1. Proposal To Schedule Fioricet®
Frederick Nichols
Todd Nitta
Radee Bun
Mike Sylva
Hope Barnes
Marketa Lanier
Han Nguyen

2. Outline Introduction Stakeholders & Alternatives
Technical & Political Feasibility, Viability
Evidence of Schedule III status
Recommended Change to the Law

3. Introduction Fioricet® Unscheduled Acetaminophen 325 mg
Butalbital 50mg
Caffeine mg
Fiorinal® Scheduled
Aspirin mg
Butalbital 50mg
Caffeine mg
**The only difference is Aspirin & Acetaminophen

4. Current Problems Since 2000/List of Abused Compounds
Fioricet® – 50 to 74 place
Scheduled Butalbital Compounds – 149 to 194 place
Pizza Ambush
Conclusion:
Fioricet® is more abused because it is more available

5. Current Law 21 CFR Part 1308 What are the criteria for scheduling
1988 – Except for certain mixtures of scheduled + non-narcotic substances
Fioricet® Included

6. Drug Abuse and Dependence (for both Fioricet® and Fiorinal®)
Drug Abuse and Dependence (for both Fioricet® and Fiorinal®) Abuse and Dependence Butalbital
Barbiturates may be habit-forming: Tolerance, psychological dependence, and physical dependence may occur especially following prolonged use of high doses of barbiturates. The average daily dose of the barbiturate addict is usually about 1500 mg. As tolerance to barbiturates develops, the amount needed to maintain the same level of intoxication increases: tolerance to a fatal dosage, however, does not increase more than two-fold. As this occurs, the margin between an intoxication dose and a fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs.

7. Overdosage (Fioricet®)
Following an acute overdose of butalbital, acetaminophen, and caffeine, toxicity may result from the barbiturate or the acetaminophen.
Signs and Symptoms
Toxicity from barbiturate poisoning includes drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.In acetaminophen overdose: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. In adults hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams.
Toxic Doses (for adults)
Butalbital Toxic dose 1 g (20 tablets Fioricet ®)
Acetaminophen Toxic dose 10 g (30 tablets Fioricet ®)
Caffeine Toxic dose 1 g (25 tablets Fioricet®)

8. How patients become addicted to Fioricet®
Prescribers/patients may be unaware that this drug is potentially habit forming because it is not listed as a controlled substance.
This may lead to unmanaged use of this drug for the following reasons:

9. How patients become addicted to Fioricet
Patients who experience tension headache and migraines are at risk of taking excessive amounts of medication in hope to facilitate immediate relief from their symptoms.
This habit can often lead to the development of rebound/interdose headaches and over a period of time these headaches may become chronic daily
headaches.
Tolerance can develop in patients, therefore they need to consume more drug to experience relief from their headache.

10. How patients become addicted to Fioricet
Case reports of patients who suffered from severe migraines developed a chemical dependence to butalbital containing products used for legitimate treatment purposes.
Withdrawal symptoms experiences by these patients were grand real seizures and associated behavioral disorders.
These patients also developed drug seeking behaviors to overcome their prescription limit.

11. Top 200 Generic Drugs by Prescription*
Top 200 Generic Drugs by Retail Sales*
Year
Rank
Drug
Units
2000 50
B/A/C
5,169
149
Butalbital Compound
1,649
2001 63
4,559
172
1,295
2002
4,660
194
1,076
Year
Rank
Drug
$ Amt
2000 80
B/A/C
65,896
120
Butalbital Compound w/Codeine
40,364
2001 74
92,443
186
Butalbital Compound
24,656
2002 68
115,520
185
29,217
* All Facts and Figures from Drug Topics.com

12. Other stake holders include:
Pharmacists – divided
scheduled in the best interests of the patient to prevent abuse
double-counting, responding to more frequent refill requests, and having to inventory another controlled substance
Physicians – divided
Patients – depend on their affiliation with the drug
Wholesalers – in favor to divert sales to comparable and more expensive drugs such as sumatriptan (Imitrex®)
Overall, we believe that the stakeholders in favor of scheduling have more valid opinions and sincere intentions regarding the outcomes of scheduling.

