Fioricet (Butalbital/Acetaminophen/Caffeine)

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD

History

Fioricet is well established, proven brand that was introduced in the US in the mid 1980s. Watson Pharmaceuticals, Inc. acquired the United States rights to the Fioricet® and Fiorinal® lines for $178 million from Novartis Pharmaceuticals Corporation in 2003. Fioricet® and Fiorinal® are based on combinations of popular pain relief compounds and are used for tension headaches:

• Fioricet® (butalbital, acetaminophen, and caffeine)
• Fioricet® with Codeine CIII (butalbital, acetaminophen, caffeine, codeine phosphate)
• Fiorinal® (butalbital, aspirin, and caffeine)
• Fiorinal® with Codeine (butalbital, aspirin, caffeine and codeine phosphate)

Watson Pharmaceuticals, Inc., headquartered in Corona, California, is a leading specialty pharmaceutical company that develops, manufactures, markets and distributes branded and generic pharmaceuticals. Watson pursues a growth strategy combining internal development, strategic alliances and collaborations and synergistic acquisitions of products and businesses.

The divestiture of Fioricet ® and Fiorinal ® allows Novartis Pharmaceuticals to focus further on its primary mission of introducing innovative new medicines across several therapeutic areas.

FDA approved indications

• relief of the symptom complex of tension (or muscle contraction) headache

Off-label & Investigational uses

• migraine headache

Butalbital/APAP/Caffeine "pros" and "cons"

Advantages:

• Widely used polypharmaceutical preparation for the treatment of migraine and tension-type headache 4
• Important efficient alternative when other medications (vasoconstrictors, opioids, or nonsteroidal anti-inflammatory agents) are ineffective or cannot be used 7
• Occasional and minor immediate adverse effects, when used properly 7
• Superior to acetaminophen with codein in alleviating and relieving emotional or psychic tension 8
• Provides faster and more sustained analgesic effect than acetaminophen with codeine 8
• Low cost due to generic availability

Disadvantages:

• Butalbital is habit-forming and potentially abusable
• Potencial for tolerance (reduced response to medication), psychological and physical dependence
• Not suitable for long-term use
• May impair mental/physical abilities (potentially hazardous tasks such as driving a car or operating machinery hould be avoided while taking Fioricet)
• May cause drug-induced (rebound) headache 6

Mechanism of action

Butalbital has generalized depressant effect on CNS and, in very high doses, has peripheral effects.
Acetaminophen has analgesic and antipyretic effects; its analgesic effects may be mediated through inhibition of prostaglandin synthetase enzyme complex.
Caffeine is thought to produce constriction of cerebral blood vessels.

Time to clear out of the system

Butalbital has half-life of about 35 hours.
Acetaminophen half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage.
Caffeine half-life is about 3 hours.

Alcohol interaction

Alcohol may produce an additive CNS depression when taken with butalbital, and should be avoided.
The lethal dose of a barbiturate is far less if alcohol is ingested.Test interactions

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

With Chemstrip bG and Dextrostix home blood glucose systems, may cause false decrease in mean glucose values.Abuse and Dependence

Butalbital, barbiturate agent, may be habit-forming. Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses. The average daily dose for the barbiturate addict is usually about 1500 mg. As tolerance develops, the amount needed to maintain the same level or intoxication increases. Tolerance to a fatal amount, however, does not increase more than two-fold. As this occurs, the margin between an intoxication and fatal dosages becomes smaller. Fioricet withdrawal and how to go off

Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of Fioricet. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal. Barbiturate-dependent persons can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the person’s regular dosage level and gradually decreasing the daily dosage as tolerated 5.

Fioricet vs. Acetaminophen with codeine

A double-blind, randomized, multicenter investigation demonstrated that both analgesics are more effective than placebo in relieving pain and muscle stiffness or contractions in the treatment of chronically recurring tension headache 8.

Fioricet is significantly better than acetaminophen with codeine in relieving and alleviating emotional or psychic tension. Also, Fioricet may have a faster and more sustained analgesic effect8.

By the end of the four-hour trial, significantly more patients achieved complete pain relief with Fioricet than with acetaminophen with codeine.

The quality and quantity of adverse reactions does not differ significantly among two analgesics.References

• 1. Physicians’ Desk Reference, 59th ed; Thomson PDR: Montvale, NJ; 2005.
• 3. Watson Pharmaceuticals Inc. is acquiring the US rights to the Fioricet and Fiorinal lines.
• 4. Silberstein SD, McCrory DC. Butalbital in the treatment of headache: history, pharmacology, and efficacy. Headache. 2001 Nov-Dec;41(10):953-67. PubMed
• 5. Romero CE, Baron JD, Knox AP, Hinchey JA, Ropper AH. Barbiturate withdrawal following Internet purchase of Fioricet. Arch Neurol. 2004 Jul;61(7):1111-2.
• 6. Young WB, Siow HC. Should butalbital-containing analgesics be banned? Yes. Curr Pain Headache Rep. 2002 Apr;6(2):151-5. PubMed
• 7. Solomon S. Butalbital-containing agents: should they be banned? No. Curr Pain Headache Rep. 2002 Apr;6(2):147-50. PubMed
• 8. Friedman AP, DiSerio FJ. Symptomatic treatment of chronically recurring tension headache: a placebo-controlled, multicenter investigation of Fioricet and acetaminophen with codeine. Clin Ther. 1987;10(1):69-81. PubMed

Published: March 31, 2008
Last updated: January 30, 2017