DESCRIPTION

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:microcrystalline cellulose, sodium starch glycolate and magnesium stearate.

 Butalbital (5-allyl-5-isobutylbarbituric acid), is a short to intermediate-acting barbiturate. It has the following structural formula:                    

C 11H 16N 2O 3                       M.W. = 224.26

Acetaminophen (4'-hydroxyacetanilide), is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula.

C 8H 9NO 2                                                           M.W. = 151.16 

Caffeine (1,3,7-trimethylxanthine), is a central nervous system stimulant. It has the following structural formula:

C 8H 10N 4O 2        M.W. = 194.19 

CLINICAL PHARMACOLOGY

Butalbital, acetaminophen, and caffeine tablets 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.

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 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 vitroplasma 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 plasmato- blood concentration ratio was almost unity, indicating that there is no preferential distribution of butalbital into either plasma or blood cells.

 See OVERDOSAGEfor 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 OVERDOSAGEfor 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 OVERDOSAGEfor 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 butalbital, acetaminophen, and caffeine tablets in the treatment of multiple recurrent headaches is unavailable. Caution in this regard is required because butalbital is habit-forming and potentially abusable.

CONTRAINDICATIONS

This product is contraindicated under the following conditions:

–Hypersensitivity or intolerance to any component of this product

 –Patients with porphyria.

WARNINGS

Butalbital is habit-forming and potentially abusable. Consequently, the extended use of butalbital, acetaminophen, and caffeine tablets 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 Tablets immediately and seek medical care if they experience these symptoms. Do not prescribe Butalbital, Acetaminophen and Caffeine Tablets for patients with acetaminophen allergy.

PRECAUTIONS

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 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 butalbital.

Autonomic Nervous System: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 OVERDOSAGEsection.

Acetaminophen:allergic reactions, rash, thrombocytopenia, agranulocytosis.

Caffeine:cardiac stimulation, irritability, tremor, dependence, nephrotoxicity, hyperglycemia.

To report SUSPECTED ADVERSE REACTIONS, contact Granules Pharmaceuticals Inc., at 1-877-770-3183 or 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. Barbituratedependent 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.

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 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 extrasystoles.

Treatment

A single or multiple drug overdose with butalbital, acetaminophen, and caffeine tablets 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 oral administration.

 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 dependence.

HOW SUPPLIED

Butalbital, Acetaminophen and Caffeine Tablets USP, 50 mg/325 mg/40 mg

Each Butalbital, Acetaminophen, and Caffeine Tablet contains butalbital 50 mg, acetaminophen 325 mg and caffeine 40 mg. Tablets are White to off-white, round shaped tablets debossed with ‘G 149’ on one side and plain on other side.

NDC: 70518-3858-00

NDC: 70518-3858-01

PACKAGING: 30 in 1 BLISTER PACK

PACKAGING: 60 in 1 BOTTLE PLASTIC

Store at 20° to 25°C (68° to 77°F) with excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]; dispense in a tight, light-resistant container as defined in the USP.

Repackaged and Distributed By:

Remedy Repack, Inc.

625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

DRUG: Butalbital, Acetaminophen and Caffeine

GENERIC: Butalbital, Acetaminophen and Caffeine

DOSAGE: TABLET

ADMINSTRATION: ORAL

NDC: 70518-3858-0

NDC: 70518-3858-1

COLOR: white

SHAPE: ROUND

SCORE: No score

SIZE: 11 mm

IMPRINT: G;149

PACKAGING: 30 in 1 BLISTER PACK

PACKAGING: 60 in 1 BOTTLE PLASTIC

ACTIVE INGREDIENT(S):

• CAFFEINE 40mg in 1
• BUTALBITAL 50mg in 1
• ACETAMINOPHEN 325mg in 1

INACTIVE INGREDIENT(S):

• SODIUM STARCH GLYCOLATE TYPE A POTATO
• MAGNESIUM STEARATE
• CELLULOSE, MICROCRYSTALLINE