Intranasal Delivery of Antiepileptic Medications for Treatment of Seizures

Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are medical emergencies. Mortality and poor neurologic outcome are directly associated with the duration of seizure activity. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Diazepam rectal gel was developed due to the need for non-injection-based delivery; however, the aesthetics of rectal delivery are not popular with patients and caregivers.
Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures at home or when actively seizing patients arrive in the emergency room. There are many factors that a practitioner and compounding pharmacist must consider when choosing a benzodiazepine for intranasal administration, including solubility of the drug, ease of passing the blood-brain barrier, and pharmacokinetic/pharmacodynamic profiles. Concentration is important as the nasal cavity can retain approximately 0.1-0.15 ml.
Under ideal conditions, most medication is absorbed from the nasal cavity and into the bloodstream within 15 to 20 minutes, thus generally avoiding the first-pass gut metabolism. Increased nasal mucus production is commonly observed with actively seizing patients, so it may be prudent to suction mucus from the nasal cavity prior to administration of intranasal midazolam. Intranasal midazolam has been extensively studied in epilepsy patients. Various devices have been used to deliver 0.2 mg/kg of midazolam injection intranasally.
Morbidity and mortality, as well as health-care resources and expenses associated with treatment of epileptic patients, could be reduced if an effective and safe transmucosal treatment was available for use by caregivers.

Neurotherapeutics. 2009 Apr;6(2):352-8.
Intranasal delivery of antiepileptic medications for treatment of seizures.
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Midazolam nasal spray has been used to reduce procedural anxiety in children, anxiety-related dyspnea, and to prevent MRI-induced claustrophobia.

Intranasal Midazolam for Managing Prolonged Seizures

Intranasal midazolam is a safe and practical alternative to rectal diazepam for managing prolonged seizures in non-hospitalized patients.

J Intellect Dev Disabil 2006 Sep;31(3):131-8
Community use of intranasal midazolam for managing prolonged seizures.
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Am J Emerg Med 2006 May;24(3):343-6
Intranasal midazolam therapy for pediatric status epilepticus.
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