Chlordiazepoxide and Amitriptyline (Chlordiazepoxide / Amitriptyline Hydrochloride) - Description and Clinical Pharmacology

CIV

5 mg/12.5 mg and 10 mg/25 mg

Rx only

DESCRIPTION

Chlordiazepoxide and Amitriptyline Hydrochloride Tablets, USP combine for oral administration, chlordiazepoxide, an agent for the relief of anxiety and tension, and amitriptyline, an antidepressant.

Chlordiazepoxide, USP is a benzodiazepine with the formula 7-chloro-2-(methylamino)-5-phenyl-3 H -1,4-benzodiazepine-4-oxide. It is a slightly yellow crystalline material and is insoluble in water. The molecular weight is 299.76. Its structural formula is:

Amitriptyline, USP is a dibenzocycloheptadiene derivative. The formula is 10,11-dihydro- N,N -dimethyl-5 H -dibenzo[a,d]cycloheptene-Δ⁵,γ-propylamine hydrochloride. It is a white or practically white crystalline compound that is freely soluble in water. The molecular weight is 313.87. Its structural formula is:

Each tablet for oral administration contains:

5 mg of chlordiazepoxide, and 12.5 mg of amitriptyline (as the hydrochloride salt)

or

10 mg of chlordiazepoxide and 25 mg of amitriptyline (as the hydrochloride salt) and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch, sodium lauryl sulfate, and titanium dioxide.

In addition, the 5 mg/12.5 mg product contains D&C Yellow No. 10 aluminum lake, FD&C Blue No. 1 aluminum lake and FD&C Yellow No. 6 aluminum lake and the 10 mg/25 mg product contains calcium sulfate and talc.

CLINICAL PHARMACOLOGY

Both components of Chlordiazepoxide and Amitriptyline Hydrochloride Tablets, USP exert their action in the central nervous system. Extensive studies with chlordiazepoxide in many animal species suggest action in the limbic system. Recent evidence indicates that the limbic system is involved in emotional response. Taming action was observed in some species. The mechanism of action of amitriptyline in man is not known, but the drug appears to interfere with the reuptake of norepinephrine into adrenergic nerve endings. This action may prolong the sympathetic activity of biogenic amines.