|Pregnancy cat.||C (US)|
|Legal status||Schedule III (US)|
Fioricet and Esgic are brand names of a combination of butalbital (a barbiturate), acetaminophen and caffeine which is indicated for the treatment of tension headaches, muscle contraction headaches and post-dural puncture headaches. Although not indicated, they are commonly used to treat migraines and other pain related ailments.
New Fioricet formulation
Per FDA guidelines recommending that manufacturers limit the dose of acetaminophen in prescription products, the formulation of fioricet has changed. "Old formulations" of fioricet contained 50 mg of butalbital, 325 mg of acetaminophen and 40 mg caffeine; "new formulations" contain 50 mg of butalbital, 300 mg of acetaminophen and 40 mg caffeine. Manufacturers were allowed to make the "old formulation" of fioricet until January 1, 2014. Currently there is no move to remove or destroy the "old formulation", allowing for an odd situation in which there could be two different formulations of fioricet in pharmacies.
|Formulation||DEA Schedule||Butalbital (mg)||Acetaminophen (mg)||Caffeine (mg)||Form|
Confusion over control status
Confusion has arisen about the controlled substance status of this medication. Per DEA listing, Fioricet is a DEA exempt prescription product. There is no logical rationale for why this is exempted from controlled substance scheduling, but it has been postulated that the concentration of butalbital with the acetaminophen (and caffeine) allows this to be an analgesic combination that the DEA allows exemption to. However peculiar it may be, Fioricet's sister product, Fiorinal, contains the same amount of butalbital per dose, combined with aspirin (and caffeine) instead of acetaminophen (and caffeine) but it is in fact a DEA Schedule III item.
Per the FDA National Drug Code Directory, "new formulations" of fioricet are listed as DEA Schedule III:
|Labeller||NDC||DEA Schedule||form||strength (Butalbital, Acetaminophen, Caffeine)||note|
|Watson Pharma||52544-080-01||CIII||capsule||300 mg, 50 mg, 40 mg||new formulation|
|Rx Pak Division of McKesson||65084-454-10||CIII||capsule||300 mg, 50 mg, 40 mg||new formulation|
|Cardinal Health||55154-3416-1||none||tablet||325 mg, 50 mg, 40 mg||old formulation|
Potential problems of two formulations
This change in designation affects mid-level providers, such as ARNPs and PAs, who are not allowed to prescribe controlled substances in some jurisdictions. Ostensibly, prescribers that are affected by this change could clearly indicate on the prescription that they would like the "old formulation" (perhaps by writing out the mg combination) until the "old formulation" is no longer available. Pharmacists dispensing or verifying this medication need to be keenly aware of the difference in formulation and CSA scheduling, as a misfill of the scheduled "new formulation" for the "old formulation" could have legal ramifications. Delays in verification and dispensing, or invalidation of a prescription due to a mid-level provider not having the ability to prescribe the controlled "newer formulation" could likewise affect patients through delays and hassles.
Usage and dosage
Fioricet is indicated for the treatment of muscle tension or muscle contraction headaches. It is also commonly prescribed for migraines although it is not FDA indicated for this use in the United States. The usual adult dose is 1-2 tablets every four hours as needed, not exceeding six tablets in a 24 hour period.
Mechanism of action
Butalbital has generalized depressant effect on central nervous system and, in very high doses, has peripheral effects. Acetaminophen has analgesic and antipyretic effects mediated by a metabolite which acts at cannabinoid receptors, contrary to popular belief it is not an antiinflammatory at safe levels (it becomes toxic at doses above 1,000mg per dose and/or 3,000mg per day). Caffeine is thought to produce constriction of cerebral blood vessels and serves to counteract the sedative effect of butalbital.
Butalbital has a half-life of about 35 hours. Acetaminophen has a half-life of about 1.25 to 3 hours, but may be increased by liver damage and after an overdose. Caffeine has a half-life of about 5 to 7 hours.
Commonly reported side effects for Fioricet include:
- Intoxicated feeling
- Substance dependence
- Shortness of breath
- Abdominal pain
Fioricet is implicated as causing repeat headaches with over-use.
