Products
Midazolam is commercially available as film-coated tablets and as a solution for injection (Dormicum, generic). It has been approved in many countries since 1982. Midazolam nasal spray has not yet been registered in many countries and must be prepared in a pharmacy as an extemporaneous formulation or imported. In 2012, a solution for use in the oral cavity was approved (Buccolam). In 2020, an oral solution was registered (Ozalin).
Structure and properties
Midazolam (C
18
H
13
ClFN
3
, M
r
= 325.8 g/mol) belongs to the imidazobenzodiazepines. It exists as a white to slightly yellow crystalline powder and is insoluble in water as a base. In the tablets, it is present as midazolammaleate. The solution for injection and the solution for oral use contain midazolam hydrochloride, which is soluble in water.
Effects
Midazolam (ATC N05CD08) has antianxiety, sedative, sleep-inducing, anticonvulsant properties and causes anterograde amnesia. The effects are rapid in onset and last only a short time. The effects are due to binding to GABA.
A
-receptors in the brain. It thereby enhances the effect of the inhibitory neurotransmitter GABA in the central nervous system.
Indications
- For the treatment of sleep disorders and as a sedative before surgical or diagnostic procedures with or without anesthesia.
- Prolonged acute seizures in infants, children and adolescents (Buccolam).
Abuse
Midazolam, like all benzodiazepines, can be abused as a narcotic and sedative.
Dosage
According to the prescribing information. Tablets should be taken with liquid immediately before bedtime because the effect is rapid. The duration of treatment should be kept as short as possible. After a longer treatment period, the drug must be gradually discontinued to avoid withdrawal symptoms.
Contraindications
- Hypersensitivity
- Severe breathing disorders
- Severe hepatic insufficiency
- Myasthenia gravis
- Sleep apnea syndrome
Midazolam must not be combined with the azole antifungals ketoconazole, itraconazole, voriconazole, and HIV protease inhibitors. These are potent CYP inhibitors that inhibit the breakdown of the active ingredient. For complete precautions, see the drug label.
Interactions
Midazolam is metabolized by CYP3A4. Corresponding drug-drug interactions are possible and should be noted. Combination with potent CYP inhibitors is not indicated because plasma concentrations may increase, leading to an increase in adverse effects and intoxication. Conversely, CYP inducers may attenuate the effects of the drug. Other interactions are possible with centrally depressant and respiratory depressant drugs and substances and with alcohol.
Adverse effects
Possible adverse effects include fatigue; increased risk of falls and fractures; psychiatric disorders such as confusion, aggression, and delusions; visual disturbances; slowing of breathing to the point of respiratory failure; skin reactions; and muscle weakness. Benzodiazepines can be addictive and cause withdrawal symptoms when discontinued rapidly.