Appropriate Use of Oral Benzodiazepines

Full update December 2020

Questions often arise regarding the safe prescribing of benzodiazepines. The charts below provide information to help you choose the most appropriate agent and dose based on indication, age, hepatic function, and drug interactions. Prescribing and deprescribing tips are included, as well as patient counseling points. Information in the charts may differ from product labeling.

Benzodiazepine Oral Dosing and Pharmacokinetics


Oral Dose

Adult Dosing (oral)
(also see footnote a)

(also see footnote c)

(Xanax, etc., generics)

0.5 mg3

Anxiety, Panic

Immediate release:

  • Initial: 0.25 mg to 0.5 mg two or three times daily, or lower in elderly (anxiety or panic)1
  • Usual: 0.25 to 0.5 mg three times daily(anxiety) or 0.5 mg three times daily (panic)2
  • Max total daily dose: 4 mg (anxiety) or 10 mg (panic), divided.1 Consider a max total daily dose of 0.75 mg/day, divided, in the elderly.1
Extended release (U.S.) (panic):
  • Initial: 0.5 mg to 1 mg once daily1
  • Usual: 3 to 6 mg once daily1
  • Max total daily dose: 10 mg1

CYP3A4 to active metabolites (likely clinically insignificant)1

12 to 15 hours2

Bromazepam (Canada)

3 mg2


  • Initial: 6 to 18 mg/day, divided2
  • Usual: 6 to 30 mg/day, divided2
  • Max total daily dose: 60 mg, divided5


Half-life: 8 to 30 hours2

(Librium [U.S.], generics

10 to 25 mg2,3


  • Initial: 5 mg two to four times daily1
  • Usual: 5 to 10 mg three to four times daily, or 20 to 25 mg three to four times daily (more severe symptoms)1
  • Max total daily dose: 100 mg, divided. Consider a max total daily dose of
    20 mg/day, divided, in the elderly.1

Alcohol withdrawal
50 to 100 mg every four to six hours as needed. Max total daily dose: 300 mg, divided1

CYP1A2 to desmethyldiazepam,b then to oxazepam by CYP3A4 and CYP2C19 (minor)1,2,4

Half-life: 100 hours2,d

(Onfi, Sympazan [U.S.], generics

10 mg2

Seizures (adjunct)

  • Initial: 5 mg once or twice daily (once daily in poor CYP2C19 metabolizers)1
  • Max total daily dose: 40 mg, divided1

CYP3A4, CYP2C19, and CYP2B6 to active metabolites1

71 to 82 hours1,d

(Klonopin [U.S.], generics)

0.25 mg2


  • Initial: 0.5 mg three times daily1
  • Usual: 2 to 8 mg/day, divided1
  • Max total daily dose: 20 mg, divided1

Anxiety: 0.25 to 0.5 mg twice daily2


  • Initial: 0.25 mg twice daily1
  • Max total daily dose: 4 mg, divided. Consider a max total daily dose of 1.5 mg/day, divided, in the elderly.1

CYP3A4 to inactive metabolites1

20 to 60 hours2

(Tranxene [U.S.], generics)

7.5 mg2


  • Initial: 3.75 mg to 15 mg twice daily, or 7.5 mg to 15 mg once daily at bedtime.1
  • Usual: 15 mg twice daily1
  • Max total daily dose: 60 mg, divided. Consider a max total daily dose of 15 mg in the elderly.1

Alcohol withdrawal
Day 1, 30 mg x 1, then 30 to 60 mg over 24 hours, in three or four divided doses. Day 2, 45 to 90 mg, divided. Day 3, 22.5 mg to 45 mg, divided. Day 4, 15 to 30 mg, divided. Taper. Discontinue when patient is stable and tapered to 7.5 mg once daily.1 Max total daily dose: 90 mg, divided.1

Seizures, adjunct (U.S.)

