Overview
Midazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties. It belongs to a class of drugs called benzodiazepines. This drug is unique from others in this class due to its rapid onset of effects and short duration of action. Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in various biomedical applications, including dentistry, cardiac surgery, and endoscopic procedures as pre-anesthetic medication, and as an adjunct to local anesthesia. This drug was initially approved by the US FDA in 1985, and has been approved for various indications since. In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults. In May 2019, the nasal spray of midazolam was approved for the acute treatment of distinctive intermittent, stereotypic seizure episodes in patients 12 years of age and older. Midazolam is considered a schedule IV drug in the United States due to the low potential for abuse and low risk of dependence.
Background
Midazolam is a short-acting hypnotic-sedative drug with anxiolytic, muscle relaxant, anticonvulsant, sedative, hypnotic, and amnesic properties. It belongs to a class of drugs called benzodiazepines. This drug is unique from others in this class due to its rapid onset of effects and short duration of action. Midazolam is available by oral, rectal, intranasal, intramuscular (IM), and intravenous (IV) routes and has been used in various biomedical applications, including dentistry, cardiac surgery, and endoscopic procedures as pre-anesthetic medication, and as an adjunct to local anesthesia. This drug was initially approved by the US FDA in 1985, and has been approved for various indications since. In late 2018, the intramuscular preparation was approved by the FDA for the treatment of status epilepticus in adults. In May 2019, the nasal spray of midazolam was approved for the acute treatment of distinctive intermittent, stereotypic seizure episodes in patients 12 years of age and older. Midazolam is considered a schedule IV drug in the United States due to the low potential for abuse and low risk of dependence.
Indication
Midazolam has different indications depending on its formulation by the FDA. Nasal For the nasal spray formulation, midazolam is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. Intravenous For the intravenous injection formulation, midazolam is indicated as an agent for sedation/anxiolysis/amnesia and prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants. The sedative, anxiolytic and amnestic use of midazolam can also be employed pre-operatively. It can also be indicated for induction of general anesthesia, before administration of other anesthetic agents or as a component of intravenous supplementation of nitrous oxide and oxygen for a balanced anesthesia. A relatively narrower dose range of midazolam and a shorter period of induction can be achieved if midazolam is combined with narcotic premedication. Finally, midazolam can be indicated as a continous intravenous infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in a critical care setting. Intramuscular For the intramusuclar injection formulation, midazolam is indicated for preoperative sedation/anxiolysis/amnesia or for treatment of status epilepticus in adults. Oral Midazolam syrup is indicated for use in pediatric patients for sedation, anxiolysis and amnesia prior to diagnostic, therapeutic or endoscopic procedures or before induction of anesthesia. It is only approved in monitored settings only and not for chronic or home use. In Europe, a buccal formulation of midazolam is also approved for the treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 3 months to < 18 years). For infants between 3-6 months of age treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available.
Associated Conditions
- Epileptic seizure
- Status Epilepticus
Research Report
Midazolam: A Comprehensive Pharmacological and Clinical Review
I. Introduction to Midazolam
A. Overview, Chemical Properties, and Brand Names
Midazolam is a potent, short-acting benzodiazepine characterized by a rapid onset of action. It is extensively utilized in clinical practice for managing seizures, inducing and maintaining anesthesia, and alleviating anxiety, particularly in procedural settings.[1] As a small molecule drug, it is identified by DrugBank ID DB00683 and CAS Number 59467-70-8.[1]
