Diazepam: Difference between revisions
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MDElliottMD (talk | contribs) Comprehensive categorization: +GABAA Positive Allosteric Modulators (General), GABAergics, Anticonvulsants / Antiepileptics, Muscle Relaxants (CNS-acting) |
Safety wave: 2020 FDA benzo-class boxed warning (Sept 23 2020) |
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{{MedTemplate | {{MedTemplate | ||
| generic | | generic = Diazepam | ||
| brand | | brand = Valium (oral, IV/IM, rectal), Diastat (rectal gel for breakthrough seizures), Valtoco (nasal spray for breakthrough seizures), Libervant (buccal film) | ||
| structure | | structure = | ||
| classes | | classes = [[:Category:Benzodiazepines|Benzodiazepine (long-acting)]], [[:Category:Anxiolytics|Anxiolytic]], [[:Category:Anticonvulsants|Anticonvulsant]], [[:Category:Skeletal muscle relaxants|Skeletal muscle relaxant]], [[:Category:Schedule IV controlled substances|Schedule IV controlled substance]] | ||
| | | uses = <vote slug="anxiety-disorders-broad-use">Anxiety disorders (FDA)</vote>, <vote slug="alcohol-withdrawal-use">Alcohol withdrawal (FDA; the classic indication for long-acting benzodiazepines)</vote>, <vote slug="preoperative-sedation-use">Preoperative sedation (FDA)</vote>, <vote slug="status-epilepticus-use">Status epilepticus (FDA, IV)</vote>, <vote slug="breakthrough-seizures-use">Breakthrough seizures (FDA, Diastat rectal gel; Valtoco intranasal)</vote>, <vote slug="acute-muscle-spasm-use">Acute muscle spasm (FDA, IV/IM)</vote>, <vote slug="cerebral-palsy-spasticity-use">Cerebral palsy spasticity (FDA)</vote> | ||
| uses | | starting_dose = Anxiety: 2-10 mg PO 2-4 times daily. Alcohol withdrawal: 10-20 mg PO/IV every 4-6 hours, symptom-triggered. Status epilepticus: 5-10 mg IV. Breakthrough seizures: Diastat rectal 0.2-0.5 mg/kg or Valtoco intranasal 5-20 mg | ||
| starting_dose | | preparations = Tablets 2, 5, 10 mg; oral solution 1, 5 mg/mL; injection 5 mg/mL; Diastat rectal gel 2.5, 5, 10, 20 mg; Valtoco nasal spray 5, 7.5, 10 mg/dose; Libervant buccal film | ||
| preparations | | fda_max = 40 mg/day (oral, anxiety) | ||
| fda_max = | | pill_id = | ||
| routes | | routes = Oral, IV, IM, rectal, intranasal, buccal | ||
| onset | | onset = 15-60 minutes (oral); 1-5 minutes (IV); 4-10 minutes (rectal or intranasal) | ||
| duration | | duration = 6-24 hours (parent); much longer when accounting for the long-lived active metabolites | ||
| halflife | | halflife = Diazepam 20-50 hours; '''N-desmethyldiazepam (nordazepam) 30-200 hours''' is the major active metabolite and accumulates substantially with chronic dosing<ref name="valium-label">FDA Prescribing Information, Valium (diazepam), Roche/Bausch, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/013263s094lbl.pdf</ref> | ||
| bioavailability | | bioavailability = ~93% (oral); ~90% (rectal)<ref name="valium-label" /> | ||
| pregnancy | | pregnancy = Some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.{{citation needed}} | ||
| legal | | legal = [[USLegal:Schedule IV|Schedule IV controlled substance]] in US. Carries the benzodiazepine class '''Boxed Warning''' for risk of fatal respiratory depression, coma, and death when combined with opioids<ref name="valium-label" /> | ||
| | | mechanism = <vote slug="diazepam-mech-claim">Classic positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and producing the full benzodiazepine effect spectrum: anxiolysis, anticonvulsant activity, skeletal muscle relaxation, and sedation. The very long elimination half-life combined with the even-longer-lived active metabolite nordazepam is the clinical signature, producing stable plasma levels with infrequent dosing.</vote> The pharmacokinetic profile produces '''self-tapering withdrawal''' as plasma levels gradually decline, the basis of diazepam's preference in alcohol withdrawal protocols. CYP3A4 and CYP2C19 substrate; CYP3A4 inhibitors substantially raise exposure<ref name="valium-label" />. | ||
