United States - English - NLM (National Library of Medicine)
BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE- butalbital, acetaminophen, and
West-Ward Pharmaceutical Corp
Butalbital, Acetaminophen, and Caffeine Capsules
BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE CAPSULES, USP
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver
transplant and death. Most of the cases of liver injury are associated with the use of
acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one
acetaminophen containing product.
Butalbital, Acetaminophen, and Caffeine is supplied in capsule form for oral administration. Each
Butalbital, USP……………………..50 mg
Acetaminophen, USP………………500 mg
Caffeine, USP…………………… …40 mg
In addition, each capsule contains the following inactive ingredients: colloidal silicon dioxide,
magnesium stearate, sodium lauryl sulfate, and sodium starch glycolate.
Capsule shell contains: D&C Red #33, D&C Yellow #10, FD&C Red #40, Gelatin and Titanium
Dioxide. The imprinting ink contains Titanium Dioxide.
Butalbital (5-allyl-5-isobutylbarbituric acid), a white, odorless, crystalline powder having a slightly
bitter taste, is a short to intermediate-acting barbiturate. It has the following structural formula:
Acetaminophen (4´-hydroxyacetanilide), a slightly bitter, white, odorless, crystalline powder, is a non-
opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:
Caffeine (1,3,7,-trimethylxanthine), a bitter, white crystalline powder or white-glistening needles, is a
central nervous system stimulant. It has the following structural formula:
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
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 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.)
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.)
INDICATIONS AND USAGE:
Butalbital, Acetaminophen, and Caffeine Capsules, USP are 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.
This product is contraindicated under the following conditions:
* Hypersensitivity or intolerance to any component of this product.
* Patients with porphyria.
Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is
Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver
transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at
doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen containing
product. The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional
as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing
The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals
who ingest alcohol while taking acetaminophen.
Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one
product that contains acetaminophen. Instruct patients to seek medical attention immediately upon
ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
Serious skin reactions
Rarely, acetaminophen may cause serious skin reactions such as acute generalized
exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis
(TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions. And
use of the drug should be discontinued at the first appearance of skin rash or any other sign of
Hypers ens itivity/anaphylaxis
There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of
acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress,
urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis
requiring emergency medical attention. Instruct patients to discontinue Butalbital, Acetaminophen and
Caffeine Capsules immediately and seek medical care if they experience these symptoms. Do not
prescribe Butalbital, Acetaminophen and Caffeine Capsules for patients with acetaminophen allergy.
Butalbital, Acetaminophen, and Caffeine Capsules 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/Caregivers:
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
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.
Do not take Butalbital, Acetaminophen and Caffeine Capsules if you are allergic to any of its
If you develop signs of allergy such as a rash or difficulty breathing stop taking Butalbital,
Acetaminophen and Caffeine Capsules and contact your healthcare provider immediately.
Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more
than the recommended dose.
In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver
and/or renal function tests.
The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors.
Butalbital, Acetaminophen, and Caffeine Capsules 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.
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.
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
Barbiturates, acetaminophen and caffeine 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.
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
Clinical studies of butalbital, acetaminophen and caffeine capsules 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
Frequently Observed: The most frequently reported adverse reactions are drowsiness,
lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, and
Infrequently Observed: All adverse events tabulated below are classified as infrequent.
Central Nervous: 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
Autonomic Nervous: dry mouth, hyperhidrosis.
Gastrointestinal: difficulty swallowing, heartburn, flatulence, constipation.
Musculoskeletal: leg pain, muscle fatigue.
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.
To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceutical Corp. at 1-877-
233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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.
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 includes 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
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
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
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
Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous
Toxic Doses (for adults):
Butalbital: toxic dose 1 g (20 capsules)
Acetaminophen: toxic dose 10 g (20 capsules)
Caffeine: toxic dose 1 g (25 capsules)
DOSAGE AND ADMINISTRATION:
Oral: one capsule every four hours. Total daily dosage should not exceed 6 capsules.
Extended and repeated use of this product is not recommended because of the potential for
Butalbital 50 mg, Acetaminophen 500 mg and Caffeine 40 mg Capsules, USP are supplied as salmon/red
capsules printed “170” in white ink and are available in:
Bottles of 100 capsules
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Protect from light and
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
West-Ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised November 2013
PRINCIPAL DISPLAY PANEL
Butalbital, Acetaminophen, and
Caffeine Tablets, USP
50 mg/500 mg/40 mg
BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE
butalbital, acetaminophen, and caffeine capsule
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:0 143-0 170
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
BUTALBITAL (UNII: KHS0 AZ4JVK) (BUTALBITAL - UNII:KHS0 AZ4JVK)
ACETAMINO PHEN (UNII: 36 2O9 ITL9 D) (ACETAMINOPHEN - UNII:36 2O9 ITL9 D)
50 0 mg
CAFFEINE (UNII: 3G6 A5W338 E) (CAFFEINE - UNII:3G6 A5W338 E)
Stre ng th
SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)
MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )
SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)
D&C RED NO . 3 3 (UNII: 9 DBA0 SBB0 L)
D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)
FD&C RED NO . 4 0 (UNII: WZB9 127XOA)
GELATIN (UNII: 2G8 6 QN327L)
TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)
SO DIUM STARCH GLYCO LATE TYPE A PO TATO (UNII: 58 56 J3G2A2)
RED (salmo n/red)
no sco re
S hap e
S iz e
West-Ward Pharmaceutical Corp
Marketing Start Date
Marketing End Date
NDC:0 143-0 170 -0 1
10 0 in 1 BOTTLE
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 40 26 1
10 /28 /19 9 8
West-Ward Pharmaceutical Corp (001230762)