DRUG INTERACTIONS SECTION.

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.

GENERAL PRECAUTIONS SECTION.

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 renal or hepatic function, or acute abdominal conditions.

GERIATRIC USE SECTION.

Geriatric Use: 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 function.

HOW SUPPLIED SECTION.

HOW SUPPLIED: 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 capsulesStore at 20 to 25C (68 to 77F) [See USP Controlled Room Temperature]. Protect from light and moisture.Dispense in tight, light-resistant container as defined in the USP using child-resistant closure.Manufactured By:West-Ward Pharmaceutical Corp.Eatontown, NJ 07724Revised November 2013.

INDICATIONS & USAGE SECTION.

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.

LABORATORY TESTS SECTION.

Laboratory Tests: In patients with severe hepatic or renal disease, effects of therapy should be monitored with serial liver and/or renal function tests.

NONTERATOGENIC EFFECTS SECTION.

Nonteratogenic Effects: Withdrawal seizures were reported in two-day-old male infant whose mother had taken butalbital-containing drug during the last two months of pregnancy. Butalbital was found in the infants serum. The infant was given phenobarbital mg/kg, which was tapered without further seizure or other withdrawal symptoms.

NURSING MOTHERS SECTION.

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 potential for serious adverse reactions in nursing infants from butalbital, acetaminophen and caffeine, decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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 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 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 and extrasystoles.. Treatment: A single or multiple overdose with this combination product is potentially lethal polydrug overdose, and consultation with 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. 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 phenobarbital.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 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 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 intervals.Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.. Toxic Doses (for adults):. Butalbital: toxic dose g (20 capsules)Acetaminophen: toxic dose 10 (20 capsules)Caffeine: toxic dose g (25 capsules).

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL. NDC 0143-1115-01Butalbital, Acetaminophen, and Caffeine Tablets, USP50 mg/500 mg/40 mgRx Only100 Tablets. NDC 0143-1115-01Butalbital, Acetaminophen, and Caffeine Tablets, USP50 mg/500 mg/40 mgRx Only100 Tablets.

PEDIATRIC USE SECTION.

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

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS: Frequently Observed: The most frequently reported adverse reactions are drowsiness, lightheadedness, dizziness, sedation, shortness of breath, nausea, vomiting, abdominal pain, 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, exctextent or depression can also occur due to intolerance, particularly in elderly or debilitated patients, or due to overdosage of 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 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.

BOXED WARNING SECTION.

HepatotoxicityAcetaminophen 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.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No adequate studies have been conducted in animals to determine whether acetaminophen or butalbital have potential for carcinogenesis, mutagenesis or impairment of fertility.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY: This combination drug product is intended as treatment for tension headache.It consists of 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.. Pharmacokinetics: 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 varying degree and binding increases directly as 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 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 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.).

CONTRAINDICATIONS SECTION.

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

DESCRIPTION SECTION.

DESCRIPTION: Butalbital, Acetaminophen, and Caffeine is supplied in capsule form for oral administration. Each capsule contains: Butalbital, USP..........................50 mgAcetaminophen, USP..................500 mgCaffeine, USP........................ ...40 mgIn 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), white, odorless, crystalline powder having slightly bitter taste, is short to intermediate-acting barbiturate. It has the following structural formula: Acetaminophen (4-hydroxyacetanilide), slightly bitter, white, odorless, crystalline powder, is non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:Caffeine (1,3,7,-trimethylxanthine), bitter, white crystalline powder or white-glistening needles, is central nervous system stimulant. It has the following structural formula:. Structural formula for Butalbital.. The structural formula for Acetaminophen. The stuctural formula for Caffeine.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION: Oral: one capsule every four hours. Total daily dosage should not exceed capsules.Extended and repeated use of this product is not recommended because of the potential for physical dependence.

DRUG & OR LABORATORY TEST INTERACTIONS SECTION.

Drug/Laboratory Test Interactions: Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.

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 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 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 barbiturate is far less if alcohol is also ingested. Major withdrawal symptoms (convulsions and delirium) may occur within 16 hours and last up to days after abrupt cessation of these drugs. Intensity of withdrawal symptoms gradually declines over 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 number of different withdrawal regimens. One method involves initiating treatment at the patients regular dosage level and gradually decreasing the daily dosage as tolerated by the patient.

PHARMACOKINETICS SECTION.

Pharmacokinetics: 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 varying degree and binding increases directly as 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 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 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.).

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 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 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 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 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.. 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 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 conducted in animals to determine whether acetaminophen or butalbital have 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, acetaminophen and caffeine can cause fetal harm when administered to pregnant woman or can affect reproduction capacity. This product should be given to pregnant woman only when clearly needed.. Nonteratogenic Effects: Withdrawal seizures were reported in two-day-old male infant whose mother had taken butalbital-containing drug during the last two months of pregnancy. Butalbital was found in the infants serum. The infant was given phenobarbital mg/kg, which was tapered without 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 potential for serious adverse reactions in nursing infants from butalbital, acetaminophen and caffeine, 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 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 function.

PREGNANCY SECTION.

Pregnancy: 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 pregnant woman or can affect reproduction capacity. This product should be given to pregnant woman only when clearly needed.. Nonteratogenic Effects: Withdrawal seizures were reported in two-day-old male infant whose mother had taken butalbital-containing drug during the last two months of pregnancy. Butalbital was found in the infants serum. The infant was given phenobarbital mg/kg, which was tapered without further seizure or other withdrawal symptoms.

SPL UNCLASSIFIED SECTION.

BUTALBITAL, ACETAMINOPHEN, AND CAFFEINE CAPSULES, USPRx Only.

TERATOGENIC EFFECTS SECTION.

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 pregnant woman or can affect reproduction capacity. This product should be given to pregnant woman only when clearly needed.

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 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 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 Capsules immediately and seek medical care if they experience these symptoms. Do not prescribe Butalbital, Acetaminophen and Caffeine Capsules for patients with acetaminophen allergy.