Zgesic

The analgesic action of acetaminophen involves peripheral influences, but the specific mechanism is as yet undetermined. Antipyretic activity is mediated through hypothalamic heat regulating centers. Acetaminophen inhibits prostaglandin synthetase. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing. Acetaminophen blocks the chemical cyclic AMP, a byproduct of prostaglandins, which cause the nerve endings to be more sensitive to pain impulses. Phenyltoloxamine Citrate is an ethanolamine type antihistamine that acts as an adjuvant analgesic, which augments the analgesic effect of acetaminophen. It has been suggested that analgesic effects of antihistamines are related to the modulation of histaminergic and serotonergic pathways. More specific mechanisms that have been postulated include interactions with one or more pain mediators such as substance P, bradykinins, prostaglandins and cyclic nucleotides. Pharmacokinetics: The behavior of the individual components is described below. 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.

Phenyltoloxamine Citrate is well absorbed following oral administration. It is metabolized in the liver and excreted in the urine predominately, as its metabolites.

This product should not be administered to patients who have previously exhibited hypersensitivity to acetaminophen or phenyltoloxamine citrate.

Do not take this product for pain more than 10 days (adults) or 5 days (children) unless directed by a physician, and do not take for fever for more than 3 days unless directed by a physician. If pain or fever persists, if new symptoms occur, or if redness or swelling is present, consult a physician immediately because these could be signs of a serious condition. Do not give this product to children under 12 years of age for the pain of arthritis unless directed by a physician. Caution should be exercised when used in patients with prostatic hypertrophy, urinary retention, bladder neck obstruction, increased ocular pressure, and asthma.

Information for Patients

Patient consultation should include the following information regarding the proper use of this product:

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 & OR LABORATORY TEST INTERACTIONS

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid. The sedative effects of phenyltoloxamine citrate are additive to the CNS depressant effects of alcohol, hypnotics, sedatives and tranquilizers.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No adequate studies have been conducted in animals to determine whether phenyltoloxamine citrate or acetaminophen have a potential for carcinogenesis, mutagenesis, or impairment of fertility.

Pregnancy

Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Zgesic Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Acetaminophen is excreted in breast milk in small amounts, but the significance of its effects on nursing infants is not known. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from phenyltoloxamine citrate and acetaminophen, a 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 children under 6 years of age have not been established.

Geriatric Use

Use with caution; antihistamines may cause dizziness, sedation, confusional states and hypotension in the elderly.

Drug Interactions

Monoamine oxidase inhibitors (MAOIs) may prolong and intensify the sedative and

anticholinergic effect of antihistamines; additive CNS effects may occur with concomitant use of alcohol and CNS depressants. Hepatotoxicity has occurred in chronic alcoholics following moderate to excessive doses of acetaminophen.

Zgesic Tablets are supplied as white, capsule-shaped tablets debossed “Zgesic” on one side, the opposite side is plain. Available in bottles of 90 tablets, NDC 64543- 400-90.

KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, CALL A DOCTOR OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Storage and Handling

Dispense in tight, light-resistant containers as defined in the USP/NF, with child resistant closures.

Store at controlled room temperature between 20°- 25°C (68°- 77°F); see USP Controlled Room Temperature. Avoid exposure to heat.

Manufactured for:

Capellon Pharmaceuticals, LLC
Fort Worth, TX  76118

Rev. 06/2010   500367

Figure 3: Container Label