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Pharmacotherapy: A Review of Benzodiazepines
By: Shaun Gutstein, PharmD
August 13th & 14th, 2019
Conflict of Interest and Disclosures of Relevant Financial
Relationships
The planners and presenters (spouse/domestic partner) of this educational activity have disclosed no healthcare related conflicts of interest, commercial interest, or have any related financial relationships/support.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Contact Hours: Nursing1.0 Contact Hour
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Objectives
1. Review the pharmacology of benzodiazepinesavailable in the United States
2. Examine the various uses of benzodiazepines inthe hospice setting, including whenbenzodiazepine use may not be appropriate
3. Calculate equivalent benzodiazepine doses
History
1955: Hoffmann-La Roche chemist, Dr. Leo Sternbach,identified the 1st benzodiazepine: chlordiazepoxide(Librium®)
1963: Diazepam (Valium) was developed
1970s: Benzodiazepines topped most frequentlyprescribed lists as popularity skyrocketed due to aperception of improved safety over barbiturates
Today: 14 unique benzodiazepines are approved bythe U.S. Food and Drug Administration (FDA)
Wick J. Consult Pharm. 2013.
Dr. Leo Sternback, Hoffman-La Roche lab
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Benzodiazepines
Generic Name Brand Name (s)Approximate Dose Equivalence (mg)
Alprazolam Xanax; Xanax XR; Alprazolam Intensol 0.5
Chlordiazepoxide Librium 10
Clobazam Onfi; Sympazan N/A
Clonazepam Klonopin 0.25
Clorazepate Tranxene 7.5
Diazepam Valium; Diastat; Diazepam Intensol 5
Estazolam ProSom N/A
Flurazepam Dalmane 30
Lorazepam Ativan; Ativan Intensol 1
Midazolam Versed 2
Oxazepam Serax 15
Quazepam Doral N/A
Temazepam Restoril 30
Triazolam Halcion 0.25
Lexicomp. 2019.
Mechanism of Action (MoA)
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Indications
• Insomnia• Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam
• Anxiety• Alprazolam, Chlordiazepoxide, Clorazepate, Diazepam, Lorazepam, Midazolam, Oxazepam
• Panic disorders• Alprazolam, Clonazepam
• Seizures• Clobazam, Clonazepam, Clorazepate, Diazepam, Lorazepam
• Muscle relaxant• Diazepam
• Alcohol withdrawal• Chlordiazepoxide, Clorazepate, Diazepam, Oxazepam
• Anesthesia• Lorazepam, Midazolam
Lexicomp. 2019.
Pharmacokinetics: Half-Life (t1/2)Benzodiazepine Parent t1/2 (hours) Active Metabolites (Max t1/2) Factors Extending t1/2
Short-Acting
Triazolam 1.5 – 5.5 Yes (5.5) Liver, Kidney, Age, DDI
Midazolam 1.8 - 6.8 Yes (6.8) Liver, Kidney, Obesity, Age, DDI
Intermediate-Acting
Oxazepam 6 – 11 No Liver, Kidney, Age, Females
Lorazepam 12 – 18 No Liver, RoA
Temazepam 3.5 – 18.4 No Liver
Estazolam 10 – 24 No Liver, DDI
Alprazolam 6.3 - 26.9 Negligible Liver, Obesity, Age, DDI
Clonazepam 17 – 60 No Liver
Long-Acting
Clorazepate Negligible Yes (160) Liver, Kidney, DDI
Flurazepam 2.5 Yes (160) Liver, Kidney, Age
Clobazam 36 – 42 Yes (82) Liver, Kidney, DDI, Age, Race
Chlordiazepoxide 24 - 48 Yes (95) Liver
Quazepam 39 Yes (73) Liver, Kidney, DDI, Age
Diazepam 44 - 72 Yes (174) Liver, Kidney, Age, DDI, RoA
DDI: Drug-Drug Interaction; RoA: Route of AdministrationLexicomp. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Relation of Half-Life to Clinical Indications of Benzodiazepines
• Generalized anxiety disorder (GAD)• Post-traumatic stress disorder, chronic (PTSD)
LongLong
• Post-traumatic stress disorder, acute• Panic disorder• Atypical anxiety disorder
IntermediateIntermediate
• Insomnia• Premedication for anesthesia• Atypical anxiety disorder• Panic disorder
ShortShort
Warnings/ Precautions
Black Box Warning:Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients for signs and symptoms of respiratory depression and sedation.
