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
Title | Posted | Study ID | Phase | Status | Sponsor |
---|---|---|---|---|---|
2025/06/27 | Not Applicable | Recruiting | CAMC Health System | ||
2025/06/13 | Phase 1 | Not yet recruiting | |||
2025/06/10 | Phase 3 | ENROLLING_BY_INVITATION | Minia University | ||
2025/05/20 | Phase 1 | Not yet recruiting | |||
2025/05/15 | Phase 1 | Active, not recruiting | |||
2025/05/09 | Phase 1 | Recruiting | |||
2025/05/08 | Phase 1 | Not yet recruiting | Chinese PLA General Hospital | ||
2025/05/04 | Phase 3 | Not yet recruiting | Federal University of São Paulo | ||
2025/04/28 | Phase 1 | Completed | |||
2025/04/18 | Phase 4 | Not yet recruiting | First Affiliated Hospital of Wannan Medical College |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
---|---|---|---|---|---|
Hospira, Inc. | 0409-2308 | INTRAMUSCULAR, INTRAVENOUS | 5 mg in 1 mL | 9/23/2022 | |
Steriscience Specialties Private Limited | 82449-205 | INTRAMUSCULAR, INTRAVENOUS | 5 mg in 1 mL | 12/13/2023 | |
Precision Dose Inc. | 68094-764 | ORAL | 2 mg in 1 mL | 12/22/2023 | |
Major Pharmaceuticals | 0904-7113 | ORAL | 2 mg in 1 mL | 10/28/2021 | |
Atlantic Biologicals Corps | 17856-0205 | ORAL | 2 mg in 1 mL | 10/19/2009 | |
Hikma Pharmaceuticals USA Inc. | 0641-6209 | INTRAMUSCULAR, INTRAVENOUS | 1 mg in 1 mL | 4/7/2023 | |
Hikma Pharmaceuticals USA Inc. | 0641-6220 | INTRAMUSCULAR, INTRAVENOUS | 1 mg in 1 mL | 3/29/2024 | |
Steriscience Specialties Private Limited | 82449-207 | INTRAVENOUS, INTRAMUSCULAR | 1 mg in 1 mL | 12/13/2023 | |
Imprimis NJOF, LLC | 71384-410 | SUBLINGUAL | 3 mg in 1 1 | 3/4/2019 | |
Cantrell Drug Company | 52533-001 | INTRAVENOUS | 1 mg in 1 mL | 1/14/2016 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
---|---|---|---|
Authorised | 9/4/2011 | ||
Authorised | 9/4/2011 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
---|---|---|---|---|---|
DORMICUM INJECTION 5 mg/5 ml | SIN03800P | INJECTION | 1 mg/ml | 2/1/1990 | |
DORMICUM TABLET 15 mg | SIN00476P | TABLET, FILM COATED | 15 mg | 4/27/1988 | |
MIDAZOLAM-HAMELN 5 MG/ML INJECTION | SIN12553P | INJECTION | 5 mg/ml | 6/16/2004 | |
MIDAZOLAM-BAXTER SOLUTION FOR INJECTION 5 MG/ML | SIN15419P | INJECTION, SOLUTION | 5mg/ml | 2/8/2018 | |
MIDAZOLAM-BAXTER SOLUTION FOR INJECTION 1 MG/ML | SIN15418P | INJECTION, SOLUTION | 1 mg/mL | 2/8/2018 | |
DORMICUM INJECTION 15 mg/3 ml | SIN00478P | INJECTION | 5 mg/ml | 4/27/1988 | |
DOMI INJECTION 5 mg/ml | SIN11039P | INJECTION | 5 mg/ml | 7/22/1999 | |
MIDAZOLAM KALCEKS SOLUTION FOR INJECTION/INFUSION 1 MG/ML | SIN16967P | INJECTION, SOLUTION | 1.0mg/mL | 3/5/2024 | |
MIDAZOLAM-HAMELN 1 MG/ML INJECTION | SIN12549P | INJECTION | 1 mg/ml | 6/3/2004 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
---|---|---|---|---|---|
Midazolam Oral Solution | 国药准字H20213321 | 化学药品 | 口服溶液剂 | 4/27/2021 | |
Midazolam Maleate Tablets | 国药准字H20253111 | 化学药品 | 片剂 | 1/8/2025 | |
Midazolam Maleate Tablets | 国药准字H20041869 | 化学药品 | 片剂 | 7/14/2020 | |
Midazolam Maleate Tablets | 国药准字HJ20140591 | 化学药品 | 片剂 | 6/17/2024 | |
Midazolam Injection | 国药准字H20031037 | 化学药品 | 注射剂 | 7/14/2020 | |
Midazolam Injection | 国药准字H20243614 | 化学药品 | 注射剂 | 4/24/2024 | |
Midazolam Injection | 国药准字H20237070 | 化学药品 | 注射剂 | 6/27/2023 | |
Midazolam Injection | 国药准字H20227066 | 化学药品 | 注射剂 | 5/19/2022 | |
Midazolam Injection | 国药准字H20153019 | 化学药品 | 注射剂 | 7/5/2021 | |
Midazolam Injection | 国药准字H20113433 | 化学药品 | 注射剂 | 7/5/2021 |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
---|---|---|---|---|---|
DORMICUM INJ 5MG/5ML | N/A | N/A | N/A | 1/5/1990 |