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) 1-11. An oral film formulation of clobazam (Sympazan®) is FDA approved for adjunctive seizure management in Lennox-Gastaut syndrome 1,2,12. A diazepam nasal formulation (Valtoco®) is FDA-approved to treat intermittent frequent seizure episodes that differ from a patient’s usual seizure pattern 1,2,13. 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 epilepsy 1,2,14. In November 2021, the FDA approved a once daily extended release formulation of lorazepam (Loreev XR®) that is approved for the treatment of anxiety disorders in adults who are already receiving three times daily dosing of lorazepam 1,2,15.
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 enterocolitis 1,2,16. Tables 1 1-15 and 2 1,2,16,17summarize the adult maximum recommended dosages for non-sedative/hypnotic benzodiazepines as monotherapy and combination therapy.
Table 1. Adult Benzodiazepine Maximum Recommended Daily Dosages: Monotherapy
| 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 | 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 (Tranxene®, Tranxene T-Tab®, 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) (Diastat®, Diastat AcuDial®, 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
Table 2. Adult Benzodiazepine Maximum Recommended Dosages: Combination Therapy
| Drug Name | Dosage Form/Strength | Treatment Indication | Maximum Recommended Dosage |
|---|---|---|---|
| chlordiazepoxide/ amitriptyline (Limbitrol®, 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) |