A retrospective study by the University of Pittsburgh School of Pharmacyshowed a 5-fold increase in the risk of opioid-related overdose during theinitial 90 days and an increase of 1.87 times on days 91 to 180
Estimated that more than 30% of opioid overdoses involve benzodiazepines
Initiate benzodiazepine (or opioid) at a lower doses (e.g. 20-50% dosereduction) and titrate based on response and tolerability
Hernandez I. JAMA. 2018.U.S. Food and Drug Administration. 2016.
National Institute on Drug Abuse. 2018.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Side Effect Profile
Central Nervous Systemo Depressant (drowsiness,
sedation, confusion, alteredstatus)
o Anterograde amnesia
o Paradoxical reactions
Gastrointestinalo Constipation
o Changes in appetite
o Xerostomia
Cardiovascularo Hypotension
Genitourinaryo Changes in urination
patterns (retention)
Ophthalmico Visual disturbance
Lexicomp. 2019.
American Geriatrics Society Beers Criteria
Tool to improve medication safety in older adults
All benzodiazepines increase risk of cognitive impairment, delirium,falls, and fractures
Older adults have increased sensitivity to benzodiazepines anddecreased metabolism of long-acting agents
Long-acting agents may be appropriate for seizure disorders, rapid eyemovement sleep disorders, benzodiazepine withdrawal, ethanolwithdrawal, severe generalized anxiety disorder, and periproceduralanesthesia in older adults
Short-acting agents (classified by AGS): Alprazolam, Estazolam,Lorazepam, Oxazepam, Temazepam, Triazolam
American Geriatrics Society 2015 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2015.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Drug Interactions
CYP3A4
Alprazolam
Chlordiazepoxide
Clobazam
Clorazepate
Diazepam
Estazolam
Midazolam
Quazepam
Triazolam
CYP2C9
Clobazam
Clorazepate
Diazepam
Quazepam
Barbie'S Car Goes Real Phast:
o CYP Inducers Barbiturates
Smoking/ St. John’s Wort
Carbamazepine
Griseofulvin
Rifampin
Phenytoin
G ♥ PACMAN:o CYP Inhibitors
Grapefruit
Protease Inhibitors
Azole antifungals
Cyclosporine, Cimetidine
Macrolides (not Azithromycin)
Amiodarone
Non-DHP CCBs (Diltiazem and Verapamil)
Lexicomp. 2019.
LOT Benzodiazepines
ALL Benzodiazepines are metabolized by the liver
The ‘LOT’ benzodiazepines are metabolized by direct, rapid conjugation
o L - Lorazepam
o O - Oxazepam
o T – Temazepam
Do not have active metabolites
Half-life remains relatively the same even in the setting of liver disease
Hayes BD. ALiEM. 2013.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Triazolam (Halcion®)
Available Formulations: tablet ($$-$$$)
Route(s) of Administration: PO
FDA Approved Indications: Insomnia
Off-Label Indications: Dental preprocedural oral sedation
Special Notes: Rapid onset (15-30min) and shorterduration of action/ t1/2 (7 hrs/ up to 5.5hrs)
Triazolam. Lexi-Drugs Online. 2019.
Midazolam (Versed®)
Available Formulations: Solution for injection ($-$$), oral syrup ($$$)
Route(s) of Administration: Solution for injection may be administered IV, IM,Subcut, IN, BUC, or PR
FDA Approved Indications:
o Anesthesia, Preoperative/ procedural sedation/ anxiolysis/ amesia (includingmechanically ventillated patients)
Off-Label Indications:
o Palliative sedation, Status epilepticus (SE)
Intranasal dosing for SE: Midazolam 5mg/mL solution for injection 0.2 mg/kg
o ½ of total dose into each nare, NTE 1mL per nare
o Use of atomizer may reduce pH induced mucosal irritation
Midazolam. Lexi-Drugs Online. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Lorazepam (Ativan®)
Available Formulations: tablet ($), oral solution ($$),solution for injection ($)
Route(s) of Administration: PO, SL, BUC, IV, IM, Subcut, PR
FDA Approved Indications: Anxiety, Insomnia due toanxiety, Anesthesia, Status epilepticus
Off-Label Indications: Alcohol withdrawal delirium/syndrome, Chemotherapy-induced nausea/ vomiting,Psychogenic catatonia, Agitation
Lorazepam. Lexi-Drugs Online. 2019.
Temazepam (Restoril®)
Available Formulations: capsule ($)
o Note: 7.5 and 22.5 mg capsules ($$$)
Route(s) of Administration: PO
FDA Approved Indications: Insomnia
Off-Label Indications: N/A
Special Notes: Low potency (30mg Temazepam = 1mgLorazepam); Consider benzodiazepine tolerance
Temazepam. Lexi-Drugs Online. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Alprazolam (Xanax®)
Available Formulations: tablet ($), oral-disintegratingtablet ($$$), oral solution ($$$)
Route(s) of Administration: PO, SL, PR
FDA Approved Indications: Anxiety and Panic Disorders
Off-Label Indications: Preoperative anxiety
Alprazolam. Lexi-Drugs Online. 2019.
