Butalbital

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# Overview
Butalbital is a combination that is FDA approved for the treatment of for the relief of the symptom complex of tension (or muscle contraction) headache.   Common adverse reactions include lightheadedness and gastrointestinal disturbances including nausea, vomiting, and flatulence, toxic epidermal necrolysis and erythema multiforme.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Butalbital, aspirin, and caffeine tablets are indicated for the relief of the symptom complex of tension (or muscle contraction) headache.
- Evidence supporting the efficacy and safety of butalbital, aspirin, and caffeine in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Butalbital in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Butalbital in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Butalbital in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Butalbital in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Butalbital in pediatric patients.

# Contraindications
- Hypersensitivity to aspirin, caffeine, or barbiturates. Patients with porphyria.

# Warnings
- Prolonged use of barbiturates can produce drug dependence, characterized by psychic dependence, and less frequently, physical dependence and tolerance. The abuse liability of butalbital, aspirin, and caffeine is similar to that of other barbiturate-containing drug combinations. Caution should be exercised when prescribing medication for patients with a known propensity for taking excessive quantities of drugs, which is not uncommon in patients with chronic tension headache.
- Butalbital, aspirin, and caffeine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly. Central Nervous System depressant effects of butalbital may be additive with those of other CNS depressants. Concurrent use with other sedative-hypnotics or alcohol should be avoided. When such combined therapy is necessary, the dose of one or more agents may need to be reduced.
- Salicylates should be used with extreme caution in the presence of peptic ulcer or coagulation abnormalities.

# Adverse Reactions

## Clinical Trials Experience
- The most frequent adverse reactions are drowsiness and dizziness. Less frequent adverse reactions are lightheadedness and gastrointestinal disturbances including nausea, vomiting, and flatulence. A single incidence of bone marrow suppression has been reported with the use of butalbital, aspirin, and caffeine. Several cases of dermatological reactions including toxic epidermal necrolysis and erythema multiforme have been reported.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Butalbital in the drug label.

# Drug Interactions
There is limited information regarding Butalbital Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): C
- Adequate studies have not been performed in animals to determine whether this drug affects fertility in males or females, has teratogenic potential, or has other adverse effects on the fetus. While there are no well-controlled studies in pregnant women, over twenty years of marketing and clinical experience does not include any positive evidence of adverse effects on the fetus. Although there is no clearly defined risk, such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus. Butalbital, aspirin, and caffeine should be used in pregnant women only when clearly needed.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Butalbital in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Butalbital during labor and delivery.

### Nursing Mothers
- The effects of butalbital, aspirin, and caffeine on infants of nursing mothers are not known. Salicylates and barbiturates are excreted in the breast milk of nursing mothers. The serum levels in infants are believed to be insignificant with therapeutic doses.

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

### Geriatic Use
There is no FDA guidance on the use of Butalbital with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Butalbital with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Butalbital with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Butalbital in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Butalbital in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Butalbital in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Butalbital in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Oral

### Monitoring
There is limited information regarding Monitoring of Butalbital in the drug label.

# IV Compatibility
There is limited information regarding IV Compatibility of Butalbital in the drug label.

# Overdosage
- The toxic effects of acute overdosage of butalbital, aspirin, and caffeine are attributable mainly to its barbiturate component, and, to a lesser extent, aspirin. Because toxic effects of caffeine occur in very high dosages only, the possibility of significant caffeine toxicity from butalbital, aspirin, and caffeine overdosage is unlikely. Symptoms attributable to acute barbiturate poisoning include drowsiness, confusion, and coma; respiratory depression; hypotension; shock. Symptoms attributable to acute aspirin poisoning include hyperpnea; acid-base disturbances with development of metabolic acidosis; vomiting and abdominal pain; tinnitus; hyperthermia; hypoprothrombinemia; restlessness; delirium; convulsions. Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium; tachycardia and extrasystoles. Treatment consists primarily of management of barbiturate intoxication and the correction of the acid-base imbalance due to salicylism. Vomiting should be induced mechanically or with emetics in the conscious patient. Gastric lavage may be used if the pharyngeal and laryngeal reflexes are present and if less than 4 hours have elapsed since ingestion. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and when necessary to provide assisted respiration. Diuresis, alkalinization of the urine, and correction of electrolyte disturbances should be accomplished through administration of intravenous fluids such as 1% sodium bicarbonate in 5% dextrose in water. Meticulous attention should be given to maintaining adequate pulmonary ventilation. Correction of hypotension may require the administration of levartherenol bitartrate or phenylephrine hydrochloride by intravenous infusion . In severe cases of intoxication, peritoneal dialysis, hemodialysis, or exchange transfusion may be lifesaving. Hypoprothrombinemia should be treated with Vitamin K, intravenously.
There is limited information regarding Chronic Overdose of Butalbital in the drug label.

