Prescribing
FDA Schedule IVForms: 15, 30mg capsule
Dose Range: 15-60 mg/day
Starting: 15-30 mg qhs
Precautions
Contraindications: Acute narrow angle glaucoma, sleep apneaSerious Side Effects: "Sleep-Driving" and other complex behavior. Overdose can result in hypotension, respiratory depression, and coma
Side Effects: sedation/somnolence, dizziness, lightheadedness, ataxia, falls
Pharmacokinetics
t½: 2° TMAX: 0.5-1°Absorption Rate: Fast
Lipid Solubility: High
Substrate of: 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: Hydroxyethylflurazepam (t½ 2-4°) and desalkylflurazepam (t½ 40-250°)
DDIs
- - CNS depression with combined use of opioids
- - 3A4 inhibitors can ↑ levels; likewise, 3A4 inducers can ↓ levels
Misc
- - rapid sedative effects (w/in 15-20 min) d/t parent drug's rapid absorption from GI tract, with an intermediate metabolite (hydroxyethylflurazepam) to sustain sleep, & a long-acting metabolite (desalkylflurazepam) that minimizes early morning awakening
- - slow accumulate of desalkylflurazepam (t½ 40-250°) can cause morning-after cognitive impairment
- - the 1st benzodiazepine specifically marketed for insomnia—highly successful, especially competing against the major sedative-hypnotics of the 1970s i.e. glutethimide, ethchlorvynol, methaqualone
Special Populations
Category D—Limited reports describing the use of flurazepam in human pregnancy have been located. The effects of this drug on the fetus should be similar to other benzodiazepines, including the risk of malformations after exposure in the 1st trimester. Maternal use near delivery may cause a syndrome of hypothermia, hypotonia, respiratory depression, withdrawal, and difficulty feeding. The manufacturer classifies flurazepam as contraindicated in pregnancy.
Low incidence of infant toxicity and AEs associated with benzodiazepine use during breastfeeding. Benzodiazepines with shorter half-lives (i.e., lorazepam, alprazolam, and oxazepam) have been found to be very low in breast milk
In most elderly patients, the slow accumulate of the desalkyl metabolites causes a morning-after cognitive impairment
2019 BEE℞S Recommendation: Avoid. Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long- acting agents; in general, all benzodiazepines increase risk of cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults. May be appropriate for seizure disorders, RBD, benzodiazepine withdrawal, EtOH withdrawal, severe GAD, and periprocedural anesthesia.
Renal insufficiency has a quantitatively small influence on pharmacokinetics; no dosage adjustments provided in the manufacturer's labeling
T½ ↑ ≈ 73% in patients with alcohol liver disease