Chemically, midazolam is 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a]benzodiazepine. A notable characteristic of its formulation is its pH-dependent solubility. In acidic solutions, such as those used for parenteral preparations, midazolam exists as an equilibrium mixture of its closed-ring form and an open-ring structure. The open-ring form contributes to its water solubility, which is advantageous for formulation. However, at physiological pH (approximately 7.4), the equilibrium shifts significantly towards the lipophilic, pharmacologically active closed-ring form, facilitating its rapid passage across the blood-brain barrier and subsequent central nervous system (CNS) effects.[2] The presence of an imidazole ring in its structure is crucial for this pH-dependent characteristic, as well as for its stability in aqueous solutions and its rapid metabolic degradation.[3] This unique chemical behavior—water solubility for administration and lipophilicity for action—is a cornerstone of its rapid onset and clinical versatility, distinguishing it from many other benzodiazepines and underpinning its widespread application in acute medical situations.[2]
Midazolam is marketed under various brand names globally, including Versed®, Seizalam®, Nayzilam®, and Buccolam®.[1]
Table 1: Midazolam - Key Identifiers and Properties
Clinical Trials
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Title | Posted | Study ID | Phase | Status | Sponsor |
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2025/04/18 | Phase 4 | Not yet recruiting | First Affiliated Hospital of Wannan Medical College | ||
2025/04/09 | Phase 1 | Completed | |||
2025/04/08 | Phase 1 | Recruiting | |||
2025/04/08 | Phase 1 | Completed | |||
2025/03/20 | Phase 4 | Completed | Hanoi Medical University | ||
2025/03/17 | Not Applicable | ENROLLING_BY_INVITATION | |||
2025/03/17 | Phase 3 | Not yet recruiting | |||
2025/03/10 | Phase 1 | Completed | |||
2025/02/19 | Phase 2 | Not yet recruiting | Asklepieion Voulas General Hospital | ||
2025/02/12 | Phase 1 | Completed | Ahon Pharmaceutical Co., Ltd. |
FDA Drug Approvals
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Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Athenex Pharmaceutical Division, LLC. | 70860-600 | INTRAVENOUS, INTRAMUSCULAR | 2 mg in 2 mL | 3/4/2024 | |
Henry Schein, Inc. | 0404-9914 | INTRAVENOUS, INTRAMUSCULAR | 5 mg in 1 mL | 1/13/2022 | |
Wockhardt USA LLC. | 64679-763 | INTRAMUSCULAR, INTRAVENOUS | 5 mg in 1 mL | 12/5/2017 | |
Cantrell Drug Company | 52533-001 | INTRAVENOUS | 1 mg in 1 mL | 5/1/2014 | |
Hikma Pharmaceuticals USA Inc. | 0143-9380 | INTRAVENOUS | 1 mg in 1 mL | 1/19/2023 | |
Cantrell Drug Company | 52533-157 | INTRAVENOUS | 0.5 mg in 1 mL | 1/12/2015 | |
Hikma Pharmaceuticals USA Inc. | 0641-6218 | INTRAMUSCULAR, INTRAVENOUS | 5 mg in 1 mL | 3/29/2024 | |
Hospira, Inc. | 0409-2305 | INTRAMUSCULAR, INTRAVENOUS | 1 mg in 1 mL | 1/3/2023 | |
Major Pharmaceuticals | 0904-7114 | ORAL | 2 mg in 1 mL | 10/28/2021 | |
Bryant Ranch Prepack | 72162-1109 | ORAL | 2 mg in 1 mL | 10/25/2023 |
EMA Drug Approvals
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Approved Product | Authorization Holder | Status | Issued Date |
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No EMA approvals found for this drug. |
HSA Drug Approvals
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Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
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No HSA approvals found for this drug. |
NMPA Drug Approvals
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Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
---|---|---|---|---|---|
Midazolam Injection | 国药准字H20227065 | 化学药品 | 注射剂 | 5/19/2022 | |
Midazolam Injection | 国药准字H20243613 | 化学药品 | 注射剂 | 4/24/2024 | |
Midazolam Injection | 国药准字H20243615 | 化学药品 | 注射剂 | 4/24/2024 | |
Midazolam Injection | 国药准字H20067040 | 化学药品 | 注射剂 | 5/7/2021 | |
Midazolam Injection | 国药准字H20067041 | 化学药品 | 注射剂 | 5/7/2021 | |
Midazolam Injection | 国药准字H19990027 | 化学药品 | 注射剂 | 7/14/2020 | |
Midazolam Injection | 国药准字H10980025 | 化学药品 | 注射剂 | 7/14/2020 | |
Midazolam Injection | 国药准字H20031071 | 化学药品 | 注射剂 | 7/14/2020 | |
Midazolam Injection | 国药准字H20223202 | 化学药品 | 注射剂 | 4/8/2022 | |
Midazolam Injection | 国药准字H20143222 | 化学药品 | 注射剂 | 7/14/2020 |
PPB Drug Approvals
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Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
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No PPB approvals found for this drug. |
TGA Drug Approvals
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