1.1. Adults
Non-sedative/hypnotic benzodiazepines and benzodiazepines with mixed indications are FDA-approved for use in the outpatient setting to manage anxiety (alprazolam, chlordiazepoxide, clorazepate, oral diazepam, lorazepam, oxazepam), panic disorder (alprazolam, clonazepam), acute musculoskeletal (MS) conditions including spasticity (oral diazepam), seizures [clobazam (Lennox-Gastaut syndrome), clonazepam, clorazepate, nasal, oral and rectal diazepam], and acute alcohol withdrawal (chlordiazepoxide, clorazepate, oral diazepam, oxazepam)1-14. An oral film formulation of clobazam (Sympazan) is FDA approved for adjunctive seizure management in Lennox-Gastaut syndrome1,2,15. A diazepam nasal formulation (Valtoco) is FDA-approved to treat intermittent frequent seizure episodes that differ from a patient’s usual seizure pattern1,2,16. Nayzilam is a nasal spray formulation of midazolam that is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity that are distinct from a patient’s usual seizure pattern in patients with epilepsy1,2,17. Loreev XR is a once daily extended release formulation of lorazepam that is FDA approved for the treatment of anxiety disorders in adults who are already receiving three times daily dosing of lorazepam1,2,18.
The chlordiazepoxide-amitriptyline combination is indicated for depression with associated anxiety symptoms, while chlordiazepoxide/clidinium is FDA-approved to control emotional and somatic factors in gastrointestinal disorders as well as adjunctive use in peptic ulcer disease, irritable bowel syndrome, and acute enterocolitis1,2,19,20. Tables 1 and 2 summarize the adult maximum recommended dosages for non-sedative/hypnotic benzodiazepines as monotherapy and combination therapy.
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage* |
|---|---|---|---|
| alprazolam (Xanax, generics) | 0.25 mg, 0.5 mg, 1 mg, 2 mg tablets, disintegrating tablets; 1 mg/ml oral solution | anxiety | Less than or equal to and greater than 65 years: 4 mg daily, in divided doses |
| alprazolam (Xanax, Xanax XR, generics) | 0.25 mg, 0.5 mg, 1 mg, 2 mg tablets, disintegrating tablets; 0.5 mg, 1 mg, 2 mg, 3 mg extended-release tablets; 1 mg/ml oral solution | panic | Less than or equal to and greater than 65 years: 10 mg daily, in divided doses for immediate release formulations |
| chlordiazepoxide (generics) | 5 mg, 10 mg, 25 mg capsule | alcohol withdrawal (AW) | Less than or equal to and greater than 65 years: 300 mg daily, in divided doses |
| anxiety | Less than 65 years: mild, moderate: 40 mg daily, in divided doses severe: 100 mg daily, in divided doses Greater than 65 years: 20 mg daily, in divided doses | ||
| clobazam (Onfi, Sympazan, generics) | 10 mg, 20 mg tablets; 2.5 mg/mL suspension; 5 mg, 10 mg, 20 mg oral soluble film | seizures associated with Lennox-Gastaut syndrome | Less than 65 years: Greater than 65 years: |
| clonazepam (Klonopin, generics) | 0.5 mg, 1 mg, 2 mg tablets; 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 2 mg disintegrating tablets | panic disorder | Less than or equal to and greater than 65 years: 4 mg daily |
| seizures | Less than or equal to and greater than 65 years: 20 mg daily | ||
| clorazepate (generics) | 3.75 mg, 7.5 mg, 15 mg tablets | AW | Less than or equal to and greater than 65 years: 90 mg daily |
| anxiety | Less than or equal to and greater than 65 years: 60 mg daily | ||
| seizures | Less than or equal to and greater than 65 years: 90 mg daily | ||
