Benzodiazepines (Oral, Nasal, Rectal)

Last Updated

Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.

Refer to the Sedative/Hypnotics criteria for sedative and hypnotic benzodiazepines.

  • Revision history
    • April 22, 2022; March 2020; March 2018; May 2017; Dec. 2014; March 2013; June 2011; Jan. 2009; April 2003; Dec. 2001; Dec. 2000; Dec. 1999; Nov. 1998; Nov. 1997; Dec. 1996.
  • Initially developed
    • Oct. 1993

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: 
weight greater than 30 kg:
40 mg/day in two divided doses weight less than or equal to 30 kg 20 mg/day in two divided doses

Greater than 65 years:
weight greater than 30 kg: 
40 mg/day in two divided doses weight less than or equal to  30 kg 20 mg/day in two divided doses 
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)

1.2. Pediatrics

Safety and effectiveness of alprazolam and combination therapies, chlordiazepoxide/amitriptyline and chlordiazepoxide/clidinium, in children less than 18 years of age have not been established.1-3,16,17 Additionally, safety and effectiveness of Loreev XR® (lorazepam) has not been established in pediatric patients, and the safety and effectiveness of Nayzilam® (midazolam) has not been established in pediatric patients less than 12 years of age .1,2,14,15.

The oral tablet and oral film formulations of clobazam are approved for use in children 2 years of age and older to manage seizures associated with Lennox-Gastaut syndrome.1,2,11,12 The diazepam nasal formulation (Valtoco®) is FDA-approved for use in patients 6 years and older to treat intermittent frequent seizure episodes that differ from a patient’s usual seizure pattern .1,2,13.

Except for alprazolam, non-sedative/hypnotic benzodiazepines are indicated for use in pediatric patients to manage anxiety or seizures.1-15 Pediatric dosages and age limitations for benzodiazepines are summarized in Table 3 1,2,4-14.

Table 3. Pediatric Benzodiazepine Maximum Recommended Dosages

Drug Name Treatment Indication Maximum Recommended Dosage
chlordiazepoxide anxiety Greater than or equal to  6 years: 30 mg daily in divided doses
clobazam seizures associated with Lennox-Gastaut syndrome
  • 2 years and older, adolescents less than or equal to 30 kg:
    • 20 mg/day in two divided doses
  • 2 years and older, adolescents greater than 30 kg:
    • 40 mg/day in two divided doses
clonazepam seizures
  • Less than 10 years or less than or equal to 30 kg:
    • 0.2 mg/kg daily in divided doses
  • Greater than or equal to 10 years or greater than  30 kg:
    • 20 mg daily in divided doses
clorazepate seizures
  • 9-12 years: 60 mg daily in divided doses
  • Greater than 12 years: 90 mg daily in divided doses
diazepam (nasal) seizures
  • 6-11 years of age:
    • 10-18 kg: 5 mg as one spray in one nostril (equates to 0.3 mg/kg dose)^
    • 19-37 kg: 10 mg as one spray in one nostril (equates to 0.3 mg/kg dose)^
    • 38-55 kg: 15 mg as 2 x 7.5 mg devices with one spray in each nostril (equates to 0.3 mg/kg dose) ^
    • 56-74 kg: 20 mg as 2 x 10 mg devices with one spray in each nostril (equates to 0.3 mg/kg dose) ^
  • Greater than or equal to 12 years of age:
    • 14-27 kg: 5 mg as one spray in one nostril (equates to 0.2 mg/kg dose)^
    • 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) musculoskeletal conditions Greater than or equal to 6 months of age: 10 mg/day in divided doses have been used; dose may be increased as needed and tolerated – no maximum dose documented
diazepam (oral) seizures Greater than or equal to 6 months of age: 10 mg/day in divided doses have been used; dose may be increased as needed and tolerated – no maximum dose documented
diazepam (rectal) seizures+
  • 2-5 years: 0.5 mg/kg/dose^
  • 6-11 years: 0.3 mg/kg/dose^
  • Greater than or equal to 12 years: 0.2 mg/kg/dose^
lorazepam anxiety Greater than or equal to 12 years: 10 mg daily in divided doses (maximum, 2 mg/dose)
  insomnia due to anxiety or situational stress Greater than or equal to 12 years: 4 mg at bedtime
midazolam (nasal) seizures Greater than or equal to 12 years: 5 mg as one spray in one nostril!
oxazepam anxiety
  • 6-12 years: dose not established;
    • 1 mg/kg/day in divided doses has been adequate
  • Greater than 12 years:
    • mild, moderate: 60 mg daily, in divided doses
    • severe: 120 mg daily, in divided doses

