin genetics guide →

Doxepin phenotype recommendations

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

Phenotype	What it means	Recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Your body breaks down doxepin much faster than normal, which may make the drug less effective. An alternative medication that is not affected by your CYP2D6 gene may be recommended.	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	You are not predicted to have an atypical response to doxepin based on your CYP2D6 gene. The standard dose is expected to be appropriate.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Your body breaks down doxepin somewhat more slowly than normal, which may lead to higher drug levels and an increased chance of side effects. A lower starting 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 doxepin much more slowly than normal, causing the drug to build up and significantly increasing the risk of side effects. An alternative medication is generally 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 processes doxepin faster than normal through the CYP2C19 pathway, which may reduce the drug's effectiveness. An alternative 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 processes doxepin faster than normal through the CYP2C19 pathway, which may reduce the drug's effectiveness. An alternative 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 doxepin at a normal rate through the CYP2C19 pathway. You are not expected to have an unusual response based on this gene.	CPIC Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Your body processes doxepin slightly slower than normal through the CYP2C19 pathway, but the standard starting dose is still expected to be appropriate.	CPIC Initiate therapy with recommended starting dose.	Optional
Poor Metabolizer CYP2C19	Your body processes doxepin much more slowly than normal through the CYP2C19 pathway, which can alter the drug's balance in your system. An alternative antidepressant or a lower dose may be 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.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Likely Intermediate Metabolizer CYP2C19	Your body likely processes doxepin slightly slower than normal through the CYP2C19 pathway, but the standard starting dose is still expected to be appropriate.	CPIC Initiate therapy with recommended starting dose.	Optional
Likely Poor Metabolizer CYP2C19	Your body likely processes doxepin much more slowly than normal through the CYP2C19 pathway, which can alter the drug's balance in your system. An alternative antidepressant or a lower dose may be 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.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
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 Sinequan

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.

Get your report Look up another medication

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.