Butalbital, Acetaminophen And Caffeine - Butalbital, Acetaminophen And Caffeine tablet prescribing information
BOXED WARNING
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.
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.
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.
CONTRAINDICATIONS
This product is contraindicated under the following conditions:
–Hypersensitivity or intolerance to any component of this product
–Patients with porphyria.
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 OVERDOSAGE section.
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 INTERACTIONS
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.
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 11 H 16 N 2 O 3 M.W. = 224.26
Acetaminophen (4'-hydroxyacetanilide), is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula.
C 8 H 9 NO 2 M.W. = 151.16
Caffeine (1,3,7-trimethylxanthine), is a central nervous system stimulant. It has the following structural formula:
C 8 H 10 N 4 O 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 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 plasmato- 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.
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.
• Bottles of 100: NDC 70010-149-01
• Bottles of 500: NDC 70010-149-05
Store and Dispense
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.
Manufactured by:
Granules Pharmaceuticals Inc.,
Chantilly, VA 20151
Revised: 04/2022
LB0034-02
