BENZODIAZEPINES

All dosing is for ADULTS unless otherwise specified. All benzodiazepines are DEA Schedule IV.

PRICING INFO

$ = 0 - $50
$$ = $51 - $100
$$$ = $101 - $150
$$$$ = > $151

Pricing based on one month of therapy at standard dosing in an adult
Pricing based on information from GoodRX.com®
Pricing may vary by region and availability

References:

1 - Package insert for drug unless otherwise specified
2 - PMID 22876380 - NICE clinical GL on alcohol withdrawal
3 - PMID 6733001 - Flurazepam study
4 - PMID 18175099 - lorazepam article
5 - Toxnet website
6 - Toxnet website
7 - Toxnet website
8 - PMID 11975064 - glaucoma
9 - PMID 6106489 - Disulfiram and oxazepam, lorazepam, librium, and diazepam
10 - PMID 2338112 - Disulfiram and alprazolam
11 - PMID 29739 - Disulfiram and librium, diazepam, and oxazepam
12 - PMID 7934566 - Disulfiram and temazepam
13 - PMID 19125841 - Febrile seizure GL
14 - PMID 28328330 - Treatment of Benzodiazepine Dependence, NEJM (2017)

Drug	Dosage forms	Dosing	Other
Alprazolam Xanax®	Tablet 0.25 mg 0.5 mg 1 mg 2 mg Orally disintegrating tablet 0.25 mg 0.5 mg 1 mg 2 mg Solution 1 mg/ml Comes in 30 ml bottles	Anxiety disorders and transient anxiety Starting: 0.25 - 0.5 mg three times a day as needed Maximum: 4 mg/day Elderly: starting dose is 0.25 mg given two to three times a day as needed Increase dose every 3 - 4 days as needed When discontinuing after chronic therapy, decrease daily dose by no more than 0.5 mg a day every 3 days	Pharmacokinetics Peak plasma concentration: 1 - 2 hours Half-life: 11.2 hours (range: 6.3 – 26.9 hours) Average half-life is prolonged in elderly (16.3 hours), liver disease (19.7 hours), and obesity (21.8 hours) Other Alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. Disulfiram (Antabuse®) does not appear to affect the metabolism of alprazolam [10] Price Generic (30 tablets) - $ Generic (30 disintegrating tablets) - $-$$ Generic (30 ml solution) - $$
Alprazolam Xanax XR®	Extended-release tablet 0.5 mg 1 mg 2 mg 3 mg	Panic disorder Starting: 0.5 - 1 mg once daily Maintenance: 3 - 6 mg once daily Maximum: 10 mg once daily Increase dose every 3 - 4 days in increments of no more than 1 mg/day When tapering off, decrease dose by no more than 0.5 mg/day every 3 days Switching from Xanax to Xanax XR Total daily Xanax dose may be given as once daily Xanax XR tablet	Pharmacokinetics Xanax XR has the same pharmacokinetics as immediate-release Xanax except that it is absorbed more slowly. The slower absorption rate results in a relatively constant concentration that is maintained between 5 and 11 hours after the dosing. High-fat meals increase the absorption of Xanax XR Peak plasma concentration: 1 - 2 hours Half-life: 11.2 hours (range: 6.3 – 26.9 hours) Average half-life is prolonged in elderly (16.3 hours), liver disease (19.7 hours), and obesity (21.8 hours) Other Do not cut, chew, crush, or break tablets Alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. Price Generic (30 tablets) - $

Drug

Dosage forms

Dosing

Other

Alprazolam

Xanax®

Tablet

0.25 mg
0.5 mg
1 mg
2 mg

Orally disintegrating tablet

0.25 mg
0.5 mg
1 mg
2 mg

Solution

1 mg/ml
Comes in 30 ml bottles

Anxiety disorders and transient anxiety

Starting: 0.25 - 0.5 mg three times a day as needed
Maximum: 4 mg/day
Elderly: starting dose is 0.25 mg given two to three times a day as needed
Increase dose every 3 - 4 days as needed
When discontinuing after chronic therapy, decrease daily dose by no more than 0.5 mg a day every 3 days

Pharmacokinetics

Peak plasma concentration: 1 - 2 hours
Half-life: 11.2 hours (range: 6.3 – 26.9 hours)
Average half-life is prolonged in elderly (16.3 hours), liver disease (19.7 hours), and obesity (21.8 hours)