Clonazepam (Klonopin®)
Available Formulations: tablet ($), oral-disintegrating tablet ($$$)
Route(s) of Administration: PO, SL, PR
FDA Approved Indications: Panic and Seizure Disorders
Off-Label Indications: Bipolar disorder (mixed or mania), Burning mouthsyndrome, Essential Tremor, Restless Leg Syndrome, Tardive dyskinesia, Ticdisorders, REM sleep behavior disorder
Special Notes: One of the most widely studied benzodiazepines for movementdisorders with anxious component due to pharmacokinetic profile
Clonazepam. Lexi-Drugs Online. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Diazepam (Valium®)
Available Formulations: tablet ($), oral solution ($$), Solution for injection($), Rectal gel ($$$)
Route(s) of Administration: PO, SL, PR, IV, IM
Oral absorption is more reliable than IM
FDA Approved Indications: Acute alcohol withdrawal, Anxiety, Muscle spasms,Seizure disorders (including Status epilepticus)
Off-Label Indications: Sedation (ICU)
Diazepam. Lexi-Drugs Online. 2019.
Insomnia
Most hypnotic benzodiazepines have rapid absorption and onset of action
o Pharmacokinetic differences can be used to clinical advantage
Sleep onset difficulties or morning sedation: Use short half-life benzodiazepine (e.g. Triazolam)
Sleep maintenance difficulties: Use longer half-life benzodiazepine (e.g. Temazepam)
Although some FDA-approved for insomnia and others for anxiety, they havesimilar pharmacodynamic properties
Ex: May use Lorazepam or Clonazepam
Note: Using multiple benzodiazepines can lead to additive effects rather thandistinct effects on different symptoms
Ex: Using Temazepam + Lorazepam
Buysse DJ. JAMA. 2013.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Breathlessness
Definition: Subjective experience of breathing discomfort which may be aresult of physiological (e.g. COPD), psychological (e.g. anxiety), andenvironmental factors (e.g. dry air)
o AKA: Dyspnea, shortness of breath, breathing difficulty, labored breathing
o One of the most common symptoms in the last year of life
Mechanism: Anxiolysis, thus relief of breathlessness
o Benzodiazepines have no effect on respiration in normal doses, (slight depressionof ventilation in higher doses)
Cochrane meta-analysis of 214 participants in eight studies that met criteria
o Only patients with COPD and cancer
Simon ST, et. al. Cochrane Database Syst Rev. 2016.
Breathlessness
No evidence for a beneficial effect of benzodiazepines in the relief ofbreathlessness in people with advanced cancer and COPD
o There is a non-significant beneficial effect, but the overall effect size is small
Consider benzodiazepines as 2nd or 3rd line treatment, when opioids and non-pharmacological measures have failed
No differences regarding the type of benzodiazepine, dose, mode andfrequency of administration, and duration of treatment.
Simon ST, et. al. Cochrane Database Syst Rev. 2016.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Agitation Benzodiazepines act on GABA receptors in the brain producing inhibitory/ sedative effects
o In agitation involving psychosis, benzodiazepines alone may only sedate a patient
Design: Single-center, double-blind, RCT conducted at an acute palliative careunit at MD Anderson Cancer Center
o 93 patients with advanced cancer
Interventions: Placebo + Haloperidol IV vs. Haloperidol IV + Lorazepam IV Results:
o Mean Richmond Agitation and Sedation Scale (RASS) score prior to medicationadministration: 1.6 points
Placebo + Haloperidol: −2.3 points
Lorazepam + Haloperidol group −4.1 points
Required fewer rescue medications
Perceived to be more comfortable by both caregivers and nurses blinded to treatment assignment
No difference in adverse events, respiratory depression, or survival
Hui D, et. al. JAMA. 2017.Wilson MP, et. al. West J Emerg Med. 2012.