# Pharmacology
There is limited information regarding Butalbital Pharmacology in the drug label.

## Mechanism of Action
- Pharmacologically, butalbital, aspirin, and caffeine combines the analgesic properties of aspirin with the anxiolytic and muscle relaxant properties of butalbital.
The clinical effectiveness of butalbital, aspirin, and caffeine in tension headache has been established in double-blind, placebo-controlled, multi-clinic trials. A factorial design study compared butalbital, aspirin, and caffeine with each of its major components. This study demonstrated that each component contributes to the efficacy of butalbital, aspirin, and caffeine in the treatment of the target symptoms of tension headache (headache pain, psychic tension, and muscle contraction in the head, neck, and shoulder region). For each symptom and the symptom complex as a whole, butalbital, aspirin, and caffeine was shown to have significantly superior clinical effects to either component alone.

## Structure

## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Butalbital in the drug label.

## Pharmacokinetics
- The behavior of the individual components is described below.
- The systemic availability of aspirin after an oral dose is highly dependent on the dosage form, the presence of food, the gastric emptying time, gastric pH, antacids, buffering agents, and particle size. These factors affect not necessarily the extent of absorption of total salicylates but more the stability of aspirin prior to absorption.
- During the absorption process and after absorption, aspirin mainly hydrolyzed to salicylic acid and distributed to all body tissues and fluids, including fetal tissues, breast milk, and the central nervous system (CNS). Highest concentrations are found in plasma, liver, renal cortex, heart, and lung. In plasma, about 50%-80% of the salicylic acid and its metabolites are loosely bound to plasma proteins.
- The clearance of total salicylates is subject to saturable kinetics; however, first-order elimination kinetics are still a good approximation for doses up to 650 mg. The plasma half-life for aspirin is about 12 minutes and for salicylic acid and/or total salicylates is about 3.0 hours.
- The elimination of therapeutic doses is through the kidneys either as salicylic acid or other biotransformation products. The renal clearance is greatly augmented by an alkaline urine as is produced by concurrent administration of sodium bicarbonate or potassium citrate.
- The biotransformation of aspirin occurs primarily in the hepatocytes. The major metabolites are salicyluric acid (75%), the phenolic and acyl glucuronides of salicylate (15%), and gentisic and gentisuric acid (1%). The bioavailability of the aspirin component butalbital, aspirin, and caffeine is equivalent to that of a solution except for a slower rate of absorption. A peak concentration of 8.80 mcg/mL was obtained at 40 minutes after a 650 mg dose.
- Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute to most of the 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%-88% of the dose) as unchanged drug or metabolites. The plasma half-life is about 35 hours. Urinary excretion products included 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% was conjugated.
- The bioavailability of the butalbital component of butalbital, aspirin, and caffeine is equivalent to that of a solution except for a decrease in the rate of absorption. A peak concentration of 2020 ng/mL is obtained at about 1.5 hours after a 100 mg dose.
- The in vitro plasma protein binding of butalbital is 45% over the concentration range of 0.5 to 20 mcg/mL. This falls within the range of plasma protein binding (20% to 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).
- 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 rapidly through metabolism and excretion in the urine. The plasma half-life is about 3.0 hours. Hepatic biotransformation prior to excretion results in about equal amounts of 1-methyl-xanthine and 1-methyluric acid. Of the 70% of the dose that has been recovered in the urine, only 3% was unchanged drug.
- The bioavailability of the caffeine component for butalbital, aspirin, and caffeine is equivalent to that of a solution except for a slightly longer time to peak. A peak concentration of 1660 ng/mL was obtained in less than an hour for an 80 mg dose

## Nonclinical Toxicology
There is limited information regarding Nonclinical Toxicology of Butalbital in the drug label.

# Clinical Studies
There is limited information regarding Clinical Studies of Butalbital in the drug label.

# How Supplied
- Butalbital, Aspirin, and Caffeine Tablets, USP 50 mg/325 mg/40 mg are White, Round, Unscored Compressed Tablets Imprinted West-ward 785.
Bottles of 30 tablets
Bottles of 50 tablets
Bottles of 100 tablets
Bottles of 500 tablets
Bottles of 1000 tablets
Unit Dose Boxes of 100 tablets
- Store at 20-25oC (68-77oF) . Protect from light and moisture.
- Dispense in tight, light-resistant container as defined in the USP using a child-resistant closure.

## Storage
There is limited information regarding Butalbital Storage in the drug label.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Butalbital in the drug label.

# Precautions with Alcohol
- Alcohol-Butalbital interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
There is limited information regarding Butalbital Brand Names in the drug label.

# Look-Alike Drug Names
There is limited information regarding Butalbital Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price