13. Alternatives
Change Fioricet® to a C-IV or C-V, which would at least give it some recognition as a substance with potential for abuse
Propose for Fioricet ® to be Scheduled as C-III at the Federal level
Pull Fioricet® from the market

14. Alternatives
Our least favored alternative:
Do Nothing

15. Controlled Substance Scheduling: Exemption Criteria
from Federal Register:
15 mg intermediate-acting barbiturate:
+ 70 mg APAP or mg ASA = Exempt
• for 50 mg Butalbital, drug must contain at least:
233 mg APAP or 627 mg ASA = Exempt
• Fioricet® = 325 mg APAP = Exempt
• Fiorinal® = 325 mg ASA = C-III

16. Technical Feasibility
Determine whether scheduling Fioricet will/will not lead to reduction in abuse
Collect data from:
Rehab Programs
Medical Establishments
WA State Law Enforcement Agencies
Compare yearly data and identify actual effects
DAWN Reports

17. Drug Abuse Warning Network (DAWN)
Top 150 Drugs Mentioned in ED Drug Abuse Episodes by Frequency, 2001:
Rank Drug Mentions % Total
APAP/Butalbital/Caffeine 1,
ASA/Butalbital/Caffeine
Top 200 Single-Drug + Multiple-Drug ED Episodes, 2001:
Rank Drug Episodes Alcohol
APAP/Butalbital/Caffeine 557 n/a
ASA/Butalbital/Caffeine 314 n/a

18. Political Viability
Determine if proposal will survive “Political Test”
Involves decision makers, officials, voters
Perspectives:
Supporters
Non-Supporters
Manufacturers
Patients

19. Administrative Operability
Determine if there is an existing administrative system to put our proposal into effect
RCW – BOP has authority and responsibility
To schedule, drug must meet 8 criteria
These relate to:
Potential for drug abuse
Patterns of abuse
Risk to public health
Psychic or physiological dependence, etc…
Consideration of FDA and DEA findings

20. Micki Kedzierski, substance abuse expert
· Fioricet  Migraine Headache  Frequent dosing
· No maintenance therapy
· Rehab is difficult
· Cost
· So should Fioricet it be scheduled?

21. Recommendation of Changes to WAC 246-887-160: Schedule III
The board finds that the following substances have potential for abuse less than substances listed in Schedules I and II, and have currently accepted medical use in treatment in the United States and that the abuse of the substances may lead to moderate or low physical dependency to high physiological dependency. The board, therefore, places each of the following substances In Schedule III.

22. Recommendation of Changes to WAC 246-887-160: Schedule III
(a) (No changes)
(b) (No changes)

23. Recommendation of Changes to WAC 246-887-160: Schedule III
(c) Depressants. Unless specifically excepted or unless listed in another schedule, any material, compound, or preparation which contains any quantity of the following substances having a depressant effect on the central nervous system:
(1) Any compound, mixture, or preparation containing:
(i) Amobarbital;
(ii) Butalbital;
(iii) Secobarbital;
(iv) Phenobarbital; (No changes after this)

24. Conclusion
Based on the evidence presented, we believe that Fioricet® should be placed in Schedule III so that it may be more tightly controlled.
To facilitate this change, the Board of Pharmacy should use its vested power under the Administrative Procedures Act and place Fioricet® on the list of drugs under WAC

25. References
[1] Chichowski, John. Addiction to painkiller blamed for pizza delivery ambush. North Jersey Media Group ;News;p A03.
[2] Physicians’ Desk Reference, 48th Ed. Montvale, NJ. ©1996:  
[3] The Online Newsmagazine for Pharmacists. Copyright © 2003 Advanstar Medical Economics at Montvale, NJ:
[4] Young WB, Siow HC. Should butalbital-containing analgesics be banned? Yes. Curr Pain Headache Rep. 2002;6(2):151-5.
[5] Drug Abuse Warning Network (DAWN). US Dept. of Health and Human Services. Rockville, MD:
[6] Revised Code of Washington , Uniform Controlled Substance Act, Article II: Standards and Schedules; 2002.
[7] Revised Code of Washington 34.05, Administrative Procedures Act; 2002.
[8] Revised Code of Washington , Uniform Controlled Substance Act, Article II: Standards and Schedules; 2002.
[9] Physicians’ Desk Reference, 48th Ed. Montvale, NJ. ©1996:
[10] Raja M, Altavista M, Azzoni A, Albanese A. Sever barbiturate withdrawal syndrome in migrainous patients. Headache. 1996;36:
[11] Revised Code of Washington , Uniform Controlled Substance Act, Article II: Standards and Schedules; 2002.