Other

Alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.
Disulfiram (Antabuse®) does not appear to affect the metabolism of alprazolam [10]

Price

Generic (30 tablets) - $
Generic (30 disintegrating tablets) - $-$$
Generic (30 ml solution) - $$

Alprazolam

Xanax XR®

Extended-release tablet

0.5 mg
1 mg
2 mg
3 mg

Panic disorder

Starting: 0.5 - 1 mg once daily
Maintenance: 3 - 6 mg once daily
Maximum: 10 mg once daily
Increase dose every 3 - 4 days in increments of no more than 1 mg/day
When tapering off, decrease dose by no more than 0.5 mg/day every 3 days

Switching from Xanax to Xanax XR

Total daily Xanax dose may be given as once daily Xanax XR tablet

Pharmacokinetics

Xanax XR has the same pharmacokinetics as immediate-release Xanax except that it is absorbed more slowly. The slower absorption rate results in a relatively constant concentration that is maintained between 5 and 11 hours after the dosing.
High-fat meals increase the absorption of Xanax XR
Peak plasma concentration: 1 - 2 hours
Half-life: 11.2 hours (range: 6.3 – 26.9 hours)
Average half-life is prolonged in elderly (16.3 hours), liver disease (19.7 hours), and obesity (21.8 hours)

Other

Do not cut, chew, crush, or break tablets
Alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.

Price

Generic (30 tablets) - $

Drug	Dosage forms	Dosing	Other
Chlordiazepoxide Librium®	Capsule 5 mg 10 mg 25 mg	Anxiety Mild-to-moderate: 5 - 10 mg three to four times a day as needed Severe: 20 - 25 mg three to four times a day as needed Elderly: 5 mg two to four times a day as needed Alcohol withdrawal Fixed dose regimen: Day 1: 20 - 30 mg four times daily Day 2: 20 - 30 mg three times daily Day 3: 20 - 30 mg twice daily Day 4: 20 - 30 mg at bedtime [2] See NICE clinical guidelines on alcohol withdrawal for more	Pharmacokinetics Peak plasma concentration: 2 hours Half-life: 24 - 48 hours Price Generic (30 capsules) - $
Chlordiazepoxide + clidinium Librax®	Capsule Chlordiazepoxide : clidinium 5 mg : 2.5 mg	Anxiety-related gastrointestinal disorders 1 - 2 capsules three to four times a day as needed Take before meals and at bedtime	Other Clidinium is an anticholinergic agent Librax® does not have FDA-approved indications Price Generic (30 capsules) - $
Chlordiazepoxide + amitriptyline Limbitrol®	Tablet Chlordiazepoxide : amitriptyline 5 mg : 12.5 mg 10 mg : 25 mg	Depression associated with anxiety 3 or 4 tablets daily given in divided doses Reduce dose to minimum effective dose Do not exceed 6 tablets a day	Other Amitriptyline is a tricyclic antidepressant Price Generic (30 tablets) - $-$$

Drug

Dosage forms

Dosing

Other

Chlordiazepoxide

Librium®

Capsule

5 mg
10 mg
25 mg

Anxiety

Mild-to-moderate: 5 - 10 mg three to four times a day as needed
Severe: 20 - 25 mg three to four times a day as needed
Elderly: 5 mg two to four times a day as needed

Alcohol withdrawal

Fixed dose regimen:

Day 1: 20 - 30 mg four times daily
Day 2: 20 - 30 mg three times daily
Day 3: 20 - 30 mg twice daily
Day 4: 20 - 30 mg at bedtime [2]

See NICE clinical guidelines on alcohol withdrawal for more

Pharmacokinetics

Peak plasma concentration: 2 hours
Half-life: 24 - 48 hours

Price

Generic (30 capsules) - $

Chlordiazepoxide + clidinium

Librax®

Capsule
Chlordiazepoxide : clidinium

5 mg : 2.5 mg

Anxiety-related gastrointestinal disorders

1 - 2 capsules three to four times a day as needed
Take before meals and at bedtime

Other

Clidinium is an anticholinergic agent
Librax® does not have FDA-approved indications

