NAYZILAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NAYZILAM (NAYZILAM).
Nayzilam (midazolam) is a benzodiazepine that enhances the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in increased chloride ion conductance, neuronal hyperpolarization, and inhibition of neuronal activity.
| Metabolism | Midazolam is primarily metabolized by the cytochrome P450 (CYP) 3A4 and CYP3A5 isoenzymes to its major metabolite, 1-hydroxymidazolam (also pharmacologically active), which is further glucuronidated. |
| Excretion | Renal excretion as metabolites (primarily glucuronide conjugates) and unchanged drug; approximately 15% recovered in urine as unchanged midazolam, with the remainder as metabolites; <1% excreted in feces via biliary elimination. |
| Half-life | Terminal elimination half-life of midazolam is 1.5–2.5 hours, but for NAYZILAM (midazolam nasal spray) the effective half-life for anticonvulsant effect is approximately 2–3 hours due to prolonged absorption; clinical context: used for seizure clusters, duration of effect may persist for 4–6 hours. |
| Protein binding | Approximately 97% bound to serum albumin; binding is saturable at high concentrations. |
| Volume of Distribution | Volume of distribution is 1–1.5 L/kg for midazolam; for NAYZILAM, systemic absorption yields a Vd of approximately 1.1 L/kg, reflecting extensive tissue distribution and high lipophilicity. |
| Bioavailability | Intranasal absolute bioavailability is approximately 50–60% compared to intravenous midazolam; relative bioavailability is consistent across doses. |
| Onset of Action | Intranasal: 10–15 minutes (range 5–20 minutes) to achieve therapeutic plasma concentrations; clinical effect on seizure cessation typically observed within 5–10 minutes. |
| Duration of Action | Duration of anticonvulsant effect is approximately 4–6 hours; clinical note: seizure recurrence may occur after 4–6 hours, and a second dose may be administered after 10 minutes if needed. |
5 mg intranasally as a single dose; may repeat once after 10 minutes if needed. Maximum 10 mg per episode.
| Dosage form | SPRAY |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh A or B): no adjustment. Severe hepatic impairment (Child-Pugh C): not recommended due to risk of excessive sedation. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; monitor for increased sensitivity and prolonged sedation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NAYZILAM (NAYZILAM).
| Breastfeeding | Midazolam is excreted into breast milk in small amounts (M/P ratio approximately 0.34). Oral bioavailability is low, but exposure in neonates may cause sedation. Use with caution; monitor infant for drowsiness and feeding difficulties. |
| Teratogenic Risk | NAYZILAM (midazolam) is a benzodiazepine. First trimester: Associated with a small increased risk of oral clefts (odds ratio ~2.0). Second and third trimesters: Chronic maternal use may lead to neonatal withdrawal, hypotonia, and respiratory depression after delivery. Avoid use near delivery due to risk of floppy infant syndrome. |
■ FDA Black Box Warning
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; AND DEPENDENCE AND WITHDRAWAL REACTIONS. Concomitant use of benzodiazepines with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate. Abuse, misuse, and addiction: The use of benzodiazepines, including NAYZILAM, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Dependence and withdrawal reactions: Abrupt discontinuation or rapid dose reduction of benzodiazepines may precipitate acute withdrawal reactions, which can be life-threatening.
| Serious Effects |
["Hypersensitivity to midazolam or any component of the formulation","Acute narrow-angle glaucoma"]
| Precautions | ["Concomitant use with opioids: risk of profound sedation, respiratory depression, coma, and death","Abuse, misuse, and addiction","Dependence and withdrawal reactions","Risk of respiratory depression","Use in patients with compromised respiratory function","Suicidal thinking and behavior","Central nervous system (CNS) depression","Use in elderly and debilitated patients","Use in patients with hepatic impairment","Use in patients with renal impairment"] |
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| Fetal Monitoring | Monitor maternal respiratory rate, oxygen saturation, and level of sedation. For fetal assessment, consider fetal heart rate monitoring after maternal administration, especially near delivery. In chronic use, monitor neonatal adaptation at birth. |
| Fertility Effects | Animal studies have shown no significant adverse effects on fertility. Human data are limited; no well-documented impact on fertility. |