Fioricet® (Butalbital, Acetaminophen, and Caffeine Tablets USP) is supplied in tablet form for oral administration.

Each tablet contains the following active ingredients:
butalbital USP . . . . . . . . . . . .50 mg
acetaminophen USP . . . . . . 325 mg
caffeine USP . . . . . . . . . . . . .40 mg

Inactive Ingredients: crospovidone, FD&C Blue #1, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid.

Butalbital (5-allyl-5-isobutylbarbituric acid), is a short to intermediate-acting barbiturate. It has the following structural formula:

C₁₁H₁₆N₂O₃          Mol. wt. 224.26

Acetaminophen (4´-hydroxyacetanilide), is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

C₈H₉NO₂              Mol. wt. 151.17

Caffeine (1,3,7-trimethylxanthine), is a central nervous system stimulant. It has the following structural formula:

C₈H₁₀N₄O₂          Mol. wt. 194.19

Last updated on RxList: 11/13/2007

Fioricet® (Butalbital, Acetaminophen, and Caffeine Tablets USP) is indicated for the relief of the symptom complex of tension (or muscle contraction) headache.

Evidence supporting the efficacy and safety of this combination product in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.

One or 2 tablets every 4 hours as needed. Total daily dosage should not exceed 6 tablets. Extended and repeated use of this product is not recommended because of the potential for physical dependence.

Fioricet® (Butalbital, Acetaminophen, and Caffeine Tablets USP)

Containing 50 mg butalbital, 325 mg acetaminophen, and 40 mg caffeine. Available as light-blue, speckled, round uncoated tablets, engraved "FIORICET " on one side, and a three-head profile "" on other side. Bottles of 100 (NDC 52544-957-01) and 500 (NDC 52544-957-05).

Storage

Store below 30°C (86°F); dispense in a tight container.

*Trademark of Medical Economics Company, Inc.

Watson Pharma, Inc., A Subsidiary of Watson Pharmaceuticals, Inc.Corona, CA 92880 USA. FDA rev date: 7/18/2002

Last updated on RxList: 11/13/2007

Frequently Observed

The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, and intoxicated feeling.

Infrequently Observed

All adverse events tabulated below are classified as infrequent.

Central Nervous System: headache, shaky feeling, tingling, agitation, fainting, fatigue, heavy eyelids, high energy, hot spells, numbness, sluggishness, seizure. Mental confusion, excitement, or depression can also occur due to intolerance, particularly in elderly or debilitated patients, or due to overdosage of butalbital.

Autonomic Nervous System: dry mouth, hyperhidrosis.

Gastrointestinal: difficulty swallowing, heartburn, flatulence, constipation.

Cardiovascular: tachycardia.

Musculoskeletal: leg pain, muscle fatigue.

Genitourinary: diuresis.

Miscellaneous: pruritus, fever, earache, nasal congestion, tinnitus, euphoria, allergic reactions.

Several cases of dermatological reactions, including toxic epidermal necrolysis and erythema multiforme, have been reported.

The following adverse drug events may be borne in mind as potential effects of the components of this product. Potential effects of high dosage are listed in the OVERDOSAGE section.

Acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis.

Caffeine: cardiac stimulation, irritability, tremor, dependence, nephrotoxicity, hyperglycemia.

DRUG ABUSE AND DEPENDENCE

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 for 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 dosage and fatal dosage becomes smaller. The lethal dose of a barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to 5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over a period of approximately 15 days. Treatment of barbiturate dependence consists of cautious and gradual withdrawal of the drug. Barbiturate-dependent patients can be withdrawn by using a number of different withdrawal regimens. One method involves initiating treatment at the patient's regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.

Butalbital, acetaminophen, and caffeine may enhance the effects of: other narcotic analgesics, alcohol, general anesthetics, tranquilizers such as chlordiazepoxide, sedative-hypnotics, or other CNS depressants, causing increased CNS depression.

Drug/Laboratory Test Interactions

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

Last updated on RxList: 11/13/2007

Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is not recommended.

General

Butalbital, acetaminophen, and caffeine tablets should be prescribed with caution in certain special-risk patients, such as the elderly or debilitated, and those with severe impairment of renal or hepatic function, or acute abdominal conditions.

Laboratory Tests

In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether acetaminophen or butalbital have a potential for carcinogenesis, mutagenesis or impairment of fertility.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Animal reproduction studies have not been conducted with this combination product. It is also not known whether butalbital, acetaminophen, and caffeine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. This product should be given to a pregnant woman only when clearly needed.

Nonteratogenic Effects

Withdrawal seizures were reported in a two-day-old male infant whose mother had taken a butalbital-containing drug during the last two months of pregnancy. Butalbital was found in the infant's serum. The infant was given phenobarbital 5 mg/kg, which was tapered without further seizure or other withdrawal symptoms.