| | | monitoring = '''Boxed warning:''' in September 2020 the FDA required an updated boxed warning across the benzodiazepine class for the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020.</ref> Physical dependence can develop with continued use even at prescribed doses, and abrupt discontinuation or rapid dose reduction can precipitate acute, sometimes life-threatening withdrawal (including seizures), so prolonged use requires a gradual, individualized taper. This is in addition to the earlier boxed warning for fatal respiratory depression, coma, and death when benzodiazepines are combined with opioids or other CNS depressants.<ref>U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016.</ref> | ||
| monitoring | |||
}} | }} | ||
== References == | |||
<references /> | |||
[[Category:Benzodiazepines]] | [[Category:Benzodiazepines]] | ||
[[Category:Anxiolytics]] | [[Category:Anxiolytics]] | ||
[[Category: | [[Category:Anticonvulsants]] | ||
[[Category: | [[Category:Skeletal muscle relaxants]] | ||
[[Category:Schedule IV controlled substances]] | |||
[[Category: | |||
Latest revision as of 18:33, 29 June 2026
Benzodiazepine (long-acting), Anxiolytic, Anticonvulsant, Skeletal muscle relaxant, Schedule IV controlled substance
Diazepam
Valium (oral, IV/IM, rectal), Diastat (rectal gel for breakthrough seizures), Valtoco (nasal spray for breakthrough seizures), Libervant (buccal film)
Experience
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Problems
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Effects
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Monitoring
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Relevant Literature
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Pharmacy
Starting dose
Anxiety: 2-10 mg PO 2-4 times daily. Alcohol withdrawal: 10-20 mg PO/IV every 4-6 hours, symptom-triggered. Status epilepticus: 5-10 mg IV. Breakthrough seizures: Diastat rectal 0.2-0.5 mg/kg or Valtoco intranasal 5-20 mg
Preparations
Tablets 2, 5, 10 mg; oral solution 1, 5 mg/mL; injection 5 mg/mL; Diastat rectal gel 2.5, 5, 10, 20 mg; Valtoco nasal spray 5, 7.5, 10 mg/dose; Libervant buccal film
US FDA Max
40 mg/day (oral, anxiety)
Common uses
Classification(s)
Pharmacology
Routes
Oral, IV, IM, rectal, intranasal, buccal
Onset
15-60 minutes (oral); 1-5 minutes (IV); 4-10 minutes (rectal or intranasal)
Duration
6-24 hours (parent); much longer when accounting for the long-lived active metabolites
Half-life
Diazepam 20-50 hours; N-desmethyldiazepam (nordazepam) 30-200 hours is the major active metabolite and accumulates substantially with chronic dosing[1]
Bioavailability
~93% (oral); ~90% (rectal)[1]
Pregnancy
Some signal for cleft palate with first-trimester exposure (debated); neonatal sedation and withdrawal with third-trimester exposure.[citation needed]
Legal status
Schedule IV controlled substance in US. Carries the benzodiazepine class Boxed Warning for risk of fatal respiratory depression, coma, and death when combined with opioids[1]
Purported mechanism
Classic positive allosteric modulator of the GABA-A receptor at the benzodiazepine binding site (α-γ subunit interface), enhancing chloride ion conductance and producing the full benzodiazepine effect spectrum: anxiolysis, anticonvulsant activity, skeletal muscle relaxation, and sedation. The very long elimination half-life combined with the even-longer-lived active metabolite nordazepam is the clinical signature, producing stable plasma levels with infrequent dosing.0 The pharmacokinetic profile produces self-tapering withdrawal as plasma levels gradually decline, the basis of diazepam's preference in alcohol withdrawal protocols. CYP3A4 and CYP2C19 substrate; CYP3A4 inhibitors substantially raise exposure[1].
Pharmacopedia is intended for reference. Nothing here is advice. In an emergency call 911; US Poison Control 1-800-222-1222. See the full disclaimer.
References
- ↑ 1.0 1.1 1.2 1.3 FDA Prescribing Information, Valium (diazepam), Roche/Bausch, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/013263s094lbl.pdf
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: FDA requiring Boxed Warning updated to improve safe use of benzodiazepine drug class. September 23, 2020.
- ↑ U.S. Food and Drug Administration. Drug Safety Communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines. August 31, 2016.