Price

Generic (30 capsules) - $

Chlordiazepoxide + amitriptyline

Limbitrol®

Tablet
Chlordiazepoxide : amitriptyline

5 mg : 12.5 mg
10 mg : 25 mg

Depression associated with anxiety

3 or 4 tablets daily given in divided doses
Reduce dose to minimum effective dose
Do not exceed 6 tablets a day

Other

Amitriptyline is a tricyclic antidepressant

Price

Generic (30 tablets) - $-$$

Drug	Dosage forms	Dosing	Other
Clonazepam Klonopin®	Tablet 0.5 mg 1 mg 2 mg Orally disintegrating tablet 0.125 mg 0.25 mg 0.5 mg 1 mg 2 mg	Adults Panic disorder Starting: 0.25 mg twice a day Maintenance: 0.5 mg twice a day Maximum: 2 mg twice a day Increase in increments of 0.125 - 0.25 mg/dose at intervals of 3 days Total daily dose may be given once daily at bedtime to minimize side effects When discontinuing, decrease by 0.125 mg/dose every 3 days Seizure disorder Starting: 0.5 mg three times a day Maximum: 20 mg/day Increase in increments of 0.5 - 1 mg/day every 3 days Children Seizure disorder (up to 10 years old or 30 kg) Starting: 0.01 - 0.03 mg/kg/day given in 2 or 3 divided doses Maintenance: 0.1 - 0.2 mg/kg/day given in 3 divided doses Maximum: 0.2 mg/kg/day Increase daily dosage by no more than 0.25 - 0.5 mg every third day	Pharmacokinetics Peak plasma concentration: 1 - 4 hours Half-life: 30 - 40 hours Other Clonazepam is likely a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. Price Generic (30 tablets) - $

Drug

Dosage forms

Dosing

Other

Clonazepam

Klonopin®

Tablet

0.5 mg
1 mg
2 mg

Orally disintegrating tablet

0.125 mg
0.25 mg
0.5 mg
1 mg
2 mg

Adults

Panic disorder

Starting: 0.25 mg twice a day
Maintenance: 0.5 mg twice a day
Maximum: 2 mg twice a day
Increase in increments of 0.125 - 0.25 mg/dose at intervals of 3 days
Total daily dose may be given once daily at bedtime to minimize side effects
When discontinuing, decrease by 0.125 mg/dose every 3 days

Seizure disorder

Starting: 0.5 mg three times a day
Maximum: 20 mg/day
Increase in increments of 0.5 - 1 mg/day every 3 days

Children

Seizure disorder (up to 10 years old or 30 kg)

Starting: 0.01 - 0.03 mg/kg/day given in 2 or 3 divided doses
Maintenance: 0.1 - 0.2 mg/kg/day given in 3 divided doses
Maximum: 0.2 mg/kg/day
Increase daily dosage by no more than 0.25 - 0.5 mg every third day

Pharmacokinetics

Peak plasma concentration: 1 - 4 hours
Half-life: 30 - 40 hours

Other

Clonazepam is likely a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.

Price

Generic (30 tablets) - $

Drug	Dosage forms	Dosing	Other
Diazepam Valium®	Tablet 2 mg 5 mg 10 mg Solution 1 mg/ml Concentrate - Intensol 5 mg/ml	Adults Anxiety disorder 2 - 10 mg two to four times a day as needed Acute alcohol withdrawal Day 1: 10 mg three to four times a day as needed Day 2 and on: 5 mg three to four times a day as needed Muscle spasm 2 - 10 mg three to four times a day as needed Elderly patients Starting: 2 - 2.5 mg one to two times a day as needed Children (≥ 6 months) No indication specified Dosing: 1 - 2.5 mg three to four times a day as needed. Increase gradually as needed and tolerated.	Pharmacokinetics Peak plasma concentration: 1 - 1.5 hours Half-life: Diazepam - up to 48 hours Active metabolite - up to 100 hours Half-life increases by approximately 1 hour for each year of age beginning with a half-life of 20 hours at 20 years of age Other Food slows absorption Diazepam is a CYP3A4 and CYP2C19 sensitive substrate. Use caution with CYP3A4 and CYP2C19 inhibitors and inducers. Price Generic (30 tablets) - $ Generic (1 mg/ml, 180 ml) - $ Generic (5 mg/ml, 30 ml) - $
Diazepam Diastat® AcuDial	Rectal gel Comes in 2.5 mg, 10 mg, and 20 mg delivery system 10 mg delivery system may be dialed to 5, 7.5, and 10 mg doses 20 mg delivery system may be dialed to 12.5, 15, 17.5, and 20 mg doses Comes in pack with 2 delivery systems	Children Acute seizure 2 - 5 years: 0.5 mg/kg 6 - 11 years: 0.3 mg/kg ≥ 12 years: 0.2 mg/kg Dose should be rounded up to next available dose A second dose may be given 4 - 12 hours after the first dose It takes ∼ 3 minutes for therapeutic concentrations to reach the brain with the rectal route [13]	Pharmacokinetics Peak plasma concentration: 1.5 hours Half-life: Diazepam - 46 hours Active metabolite - 71 hours It takes ∼ 3 minutes for therapeutic concentrations to reach the brain with the rectal route [13] Other Comes in a single dose rectal delivery system Applicator can be dialed to appropriate dose See patient instructions for proper delivery technique Price Generic (2 delivery systems) - $$$-$$$$