Nursing Mothers

Caffeine, barbiturates, and acetaminophen are excreted in breast milk in small amounts, but the significance of their effects on nursing infants is not known. Because of potential for serious adverse reactions in nursing infants from butalbital, acetaminophen, and caffeine, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Geriatric Use

Clinical studies of Fioricet® (Butalbital, Acetaminophen, and Caffeine Tablets USP) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Butalbital is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Last updated on RxList: 11/13/2007

Following an acute overdosage of butalbital, acetaminophen, and caffeine, toxicity may result from the barbiturate or the acetaminophen. Toxicity due to caffeine is less likely, due to the relatively small amounts in this formulation.

Signs and Symptoms

Toxicity from barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; and hypovolemic shock.

In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necroses, hypoglycemic coma, and thrombocytopenia may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. In adults hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams.

Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia and extrasystoles.

Treatment

A single or multiple overdose with this combination product is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended.

Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. Pressors should be avoided. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and when necessary, to provide assisted respiration. If renal function is normal, forced diuresis may aid in the elimination of the barbiturate. Alkalinization of the urine increases renal excretion of some barbiturates, especially phenobarbital.

Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously.

If the dose of acetaminophen may have exceeded 140 mg/kg, acetylcysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels four or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals.

Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.

Toxic Doses (for adults)

In all cases of suspected overdosage, call your Regional Poison Control Center to obtain the most up-to-date information about the treatment of overdosage. Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians' Desk Reference®*.

This product is contraindicated under the following conditions:

- Hypersensitivity or intolerance to any component of this product
- Patients with porphyria.

Last updated on RxList: 11/13/2007

This combination drug product is intended as a treatment for tension headache.

It consists of a fixed combination of butalbital, acetaminophen, and caffeine. The role each component plays in the relief of the complex of symptoms known as tension headache is incompletely understood.

Pharmacokinetics

The behavior of the individual components is described below.

Butalbital

Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most tissues in the body. Barbiturates in general may appear in breast milk and readily cross the placental barrier. They are bound to plasma and tissue proteins to a varying degree and binding increases directly as a function of lipid solubility.

Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parent drug (about 3.6% of the dose), 5-isobutyl-5-(2, 3-dihydroxypropyl) barbituric acid (about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), products with the barbituric acid ring hydrolyzed with excretion of urea (about 14% of the dose), as well as unidentified materials. Of the material excreted in the urine, 32% is conjugated.

The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5-20 mcg/mL. This falls within the range of plasma protein binding (20%-45%) reported with other barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity, indicating that there is no preferential distribution of butalbital into either plasma or blood cells.

See OVERDOSAGE for toxicity information.

Acetaminophen

Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug.

See OVERDOSAGE for toxicity information.

Caffeine

Like most xanthines, caffeine is rapidly absorbed and distributed in all body tissues and fluids, including the CNS, fetal tissues, and breast milk.

Caffeine is cleared through metabolism and excretion in the urine. The plasma half-life is about 3 hours. Hepatic biotransformation prior to excretion results in about equal amounts of 1-methylxanthine and 1-methyluric acid. Of the 70% of the dose that is recovered in the urine, only 3% is unchanged drug.

See OVERDOSAGE for toxicity information.

Last updated on RxList: 11/13/2007

This product may impair mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product.

Alcohol and other CNS depressants may produce an additive CNS depression when taken with this combination product, and should be avoided.

Butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

For information on use in geriatric patients, see PRECAUTIONS/Geriatric Use.

Last updated on RxList: 11/13/2007

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BUTALBITAL/ACETAMINOPHEN/CAFFEINE - ORAL

(uh-seet-uh-MEE-no-fen/KAF-een/byou-TAL-bih-tall)

COMMON BRAND NAME(S): Esgic, Fioricet

USES: This combination medication is used to treat tension headaches. Acetaminophen helps to decrease the pain from the headache. Caffeine helps increase the effects of acetaminophen. Butalbital is a sedative that helps to decrease anxiety and cause sleepiness and relaxation.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat migraine headaches.

HOW TO USE: Take this medication by mouth with or without food, usually every 4 hours as needed or as directed by your doctor.

The dosage is based on your medical condition and response to therapy. This medication works best if it is used as the first signs of a headache occur. If you wait until the headache has worsened, the medication may not work as well.

This medication may cause dependence, especially if it has been used regularly for an extended time or if it has been used in high doses. In such cases, withdrawal reactions (e.g., nausea/vomiting, mental/mood changes, seizures) may occur if you suddenly stop this drug. To prevent withdrawal reactions when stopping extended, regular treatment with this drug, gradually reduce the dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Though very unlikely, abnormal drug-seeking behavior (addiction) is possible with this medication. To lessen the risk of becoming addicted, do not increase your dose, take it more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

This medication contains acetaminophen. Do not take more acetaminophen than recommended. (See also Side Effects, Drug Interactions sections.)