  • Initial: 7.5 mg two or three times daily1
  • Max total daily dose: 90 mg, divided1

Decarboxylated in gastrointestinal tract to desmethyldiazepamb (active moiety), then to oxazepam by CYP3A4 and CYP2C19 (minor).1

Half-life: 100 hours2,d

(Valium, generics)

5 mg2

Anxiety: 2 to 10 mg two to four times daily. Max total daily dose: 40 mg, divided. Consider a max total daily dose of 5 mg, divided, in the elderly.1

Seizures (adjunct): 2 to 10 mg two to four times daily. Max total daily dose: 40 mg, divided.1

Muscle spasms (adjunct): 2 to 10 mg three to four times daily. Max total daily dose: 40 mg, divided.1,6 Consider a max total daily dose of 5 mg, divided, in the elderly.1

Alcohol withdrawal 10 mg three to four times daily x 24 hours, then 5 mg three to four times daily as needed.6,7

CYP3A4, CYP2C9, CYP2C19, and CYP1A2 to desmethyldiazepamb (major), temazepam (minor), and oxazepam (minor)1,2

Half-life: 100 hours2,d

Estazolam (U.S.)

1 mg3


  • Initial: 0.5 to 1 mg at bedtime1
  • Max daily dose: 2 mg at bedtime. Consider a max dose of 0.5 mg at bedtime in the elderly.1

CYP3A4 to active metabolites (likely clinically insignificant)1

10 to 24 hours1


15 mg2

Insomnia: 15 to 30 mg at bedtime. Consider a max of 15 mg at bedtime in the elderly.1

CYP3A4 and CYP2C9 to active metabolites.1,2

47 to 100 hours1,d

(Ativan, generics)

1 mg2


  • Initial: 1 to 3 mg/day, divided two or three times daily1
  • Usual dose: 2 to 6 mg/day, divided1
  • Max total daily dose: 10 mg, divided. Consider a max total daily dose of 2 mg/day, divided, in the elderly.1

Insomnia due to anxiety or situational stress: 1 to 4 mg at bedtime as needed.1 Consider a max dose of 1 mg at bedtime as needed in the elderly.1

Glucuronidation to inactive metabolite1

Half-life: 9 to 22 hours1

Nitrazepam (Canada)

5 mg2

Insomnia: 2.5 to 10 mg at bedtime (5 mg max in elderly)8

CYP2E1 to inactive metabolite.2

16 to 55 hours2


15 mg2


  • Initial: 10 mg to 15 mg three to four times daily1
  • Max total daily dose: 120 mg, divided. Consider a max total daily dose of 30 mg/day, divided, in elderly.1

Alcohol withdrawal: 15 to 30 mg three to four times daily. Elderly may need a lower dose initially.1

Glucuronidation to inactive metaboltes1

Half-life: 5 to 15 hours1

Quazepam (U.S.)
(Doral, generics)

7.5 mg3

7.5 to 15 mg at bedtime. Consider a max of 7.5 mg at bedtime in the elderly.1

CYP3A4 (major) and CYP2C9 and CYP2C19 to active metabolites1

Half-life: 47 to 100 hours1,d

Temazepam (Restoril, generics)

15 mg3


  • Initial: 7.5 mg to 30 mg at bedtime1
  • Max 30 mg at bedtime. Consider a max of 15 mg at bedtime in elderly.1

Glucuronidation to inactive metabolites1

Half-life: 8 to 15 hours1

Triazolam (Halcion, generics)

0.25 mg2


  • Initial: 0.125 to 0.25 mg at bedtime1
  • Max 0.5 mg at bedtime. Consider a max of 0.125 mg at bedtime in the elderly.1

CYP3A4 to inactive metabolites1,2

Half-life: 1.5 to 5.5 hours1

  1. In general, start with the lowest dose in elderly, debilitated, or hepatically impaired patients and increase slowly.1,2
  2. Desmethyldiazepam: long-acting metabolite responsible at least in part for therapeutic and toxic effects of diazepam, clorazepate, and chlordiazepoxide.3
  3. For the elderly, and for patients with liver disease, benzos that undergo glucuronidation (lorazepam, oxazepam, temazepam) are preferred over those that undergo oxidative metabolism (e.g., CYP450), especially those with long-acting metabolites: flurazepam, chlordiazepoxide, clorazepate, quazepam, and diazepam.1-3 See our chart, Cytochrome P450 (CYP) Drug Interactions, for help identifying potential drug interactions based on metabolic pathway.
  4. Includes active metabolite(s).


Preferred Oral Benzodiazepine per Condition

Benzodiazepines are among the treatment options for several conditions but are not usually the drugs of first choice for chronic use. The chart below addresses preferred benzodiazepines for given conditions when a benzodiazepine might be appropriate.


Preferred Benzodiazepine


Alcohol withdrawal

Chlordiazepoxide, diazepam, lorazepam, or oxazepam.9

See our chart, Outpatient Alcohol Detox and Relapse Prevention, for details to help you choose among them.

