Diazepam: Difference between revisions
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MDElliottMD (talk | contribs) parser-claude: Diazepam MedTemplate refill, Top 300 stub upgrade |
Safety wave: 2020 FDA benzo-class boxed warning (Sept 23 2020) |
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| 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" /> | | 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" />. | | 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> | |||
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