Inform your doctor if you notice increased use of this medication, a worsening of headaches, an increase in the number of headaches, the medication not working as well, or use of this medication for more than 2 headache episodes a week. Your doctor may need to change your medication and/or add a separate medication to prevent the headaches.

SIDE EFFECTS: Nausea, vomiting, abdominal pain, shaking (tremor), shortness of breath, lightheadedness, dizziness, or drowsiness may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes, fainting, seizure, fast/irregular heartbeat, increased thirst/urination.

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding, change in the amount of urine.

If you do not have liver problems, the adult maximum dose of acetaminophen is 4 grams per day (4000 milligrams). If you take more than the maximum daily amount, it may cause serious (possibly fatal) liver disease. Seek immediate medical attention if you have any of the following symptoms of liver damage: persistent nausea/vomiting, yellowing eyes/skin, dark urine, severe stomach/abdominal pain, extreme tiredness.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking this medication, tell your doctor or pharmacist if you are allergic to acetaminophen, caffeine, or butalbital; or to other barbiturates (e.g., phenobarbital) or xanthine derivatives (e.g., theophylline); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: severe breathing problems (e.g., bronchopneumonia), a certain enzyme disorder (porphyria).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, personal or family history of regular use/abuse of drugs/alcohol, mental/mood disorders, abdominal/stomach problems (e.g., stomach ulcer), heart disease (e.g., irregular heartbeat, recent heart attack).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or taking part in any other activity that requires alertness. Avoid alcoholic beverages because they may increase the risk of this drug's side effects.

Before having surgery, tell your doctor or dentist that you are using this medication.

This product contains acetaminophen, which may cause liver damage. Daily use of alcohol, especially when combined with acetaminophen, may increase your risk for liver damage. Check with your doctor or pharmacist for more information.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects while using this drug.

During pregnancy, this medication should be used only when clearly needed. Using it for long periods or in high doses near the expected delivery date is not recommended because of possible harm to the unborn baby. Discuss the risks and benefits with your doctor. Infants born to mothers who have used this medication for an extended time may have withdrawal symptoms such as irritability, abnormal/persistent crying, vomiting, seizures, or diarrhea. Tell your doctor immediately if you notice any of these symptoms in your newborn.

This drug passes into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because very serious interactions may occur: sodium oxybate.

If you are currently using the medication listed above, tell your doctor or pharmacist before starting this medication.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: adenosine, anti-seizure drugs (e.g., carbamazepine, phenytoin), beta agonists (e.g., albuterol), drugs affecting liver enzymes that remove this medication from your body (such as macrolide antibiotics including erythromycin, cimetidine, disulfiram, valproic acid, fluvoxamine, MAO inhibitors including furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine), isoniazid, lithium, methoxyflurane, phenothiazines (e.g., chlorpromazine).

This drug can speed up the removal of other drugs from your body by affecting certain liver enzymes. These affected drugs include "blood thinners" (e.g., warfarin), cyclosporine, corticosteroids such as prednisone, estrogen, felodipine, metronidazole, quinidine, certain beta blockers such as metoprolol, theophylline, doxycycline.

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as certain antihistamines (e.g., diphenhydramine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., risperidone, amitriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain caffeine or drowsiness-causing ingredients. Also keep in mind that certain beverages (e.g., coffee, colas, tea) contain caffeine. Ask your pharmacist about using those products safely.

Acetaminophen is an ingredient in many nonprescription products and in some combination prescription medications. Read the labels carefully before taking other pain relievers, fever reducers, or cold products to see if they also contain acetaminophen. Consult your pharmacist if you are uncertain whether your other prescription or nonprescription products contain acetaminophen. (See also adult maximum daily dose information in Side Effects section.)

This medication may decrease the effectiveness of combination-type birth control pills. This can result in pregnancy. Ask your doctor or pharmacist for details, and discuss whether you should use additional reliable birth control methods while taking any of these drugs.

This medication may interfere with certain medical/laboratory tests (including urine 5-HIAA levels, urine VMA levels, urine catecholamine levels, dipyridamole-thallium imaging tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness, slow breathing, severe dizziness, persistent nausea/vomiting.

NOTES: Do not share this medication with others.

Massage, hot baths, and other relaxation methods can help with tension headaches. Consult your doctor or pharmacist for more details.

Laboratory and/or medical tests (e.g., liver and kidney function tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: Not applicable.

STORAGE: Store at room temperature below 86 degrees F (30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised September 2008 Copyright(c) 2008 First DataBank, Inc.