Dosing & Uses
Dosage Forms & Strengths
tablet: Schedule IV
- 3.75mg
- 7.5mg
- 15mg
Anxiety
30 mg/day PO in divided doses; adjust dose gradually within range of 15-60 mg/day
When administered as single daily HS dose, initial dosage is 15 mg; after initial dose, response of patient may require subsequent dosage adjustment
Seizure
7.5 mg PO q8hr; increase by < 7.5 mg/week; 90 mg/day maximum
Acute Alcohol Withdrawal
Day 1: Initial 30 mg PO once, THEN 30-60 mg in divided doses, no more than 90 mg
Day 2: 45-90 mg PO in divided doses
Day 3: 22.5-45 mg PO in divided doses
Day 4: 15-30 mg PO in divided doses
Day 5 onwards: 7.5-15 mg PO in divided doses
Discontinue when stable
Dosage Forms & Strengths
tablet: Schedule IV
- 3.75mg
- 7.5mg
- 15mg
Partial Seizures
<9 years: Not recommended
9-12 years: 7.5 mg PO BID initially; increase by <7.5 mg qWeek to 60 mg/day maximum
>12 years: As in adults
Not drug of choice in elderly because of long-acting metabolite; long-acting benzodiazepines associated with falls in elderly
Anxiety
7.5 mg PO qDay or q12hr
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
Frequency Not Defined
Drowsiness
Dizziness
Nervousness
Headache
Confusion
GI complaints
Dry mouth
Blurred vision
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
Narrow-angle glaucoma
Caution
Benzodiazepines expose users to risks of abuse, misuse, and addiction, which can lead to overdose or death; abuse and misuse of benzodiazepines often (but not always) involve use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death
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
Therapy not recommended for use in depressive neuroses or psychotic reactions
Patients receiving therapy should be cautioned against engaging in hazardous occupations requiring mental alertness, including heavy machinery
Therapy has central nervous system (CNS) effect; avoid simultaneous use of other CNS depressant drug; effects of alcohol may be increased
For patients treated more frequently than recommended, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose), to reduce risk of withdrawal reactions
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
Patients taking drug for prolonged periods should have blood counts and liver function tests done periodically; the usual precautions in treating patients with impaired renal or hepatic function should also be observed
In elderly or debilitated patients, initial dose should be small, and increments should be made gradually, in accordance with response of patient, to preclude ataxia or excessive sedation
Suicidal behavior and ideation
- Antiepileptic drugs (AEDs), increase risk of suicidal thoughts or behavior in patients taking drugs for any indication
- Monitor patients treated with any AED for any indication for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
- Increased risk of suicidal thoughts or behavior with AEDs reported as early as one week after starting drug treatment with AEDs; epilepsy and many other illnesses for which AEDs are prescribed are associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior
- Should suicidal thoughts and behavior emerge during treatment, prescriber needs to consider whether emergence of these symptoms in any given patient may be related to illness being treated
Pregnancy & Lactation
Pregnancy Category: Not available. An increased risk of congenital malformations associated with the use of minor tranquilizers during the first trimester of pregnancy has been suggested in several studies. Pregnant patients taking clorazepate should enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. More information can be found at http://www.aedpregnancyregistry.org
Lactation: enters breast milk; do not nurse
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
Enhances the inhibitory effect of GABA on neuronal excitability by increasing neuronal membrane permeability to chloride ions
Pharmacokinetics
Half-Life: 50-70 hr
Time to peak: ~ 1 hr
Protein Bound: 97-98%
Metabolism: Hydroxylation, glucuronic acid conjugation
Metabolites: Desmethyldiazepam (nordiazepam), oxazepam
Excretion: Urine
Onset of action: 1-2 hr
Duration: Variable 8-24 hr
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Patient Handout
Formulary
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Adding plans allows you to:
- View the formulary and any restrictions for each plan.
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