Legend:

  • ^ May give second diazepam nasal or rectal 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

2. Duration of Therapy

Anxiety disorders are considered chronic disorders with low spontaneous remission rates and high rates of relapse. Pharmacotherapy for generalized anxiety disorder (GAD) in adults includes antidepressants, benzodiazepines, buspirone, hydroxyzine and pregabalin. Treatment duration for GAD ranges from 3 to 12 months to accomplish treatment goals of symptom remission and improvement in quality of life. Although antidepressants are now considered drugs of choice for managing GAD, benzodiazepines are used frequently for short-term management of anxiety, as an adjunct to initiating antidepressant therapy, or improvement in sleep disturbances associated with GAD and/or antidepressant therapy. Benzodiazepines provide symptom improvement more rapidly than antidepressants and are more effective in managing somatic complaints rather than psychic symptoms. Although longer-term use is considered relatively safe and effective for benzodiazepines, the potential for abuse, dependence and withdrawal does exist 18-19.

In pediatric patients, selective serotonin reuptake inhibitors (SSRIs) are agents of choice to manage childhood anxiety disorders, with serotonin norepinephrine reuptake inhibitors (SNRIs) being recommended as another treatment option. The most recent guidelines published by the American Academy of Child & Adolescent Psychiatry state that there is insufficient evidence to draw conclusions about the benefits or harms of benzodiazepine therapy in pediatric patients with anxiety disorders20.

Panic disorder (PD) is a chronic, recurring condition requiring drug therapy suitable for prolonged use. The acute treatment phase for PD lasts approximately 12 weeks, and most patients require an additional 12 to 18 months of therapy to optimize treatment response and prevent relapse. SSRIs are the agents of choice to manage PD, although benzodiazepines are frequently prescribed as well, usually in combination with antidepressant therapy18. While benzodiazepines are effective in the short-term treatment of panic disorder due to rapid onset of action, long-term treatment may be less desirable due to the potential for dependence. Unlike anxiety disorder patients, patients with panic disorder are less successful at discontinuing benzodiazepine therapy. Additionally, there is a high prevalence of comorbid depression and/or bipolar disorder in patients with panic disorder. Benzodiazepines are less effective than other available agents when panic disorder coexists with other mood disorders. Therefore, patients with panic disorder and other psychiatric comorbidities may benefit from short-term therapy with a benzodiazepine, with chronic management incorporating mood stabilizing or antidepressant agents that are also effective in panic disorder19. Alprazolam has been studied more than other available benzodiazepines for the treatment of panic disorder, although clonazepam, lorazepam, and diazepam have also been evaluated. Most studies evaluating benzodiazepine use in panic disorder have been short-term studies (less than 8 weeks in duration). A few long-term panic disorder studies evaluating alprazolam have demonstrated sustained reductions in panic attack frequency when alprazolam has been administered for 6 to 8 months21. Benzodiazepines should be tapered when discontinued, as patients may experience a withdrawal syndrome if therapy is discontinued abruptly. Benzodiazepine elimination half-life and seizure history for the patient also influence the taper duration. Patients receiving benzodiazepines in lower doses for shorter times periods (less than six months) may be effectively tapered over two to eight weeks, while patients receiving benzodiazepines with a short elimination half-life, in higher doses, and/or for a longer duration (six months or longer) may require a slow taper over two to four months18,19,21.

Benzodiazepines should be prescribed on a short-term basis to manage anxiety disorders. Benzodiazepine doses should be tapered rather than discontinued abruptly to avoid withdrawal symptoms. Patients receiving benzodiazepines for up to 6 months should be tapered over 2 to 8 weeks, while patients treated with benzodiazepines for up to 12 months should be tapered over 2 to 4 months18,19,21<.

While concerns for benzodiazepine tolerance and withdrawal exist, patients may benefit from long-term use of benzodiazepines in panic disorder to minimize symptom recurrence. Additionally, significant problems with benzodiazepine dose escalation have not surfaced with chronic use for panic disorder18,19,21.

The use of benzodiazepines as an anti-epileptic is not limited in duration.

3. Duplicative Therapy

The combined use of two or more benzodiazepines is not supported in the literature and therefore is not recommended. The concurrent use of two or more benzodiazepines will be reviewed.

4. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for nonsedative/hypnotic benzodiazepines are summarized in Table 4 1-17. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Table 4. Benzodiazepine (nonsedative/hypnotic) Drug-Drug Interactions

Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level*
alprazolam CYP3A4 inhibitors (e.g., azole anti-fungals, macro-lides, NNRT inhibitors, protease inhibitors) adjunctive administration may result in enhanced oxidized BZD pharmacologic effects and/or toxicity, including significant sedation and/or respiratory depression, as alprazolam is metabolized by CYP3A4 avoid combined therapy with most CYP3A4 inhibitors, if possible contraindicated -azole antifungals, NNRT inhibitors, protease inhibitors; moderate -macrolides (DrugReax) 1 – severe (azole antifungals, NNRT inhibitors, protease inhibitors); 3-moderate (macrolides) (CP)
alprazolam phenytoin combined use may induce alprazolam metabolism and decrease alprazolam pharmacologic effects monitor for reduced alprazolam clinical effects and adjust doses as necessary 3-moderate (CP)
benzodiazepines (BZDs) central nervous system (CNS) depressants concurrent administration may potentiate respiratory depression, especially with overdosage monitor for respiratory depression; adjust doses as necessary major (DrugReax) 2-major (CP)
BZDs sodium oxybate (Xyrem®) combined use may lead to increased respiratory depression due to additive CNS/ respiratory depressive effects adjunctive use should be avoided; if concurrent use necessary, closely monitor for respiratory depression; dosage reductions for one or both medications may be needed major (DrugReax) 1-severe (CP)
clobazam drugs metabolized by CYP2C19 (e.g., clopidogrel, cimetidine, fluconazole) co-administration may result in increased clobazam serum levels and increased pharmacologic and/or adverse effects as clobazam is partially metabolized by CYP2C19 monitor for enhanced clobazam pharmacologic/adverse effects; adjust clobazam dose as necessary moderate (DrugReax) 3-moderate (CP)
other oxidized BZDs (chlor-diazepoxide, clonazepam, diazepam) CYP3A4 inhibitors [e.g., azole antifungals, macrolides, non-nucleoside reverse transcriptase (NNRT) inhibitors, protease inhibitors] adjunctive administration may result in enhanced oxidized BZD pharmacologic effects and/or toxicity, including significant sedation and/or respiratory depression, as oxidized BZDs are metabolized by CYP3A4 avoid combined therapy, if possible; if concurrent with BZD necessary, monitor for increased sedation, respiratory depression, or consider a BZD metabolized by glucuronidation (e.g., oxazepam) moderate (DrugReax) 2-major (protease inhibitors); 3- moderate (azoles, macrolides, NNRT inhibitors) (CP)
oxidized BZDs (e.g., alprazolam, chlordiazepoxide, clonazepam, diazepam) CYP3A4 inducers (e.g., carbamazepine, rifamycins) combined use may result in increased oxidized BZD clearance, reduced oxidized BZD serum levels, and decreased pharmacologic effects; oxidized BZDs are metabolized by CYP3A4 monitor oxidized BZD clinical response and adjust dose as needed; may also consider substituting a BZD metabolized by glucuronidation (e.g., oxazepam) moderate (DrugReax) 2-major, 3-moderate (CP)
select BZDs (chlordiazepoxide,  diazepam) phenytoin concomitant use may result in unpredictable effects on serum phenytoin levels (may increase, decrease, or not change) due to unknown effect on phenytoin metabolism; phenytoin may induce BZD metabolism, reduce BZD serum levels, and decrease BZD pharmacologic effects closely monitor serum phenytoin levels and observed for altered pharmacologic effects (reduced efficacy, increased toxicity); monitor for reduced BZD clinical effects and adjust doses as necessary major (diazepam), moderate (chlordiazepoxide) (DrugReax) 3-moderate (CP)
chlordiazepoxide/amitriptyline amphetamines combined administration may increase potential for serotonin syndrome as both medications target the serotonin neurotransmitter system if adjunctive therapy is necessary, start with lower doses and monitor for signs/ symptoms of serotonin syndrome; discontinue both medications if serotonin syndrome develops major (DrugReax) 2-major (CP)
chlordiazepoxide/amitriptyline monoamine oxidase inhibitors increased risk of serotonin syndrome with amitriptyline (e.g., mental status changes, hyperpyrexia, restless, shivering, hypertonia, tremor) due to serotonin metabolism inhibition by monoamine oxidase allow 14 days after MAOI discontinuation before initiating other tricyclic antidepressant therapy contraindicated (DrugReax) 1-severe (CP)
chlordiazepoxide/amitriptyline QT interval-prolonging drugs co-administration with QT interval-prolonging drugs may increase risk of QT interval prolongation and torsades de pointes as amitriptyline also prolongs the QT interval avoid concurrent use; if adjunctive use necessary, monitor for increased pharmacologic/toxic effects; adjust dose as necessary or discontinue therapy contraindicated (DrugReax) 1-severe, 2-major (CP)
midazolam CYP3A4 inhibitors May result in prolonged sedation because of a decreased clearance of midazolam Avoid co-administration of midazolam with moderate or strong CYP3A4 inhibitors. Use with caution with co-administered with mild CYP3A4 inhibitors Contraindicated (strong CYP3A4 inhibitors), Major (moderate CYP3A4 inhibitors) (Micromedex)
  Opioids Concomitant use increases the risk of respiratory depression Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate. Minimize dosages and durations to the minimum required Major (Micromedex)
  central nervous system depressants Concomitant use may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect Reserve concomitant use for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required Major (Micromedex)

