Dosing & Uses
Dosage Forms & Strengths
capsule: Schedule IV
- 7.5mg
- 15mg
- 22.5mg
- 30mg
Insomnia
15-30 mg PO qHS
Debilitated patients: 7.5 mg PO qHS
Discontinuation: Gradually taper after extended therapy; abrupt discontinuation should be avoided
Safety and efficacy not established
Insomnia
7.5 mg PO qHS; limit use to 10-14 days
Preferred drug in elderly when benzodiazepine indicated because of lack of active metabolite
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
1-10%
Drowsiness (9.1%)
Dizziness (4.5%)
Lethargy (4.5%)
Hangover (2.5%)
Diarrhea (1.7%)
Euphoria (1.5%)
Weakness (1.4%)
Confusion (1.3%)
Vertigo (1.2%)
< 1%
Amnesia
Angioedema
Blood dyscrasias
Sleep-related behavior (eg, sleep driving, sleep cooking, sleep eating)
Ataxia
Warnings
Black Box Warnings
Risks from concomitant use with opioids
- Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death
- Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate
- Limit dosages and durations to the minimum required
- Follow patients for signs and symptoms of respiratory depression and sedation
- Inform patients and caregivers that potentially fatal additive effects may occur if drug is used with opioids and that such drugs should not be used concomitantly unless supervised by a health care provider
- Prescribers should advise caregivers that they expect to be informed immediately if a patient develops any new findings which are not typical of the patient’s characteristic seizure episode
Addiction, abuse, and misuse
- On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death
- Physical dependence can occur when taken steadily for several days to weeks, even as prescribed
- Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening
- Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction
- Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions
- Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk
Contraindications
Documented hypersensitivity
Acute alcohol intoxication
Narrow-angle glaucoma (questionable)
Caution
Use caution in COPD, sleep apnea, renal/hepatic disease, impaired gag reflex, open-angle glaucoma (questionable), alcoholism, respiratory disease, depression, suicidal ideation
May impair ability to perform hazardous tasks
Caution with IV use in shock, coma, and depressed respiration and in patients who recently received other respiratory depressants
Anterograde amnesia may occur
Use caution in patients with history of drug abuse or acute alcoholism; tolerance, psychological and physical dependence may occur with prolonged use
Use in myasthenia gravis is allowed in limited circumstances
Use caution in severe respiratory depression and depressed neuroses, psychotic reactions
Paradoxical hyperactive aggressive behavior reported
Therapy can cause drowsiness and a decreased level of consciousness; patients, particularly the elderly, are at higher risk of falls
May cause hyperactive or aggressive behavior
Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency
Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate
For patients using treated more frequently than recommended, to reduce risk of withdrawal reactions, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose)
Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use
In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months
Pregnancy & Lactation
Pregnancy Category: X
Lactation: Avoid if breastfeeding
Minor tranquilizers should be avoided in 1st trimester of pregnancy due to increased risk of congenital malformations
Maternal use shortly before delivery is associated with floppy infant syndrome (good and consistent evidence)
Prenatal benzodiazepine exposure slightly increased oral cleft risk (limited or inconsistent evidence)
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing membrane permeability to chloride ions, which in turn increases the inhibitory activity of GABA on neuronal excitability.
Absorption
Peak plasma time: 2-3 hr
Peak plasma concentration: 260-210 ng/mL
Distribution
Protein bound: 96%
Vd: 1.4 L/kg
Metabolism
Metabolized by CYP3A4 (minor), glucuronic acid conjugation
Metabolites: Inactive
Elimination
Half-life elimination: 9.5-12.4 hr
Excretion: Urine (80-90%)
Images
Patient Handout
Formulary
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