Clinically significant pharmacokinetic drug interactions with benzodiazepines
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The reports of interactions between benzodiazepines (BZPs) and other drugs (e.g., antidepressants, selective serotonin reuptake inhibitors, antiulcer drugs, antiepileptic drugs, macrolide antibiotics) during their combined use are reviewed. In general, metabolism of BZPs is delayed when combined with a number of other drugs but some reports have suggested otherwise. In recent years, the cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of BZPs has also been identified. BZPs are mainly catalysed by CYP3A4. When published reports are studied, it appears necessary to be exceptionally careful about interactions mainly between BZPs and selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics and antimycotics. More information is necessary to identify individuals at greatest risk of drug interactions and adverse events.
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Benzodiazepine metabolism is primarily catalyzed by CYP-dependent hydroxylation, demethylation, and nitroreduction.
“Benzodiazepine metabolism is primarily catalyzed by CYP-dependent hydroxylation, demethylation and nitroreduction (26,44,45).”
From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [44]
Potent enzyme inducers such as phenytoin, phenobarbital, and carbamazepine substantially increase clearance and reduce the half-life of certain benzodiazepines.
“Conversely, potent enzyme inducers (e.g.phenytoin, phenobarbital and carbamazepine) substantially increase clearance and reduce the t 1 ⁄ 2 of certain BZDs (44).”
From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [44]
Benzodiazepines interact with certain antidepressants, antiepileptic drugs, sedative antihistamines, opiates, antipsychotics, and alcohol, potentially causing additive sedative effects.
“Benzodiazepines interact with other drugs such as certain antidepressants, AEDs (e.g.phenobarbital, phenytoin and carbamazepine), sedative antihistamines, opiates, antipsychotics and alcohol (44,57,59), which may result in additive sedative effects.”
From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [44]
Selective serotonin reuptake inhibitors, cimetidine, macrolide antibiotics, and antimycotics may inhibit CYP isoenzymes and benzodiazepine metabolism, increasing plasma benzodiazepine concentrations.
“Clinicians should exercise particular caution when using BZDs with selective serotonin reuptake inhibitors, cimetidine, macrolide antibiotics and antimycotics; these drugs may inhibit reactions catalyzed by certain CYP isoenzymes and, therefore, inhibit the metabolism of many BZDs, which results in increased plasma BZD concentrations (44).”
From Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics (2008) · cites this paper as [44]
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Cited by
Sorted by citations
Benzodiazepines in epilepsy: Pharmacology and pharmacokinetics
Riss, J., Cloyd, J., Gates, J., & Collins, S. (2008) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.2008.01004.x · Cited by 511 · see citing works
Gender-related differences in pharmacokinetics and their clinical significance
Tanaka, E. (1999) · Journal of Clinical Pharmacy and Therapeutics · doi:10.1046/j.1365-2710.1999.00246.x · Cited by 281 · see citing works
Self-citationBenzodiazepines and sleep architecture: a systematic review
Sousa Martins Silva, A., de Mendonça, F. M. R., de Mendonça, G. P. R. R., Souza, L. C., Galvão, L. P., Paiva, H. S., de Azevedo Marques Périco, C., Torales, J., Ventriglio, A., & Maurício Castaldelli-Maia, J. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210618103344 · Cited by 149 · see citing works
- Authors
- Tanaka, E.
- Affiliations
- University of Tsukuba (JP)
- Corresponding author
- Tanaka, E.
- Venue
- Journal of Clinical Pharmacy and Therapeutics
- Publisher
- Wiley
- Published
- 1999-10
- Volume
- 24
- Issue
- 5
- Pages
- 347-355
- ISSN
- 0269-4727 (ISSN-L)
- 1365-2710
- OpenAlex
- W2150753312
- Cited by
- 52
- References
- 103
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2021: 4 · 2020: 1 · 2018: 1 · 2017: 3 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 0.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Pharmacy and Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and pharmacology of benzodiazepine derivatives
- Keywords
- benzodiazepines, drug interactions, pharmacokinetics, CYP3A4, selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics, antidepressants, drug metabolism, adverse drug reactions
- MeSH terms
- Animals, Benzodiazepines, Drug Interactions, Humans, Anti-Anxiety Agents
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