- Stevens–Johnson syndrome, an adverse reaction to barbiturates
The treatment of Fioricet overdose is complicated by the presence of two substances which are highly toxic when taken in excessive amounts. Fioricet overdoses generally result in toxic amounts of both acetaminophen and butalbital being consumed at once, requiring both overdoses to be treated at once. Fioricet overdose by anyone and/or any consumption by persons to whom it is not prescribed (particularly children) is always a medical emergency and medical attention must be sought immediately if an overdose or consumption by other persons is suspected. Fioricet overdose is often fatal and symptoms may not present for hours following consumption, once initial overdose symptoms present they can progress rapidly and there may not be time to reach appropriate medical care after this point.
Acetaminophen over exerts its toxicity through the production of a toxic metabolite which produces liver damage in doses of 3,000mg or more per day and acute liver failure in doses above that. The specific antidote to acetaminophen overdose is N-acetyl-cysteine. Kindey failure and stomach bleeding may also occur.
Butalbital overdoses exerts its toxicity through excessive sedation resulting in respiratory depression and ultimately death via hypoxia. Nonlethal overdoses may also result in coma and death. There is no specific antidote to butalbital overdose and treatment is supportive, common treatment regimens generally include the administration of intravenous administration of saline, naloxone, thiamine, glucose, NaHCO3 to alkalize the urine to increase rate of excretion, and activated charcoal via nasogastric tube. It is not uncommon for doctor to recommend observation of the patient in the Emergency Department for a number of hours or admission to the hospital for several days of observation if symptoms are severe and to counsel the patient on drug abuse and/or refer them for psychiatric evaluation.
|Name||DEA Schedule||Acetaminophen (mg)||Aspirin (mg)||Butalbital (mg)||Caffeine (mg)||Codeine (mg)||Labeller||Form||End Marketing Date|
|Esgic||CIII||325||50||40||Forrest Laboratories, Inc||capsule, tablet|
|Esgic Plus||CIII||500||50||40||Forrest Laboratories, Inc; A-S Medication Solutions LLC||capsule, tablet||6/29/2014; 8/10/2015|
|Fioricet (new formulation)||CIII||300||50||40||Watson Pharma, Inc.||capsule|
|Fioricet (old formulation)||none||325||50||40||Cardinal Health||tablet||1/1/2014|
|Fioricet with codeine||CIII||300||50||40||30||Watson Pharma, Inc.||capsule|
|Fiorinal||CIII||325||50||40||Watson Pharma, Inc.||capsule|
|Fiorinal with codeine||CIII||325||50||40||30||Watson Pharma, Inc.||capsule|
|Phrenilin||CIII||325||50||Valeant Pharmaceuticals International||tablet|
|Phrenilin Forte||CIII||650||50||Valeant Pharmaceuticals International||capsule|
|Phrenilin with caffeine and codeine||CIII||325||50||40||30||Valeant Pharmaceuticals North America||capsule|
- Food and Drug Administration. FDA drug safety communication: prescription acetaminophen products to be limited to 325 mg per dosage unit; boxed warning will highlight potential for severe liver failure.
- (Old formulation) Fioricet package insert, Cardinal Health, Inc.
- (New formulation) Fioricet package insert, Watson Pharma, Inc.
- FDA National Drug Code Directory
- Fioricet at RxList
- A Hidden Cause of Headache Pain - New York Times
- Esgic tablet package insert, Forest Laboratories, Inc
- Esgic capsule package insert, Forest Laboratories, Inc
- Esgic Plus capsule package insert, Forest Laboratories, Inc
- Esgic Plus tablet package insert, Forest Laboratories, Inc
- Esgic Plus tablet package insert, A-S Medication Solutions LLC
- Fioricet with codeine capsule package insert, Watson Pharma, Inc
- Fiorinal capsule package insert, Watson Pharma, Inc
- Fiorinal with codeine capsule package insert, Watson Pharma, Inc
- Phrenilin tablet package insert, Valeant Pharmaceuticals North America
- Phrenilin Forte capsule package insert, Valeant Pharmaceuticals International
- Phrenilin (butalbital, acetaminophen, caffeine, and codeine phosphate) capsule package insert, Valeant Pharmaceuticals North America