Drug

Dosage forms

Dosing

Other

Diazepam

Valium®

Tablet

2 mg
5 mg
10 mg

Solution

1 mg/ml

Concentrate - Intensol

5 mg/ml

Adults

Anxiety disorder

2 - 10 mg two to four times a day as needed

Acute alcohol withdrawal

Day 1: 10 mg three to four times a day as needed
Day 2 and on: 5 mg three to four times a day as needed

Muscle spasm

2 - 10 mg three to four times a day as needed

Elderly patients

Starting: 2 - 2.5 mg one to two times a day as needed

Children (≥ 6 months)

No indication specified

Dosing: 1 - 2.5 mg three to four times a day as needed. Increase gradually as needed and tolerated.

Pharmacokinetics

Peak plasma concentration: 1 - 1.5 hours
Half-life:

Diazepam - up to 48 hours
Active metabolite - up to 100 hours
Half-life increases by approximately 1 hour for each year of age beginning with a half-life of 20 hours at 20 years of age

Other

Food slows absorption
Diazepam is a CYP3A4 and CYP2C19 sensitive substrate. Use caution with CYP3A4 and CYP2C19 inhibitors and inducers.

Price

Generic (30 tablets) - $
Generic (1 mg/ml, 180 ml) - $
Generic (5 mg/ml, 30 ml) - $

Diazepam

Diastat® AcuDial

Rectal gel

Comes in 2.5 mg, 10 mg, and 20 mg delivery system
10 mg delivery system may be dialed to 5, 7.5, and 10 mg doses
20 mg delivery system may be dialed to 12.5, 15, 17.5, and 20 mg doses
Comes in pack with 2 delivery systems

Children

Acute seizure

2 - 5 years: 0.5 mg/kg
6 - 11 years: 0.3 mg/kg
≥ 12 years: 0.2 mg/kg

Dose should be rounded up to next available dose
A second dose may be given 4 - 12 hours after the first dose
It takes ∼ 3 minutes for therapeutic concentrations to reach the brain with the rectal route [13]

Pharmacokinetics

Peak plasma concentration: 1.5 hours
Half-life:

Diazepam - 46 hours
Active metabolite - 71 hours

It takes ∼ 3 minutes for therapeutic concentrations to reach the brain with the rectal route [13]

Other

Comes in a single dose rectal delivery system
Applicator can be dialed to appropriate dose
See patient instructions for proper delivery technique

Price

Generic (2 delivery systems) - $$$-$$$$

Drug	Dosage forms	Dosing	Other
Flurazepam Dalmane®	Capsule 15 mg 30 mg	Insomnia 30 mg one time before bedtime as needed 15 mg may be sufficient in elderly and debilitated patients	Pharmacokinetics Peak plasma concentration: 30 - 60 minutes Half-life: Flurazepam: 2.3 hours Active metabolite: 47 - 100 hours [3] Price Generic (30 capsules) - $

Drug

Dosage forms

Dosing

Other

Flurazepam

Dalmane®

Capsule

15 mg
30 mg

Insomnia

30 mg one time before bedtime as needed
15 mg may be sufficient in elderly and debilitated patients

Pharmacokinetics

Peak plasma concentration: 30 - 60 minutes
Half-life:

Flurazepam: 2.3 hours
Active metabolite: 47 - 100 hours [3]

Price

Generic (30 capsules) - $

Drug	Dosage forms	Dosing	Other
Lorazepam Ativan®	Tablet 0.5 mg 1 mg 2 mg Solution 2 mg/ml Comes in 30 ml bottle	Anxiety Starting: 2 - 3 mg/day given in two to three divided doses Maintenance: 2 - 6 mg/day given in two to three divided doses Elderly: 1 - 2 mg/day given in two to three divided doses Insomnia 2 - 4 mg given once at bedtime	Pharmacokinetics Peak plasma concentration: 2 hours Half-life: 12 hours Lorazepam is metabolized by glucuronide conjugation Liver and kidney disease only have a minor effect on lorazepam pharmacokinetics [4] Other Lorazepam is safe in breastfeeding [5] Disulfiram (Antabuse®) does not appear to affect the metabolism of lorazepam [9] Price Generic (30 tablets) - $

Drug

Dosage forms

Dosing

Other

Lorazepam

Ativan®

Tablet

0.5 mg
1 mg
2 mg

Solution

2 mg/ml
Comes in 30 ml bottle

Anxiety

Starting: 2 - 3 mg/day given in two to three divided doses
Maintenance: 2 - 6 mg/day given in two to three divided doses
Elderly: 1 - 2 mg/day given in two to three divided doses

Insomnia

2 - 4 mg given once at bedtime

Pharmacokinetics

Peak plasma concentration: 2 hours
Half-life: 12 hours
Lorazepam is metabolized by glucuronide conjugation
Liver and kidney disease only have a minor effect on lorazepam pharmacokinetics [4]

Other

Lorazepam is safe in breastfeeding [5]
Disulfiram (Antabuse®) does not appear to affect the metabolism of lorazepam [9]

Price

Generic (30 tablets) - $

Drug	Dosage forms	Dosing	Other
Oxazepam Serax®	Capsule 10 mg 15 mg 30 mg	Mild-to-moderate anxiety 10 - 15 mg three to four times a day as needed Severe anxiety 15 - 30 mg three to four times a day as needed Alcohol withdrawal 15 - 30 mg three to four times a day as needed Elderly Starting: 10 mg three times a day as needed Maintenance: 15 mg three to four times a day as needed	Pharmacokinetics Peak plasma concentration: 3 hours Half-life: 8.2 hours Oxazepam is metabolized by glucuronide conjugation Other Oxazepam is safe in breastfeeding [6] Oxazepam is the short-acting metabolite of diazepam [6] Disulfiram (Antabuse®) does not appear to affect the metabolism of oxazepam [9] Price Generic (30 capsules) - $

Drug

Dosage forms

Dosing

Other

Oxazepam

Serax®

Capsule

10 mg
15 mg
30 mg

Mild-to-moderate anxiety

10 - 15 mg three to four times a day as needed

Severe anxiety

15 - 30 mg three to four times a day as needed

Alcohol withdrawal

15 - 30 mg three to four times a day as needed

Elderly

Starting: 10 mg three times a day as needed
Maintenance: 15 mg three to four times a day as needed

Pharmacokinetics

Peak plasma concentration: 3 hours
Half-life: 8.2 hours
Oxazepam is metabolized by glucuronide conjugation

Other

Oxazepam is safe in breastfeeding [6]
Oxazepam is the short-acting metabolite of diazepam [6]
Disulfiram (Antabuse®) does not appear to affect the metabolism of oxazepam [9]

Price

Generic (30 capsules) - $

Drug	Dosage forms	Dosing	Other
Quazepam Doral®	Tablet 15 mg	Insomnia Starting: 7.5 mg once at bedtime Maintenance: 7.5 - 15 mg once at bedtime	Pharmacokinetics Peak plasma concentration: 2 hours Half-life: Quazepam: 39 hours Active metabolite: 73 hours Other Tablet is scored so that it can be halved Price Generic (30 capsules) - ?, not currently available

Drug

Dosage forms

Dosing

Other

Quazepam

Doral®

Tablet

15 mg

Insomnia

Starting: 7.5 mg once at bedtime
Maintenance: 7.5 - 15 mg once at bedtime

Pharmacokinetics

Peak plasma concentration: 2 hours
Half-life:

Quazepam: 39 hours
Active metabolite: 73 hours

Other

Tablet is scored so that it can be halved

Price

Generic (30 capsules) - ?, not currently available

Drug	Dosage forms	Dosing	Other
Temazepam Restoril®	Capsule 7.5 mg 15 mg 22.5 mg 30 mg	Insomnia Starting: 15 mg one time at bedtime Maintenance: 7.5 - 30 mg one time at bedtime Elderly: 7.5 mg one time at bedtime	Pharmacokinetics Peak plasma concentration: 1.5 hours Half-life (biphasic): Short: 0.4 - 0.6 hours Terminal: 8.8 hours Other Temazepam is a metabolite of diazepam [7] Temazepam appears to be safe in breastfeeding [7] Price Generic (30 capsules) - $

Drug

Dosage forms

Dosing

Other

Temazepam

Restoril®

Capsule

7.5 mg
15 mg
22.5 mg
30 mg

Insomnia

Starting: 15 mg one time at bedtime
Maintenance: 7.5 - 30 mg one time at bedtime
Elderly: 7.5 mg one time at bedtime

Pharmacokinetics

Peak plasma concentration: 1.5 hours
Half-life (biphasic):

Short: 0.4 - 0.6 hours
Terminal: 8.8 hours

Other

Temazepam is a metabolite of diazepam [7]
Temazepam appears to be safe in breastfeeding [7]

Price

Generic (30 capsules) - $

BENZODIAZEPINE SIDE EFFECTS
Drowsiness Loss of coordination Memory impairment Trouble speaking (dysarthria) Fatigue/tiredness Confusion Altered libido - increased or decreased Appetite changes - increased or decreased Low blood pressure (hypotension) Dizziness Increased salivation - clonazepam

BENZODIAZEPINE PRECAUTIONS / CONTRAINDICATIONS
All benzodiazepines Pregnancy - benzodiazepines may cause fetal harm and should be avoided in pregnancy Acute narrow angle glaucoma - acute narrow angle glaucoma is listed as a contraindication in most benzodiazepine package inserts. In the medical literature, there is very little information regarding this interaction. It's unclear if benzodiazepines have any effect on narrow-angle glaucoma. [8] Drug addiction and abuse - benzodiazepines are both psychologically and physically addictive medications. Use caution in susceptible patients. Withdrawal reactions - abrupt withdrawal reactions including heightened perception, impaired concentration, alteration in sense of smell, paresthesias, muscle cramps, diarrhea, headache, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, and decreased appetite may occur Seizure - abrupt withdrawal or dose reductions may lead to seizures. Patients on higher doses and longer courses of therapy are at greater risk. Doses should be tapered slowly when appropriate. Decreased alertness - benzodiazepines depress CNS activity and may impair the ability to operate motor vehicles and other dangerous machinery Respiratory depression - benzodiazepines may suppress respiratory drive. Use with caution in patients with respiratory disease. Allergic reactions - in rare cases, benzodiazepines have been associated with anaphylactoid reactions including angioedema Neonatal withdrawal - infants born to mothers who are taking benzodiazepines may be at risk for withdrawal symptoms. Flaccidity and respiratory depression may occur immediately after birth. Nursing - most benzodiazepines are excreted in breastmilk and may cause lethargy and weight loss in exposed infants. Lorazepam, oxazepam, and temazepam appear to be safe in breastfeeding. [5,6,7] Kidney disease - elimination may be reduced. Use caution. Liver disease - elimination may be reduced. Use caution. Alprazolam (Xanax®) Asian patients - maximal concentrations and half-life are 15 - 25% higher in Asian patients Cigarette smoking - alprazolam concentrations may be reduced by as much as 50% in smokers compared to nonsmokers Uricosuric effect - alprazolam has a weak uricosuric effect