Benzodiazepines are the drugs of choice for management of alcohol withdrawal.9

Parenteral forms of diazepam and lorazepam are available.


No agent clearly superior in regard to efficacy.3

Consider agent with medium or long half-life which has been used more extensively for anxiety disorders: clonazepam, lorazepam, or diazepam.3 Shorter acting agents pose higher risk of withdrawal, rebound, and abuse.3,10

Ideally, for short-term use only (e.g., for two to six weeks, until antidepressant starts to work, then taper).3

Other roles include treatment of patients who have failed other medications (e.g., SSRI, SNRI, pregabalin), patients who cannot tolerate other medication classes.11

Alprazolam is one of the most abused benzodiazepines; a quick onset leads to euphoria.3 Accounts for one in ten ER visits in U.S. due to drug misuse.12 More toxic in overdose than other benzos.12 Missed doses or discontinuation can cause significant withdrawal quickly.10 May be difficult to taper/discontinue.3 Risk of breakthrough anxiety with immediate-release product.3 Sustained-release product (U.S.) may have less abuse potential.3

Diazepam has fastest onset (<1 hour).2

Diazepam duration of effect shorter than lorazepam despite long half-life; it is lipophilic and quickly redistributes out of the brain.3,13

Consider propranolol for performance anxiety.3

For more information on treatment of anxiety, see our chart, Pharmacotherapy of Anxiety: Beyond the First Line Agents.


Temazepam (Restoril, generics) (favorable benefit vs risk).14

See our chart, Comparison of Insomnia Treatments (U.S. subscribers; Canadian subscribers), for non-benzodiazepine alternatives.

Panic attacks

Clonazepam, lorazepam, or diazepam (most evidence of efficacy).11

Benzodiazepines generally not first-line.11 Can use as adjunct to antidepressant to achieve symptom control acutely or to relieve residual anxiety.11

See comments under “Anxiety” regarding alprazolam.

Low back pain

Most evidence for diazepam.15

See our chart, Muscle Relaxants, for details regarding use.

For alternatives, see our charts, Treatment of Acute Low Back Pain and Treatment of Chronic Low Back Pain.

Tips for Prescribing and Deprescribing Benzodiazepines


Suggested Strategies or Resources

Educate patients about benzodiazepine safety.

In the U.S., benzodiazepines are dispensed with a MedGuide that covers risks.17

Consider these patient counseling points when talking to patients about starting a benzodiazepine:

  • Like all medications, benzos have risks. These risks include:
    • Feeling sleepy, dizzy, clumsy, or confused.6 This can cause falls or accidents.22
    • If you take a benzo at bedtime, you might get up without being fully awake and do something you do not know you are doing. This could include driving, eating, talking, or sleepwalking.1
    • Tolerance. This means that over time, your benzo might not work as well as it once did.16
    • Dependence. This means that some patients don’t feel well when they stop using benzos. This occurs most often when the benzo is taken regularly for several days to weeks.17
    • Mood or behavior problems.7
    • Misuse or abuse.17
  • To use benzos safely, you should:
    • Avoid alcohol. Also avoid narcotic pain meds like oxycodone or hydrocodone. These mixtures can cause you to become too sedated, or even slow your breathing to a dangerous level.17
    • Take your benzo exactly as prescribed. Do not increase the dose on your own.7
    • Report unusual changes in behavior or mood.7
    • Seek immediate medical care for trouble breathing.17
    • Keep your benzo in a safe place. Tell only a few people you trust that you are taking it. Do not share it with others.

Safely initiate a benzodiazepine.

Consider all therapeutic options for management of the patient’s condition, and provide information about non-drug alternatives.17

Limit dosages and durations to the minimum required.21 Have an exit plan.23

Some experts suggest follow-up in one to four weeks.

Screen for potentially problematic drug interactions (e.g., opioids).19,21

Before prescribing and throughout treatment, assess the patient’s risk of abuse, misuse, and addiction.17 Screening and assessment tools are available at:

Educate patients about

benzodiazepine discontinuation and get patient buy-in.

First, ask patients what their goals and preferences are regarding their benzodiazepine.16 Involve the caregiver, or care team in a long-term care setting.22 Consider addressing the following benefits of discontinuation:

  • Discontinuation of your benzodiazepine may improve alertness and thinking, and reduce fall risk.16
  • There may be options for treating your condition that are better for you than your benzo.17
  • These options may or may not be a medication. For example, there are things you can do to help sleep, anxiety, and low back pain that do not involve pills.