| diazepam (nasal) (Valtoco) | 5 mg as one 5 mg device, 10 mg as one 10 mg device, 15 mg as 2 x 7.5 mg devices, 20 mg as 2 x 10 mg devices nasal liquid | seizures | 28-50 kg: 10 mg as one spray in one nostril (equates to 0.2 mg/kg dose)^ 51-75 kg: 15 mg as 2 x 7.5 mg devices with one spray in each nostril (equates to 0.2 mg/kg dose)^ Greater than or equal to 76 kg^: 20 mg as 2 x 10 mg devices with one spray in each nostril (equates to 0.2 mg/kg dose)^ |
| diazepam (oral) (Valium, Diazepam Intensol, generics) | 2 mg, 5 mg, 10 mg oral tablets; 5 mg/mL, 5 mg/5 mL oral solution | AW | Less than or equal to and greater than 65 years: 40 mg daily |
| anxiety | Less than or equal to and greater than 65 years: 40 mg daily | ||
| musculoskeletal conditions | Less than or equal to and greater than 65 years: 40 mg daily | ||
| seizures | Less than or equal to and greater than 65 years: 40 mg daily | ||
| diazepam (rectal) (generics) | 2.5 mg, 10 mg, 20 mg rectal gel | seizures | Less than or equal to and greater than 65 years: 0.2 mg/kg; may be repeated once 4-12 hours after initial dose+ |
| lorazepam (Ativan, Loreev XR, generics) | 0.5 mg, 1 mg, 2 mg tablets; 1 mg, 1.5 mg, 2 mg, 3 mg extended-release capsules; 2 mg/mL solution | anxiety | Less than or equal to and greater than 65 years: 10 mg daily, in divided doses |
| lorazepam (Ativan, generics) | insomnia due to anxiety or transient situational stress | Less than or equal to and greater than 65 years: 4 mg at bedtime | |
| Midazolam (nasal) (Nayzilam) | 5 mg nasal spray | seizures | Less than or equal to and greater than 65 years: 5 mg as one spray in one nostril! |
| oxazepam (generics) | 10 mg, 15 mg, 30 mg capsule | AW | Less than or equal to 65 years: 120 mg daily in divided doses Greater than 65 years: 60 mg daily in divided doses# |
| oxazepam | anxiety | Less than or equal to 65 years: mild, moderate: 60 mg daily in divided doses severe: 120 mg daily in divided doses Greater than 65 years: 60 mg daily in divided doses |
Legend:
- * Benzodiazepine doses should be reduced to lowest effective dose, if possible, in the elderly (patients greater than 65 years of age), to minimize oversedation; these patients are more sensitive to pharmacologic effects of these agents
- ^May give second diazepam nasal dose at least 4 hours after first dose, if necessary; may not use more than 2 doses to treat single episode; may not treat more than 1 episode/5 days or more than 5 episodes/month
- + Dose rounded up to nearest commercially available unit dose (in multiples of 2.5 mg); should not be administered by caregivers outside the hospital more frequently than one course every 5 days with a maximum of 5 courses per month; not for chronic administration to minimize potential for development of tolerance
- ! May give second midazolam nasal dose 10 minutes after first dose, if necessary; may not use more than 2 doses to treat a single episode. Nasal midazolam should be used to treat no more than one episode every three days and no more than 5 episodes per month
- # In elderly patients, doses up to 120 mg/day may be needed to treat AW
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
|---|---|---|---|
| chlordiazepoxide/ amitriptyline ( generics) | 5 mg/12.5 mg tablets 10 mg/25 mg double-strength tablets | depression with concurrent anxiety symptoms | 60 mg chlordiazepoxide/ 150 mg amitriptyline daily in divided doses |
| chlordiazepoxide/ clidinium (Librax, generics) | 5 mg/ 2.5 mg capsule | emotional/ somatic factors in gastro-intestinal disorders; adjunctive therapy in peptic ulcer disease, irritable bowel syndrome, and acute enterocolitis | 40 mg/20 mg per day (2 capsules 4 times daily) |