Antitussive Hydrocodone and Homatropine Methylbromide (Hydrocodone Bitartrate / Homatropine Methylbromide) - Description and Clinical Pharmacology

DESCRIPTION

Hydrocodone bitartrate and homatropine methylbromide tablets contains hydrocodone (dihydrocodeinone) bitartrate, a semisynthetic centrally-acting narcotic antitussive. Homatropine methylbromide is included in a subtherapeutic amount to discourage deliberate overdosage.

Each hydrocodone bitartrate and homatropine methylbromide tablet for oral administration contains:

Hydrocodone bitartrate, USP        5 mg

Homatropine methylbromide, USP 1.5 mg

Hydrocodone bitartrate and Homatropine methylbromide tablets also contain: citric acid, colloidal silicon dioxide, lactose anhydrous, magnesium stearate, microcrystalline cellulose, starch pregelatinized, and stearic acid.

The hydrocodone component is 4,5 α-Epoxy-3-methoxy-17-methylmorphinone-6-one tartrate (1:1) hydrate (2:5), a fine white crystal or crystalline powder, which is derived from the opium alkaloid. thebaine, has a molecular weight of (494.50), and may be represented by the following structural formula:

C₁₈H₂₁NO₃·C₄H₆O₆ · 2 1/2H₂O

HYDROCODONE BITARTRATE

Homatropine methylbromide is 8-Azoniabicyclo [3.2.1]octane, 3[(hydroxyphenylacetyl)oxy]-8,8-dimethyl-,bromide, endo-; a white crystal or fine white crystalline powder, with a molecular weight of (370.29) and the following structural formula:

C₁₇H₂₄BrNO₃

HOMATROPINE METHYLBROMIDE

CLINICAL PHARMACOLOGY

Hydrocodone is a semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone, like other opium derivatives, will depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system are insignificant. Hydrocodone can produce miosis, euphoria, physical and physiological dependence.

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.

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.