BENZODIAZEPINE PRECAUTIONS / CONTRAINDICATIONS

All benzodiazepines

Pregnancy - benzodiazepines may cause fetal harm and should be avoided in pregnancy
Acute narrow angle glaucoma - acute narrow angle glaucoma is listed as a contraindication in most benzodiazepine package inserts. In the medical literature, there is very little information regarding this interaction. It's unclear if benzodiazepines have any effect on narrow-angle glaucoma. [8]
Drug addiction and abuse - benzodiazepines are both psychologically and physically addictive medications. Use caution in susceptible patients.
Withdrawal reactions - abrupt withdrawal reactions including heightened perception, impaired concentration, alteration in sense of smell, paresthesias, muscle cramps, diarrhea, headache, anxiety, tension, depression, insomnia, restlessness, confusion, irritability, and decreased appetite may occur
Seizure - abrupt withdrawal or dose reductions may lead to seizures. Patients on higher doses and longer courses of therapy are at greater risk. Doses should be tapered slowly when appropriate.
Decreased alertness - benzodiazepines depress CNS activity and may impair the ability to operate motor vehicles and other dangerous machinery
Respiratory depression - benzodiazepines may suppress respiratory drive. Use with caution in patients with respiratory disease.
Allergic reactions - in rare cases, benzodiazepines have been associated with anaphylactoid reactions including angioedema
Neonatal withdrawal - infants born to mothers who are taking benzodiazepines may be at risk for withdrawal symptoms. Flaccidity and respiratory depression may occur immediately after birth.
Nursing - most benzodiazepines are excreted in breastmilk and may cause lethargy and weight loss in exposed infants. Lorazepam, oxazepam, and temazepam appear to be safe in breastfeeding. [5,6,7]
Kidney disease - elimination may be reduced. Use caution.
Liver disease - elimination may be reduced. Use caution.

Alprazolam (Xanax®)

Asian patients - maximal concentrations and half-life are 15 - 25% higher in Asian patients
Cigarette smoking - alprazolam concentrations may be reduced by as much as 50% in smokers compared to nonsmokers
Uricosuric effect - alprazolam has a weak uricosuric effect

BENZODIAZEPINE DRUG INTERACTIONS
All benzodiazepines Central Nervous System (CNS) Depressants - benzodiazepines may potentiate the effects of other CNS depressants (e.g. opiates, alcohol, anticonvulsants, antihistamines, etc.). Risk for adverse events may be increased. Use caution when combining. Alprazolam (Xanax®) CYP3A4 inducers and inhibitors - alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. Ketoconazole and itraconazole - alprazolam should not be given with ketoconazole or itraconazole since they are strong CYP3A4 inhibitors and toxicity may occur Digoxin - alprazolam may increase blood levels of digoxin Desipramine and imipramine - alprazolam may increase blood levels of desipramine and imipramine Chlordiazepoxide (Librium®) Disulfiram (Antabuse®) - disulfiram decreases the clearance of chlordiazepoxide. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [9] Clonazepam (Klonopin®) CYP3A4 inducers and inhibitors - clonazepam appears to be a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. Diazepam (Valium®) CYP3A4 inducers and inhibitors - diazepam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors. CYP2C19 inducers and inhibitors - diazepam is a CYP2C19 sensitive substrate. Use caution with CYP2C19 inducers and inhibitors. Disulfiram (Antabuse®) - disulfiram decreases the clearance of diazepam. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [9,11] Lorazepam (Ativan®) Valproate - valproate decreases lorazepam clearance. Lorazepam dose should be decreased by 50% when taken with valproate. Probenecid - probenecid decreases lorazepam clearance. Lorazepam dose should be decreased by 50% when taken with probenecid. Temazepam (Restoril®) Disulfiram (Antabuse®) - disulfiram may decrease the clearance of temazepam. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [12]

BENZODIAZEPINE DRUG INTERACTIONS

All benzodiazepines

Central Nervous System (CNS) Depressants - benzodiazepines may potentiate the effects of other CNS depressants (e.g. opiates, alcohol, anticonvulsants, antihistamines, etc.). Risk for adverse events may be increased. Use caution when combining.

Alprazolam (Xanax®)

CYP3A4 inducers and inhibitors - alprazolam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.
Ketoconazole and itraconazole - alprazolam should not be given with ketoconazole or itraconazole since they are strong CYP3A4 inhibitors and toxicity may occur
Digoxin - alprazolam may increase blood levels of digoxin
Desipramine and imipramine - alprazolam may increase blood levels of desipramine and imipramine

Chlordiazepoxide (Librium®)

Disulfiram (Antabuse®) - disulfiram decreases the clearance of chlordiazepoxide. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [9]

Clonazepam (Klonopin®)

CYP3A4 inducers and inhibitors - clonazepam appears to be a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.

