Documented interactions for Fioricet, Butalbital/Acetaminophen/Caffeine (Butalbital, acetaminophen and caffeine (tablet)). Each entry cites the prescribing information or FDA safety communication it is based on.
| Severity | Interacts with | Class | Concern |
|---|---|---|---|
| Contraindicated | MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) | Monoamine oxidase inhibitor | Opioid with MAO inhibitors is contraindicated |
| Major | Alcohol (ethanol) | CNS depressant | Butalbital combination with alcohol: additive CNS and respiratory depression |
| Major | Alcohol (ethanol) | CNS depressant | Opioid with alcohol: additive respiratory depression |
| Major | MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) | Monoamine oxidase inhibitor | Butalbital combinations with MAO inhibitors: caution |
| Major | Other acetaminophen-containing products (Tylenol, Excedrin, cold medicines) | Acetaminophen-containing product | Duplicate acetaminophen dosing across combination products |
| Major | Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) | Benzodiazepine | Opioid with benzodiazepine: risk of profound sedation, respiratory depression, coma, and death |
| Major | Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) | CNS depressant | Opioid with other CNS depressants: additive respiratory depression |
| Major | Other gabapentinoids (gabapentin, pregabalin) | Gabapentinoid | Opioid with gabapentinoid: serious breathing difficulties |
| Major | Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) | Opioid | Butalbital combination with opioids: additive respiratory depression |
| Major | Other sedatives (butalbital, barbiturates, carisoprodol, sedating antihistamines) | Sedative / barbiturate | Butalbital combination with other sedatives: additive CNS depression |
With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor
MAO inhibitors potentiate opioid effects and impair metabolism.
Severe unpredictable reactions including respiratory depression and death.
Do not combine.
Basis: Opioid-containing product labeling, Contraindications. source
With: Alcohol (ethanol) CNS depressant
Butalbital is a barbiturate; alcohol compounds its sedative effect.
Respiratory depression, sedation, and death.
Avoid alcohol entirely.
Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source
With: Alcohol (ethanol) CNS depressant
Both agents depress the central nervous system and breathing.
Respiratory depression, deep sedation, coma, and death.
Avoid alcohol during opioid therapy.
Basis: Opioid-containing product labeling, Warnings and Precautions. source
With: MAO inhibitors (phenelzine, tranylcypromine, linezolid, methylene blue) Monoamine oxidase inhibitor
Barbiturates and MAO inhibitors can produce unpredictable central nervous system effects.
Labeling states that butalbital-containing products should not be taken with MAO inhibitors.
Do not combine without explicit prescriber direction.
Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source
With: Other acetaminophen-containing products (Tylenol, Excedrin, cold medicines) Acetaminophen-containing product
Acetaminophen from multiple products accumulates in the liver.
Acetaminophen overdose is a leading cause of acute liver failure.
Keep total acetaminophen from all products at or below the labeled daily maximum.
Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source
With: Other benzodiazepines (diazepam, clonazepam, lorazepam, alprazolam, temazepam) Benzodiazepine
Additive depression of the central nervous system and respiratory drive.
FDA requires a boxed warning on opioid-containing products describing this combination.
Avoid where possible. If used, lowest effective doses for the shortest duration with monitoring.
Basis: FDA Drug Safety Communication (2016); opioid boxed warning. source
With: Other CNS depressants (opioids, benzodiazepines, sleep aids, sedating antihistamines, gabapentinoids, muscle relaxants) CNS depressant
Additive central nervous system depression and slowed breathing.
Respiratory depression and overdose, particularly in older adults.
Disclose all sedating medications to the prescriber and pharmacist.
Basis: Opioid-containing product labeling, Warnings and Precautions. source
With: Other gabapentinoids (gabapentin, pregabalin) Gabapentinoid
Additive respiratory depression.
FDA warns of serious breathing difficulties and increased risk of death.
Use the lowest effective gabapentinoid dose and monitor for slowed breathing.
Basis: FDA Drug Safety Communication (2021). source
With: Other opioids (morphine, fentanyl, methadone, oxycodone, hydromorphone, tramadol) Opioid
Barbiturates and opioids both depress respiration.
Respiratory depression, deep sedation, and death.
Avoid where possible; monitor for slowed breathing.
Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Warnings. source
With: Other sedatives (butalbital, barbiturates, carisoprodol, sedating antihistamines) Sedative / barbiturate
Additive sedative effects.
Excessive sedation and respiratory depression.
Review all sedating medications with the prescriber.
Basis: Butalbital, acetaminophen, and caffeine tablets prescribing information, Drug Interactions. source
We have documented 10 interaction classes for Fioricet, Butalbital/Acetaminophen/Caffeine 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.
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.
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.
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.