Midazolam

NAYZILAM 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. NAYZILAM is a benzodiazepine 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.

The exact mechanism of action for midazolam is not fully understood, but it is thought to involve potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA A receptor.

Administer NAYZILAM by the nasal route only. Initial Dose: Administer one spray (5 mg dose) into one nostril. Second Dose: One additional spray (5 mg dose) into the opposite nostril may be administered after 10 minutes if the patient has not responded to the initial dose. Maximum Dosage and Treatment Frequency: Do not use more than 2 doses of NAYZILAM to treat a seizure cluster. It is recommended that NAYZILAM be used to treat no more than one episode every three days and treat no more than five episodes per month.

NAYZILAM is contraindicated in patients with: Known hypersensitivity to midazolam. Acute narrow-angle glaucoma. Patients with hypersensitivity to midazolam. Patients with acute narrow-angle glaucoma

Boxed warning: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation. CNS Depression From Concomitant Use With Other CNS Depressants or Moderate or Strong CYP3A4 Inhibitors: May cause an increased CNS-depressant effect when used with alcohol or other CNS depressants. Concomitant use with moderate or strong CYP3A4 inhibitors may result in prolonged sedation because of a decrease in plasma clearance of midazolam. Suicidal Behavior and Ideation: Antiepileptic drugs increase the risk of suicidal ideation and behavior.

The following serious adverse reactions are discussed in more detail in other sections of the labeling: Risks from Concomitant Use with Opioids Abuse, Misuse, and Addiction Dependence and Withdrawal Reactions After Use of NAYZILAM More Frequently Than Recommended Risks of Cardiorespiratory Adverse Reactions CNS Depression from Concomitant Use with Other CNS Depressants or Moderate or Strong CYP3A4 Inhibitors Suicidal Behavior and Ideation Impaired Cognitive Function Glaucoma Neonatal Sedation and Withdrawal Syndrome Other Adverse Reactions The most common adverse reactions (≥5% in any NAYZILAM treatment group) were somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea

Table 3: Clinically Significant Drug Interactions With NAYZILAM CYP3A4 Inhibitors Clinical Impact: Concomitant use of CYP3A4 inhibitors may result in prolonged sedation because of a decrease in plasma clearance of midazolam. Intervention: Avoid co-administration of NAYZILAM with moderate or strong CYP3A4 inhibitors. NAYZILAM should be used with caution when co-administered with mild CYP3A4 inhibitors. Examples: Moderate CYP3A4 inhibitors: erythromycin, diltiazem, verapamil Strong CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin

Store at controlled room temperature 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F).