General Information

Nayzilam (midazolam) is a benzodiazepine.

Nayzilam is specifically 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 supplied as a spray for intranasal administration. The following should be considered prior to initiation of treatment:

• For patients at increased risk of respiratory depression from benzodiazepines, administration of Nayzilam under healthcare professional supervision should be considered prior to treatment with Nayzilam; this administration may be performed in the absence of a seizure episode.
• Prior to treatment, the healthcare professional should instruct the individual administering Nayzilam on how to identify seizure clusters and use the product appropriately. Patients and caregivers should be counseled to read carefully the “Instructions for Use” for complete directions on how to properly administer Nayzilam.

The recommended dose is as follows: Initial Dose: Administer one spray (5 mg dose) into one nostril. Second Dose (if needed): 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. A second dose of Nayzilam should not be administered if the patient has trouble breathing or if there is excessive sedation that is uncharacteristic of the patient during a seizure cluster episode. Maximum Dosage and Treatment Frequency: Do not use more than 2 doses of Nayzilam to treat a single episode. It is recommended that Nayzilam be used to treat no more than one episode every three days and no more than 5 episodes per month

Clinical Results

FDA Approval

The FDA approval of Nayzilam 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 was based on a randomized, double-blind, placebo-controlled trial. The trial enrolled patients with epilepsy on a stable regimen of antiepileptic drugs who were identified by their physicians as having intermittent, stereotypic episodes of frequent seizure activity that were distinct from the patient’s usual seizure pattern. The study was conducted in two phases: an open-label Test Dose Phase followed by a randomized, double-blind, placebo-controlled, Comparative Phase. In the Test Dose Phase, tolerability was assessed in 292 patients who, in the absence of a seizure, received two 5 mg doses of Nayzilam (10 mg total dosage) separated by 10 minutes. Patients were excluded from participation in the Comparative Phase if they failed to meet pre-defined blood pressure, heart rate, sedation, electrocardiogram, and peripheral oxygen saturation criteria. In the Comparative Phase, 201 patients treated a single seizure cluster episode in an outpatient setting with either a blinded dose of Nayzilam 5 mg (134 patients) or placebo (67 patients). If the seizure activity persisted or recurred, patients in both groups had the option to receive a subsequent unblinded dose of Nayzilam 5 mg to be used between 10 minutes and 6 hours after administration of the initial blinded dose of study drug. The primary efficacy endpoint was treatment success, defined as the termination of seizures within 10 minutes after the initial blinded dose of study drug and the absence of a recurrence of seizures within 6 hours of the initial blinded dose of study drug. A statistically significantly higher percentage of Nayzilam-treated patients met the primary efficacy endpoint. Numerical differences in favor of Nayzilam were observed on each of the components of the treatment success responder definition; termination of seizure(s) within 10 minutes after initial dose of study drug (80.6 versus 70.1%) and the absence of seizure recurrence between 10 minutes and 6 hours after the initial dose of study drug (58.2 versus 37.3%).

Side Effects

Adverse effects associated with the use of Nayzilam may include, but are not limited to, the following:

somnolence

headache

nasal discomfort

throat irritation

rhinorrhea

The Nayzilam drug label comes with the following Black Box Warning: Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.Reserve concomitant prescribing of these drugs for use in 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.