Diazepam (Valium®)

CYP3A4 inducers and inhibitors - diazepam is a CYP3A4 sensitive substrate. Use caution with CYP3A4 inducers and inhibitors.
CYP2C19 inducers and inhibitors - diazepam is a CYP2C19 sensitive substrate. Use caution with CYP2C19 inducers and inhibitors.
Disulfiram (Antabuse®) - disulfiram decreases the clearance of diazepam. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [9,11]

Lorazepam (Ativan®)

Valproate - valproate decreases lorazepam clearance. Lorazepam dose should be decreased by 50% when taken with valproate.
Probenecid - probenecid decreases lorazepam clearance. Lorazepam dose should be decreased by 50% when taken with probenecid.

Temazepam (Restoril®)

Disulfiram (Antabuse®) - disulfiram may decrease the clearance of temazepam. Consider using another benzodiazepine that has not been shown to interact with disulfiram (alprazolam, oxazepam, lorazepam). [12]

BENZODIAZEPINE WITHDRAWAL SYMPTOMS
Overview Withdrawal symptoms typically develop within 2 - 3 days with shorter-acting agents and within 5 - 10 days with longer-acting agents Withdrawal symptoms can be psychiatric, autonomic, and neurologic Psychiatric symptoms Anxiety Insomnia Depression Irritability Psychosis/delirium Autonomic symptoms Tremor Sweating Nausea and vomiting Shortness of breath Increased heart rate Elevated blood pressure Muscle tension Neurologic symptoms Seizures Cognitive impairment Memory impairment Sound sensitivity Photophobia Hypersomnia Muscle tension/spasms Motor tics

BENZODIAZEPINE WITHDRAWAL SYMPTOMS

Overview

Withdrawal symptoms typically develop within 2 - 3 days with shorter-acting agents and within 5 - 10 days with longer-acting agents
Withdrawal symptoms can be psychiatric, autonomic, and neurologic

Psychiatric symptoms

Anxiety
Insomnia
Depression
Irritability
Psychosis/delirium

Autonomic symptoms

Tremor
Sweating
Nausea and vomiting
Shortness of breath
Increased heart rate
Elevated blood pressure
Muscle tension

Neurologic symptoms

Seizures
Cognitive impairment
Memory impairment
Sound sensitivity
Photophobia
Hypersomnia
Muscle tension/spasms
Motor tics

BENZODIAZEPINE WITHDRAWAL PREVENTION / TREATMENT
Prevention - taper dose In order to prevent withdrawal symptoms, benzodiazepines should be tapered over a period of 4 - 8 weeks Patients who are taking multiple benzodiazepines should be switched to one, preferably diazepam because it has a long half-life Regimens for tapering include the following: Reduce the dose by 50% every week OR Reduce the daily dose by 10 - 25% every 2 weeks [14] Treatment Patients taking very high doses (e.g. ≥ 100 mg of diazepam or equivalent a day) should have inpatient withdrawal Treatment of withdrawal symptoms may include the following: Insomnia - trazodone, mirtazapine, melatonin, antihistamines Depression and mood disorders - SSRIs, mood stabilizer (e.g. carbamazepine), antipsychotics Anxiety - beta blockers, SSRIs, gabapentin, hydroxyzine, buspirone [14]

BENZODIAZEPINE WITHDRAWAL PREVENTION / TREATMENT

Prevention - taper dose

In order to prevent withdrawal symptoms, benzodiazepines should be tapered over a period of 4 - 8 weeks
Patients who are taking multiple benzodiazepines should be switched to one, preferably diazepam because it has a long half-life

Regimens for tapering include the following:

Reduce the dose by 50% every week OR
Reduce the daily dose by 10 - 25% every 2 weeks [14]

Treatment

Patients taking very high doses (e.g. ≥ 100 mg of diazepam or equivalent a day) should have inpatient withdrawal
Treatment of withdrawal symptoms may include the following:

Insomnia - trazodone, mirtazapine, melatonin, antihistamines
Depression and mood disorders - SSRIs, mood stabilizer (e.g. carbamazepine), antipsychotics
Anxiety - beta blockers, SSRIs, gabapentin, hydroxyzine, buspirone [14]