Acute Seizures/ Status Epilepticus (SE)
1st Line:o Midazolam IM (10mg for > 40kg, 5mg 13-40kg, single dose) OR
o Lorazepam IV (0.1mg/kg/dose, max 4mg/ dose, may repeat dose once) OR
o Diazepam IV (0.15-0.2mg/kg/dose, max 10mg/ dose, may repeat dose once)
2nd Line:o Diazepam PR (0.2-0.5mg/kg, max 20mg/ dose, single dose) OR
o Midazolam IN or BUC
Difficult to utilize parenteral therapies in the home/ nursing home setting
o Lorazepam 2-4mg PO/SL/PR q5min prn active seizure, NTE 8mg/ episode
o Diazepam 10mg PO/SL/PR, may repeat dose once
o Midazolam IN or BUC
Glauser T, et. al. Epilepsy Curr. 2016.Diazepam. Lexi-Drugs Online. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Seizure Maintenance Therapy
Benzodiazepine are useful when the patient is no longer able to utilize oralroute
o Many benzodiazepines may be administered SL or PR (e.g. Lorazepam,Clonazepam)
Minimal history is available
Clonazepam: 1.5 mg given in 3 divided doses; may increase by 0.5 to 1 mgevery 3rd until seizures are controlled or adverse effects seen (max: 20mg/day)
Lorazepam: 0.5 – 2 mg po 2-4 times daily
Clonazepam. Lexi-Drugs Online. 2019.Lorazepam. Lexi-Drugs Online. 2019.
Myoclonus
Diazepam’s skeletal muscle relaxant properties 1st described in initial studiesdating back to its discovery in 1963
Myoclonic action of benzodiazepines is thought to be the enhancement ofGABA neurotransmission via benzodiazepine receptor in brain and spinal cord
o Treatment option for opioid-induced myoclonus
Dosing:
Diazepam 2-10mg po 3-4 times daily
Clonazepam 0.5-6mg/day or greater
Valium®. Roche Laboratories Inc. 2008.Caviness JN. Neurotherapeutics. 2014.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Nausea and Vomiting
GABA-mediated antiemetic and anxiolytic properties
Proven effective as an adjunct for chemotherapy inducednausea/ vomiting (CINV) and anticipatory nausea/vomiting (ANV)
Lorazepam 0.5 to 2 mg PO/SL/PR/IV q6h prn N/V
Lorazepam. Lexi-Drugs Online. 2019.Berger MJ, et. al. J Natl Compr Canc Netw. 2017.
Palliative Sedation
Use of sedative medications to reduce patients’ consciousness in orderto manage end-of-life symptoms that have become refractory andintolerable
Midazolam is metabolized to a lipophilic compound that rapidlypenetrates the central nervous system and brief duration of action
o Continuous infusion
Dosing: Midazolam continuous IV/ Subcut infusion: Initial: 0.5-1mg/hr
o Usual dosage range: 1 to 20 mg/hr
o May administer loading or intermittent bolus doses
Use of midazolam in this setting should be done in close consult withor by an experienced palliative care provider.
Midazolam. Lexi-Drugs Online. 2019.Cherny NI, et. al. Ann Oncol. 2014.
Maltoni M, et. al. J Clin Oncol. 2012
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Other Uses for End of Life Symptom Management
Hiccups:o Midazolam subcutaneous infusion 10-60mg/24hrs shown effective for
refractory intractable hiccups of peripheral etiology for terminal patient
Restless Leg Syndrome:o Useful to improve sleep and reduce anxiety
o Clonazepam 0.5-1mg po QHS has been studied
Essential Tremor (ET):o Alprazolam 0.125 to 3 mg/day or Clonazepam 0.5 to 6 mg/day showed
symptom improvement in small trials
Carlos K, et. al. Cochrane Database Syst Rev. 2017. Jeon YS, et. al. BMJ Support Palliat Care. 2018.
Zesiewicz TA, et. al. Neurology. 2005.
Discontinuing Benzodiazepines
Rebound/ withdrawal symptoms may occur following abrupt discontinuation orlarge decreases in dose
o Tremorso Anxietyo Perceptual disturbanceso Dysphoriao Psychosiso Seizures
Onset of withdrawal is variableo Period of use, how rapidly use was tapered, pharmacokinetics properties, genetics, use
of Flumazenil
Treatment: Long-acting benzodiazepine (e.g. Clonazepam, Diazepam), titrate toresponse (without adverse effect), then tapered over several months
Alprazolam. Lexi-Drugs Online. 2019.Chang F. CPJ. 2005.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Discontinuing Benzodiazepines
Strategies for Benzodiazepine Tapering:1. Low-Dose:
o Decrease by 20% each week
2. Direct taper:
o Decrease by 25% the first week, by 25% the second week, then by about 10% everyweek (even slower after prolonged use)
3. Diazepam:
o Convert to short or intermediate t1/2 BDZ at equivalent dose, then taper Decrease by 25% the 1st week, 25% the 2nd week, then by 12.5% every seven days
Start with 50% diazepam dose equivalent & reduce by 10% to 20% daily (5% to 10% if diazepam dose >60 mg)
Decrease diazepam equivalent by 2 mg every 1-2 weeks until 1/2 of initial dose reached, then by 1 mg every 1-2 weeks
4. Alprazolam:
o Decrease by no more than 0.5mg every three days.
o Consider slower taper for patients taking >4 mg/day for 3 months.