Regarding the discontinuation process, consider addressing the following points:

  • You must not stop your benzo on your own. If you are dependent on your benzo and stop it all of a sudden, you might have withdrawal symptoms. Examples include:
    • More common: anxiety, irritability, trouble sleeping, sweating, gastrointestinal symptoms.16,18
    • Possible but uncommon: seizures, seeing or hearing things that aren’t there.16,17
  • The condition your benzo is being used to treat might get worse during discontinuation. We will work together to control it to the extent possible before stopping your benzo.22
  • Depending on the dose, how often you take it, and for how long you have been taking it, you may need to slowly decrease (taper) the dose. You will be given specific advice for the taper. If you feel worse during this process, don’t be discouraged. Your plan can be adjusted if this happens. Most symptoms are mild and short-term (days to weeks).16
  • If the benzodiazepine cannot be completely discontinued, a dose reduction is still a partial success.22

Consider sharing the validated EMPOWER brochure, available at

Identify patients for whom benzodiazepines should be tapered.

Patients ≥65 years of age18

Patients <65 years of age who have used a benzo most days of the week for >4 weeks.16

Be aware that case reports describe a wide range of time to dependence, with some reporting the onset as early as days to weeks after the start of a benzodiazepine.17

Identify strategies for a successful benzodiazepine taper.

Monitor every one to two weeks.16

Consider an especially slow taper (e.g., at least six to 12 weeks) for patients taking alprazolam; patients taking a high dose (e.g., alprazolam >4 mg/day); patients taking a benzo for >2 to 3 months; and for patients with panic disorder or a seizure disorder.2,11,24

Be prepared to address severe or life-threatening withdrawal reactions include catatonia, seizures, delirium tremens, depression, suicidal or homicidal thoughts, mania, or psychosis.17

Also watch for a protracted withdrawal syndrome that persists beyond initial benzodiazepine withdrawal. Symptoms may last as long as 12 months, and include depression, cognitive impairment, insomnia, anxiety, motor symptoms, paresthesia, or tinnitus.17

In case of worsening of underlying condition or withdrawal symptoms, maintain benzodiazepine dose or increase to the previous step for one to two weeks, then taper more slowly.16,17,22

Incorporate non-drug approaches to manage underlying conditions (e.g., sleep hygiene, cognitive behavioral therapy).16

For patients on both an opioid and benzodiazepine, it may be safer and more practical to taper the opioid first.19 The benzodiazepine may help with opioid withdrawal.19

Depending on patient reliability, consider having the pharmacist dispense only a week’s worth of medication (or less) at a time.26

Provide a written tapering plan to improve chance of success.18

Formulate a benzodiazepine tapering plan for your patient.

There is no one tapering schedule suitable for all patients.17 Suggested tapering regimens include:

  • Reduce dose by 25% every one to two weeks (commonly used).19
  • Reduce dose by 25% every two weeks until lowest available dose is reached. Then progressively reduce dosing frequency (e.g., for insomnia, schedule drug-free nights).16
  • Reduce dose by 25% weekly for three weeks, or every two weeks for six weeks, then reduce by 12.5% for two weeks.16
  • Reduce dose by 25% weekly for four weeks, or reduce by 25% for three weeks, then by 12.5% every four days for one week.16
  • Reduce by 25% weekly for the first two weeks, then by 10% per week.20
  • Reduce dose by 10% every one to two weeks, until 20% of original dose is reached, then taper by 5% every two to four weeks.26
  • Taper by no more than 5 mg diazepam equivalent per week. When 20 mg diazepam equivalent is reached, slow the taper to 1 to 2 mg diazepam equivalent per week).26 The “Benzodiazepine Dosing and Pharmacokinetics” table above provides approximate equivalent doses.
  • Alprazolam: decrease by no more than 0.5 mg increments. If taking ≥6 mg/day, consider decreasing by 0.5 mg every two to three weeks. When at 2 mg/day, decrease by 0.25 mg every two to three weeks.24
  • In panic disorder, taper the benzodiazepine by no more than 10% of the dose weekly, such that the taper is completed over two to seven months.24,25

Special considerations:

  • If the dosage form does not allow for a 25% reduction, consider a 50% reduction initially, then switch to lorazepam or oxazepam for the end of the taper.16
  • Switching and stabilizing on a longer-acting agent (e.g., clonazepam) before tapering is sometimes done, but may not be superior.16,22,26 The “Benzodiazepine Dosing and Pharmacokinetics” table above provides approximate equivalent doses.

