Butalbital, Acetaminophen and Caffeine (Butalbital / Acetaminophen / Caffeine) - Description and Clinical Pharmacology

Rx Only

Code 886A00          Rev. 01/03

DESCRIPTION

Butalbital, Acetaminophen and Caffeine Tablets, USP is supplied in tablet form for oral administration.

Butalbital (5‑allyl‑5‑isobutylbarbituric acid), a slightly bitter, white, odorless, crystalline powder, is a short to intermediate‑acting barbiturate. It has the following structural formula:

C₁₁H₁₆N₂O₃                                                                                                                   MW = 224.26

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:

C₈H₉NO₂                                                                                                                     MW = 151.16

Caffeine (1,3,7‑trimethylxanthine), a bitter, white powder or white‑glistening needles, is a central nervous system stimulant. It has the following structural formula:

C₈H₁₀N₄O₂                                                                                                                MW = 194.19

Each Butalbital, Acetaminophen and Caffeine Tablet, USP contains:

Butalbital......…....................................50 mg

Warning: May be habit-forming.

Acetaminophen ………………………750 mg

Caffeine ………………………………40 mg

In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, microcrystalline cellulose, povidone, pregelatinized corn starch and stearic acid. Film coating composed of: carnauba wax, hypromellose, polyethylene glycol, titanium dioxide, D&C Red No. 27 aluminum lake, FD&C Blue No. 1 aluminum lake, D&C Red No. 30 aluminum lake.

CLINICAL PHARMACOLOGY

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.

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 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 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.)