Contains acetaminophen, butalbital, caffeine and codeineStrong evidence

Is Acetaminophen, Butalbital, Caffeine and Codeine (Fioricet with Codeine) affected by genetics?

Partially. 2 of 4 ingredients have pharmacogenetic evidence.

Genes CYP1A2 CYP2D6

Acetaminophen, butalbital, caffeine and codeine contains 4 active ingredients, and 2 of them have published pharmacogenetic guidelines. The relevant genes are CYP1A2, CYP2D6. Your genotype can change how that ingredient behaves in your body, while the other ingredients aren't affected by genetics in any clinically established way. The strongest evidence level on this page is Strong, from the published guidelines shown below.

Also sold as Fioricet with Codeine.

Pharmacogenetic guidelines are written for one ingredient at a time, so the guidance below is for each ingredient on its own. What your genes mean for a combination product is less clear, because the dose and the other ingredients can change things. If you take Acetaminophen, butalbital, caffeine and codeine, it's worth talking over with your prescriber or pharmacist. How we handle combination products.

What's in Acetaminophen, butalbital, caffeine and codeine

Acetaminophen No known pharmacogenetics

No strong published pharmacogenetic guideline currently applies to acetaminophen.

Butalbital No known pharmacogenetics

No strong published pharmacogenetic guideline currently applies to butalbital.

Caffeine Affected by CYP1A2

Affected by CYP1A2. Guidance from Gene2Rx, moderate evidence.

Read the full caffeine genetics guide

Codeine Affected by CYP2D6

Affected by CYP2D6. Guidance from CPIC, FDA, strong evidence.

Read the full codeine genetics guide

Caffeine phenotype recommendations

Published guidance from Gene2Rx on how caffeine should be dosed or substituted based on your CYP1A2 phenotype.

Phenotype	What it means	Recommendation	Evidence
Ultrarapid MetabolizerCYP1A2	Your CYP1A2 enzyme is the more easily switched-on type, so caffeine may wear off a little sooner, especially if you smoke. This does not change the usual advice on how much caffeine is too much.	Gene2Rx Caffeine may be cleared quickly, shortening its stimulant effect, particularly in smokers. Advise against compensating with larger or more frequent servings; keep total intake within standard limits.	Moderate
Rapid MetabolizerCYP1A2	Caffeine may wear off slightly sooner for you than average. The usual advice on caffeine limits applies.	Gene2Rx Caffeine may be cleared somewhat faster than average. Standard advice on moderate intake applies.	Moderate
Normal MetabolizerCYP1A2	Your body clears caffeine at an expected rate. The usual advice on caffeine limits applies.	Gene2Rx Follow standard moderate intake guidance (up to 400 mg a day for most adults).	Not rated
Intermediate MetabolizerCYP1A2	You clear caffeine a bit more slowly, so its effects last longer. Usual amounts are fine, but late-day coffee may hurt your sleep.	Gene2Rx Standard advice on moderate caffeine intake; late-day caffeine may disturb sleep.	Not rated
Slow MetabolizerCYP1A2	You clear caffeine slowly, so it stays in your body longer. Drinking less can prevent jitters and poor sleep and may lower heart risks.	Gene2Rx Recommend reduced intake (e.g. 100 mg a day or less) and longer intervals between servings to avoid adverse effects.	Moderate
IndeterminateCYP1A2	We could not determine how this gene affects how you process caffeine.	Gene2Rx Follow general caffeine guidelines and monitor personal tolerance.	Not rated
Not availableCYP1A2	Your data did not include a result for this gene, so we cannot say how you process caffeine.	Gene2Rx Follow general caffeine guidelines and monitor personal tolerance.	Not rated

Source: Gene2Rx

Codeine phenotype recommendations

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

Phenotype	What it means	Recommendation	Evidence
Ultrarapid MetabolizerCYP2D6	Your body turns codeine into morphine too fast, which can cause dangerous side effects. A different pain reliever is usually suggested.	CPIC Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid. FDA Codeine is contraindicated in children under 12 years. Refer to FDA labeling, which warns of life-threatening respiratory depression in ultrarapid metabolizers.	Strong
Normal MetabolizerCYP2D6	Your body processes codeine normally, so the usual dose should work as expected.	CPIC Use codeine label recommended age- or weight-specific dosing. FDA Initiate therapy with recommended starting dose.	Strong
Intermediate MetabolizerCYP2D6	Your body turns codeine into its active form more slowly. The usual dose is used. If it doesn't ease your pain, your doctor may try another pain reliever.	CPIC Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid. FDA Initiate therapy with recommended starting dose.	Moderate
Poor MetabolizerCYP2D6	Your body turns very little codeine into its active form, so it likely won't ease your pain. A different pain reliever is usually suggested.	CPIC Avoid codeine use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-tramadol opioid. FDA No specific dosing change; codeine may be less effective. Refer to FDA labeling.	Strong
IndeterminateCYP2D6	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	Not rated
Not availableCYP2D6	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	Not rated

Sources: CPIC, FDA

The genes behind the guidance

CYP1A2 Cytochrome P450 1A2

CYP1A2 is the liver enzyme that clears caffeine, clozapine, and a handful of other drugs. Its activity is shaped by both genetics and lifestyle (smoking speeds it up, certain foods slow it down), but the underlying gene still sets your baseline. About 40 percent of people carry a variant that classifies them as rapid metabolizers; the rest process caffeine at an average or slower rate.

Rapid metabolizers clear caffeine quickly and may feel less effect from a given dose. Slower metabolizers feel caffeine longer and at lower doses.

See all drugs affected by CYP1A2

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).

The v4 report preserves the activity score used in its interpretation. Some medicines use a combined CYP2D6/CYP2C19 recommendation. CYP2D6 inhibitors can change functional metabolism; a genotype alone does not capture that effect.

See all drugs affected by CYP2D6

Browse the full drug classes: Other substances, Pain medications.

Related medications

Find out how your genetics affect Acetaminophen, butalbital, caffeine and codeine

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 my 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.