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Fioricet Interactions: What to Avoid

Documented interactions for Fioricet (butalbital, acetaminophen, and caffeine). Each entry cites the prescribing information or FDA safety communication it is based on.

8 major1 moderate

Interaction summary

SeverityInteracts withClassConcern
MajorAlcohol (ethanol)CNS depressantButalbital combination with alcohol: additive CNS and respiratory depression
MajorAlcohol (ethanol)CNS depressantSedative with alcohol: additive CNS depression
MajorMAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue)Monoamine oxidase inhibitorButalbital combinations with MAO inhibitors: caution
MajorOther acetaminophen-containing products (Tylenol, Excedrin, cold medicines)Acetaminophen-containing productDuplicate acetaminophen dosing across combination products
MajorOther CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants)CNS depressantSedative with other CNS depressants
MajorOther opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol)OpioidButalbital combination with opioids: additive respiratory depression
MajorOther opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol)OpioidSedative with opioids: additive respiratory depression
MajorOther sedatives (butalbital, barbiturates, carisoprodol, sedating antihistamines)Sedative / barbiturateButalbital combination with other sedatives: additive CNS depression
ModerateOrexin receptor antagonists (suvorexant, lemborexant, daridorexant)Sedative-hypnotic (dual orexin antagonist)Sedative with orexin receptor antagonists: additive CNS depression

Detailed interactions

Major

Butalbital combination with alcohol: additive CNS and respiratory depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Butalbital is a barbiturate with long-acting sedative effects; alcohol compounds the effect.

What can happen

Respiratory depression, sedation, and death. Barbiturate labeling states the combination is particularly hazardous.

What to do

Avoid alcohol entirely. Butalbital-containing products are also on the FDA list to avoid for older adults.

Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings and Precautions. source

Major

Sedative with alcohol: additive CNS depression

With: Alcohol (ethanol) CNS depressant

Why it happens

Combined central nervous system depression.

What can happen

Respiratory depression, deep sedation, and death.

What to do

Avoid alcohol.

Basis: Sedative-hypnotic prescribing information, Warnings. source

Major

Butalbital combinations with MAO inhibitors: caution

With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor

Why it happens

Barbiturates and MAO inhibitors can produce unpredictable central nervous system effects.

What can happen

Labeling states that butalbital-containing products should not be taken with MAO inhibitors.

What to do

Do not combine without explicit prescriber direction.

Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source

Major

Duplicate acetaminophen dosing across combination products

With: Other acetaminophen-containing products (Tylenol, Excedrin, cold medicines) Acetaminophen-containing product

Why it happens

Acetaminophen from multiple products accumulates in the liver.

What can happen

Acetaminophen overdose is a leading cause of acute liver failure.

What to do

Keep total acetaminophen from all products at or below the labeled daily maximum.

Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source

Major

Sedative with other CNS depressants

With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant

Why it happens

Additive central nervous system depression.

What can happen

Excessive sedation and respiratory depression.

What to do

Review all sedating medications with the prescriber.

Basis: Sedative-hypnotic prescribing information, Drug Interactions. source

Major

Butalbital combination with opioids: additive respiratory depression

With: Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) Opioid

Why it happens

Barbiturates and opioids both depress the central nervous system and respiratory drive.

What can happen

Respiratory depression, deep sedation, and death.

What to do

Avoid where possible; if used, monitor closely for slowed breathing.

Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source

Major

Sedative with opioids: additive respiratory depression

With: Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) Opioid

Why it happens

Additive central nervous system and respiratory depression.

What can happen

Respiratory depression and overdose.

What to do

Avoid where possible; monitor for slowed breathing.

Basis: Sedative-hypnotic prescribing information, Drug Interactions. source

Major

Butalbital combination with other sedatives: additive CNS depression

With: Other sedatives (butalbital, barbiturates, carisoprodol, sedating antihistamines) Sedative / barbiturate

Why it happens

Additive sedative effects from barbiturate and other central nervous system depressants.

What can happen

Excessive sedation and respiratory depression.

What to do

Review every sedating medication with the prescriber or pharmacist.

Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Drug Interactions. source

Moderate

Sedative with orexin receptor antagonists: additive CNS depression

With: Orexin receptor antagonists (suvorexant, lemborexant, daridorexant) Sedative-hypnotic (dual orexin antagonist)

Why it happens

Additive sedative effects from two sleep-promoting drug classes.

What can happen

Excessive sedation and impaired coordination.

What to do

Only one sleep medication should generally be used at a time.

Basis: Sleep medication prescribing information, Drug Interactions. source

Common questions

What should I know about Fioricet interactions?

We have documented 9 interaction classes for Fioricet in our dataset. Usually avoided, or used only with explicit prescriber oversight and close monitoring. The most serious items on this page are marked contraindicated or major.

Can I take Fioricet with alcohol?

Alcohol interacts with most of the medications on this site because it adds to sedation and slows breathing. For the specific documented risk, see the relevant entry above. The general rule from labeling is to avoid alcohol.

Does an empty result mean Fioricet is safe with other drugs?

No. An empty result only means our curated dataset has no matching rule. A pharmacist can run a full interaction screen against every medication and supplement you take.

Related

Editorial Review Board

Clinical review by licensed pharmacists (PharmD)

Every page on this site is reviewed against current FDA prescribing information, DailyMed labelling, DEA scheduling regulations and MedlinePlus monographs before publication. Reviewers have no commercial relationship with any manufacturer or pharmacy.

Last substantive review: October 01, 2026

Sources & references

DailyMed — full prescribing information (National Library of Medicine)
FDA prescribing information (accessdata.fda.gov)
MedlinePlus drug information (National Library of Medicine)
PubChem compound record (National Institutes of Health)
21 CFR Part 1308 — Controlled Substances (eCFR)
Drug Enforcement Administration — drug scheduling

Important

This site provides educational information only and does not sell, prescribe or dispense medications. Always consult a licensed healthcare provider. This page is not medical advice.