BOXED WARNING SECTION.


Hepatotoxicity 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.


PRINCIPAL DISPLAY PANEL NDC 0143-1115-01 Butalbital , Acetaminophen, and Caffeine Tablets, USP 50 mg/500 mg/40 mg Rx Only 100 Tablets

ADVERSE REACTIONS SECTION.


ADVERSE REACTIONS: Frequently Observed: The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominalpain, and intoxicated feeling. 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 depressioncan also occur due to intolerance, particularly in elderly or debilitated patients, or due to overdosageof butalbital. Autonomic Nervous: 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 ofthis 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.

INDICATIONS & USAGE SECTION.


INDICATIONS AND USAGE: Butalbital, Acetaminophen, and Caffeine Capsules, USP are indicated for the relief of the symptom complexof tension (or muscle contraction) headache. Evidence supporting the efficacy and safety of this combination product in the treatment of multiplerecurrent headaches is unavailable. Caution in this regard is required because butalbital ishabit-forming and potentially abusable.

DRUG ABUSE AND DEPENDENCE SECTION.


DRUG ABUSE AND DEPENDENCE: Abuse and Dependence: Butalbital :Barbiturates may be habit - forming: Tolerance, psychological dependence, and physical dependence may occur especially followingprolonged use of high doses of barbiturates. The average daily dose for the barbiturateaddict is usually about 1500 mg. As tolerance to barbiturates develops, the amount needed tomaintain the same level of intoxication increases; tolerance to a fatal dosage, however, does notincrease more than two-fold. As this occurs, the margin between an intoxication dosage and fataldosage 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 to5 days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declinesover a period of approximately 15 days. Treatment of barbiturate dependence consists of cautiousand 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'sregular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

DOSAGE & ADMINISTRATION SECTION.


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 physicaldependence.

SPL UNCLASSIFIED SECTION.


BUTALBITAL , ACETAMINOPHEN, AND CAFFEINE CAPSULES, USP Rx Only

HOW SUPPLIED SECTION.


HOW SUPPLIED: Butalbital50 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 25C (68 to 77F)[See USP Controlled Room Temperature]. Protect from light and moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Manufactured By: West-Ward Pharmaceutical Corp. Eatontown, NJ 07724 Revised November 2013

DESCRIPTION SECTION.


DESCRIPTION: Butalbital, Acetaminophen, and Caffeine is supplied in capsule form for oral administration. Each capsule contains: Butalbital, USP..50 mg Acetaminophen, USP500 mg Caffeine, USP40 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:

OVERDOSAGE SECTION.


OVERDOSAGE: 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 tothe 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 seriousadverse effect. Renal tubular necroses, hypoglycemic coma and thrombocytopenia may alsooccur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting,diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may notbe apparent until 48 to 72 hours post-ingestion. In adults hepatic toxicity has rarely been reportedwith 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 andextrasystoles. 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 drugabsorption. 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 gastricemptying. The first dose should be accompanied by an appropriate cathartic. If repeateddoses are used, the cathartic might be included with alternate doses as required. Hypotension isusually hypovolemic and should respond to fluids. Pressors should be avoided. A cuffed endotrachealtube 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 eliminationof 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 casesof intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemiaoccurs 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 ormore hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophenassay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeatedat 24-hour intervals. Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration. 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)

PRECAUTIONS SECTION.


PRECAUTIONS: General: 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 renalor 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. Suchtasks 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. Do not take Butalbital, Acetaminophen and Caffeine Capsules if you are allergic to any of its ingredients. 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. 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 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 conductedin 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, acetaminophenand caffeine can cause fetal harm when administered to a pregnant woman or can affectreproduction 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. Butalbitalwas found in the infant's serum. The infant was given phenobarbital 5 mg/kg, which was taperedwithout further seizure or other withdrawal symptoms. Nursing Mothers: 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 potentialfor serious adverse reactions in nursing infants from butalbital, acetaminophen and caffeine, adecision should be made whether to discontinue nursing or to discontinue the drug, taking intoaccount 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 butalbital, acetaminophen and caffeine capsules did not includesufficient numbers of subjects aged 65 and over to determine whether they respond differentlyfrom younger subjects. Other reported clinical experience has not identified differences inresponses between the elderly and younger patients. In general, dose selection for an elderlypatient should be cautious, usually starting at the low end of the dosing range, reflecting thegreater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease orother drug therapy. Butalbital is known to be substantially excreted by the kidney, and the risk of toxic reactions to thisdrug may be greater in patients with impaired renal function. Because elderly patients are morelikely to have decreased renal function, care should be taken in dose selection, and it may be usefulto monitor renal function.

CLINICAL PHARMACOLOGY SECTION.


CLINICAL PHARMACOLOGY: This combination drug product is intended as a treatment for tensionheadache. It consists of a fixed combination of butalbital, acetaminophen, and caffeine. The role each componentplays in the relief of the complex of symptoms known as tension headache is incompletelyunderstood. Pharmacokinetics: The behavior of the individual components is described below. Butalbital: Butalbital is well absorbed from the gastrointestinal tract and is expected to distribute tomost tissues in the body. Barbiturates in general may appear in breast milk and readily cross theplacental barrier. They are bound to plasma and tissue proteins to a varying degree and bindingincreases directly as a function of lipid solubility. Elimination of butalbital is primarily via the kidney (59% to 88% of the dose) as unchanged drugor metabolites. The plasma half-life is about 35 hours. Urinary excretion products include parentdrug (about 3.6% of the dose), 5-isobutyl-5-(2,3-dihydroxypropyl) barbituric acid (about 24% ofthe dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl) barbituric acid (about 4.8% of the dose), productswith 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 to20 mcg/mL. This falls within the range of plasma protein binding (20% to 45%) reported withother barbiturates such as phenobarbital, pentobarbital, and secobarbital sodium. The plasma-to-blood concentration ratio was almost unity indicating that there is no preferential distribution ofbutalbital into either plasma or blood cells. (See OVERDOSAGE for toxicity information.) Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributedthroughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may beincreased by liver damage and following overdosage. Elimination of acetaminophen is principally byliver metabolism (conjugation) and subsequent renal excretion of metabolites. Approximately85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronideconjugate, 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 andfluids, including the CNS, fetal tissues, and breast milk. Caffeine is cleared through metabolism and excretion in the urine. The plasma half-life is about 3hours. Hepatic biotransformation prior to excretion, results in about equal amounts of 1-methylxanthineand 1-methyluric acid. Of the 70% of the dose that is recovered in the urine, only 3% isunchanged drug. (See OVERDOSAGE for toxicity information.)

CONTRAINDICATIONS SECTION.


CONTRAINDICATIONS: This product is contraindicated under the following conditions: * Hypersensitivity or intolerance to any component of this product. * Patients with porphyria.

WARNINGS SECTION.


WARNINGS: Butalbital is habit-forming and potentially abusable. Consequently, the extended use of this product is not recommended. Hepatotoxicity 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. Serious skin reactions Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematouspustulosis (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 hypersensitivity. Hypersensitivity/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 Capsulesimmediately and seek medical care if they experience these symptoms. Do not prescribe Butalbital, Acetaminophen and Caffeine Capsules for patients with acetaminophen allergy.