Do not use Fioricet if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.
You should not use Fioricet if you are allergic to acetaminophen, butalbital, or caffeine, if you have porphyria, or if you have recently used alcohol, sedatives, tranquilizers, or other narcotic medications.
To make sure Fioricet is safe for you, tell your doctor if you have:
- liver disease, cirrhosis, a history of alcoholism or drug addiction, or if you drink more than 3 alcoholic beverages per day;
- kidney disease;
- asthma, sleep apnea, or other breathing disorder;
- stomach ulcer or bleeding;
- a history of skin rash caused by any medication;
- a history of mental illness or suicidal thoughts; or
- if you use medicine to prevent blood clots.
It is not known whether Fioricet will harm an unborn baby. If you use butalbital while you are pregnant, your baby could become dependent on the drug. This can cause life-threatening withdrawal symptoms in the baby after it is born. Babies born dependent on habit-forming medicine may need medical treatment for several weeks. Tell your doctor if you are pregnant or plan to become pregnant.
This medicine can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.
Clinical Pharmacology of Fioricet
Fioricet is a combination medication that includes butalbital, acetaminophen, and caffeine. Each component has a distinct pharmacological profile, contributing to the overall therapeutic effect in treating tension headaches.
Components and Their Mechanisms of Action
- Butalbital
- Class: Barbiturate
- Mechanism: Butalbital enhances the activity of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the central nervous system (CNS). This action results in CNS depression, leading to sedative and muscle-relaxant effects, which can help alleviate the muscle tension often associated with tension headaches.
- Pharmacokinetics:
- Absorption: Well absorbed from the gastrointestinal tract.
- Distribution: Widely distributed throughout the body and crosses the blood-brain barrier.
- Metabolism: Metabolized primarily in the liver.
- Elimination: Excreted mainly in the urine as metabolites; the half-life ranges from 35 to 88 hours.
- Acetaminophen
- Class: Analgesic and antipyretic
- Mechanism: Acetaminophen works by inhibiting the synthesis of prostaglandins in the CNS and peripherally blocking pain impulse generation. It also acts on the hypothalamic heat-regulating center to produce antipyresis.
- Pharmacokinetics:
- Absorption: Rapid and almost complete absorption from the gastrointestinal tract.
- Distribution: Widely distributed throughout most body tissues, crosses the placenta, and is present in breast milk.
- Metabolism: Metabolized primarily in the liver via conjugation to glucuronide and sulfate.
- Elimination: Excreted in urine mainly as metabolites; the half-life is about 2 to 3 hours in adults.
- Caffeine
- Class: CNS stimulant
- Mechanism: Caffeine is a methylxanthine that acts as a central nervous system stimulant. It antagonizes adenosine receptors, resulting in increased neuronal firing and the release of neurotransmitters like dopamine and norepinephrine. This action can enhance alertness and counteract the sedative effects of butalbital.
- Pharmacokinetics:
- Absorption: Rapidly and completely absorbed from the gastrointestinal tract.
- Distribution: Distributed throughout all body tissues, including the CNS.
- Metabolism: Metabolized in the liver primarily via demethylation.
- Elimination: Excreted in the urine, mainly as metabolites; the half-life ranges from 3 to 7 hours in adults.
Therapeutic Uses
Fioricet is primarily indicated for the relief of complex tension (or muscle contraction) headaches. The combination of a sedative (butalbital), a pain reliever (acetaminophen), and a stimulant (caffeine) addresses different aspects of headache pain and tension.
Clinical Considerations
- Efficacy:
- Fioricet is effective in reducing headache symptoms due to its multi-modal action—relieving pain, reducing muscle tension, and combating sedation.
- Safety:
- Butalbital: Risk of dependency and tolerance with prolonged use.
- Acetaminophen: Risk of hepatotoxicity, especially at high doses or with chronic use.
- Caffeine: Potential for exacerbating anxiety, insomnia, or gastrointestinal discomfort.
- Contraindications:
- Hypersensitivity to any component.
- Severe hepatic impairment due to the acetaminophen component.
- Porphyria because of the butalbital component.
- Drug Interactions:
- CNS Depressants: Enhanced sedative effects when combined with other CNS depressants (e.g., alcohol, benzodiazepines).
- Hepatic Enzyme Inducers/Inhibitors: Drugs that affect liver enzymes can alter the metabolism of butalbital and acetaminophen.
- Anticoagulants: Acetaminophen can affect the anticoagulant properties of warfarin and other similar drugs.
- Adverse Effects:
- Common: Drowsiness, dizziness, nausea, and abdominal pain.
- Serious: Hepatotoxicity (from acetaminophen), respiratory depression (from butalbital), and dependence or withdrawal symptoms (from butalbital).
General Information About Fioricet
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.
Information for Patients
Fioricet 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 Fioricet, 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.
Laboratory Tests
In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.
Drug Interactions
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.
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 Fioricet. 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.