DESCRIPTION
ZYDONE (hydrocodone bitartrate and acetaminophen tablets), for oral administration, contain hydrocodone bitartrate and acetaminophen in the following strengths:
| Hydrocodone Bitartrate, USP |
5 mg |
| Acetaminophen, USP |
400 mg |
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| Hydrocodone Bitartrate, USP |
7.5 mg |
| Acetaminophen, USP |
400 mg |
| Hydrocodone Bitartrate, USP |
10 mg |
| Acetaminophen, USP |
400 mg |
In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid. The 5 mg/400 mg strength contains FD&C Yellow No. 10; 7.5 mg/400 mg contains FD&C Blue No. 2; and 10 mg/400 mg contains FD&C Red No. 40.
ZYDONE Tablets meet USP Dissolution Test 1.
Hydrocodone bitartrate is an opioid analgesic and antitussive and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4,5α-Epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula:
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:
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CLINICAL PHARMACOLOGY
Hydrocodone is a semisynthetic opioid analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. In addition to analgesia, opioids may produce drowsiness, changes in mood and mental clouding.
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.
Pharmacokinetics
The behavior of the individual components is described below.
Hydrocodone
Following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 ± 5.2 ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours and the half-life was determined to be 3.8 ± 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-β-hydroxymetabolites.
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.
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