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. |
| Molecular Weight | 323.14 |
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 | Avoid due to potential risk of major congenital malformations; limited data, but rare case reports of cleft palate with benzodiazepines. |
| 2nd trimester | Use only if clearly needed; risk of fetal benzodiazepine exposure associated with preterm birth and low birth weight. |
| 3rd trimester | Avoid; neonatal withdrawal (floppy infant syndrome, respiratory depression) and hypotonia possible with chronic use. |
Clinical note
Comprehensive clinical and safety monograph for NAYZILAM (NAYZILAM).
| Placental transfer | Crosses placenta; measurable fetal serum levels achieved rapidly after maternal administration. |
| Breastfeeding | Excreted into breast milk in low amounts; monitor infant for sedation, poor feeding, and weight gain. Use caution, especially with repeated doses. |
■ 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 benzodiazepineAcute narrow-angle glaucomaSevere respiratory insufficiency (COPD with hypercapnia, sleep apnea)
| 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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| Lactation Rating |
| L3 (Moderately Safe) |
| 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. |
| 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. |
| Food/Dietary | None known. Naloxone is not affected by food intake as it is administered intranasally. No dietary restrictions required. |
| Clinical Pearls | NAYZILAM (naloxone hydrochloride nasal spray) is indicated for the emergency treatment of known or suspected opioid overdose, including respiratory or central nervous system depression. For maximal efficacy, administer at the first sign of opioid overdose, such as unresponsiveness or respiratory depression. One spray delivers 4 mg naloxone; a second dose may be given after 2-3 minutes if needed. Repeat doses may be necessary due to half-life of naloxone (shorter than many opioids); monitor for recurrence of overdose. Use in patients with known or suspected opioid dependence may precipitate acute withdrawal. Store at controlled room temperature (20°C-25°C). |
| Patient Advice | Use NAYZILAM exactly as prescribed for emergency opioid overdose. · Administer one spray into one nostril; if no response after 2-3 minutes, administer a second dose in the other nostril. · Call emergency medical services immediately after administering first dose. · Lay patient on their back, support neck, and insert nozzle into nostril; press plunger firmly to release dose. · After administration, turn patient on their side (recovery position) to prevent aspiration if vomiting occurs. · Report any signs of opioid withdrawal (e.g., agitation, nausea, sweating) to healthcare provider. · Do not use if seal is broken or expired. Store at room temperature away from light and moisture. |