Is butalbital-acetaminophen-caffeine (barbiturate-acetaminophen-caffeine) a controlled substance?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: October 7, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Butalbital-Acetaminophen-Caffeine is a Schedule III Controlled Substance

Yes, butalbital-acetaminophen-caffeine 50 mg-325 mg-40 mg tablet is a controlled substance due to the butalbital component, which is a barbiturate with potential for abuse and dependence. 1

Classification and Composition

  • Butalbital is a short to intermediate-acting barbiturate that acts on GABA receptors in the central nervous system 1
  • The combination product contains 50 mg butalbital, 325 mg acetaminophen, and 40 mg caffeine 1
  • As a barbiturate-containing product, it falls under Schedule III controlled substance regulations 2

Clinical Uses and Concerns

  • Indicated only for the relief of tension (muscle contraction) headache symptoms 1
  • Evidence supporting efficacy for multiple recurrent headaches is unavailable 1
  • The FDA label explicitly warns that butalbital is habit-forming and potentially abusable 1
  • Barbiturate-containing analgesics like this combination have significant potential for:
    • Physical and psychological dependence 3, 4
    • Medication overuse headache 4
    • Withdrawal syndromes upon discontinuation 3, 5

Pharmacological Properties and Risks

  • Butalbital is primarily metabolized in the liver through the cytochrome P450 system 2
  • It can induce the CYP enzyme system, potentially affecting metabolism of other medications 2
  • When combined with other CNS depressants (alcohol, opiates, benzodiazepines), it has additive depressant effects on the CNS and respiratory system 2
  • Withdrawal symptoms typically appear 2-4 days after discontinuation and may include:
    • Anxiety, restlessness, insomnia, tremor
    • Seizures, delirium, hallucinations
    • In severe cases: hyperthermia, circulatory failure, death 3

Perioperative Considerations

  • For patients on long-term butalbital, abrupt discontinuation should be avoided 2
  • If time allows before surgery, it should be weaned over 2 weeks 2
  • If unable to wean prior to surgery, it should be continued perioperatively to avoid withdrawal 2
  • Additive effects with anesthetics may cause hypotension, profound sedation, and potentially death 2

Evidence on Efficacy and Safety

  • No evidence shows clinically important enhancement of analgesic efficacy due to the butalbital component 6
  • Simpler analgesic formulations (acetaminophen, NSAIDs) or specific anti-migraine drugs are generally preferred 6
  • Butalbital-containing products should be avoided in elderly patients and should not be used in children 6
  • There are potential teratogenic concerns, with some studies suggesting associations between maternal butalbital use and certain congenital heart defects 7

Clinical Recommendations

  • Due to its controlled substance status, prescriptions require appropriate DEA documentation and cannot be refilled as easily as non-controlled medications 2
  • To minimize risk of dependence, limit use to no more than twice weekly 2
  • Consider preventive migraine therapy if medication overuse is suspected or considered a risk 2
  • For patients already taking butalbital-containing products, reevaluation of treatment is recommended 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.