Prepared by the Editors of Therapeutic Research Center (361206).


  1. Clinical Pharmacology powered by ClinicalKey. Tampa (FL): Elsevier. 2020. (Accessed November 3, 2020).
  2. e-CPS [Internet]. Ottawa (ON): Canadian Pharmacists Association; c2020. Benzodiazepines. CPhA monograph (May 2015). (Accessed November 3, 2020).
  3. Bostwick JR, Gardner KN. Anxiety disorders. In: Zeind CS, Carvalho MG, editors. Applied Therapeutics: The Clinical Use of Drugs. 11th ed. Philadelphia, PA: Wolters Kluwer Health, 2018: 1731-61.
  4. Mayo Clinic Laboratories. Benzodiazepines. (Accessed November 3. 2020).
  5. Product monograph for Teva-bromazepam. Teva Canada. Toronto, CA M1B 2K9. September 2019.
  6. Product information for Valium. Roche Laboratories. Little Falls, NJ 07424. June 2017.
  7. Product monograph for Valium. Hoffman-La Roche. Mississauga, ON L5N 5M8. April 2018.
  8. Product monograph for Mogadon. AA Pharma. Vaighan, ON L4K 4N7. September 2019.
  9. Clinical Resource, Outpatient Alcohol Detox and Relapse Prevention. Pharmacist’s Letter/Prescriber’s Letter. February 2019.
  10. Cosci F, Chouinard G. Acute and persistent withdrawal syndroms following discontinuation of psychotropic medications. Psychother Psychosom 2020;89:283-306.
  11. Katzman MA, Bleau P, Blier P, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders. BMC Psychiatry 2014;14(Suppl 1):S1-83.
  12. Bush DM. Emergency department visits involving nonmedical use of the anti-anxiety medication alprazolam. SAMHSA. The CBHSQ Report May 22, 2014. (Accessed November 5, 2020).
  13. Dundee JW, McGowan WA, Lilburn JK, et al. Comparison of the actions of diazepam and lorazepam. Br J Anaesth 1979;51:439-46 [abstract].
  14. Sateia MJ, Buysse DJ, Krystal AD, et al. Clinical practice guideline for the pharmacologic treatment of chronic insomnia in adults: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2017;13:307-49.
  15. Van Tulder MW, Touray T, Furlan AD, et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev 2003;2:CD004252.
  16. Pottie K, Thompson W, Davies S, et al. Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guidelines. Can Fam Physician 2018;64:339-51.
  17. FDA Drug Safety Communication. FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020. (Accessed November 5, 2020).
  18. Tannenbaum C, Martin P, Tamblyn R, et al. Reduction of inappropriate benzodiazepine prescriptions among older adults through direct patient education: the EMPOWER cluster randomized trial. JAMA Intern Med 2014;174:890-8.
  19. Dowell D, Haegerich TM, Chou R. CDC Guideline for prescribing opioids for chronic pain - United States, 2016. MMWR Recomm Rep 2016;65:1-49.
  20. Chang F. Strategies for benzodiazepine withdrawal in seniors. CPJ 2005;138:38-40.
  21. Health Canada. Updated to safety labelling for benzodiazepines and benzodiazepine-like drugs. October 30, 2020. (Accessed November 6, 2020).
  22. Ng BJ, :Le Couteur DG, Hilmer SN. Deprescribing benzodiazepines in older patients: impact of interventions targeting physicians, pharmacists, and patients. Drugs Aging 2018;35:493-521.
  23. Kaiser Permanente. Benzodiazepine and Z-drug safety guideline. January 2019. (Accessed November 6, 2020).
  24. Product monograph for Xanax. Upjohn Canada. Kirkland, QC H9J 2M5. May 2020.
  25. American Psychiatric Association. Practice guideline for the treatment of patients with panic disorder. 2nd edition. January 2009. (Accessed November 9, 2020).
  26. National Opioid Use Guideline Group. Canadian guideline for safe and effective use of opioids for chronic non-cancer pain. Part B. Recommendations for practice. (Accessed November 7, 2020).

Cite this document as follows: Clinical Resource, Appropriate Use of Oral Benzodiazepines. Pharmacist’s Letter/Prescriber’s Letter. December 2020.

Related Articles