Alprazolam. Lexi-Drugs Online. 2019.Chang F. CPJ. 2005.
Flumazenil (Romazicon®)
FDA approved for BDZ reversal and management of overdose
BDZ Receptor Antagonist: Competitively inhibits the activity at thebenzodiazepine receptor site on the GABA/benzodiazepine receptorcomplex
o Does not antagonize effect ethanol, barbiturates, general anesthetics,and opioids
Rapidly acting with short half-life, must be administered repeatedly
May precipitate benzodiazepine withdrawal in patients who arebenzodiazepine dependent
Management of benzodiazepine overdose:
o Usual dosing: 0.2mg IV over 30 sec.; if the desired level of consciousness is not obtained30 sec. after the dose, 0.3mg can be given over 30 sec.
o Repeat doses: 0.5 mg over 30 sec at 1-min intervals, up to 3-5mg
Flumazenil. Lexi-Drugs Online. 2019.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Converting Benzodiazepines
Benzodiazepine Approximate Dose Equivalence (mg)
Alprazolam 0.5
Clonazepam 0.25
Diazepam 5
Lorazepam 1
Midazolam 2
Temazepam 30
PT is a 98 y.o. taking Diazepam 5mg PO TID. The MD would like to convert PT to Lorazepam. What is the correct dose?
Converting Benzodiazepines
2. Cross multiply
=
=
1. Set up ratio
3. Set up new equation
5 ∗ 15 ∗ 1
4. Solve for X
1 ∗ 15
5
5. Answer
orLorazepam1mgpoTID
The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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Questions?
Presenter: Shaun Gutstein, PharmD Contact: [email protected]
Coordinator: Suzanne Stewart Contact: [email protected]
References1. Alprazolam. In: Lexi-Drugs Online. New York, NY : Lexi-Comp, Inc.; Updated August 6, 2019; Accessed June 22, 2019.2. American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 Updated Beers Criteria for Potentially
Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2015; 63(11): 2227-46.3. Benzodiazepine Comparison Table. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. New York, NY. Available at: http://online.lexi.com.
Accessed June 22, 2019.4. Berger MJ, Ettinger DS, Aston J, et. al. NCCN Guidelines Insights: Antiemesis, Version 2.2017. J Natl Compr Canc Netw. 2017; 15(7): 883-893.5. Buysse DJ. Insomnia. JAMA. 2013; 309(7): 706-16. 6. Carlos K, Prado GF, Teixeira CD, et. al. Benzodiazepines for restless legs syndrome. Cochrane Database Syst Rev. 2017; 3: CD006937. Caviness JN. Treatment of Myoclonus. Neurotherapeutics. 2014; 11(1): 188–200.8. Center for Drug Evaluation and Research. New Safety Measures Announced for Opioid Analgesics, Prescription Opioid Cough Products, and
Benzodiazepines. U.S. Food and Drug Administration. https://www.fda.gov/drugs/information-drug-class/new-safety-measures-announced-opioid-analgesics-prescription-opioid-cough-products-and. Published August 31, 2016. Accessed June 22, 2019.
9. Chang F. Strategies for benzodiazepine withdrawal in seniors. CPJ. 2005; 138(8):38-40. 10. Cherny NI, ESMO Guidelines Working Group. ESMO Clinical Practice Guidelines for the management of refractory symptoms at the end of life and
the use of palliative sedation. Ann Oncol. 2014; 25 Suppl 3: iii143-52.11. Clonazepam. In: Lexi-Drugs Online. New York, NY : Lexi-Comp, Inc.; Updated August 5, 2019; Accessed June 22, 2019. 12. Flumazenil. In: Lexi-Drugs Online. New York, NY : Lexi-Comp, Inc.; Updated July 19, 2019; Accessed June 22, 2019.13. Glauser T, Shinnar S, Gloss D, et. al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the
Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016; 16(1): 48-61.14. Hayes BD. Academic Life in Emergency Medicine. All Benzodiazepines are Metabolized by the Liver. Available at:
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The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.
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The material in this presentation is for informational and educational purposes only and is not a substitute for medical advice, diagnosis, or treatment provided by a qualified health care provider. All information contained in this presentation is protected by copyright and remains the property of ProCare HospiceCare. All rights are reserved.