Legend:

  • *CP = Clinical Pharmacology

5. References

  1. IBM Micromedex® DRUGDEX® (electronic version). IBM Watson Health, Greenwood Village, Colorado, USA. Available at: https://www-micromedexsolutions-com.libproxy.uthscsa.edu/ (cited: March 27, 2022).
  2. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2022. Available at: http://www.clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed March 27, 2022.
  3. Alprazolam (Xanax®) oral tablet package insert. Pharmacia & Upjohn Company, LLC. September 2021.
  4. Chlordiazepoxide oral capsule package insert. Epic Pharma, LLC. March 2022.
  5. Clorazepate oral tablet package insert. Mylan Pharmaceuticals, Inc. June 2020.
  6. Diazepam (Valium®) oral tablet package insert. Roche Laboratories, Inc. November 2019.
  7. Diazepam (Diastat®, Diastat® AcuDial™) rectal delivery system package insert. Bausch Health US, LLC. March 2021.
  8. Lorazepam (Ativan®) oral tablet package insert. Bausch Health US, LLC. February 2021.
  9. Oxazepam oral capsule package insert. Actavis Pharma, Inc. September 2021.
  10. Clonazepam (Klonopin®) package insert. Genentech, Inc. December 2019.
  11. Clobazam (Onfi®) Package Insert. Lundbeck Inc., February 2021.
  12. Clobazam oral film (Sympazan®) package insert. Aquestive Therapeutics, Inc., March 2021.
  13. Diazepam nasal spray (Valtoco®) package insert. Neurelis, Inc., February 2022.
  14. Midazolam (Nayzilam®) nasal spray package insert. UCB, Inc. February 2021.
  15. Lorazepam (Loreev XR®) extended-release capsule package insert. Almatica Pharma, LLC. February 2022.
  16. Chlordiazepoxide/amitriptyline package insert. Mylan Pharmaceuticals, Inc., December 2021.
  17. Chlordiazepoxide/clidinium (Librax®) package insert. Bausch Health US LLC, February 2021.
  18. Melton ST, Kirkwood CK. Chapter 87. Anxiety disorders I: generalized anxiety, panic, and social anxiety disorders (Chapter). In: DiPiro JT, Yee GC, Posey LM, et al. Pharmacotherapy: a pathophysiologic approach. 11th ed. New York, McGraw-Hill, 2019. Access Pharmacy Web site. Available at:  http://accesspharmacy.mhmedical.com.ezproxy.lib.utexas.edu/content.aspx?bookid=1861&sectionid=146065193. Accessed March 28, 2022.
  19. Locke AB, Kirst N, Shultz CG. Diagnosis and management of generalized anxiety disorder and panic disorder in adults. AFP. 2015;91(9):617-624.
  20. Walter HJ, Bukstein OG, Abright AR, et al. Clinical practice guideline for the assessment and treatment of children and adolescents with anxiety disorders. Journal of the American Academy of Child & Adolescent Psychiatry. 2020;59(10):1107-1124.
  21. Work Group on Panic Disorder. American Psychiatric Association Practice Guidelines. Practice guideline for the treatment of patients with panic disorder, second edition. Available at:  http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/panicdisorder.pdf. Accessed March 28, 2022.