Dalmane is available as capsules containing 15 mg or 30 mg flurazepam hydrochloride. Each 15-mg capsule also contains cornstarch, lactose, magnesium stearate and talc; gelatin capsule shells contain the following dye systems: D&C Red No. 28, FD&C Red No. 40, FD&C Yellow No. 6 and D&C Yellow No. 10. Each 30-mg capsule also contains cornstarch, lactose and magnesium stearate; gelatin capsule shells contain the following dye systems: FD&C Blue No. 1, FD&C Yellow No. 6, D&C Yellow No. 10 and either FD&C Red No. 3 or FD&C Red No. 40.
Flurazepam hydrochloride is chemically 7-chloro-1-[2-(diethylamino)ethyl]-5-(o -fluorophenyl)-1,3-dihydro-2 H -1,4-benzodiazepin-2-one dihydrochloride. It is a pale yellow, crystalline compound, freely soluble in USP alcohol and very soluble in water. It has a molecular weight of 460.826 and the following structural formula:
Flurazepam hydrochloride is rapidly absorbed from the GI tract. Flurazepam is rapidly metabolized and is excreted primarily in the urine. Following a single oral dose, peak flurazepam plasma concentrations ranging from 0.5 to 4.0 ng/mL occur at 30 to 60 minutes post-dosing. The harmonic mean apparent half-life of flurazepam is 2.3 hours. The blood level profile of flurazepam and its major metabolites was determined in man following the oral administration of 30 mg daily for 2 weeks. The N1-hydroxyethyl-flurazepam was measurable only during the early hours after a 30-mg dose and was not detectable after 24 hours. The major metabolite in blood was N1-desalkyl-flurazepam, which reached steady-state (plateau) levels after 7 to 10 days of dosing, at levels approximately 5- to 6-fold greater than the 24-hour levels observed on Day 1. The half-life of elimination of N1-desalkyl-flurazepam ranged from 47 to 100 hours. The major urinary metabolite is conjugated N1-hydroxyethyl-flurazepam which accounts for 22% to 55% of the dose. Less than 1% of the dose is excreted in the urine as N1-desalkyl-flurazepam.
This pharmacokinetic profile may be responsible for the clinical observation that flurazepam is increasingly effective on the second or third night of consecutive use and that for 1 or 2 nights after the drug is discontinued both sleep latency and total wake time may still be decreased.
Geriatric Pharmacokinetics: The single dose pharmacokinetics of flurazepam were studied in 12 healthy geriatric subjects (aged 61 to 85 years). The mean elimination half-life of desalkyl-flurazepam was longer in elderly male subjects (160 hours) compared with younger male subjects (74 hours), while mean elimination half-life was similar in geriatric female subjects (120 hours) and younger female subjects (90 hours). After multiple dosing, mean steady-state plasma levels of desalkyl-flurazepam were higher in elderly male subjects (81 ng/mL) compared with younger male subjects (53 ng/mL), while values were similar between elderly female subjects (85 ng/mL) and younger female subjects (86 ng/mL). The mean washout half-life of desalkyl-flurazepam was longer in elderly male and female subjects (126 and 158 hours, respectively) compared with younger male and female subjects (111 and 113 hours, respectively). 1