United States - English - NLM (National Library of Medicine)
BUTALBITAL, ACETAMINOPHEN AND CAFFEINE- butalbital, acetaminophen, and
Bryant Ranch Prepack
BUTALBITAL, ACETAMINOPHEN AND CAFFEINE TABLETS, USP
50 mg/325 mg/40 mg
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 Tablets, USP are 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: colloidal silicon dioxide, croscarmellose sodium, crospovidone, 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:
Acetaminophen (4'-hydroxyacetanilide), is a non-opiate, non-salicylate analgesic and antipyretic. It has
the following structural formula.
Caffeine (1,3,7-trimethylxanthine), is a central nervous system stimulant. It has the following structural
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.
The behavior of the individual components is described below.
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
See OVERDOSAGE for toxicity information.
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.
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
See OVERDOSAGE for toxicity information.
INDICATIONS AND USAGE
Butalbital, acetaminophen 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 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.
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 products.
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.
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 Tablets, USP immediately and seek medical care if they experience
these symptoms. Do not prescribe Butalbital, Acetaminophen and Caffeine Tablets, USP for
patients with acetaminophen allergy.
Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is
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/Caregivers
Do not take Butalbital, Acetaminophen and Caffeine Tablets, USP 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 Tablets, USP 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.
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.
For information on use in geriatric patients, see PRECAUTIONS/Geriatric Use.
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 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 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
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.
Safety and effectiveness in pediatric patients below the age of 12 have not been established.
Clinical studies of butalbital, acetaminophen and caffeine tablets 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
The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation,
shortness of breath, nausea, vomiting, abdominal pain, and intoxicated feeling.
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
Autonomic Nervous System: 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.
DRUG ABUSE AND DEPENDENCE
Abuse and Dependence
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 coagulation defects 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.
Acute caffeine poisoning may cause insomnia, restlessness, tremor, and delirium, tachycardia and
A single or multiple drug 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.
Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as
indicated. Assisted or controlled ventilation should also be considered.
Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine
(NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have
occurred within a few hours of presentation. Serum acetaminophen levels should be obtained
immediately if the patient presents 4 hours or more after ingestion to assess potential risk of
hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To
obtain the best possible outcome, NAC should be administered as soon as possible where impending or
evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude
Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing
absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs
early in the course of intoxication.
DOSAGE AND ADMINISTRATION
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
Butalbital, Acetaminophen and Caffeine Tablets, USP
Containing 50 mg butalbital, 325 mg acetaminophen and 40 mg caffeine. Available as white, round
shaped tablets, debossed "2355" on one side, and debossed "V" on the reverse side.
Bottles of 60: NDC 0603-2544-20
Bottles of 90: NDC 0603-2544-02
Bottles of 100: NDC 0603-2544-21
Bottles of 500: NDC 0603-2544-28
Bottles of 1000: NDC 0603-2544-32
Store and Dispense
Store at 20°-25°C (68°-77°F) with excursions permitted between 15°-30°C (59°-86°F) [see USP
Controlled Room Temperature]; dispense in a tight, light-resistant container as defined in the USP.
Huntsville, AL 35811
Butalbital APAP w/Caff 50/325/40mg Tab
BUTALBITAL, ACETAMINOPHEN AND CAFFEINE
butalbital, acetaminophen, and caffeine tablet
Product T ype
Ite m Code (Source )
NDC:6 36 29 -
1774(NDC:0 6 0 3-2544)
Route of Administration
DEA Sche dule
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)
CAFFEINE (UNII: 3G6 A5W338 E) (CAFFEINE - UNII:3G6 A5W338 E)
Stre ng th
SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)
CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )
MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )
CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)
STEARIC ACID (UNII: 4ELV7Z6 5AP)
CRO SPO VIDO NE (UNII: 6 8 40 19 6 0 MK)
PO VIDO NES (UNII: FZ9 8 9 GH9 4E)
STARCH, CO RN (UNII: O8 232NY3SJ)
no sco re
S hap e
S iz e
Bryant Ranch Prepack
Marketing Start Date
Marketing End Date
NDC:6 36 29 -1774-1
20 in 1 BOTTLE
NDC:6 36 29 -1774-2
30 in 1 BOTTLE
NDC:6 36 29 -1774-3
6 0 in 1 BOTTLE
NDC:6 36 29 -1774-4
9 0 in 1 BOTTLE
NDC:6 36 29 -1774-5
50 in 1 BOTTLE
NDC:6 36 29 -1774-6
6 in 1 BOTTLE
NDC:6 36 29 -1774-7
120 in 1 BOTTLE
NDC:6 36 29 -1774-8
40 in 1 BOTTLE
NDC:6 36 29 -1774-9
12 in 1 BOTTLE
NDC:6 36 29 -1774-0
8 4 in 1 BOTTLE
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 40 511
0 8 /27/20 0 3
Bryant Ranch Prepack (171714327)
Bryant Ranch Prepack (171714327)
Ad d re s s
Busine ss Ope rations
Bryant Ranch Prepack
REPACK(6 36 29 -1774) , RELABEL(6 36 29 -1774)