Dosage & Administration
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.
By using PrescriberAI, you agree to the AI Terms of Use.
Nayzilam Prescribing Information
- 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 [see Warnings and Precautions (5.1) and Drug Interactions (7.2)].
- The use of benzodiazepines, including NAYZILAM, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing NAYZILAM and throughout treatment, assess each patient's risk for abuse, misuse, and addiction [see Warnings and Precautions (5.2)].
- The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although NAYZILAM is indicated only for intermittent use [see Indications and Usage (1) and Dosage and Administration (2)], if used more frequently than recommended abrupt discontinuation or rapid dosage reduction of NAYZILAM may precipitate acute withdrawal reactions, which can be life-threatening. For patients using NAYZILAM more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue NAYZILAM [see Warnings and Precautions (5.3)].
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.
Instructions Prior to Dosing
NAYZILAM prescribers should consider the following 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 [see Warnings and Precautions (5.4)].
Prior to treatment, the healthcare professional should instruct the individual administering NAYZILAM on how to identify seizure clusters and use the product appropriately [see Patient Counseling Information: Administration Information (17)]. Patients and caregivers should be counseled to read carefully the "Instructions for Use" for complete directions on how to properly administer NAYZILAM.
Dosage Information
Administer NAYZILAM by the nasal route only.
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 [see Warnings and Precautions (5.4)].
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 [see Drug Abuse and Dependence (9.4)].
NAYZILAM is supplied as a single-dose nasal spray unit containing 5 mg of midazolam in 0.1 mL solution.
Pregnancy
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as NAYZILAM, during pregnancy. Healthcare providers are encouraged to recommend that pregnant women who are taking NAYZILAM during pregnancy enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.
Risk Summary
Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.9) and Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data).
Administration of midazolam to rats and rabbits during the period of organogenesis or to rats during late pregnancy and throughout lactation at doses greater than those used clinically did not result in any apparent adverse effects on development (see Animal Data). However, published data for midazolam and other benzodiazepines suggest the possibility of neuronal cell death and long-term effects on neurobehavioral and immunological function in animals following prenatal or early postnatal exposure at clinically relevant doses.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to NAYZILAM during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to NAYZILAM during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.9)].
Data
Human Data
Published data from observational studies on the use of benzodiazepines during pregnancy do not report a clear association with benzodiazepines and major birth defects. Although early studies reported an increased risk of congenital malformations with diazepam and chlordiazepoxide, there was no consistent pattern noted. In addition, the majority of more recent case-control and cohort studies of benzodiazepine use during pregnancy, which were adjusted for confounding exposures to alcohol, tobacco and other medications, have not confirmed these findings.
Animal Data
When midazolam (0, 0.2, 1, or 4 mg/kg/day) was administered intravenously to pregnant rats during the period of organogenesis, no adverse effects on embryofetal development were observed. The highest dose tested, which was associated with minimal evidence of maternal toxicity, is approximately 4 times the maximum recommended human dose (MRHD) of 10 mg based on body surface area (mg/m2).
When midazolam (0, 0.2, 0.6, and 2 mg/kg/day) was administered intravenously to rabbits during the period of organogenesis, no adverse effects on embryofetal development were reported. The high dose, which was not associated with evidence of maternal toxicity, is approximately 4 times the MRHD on a mg/m2 basis.
When midazolam (0, 0.2, 1, or 4 mg/kg/day) was administered intravenously to female rats during late gestation and throughout lactation, no clear adverse effects were noted in the offspring. The high dose, which was not associated with evidence of maternal toxicity, is approximately 4 times the MRHD on a mg/m2 basis.
In published animal studies, administration of benzodiazepines, including midazolam, or other drugs that enhance GABAergic neurotransmission to neonatal rats has been reported to result in widespread apoptotic neurodegeneration in the developing brain at plasma concentrations relevant for seizure control in humans. The window of vulnerability to these changes in rats (postnatal days 0-14) includes a period of brain development corresponding to that taking place during the third trimester of pregnancy in humans.
Lactation
Risk Summary
Midazolam is excreted in human milk. There are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk. There are no data on the effects of midazolam on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for NAYZILAM and any potential adverse effects on the breastfed infant from NAYZILAM or from the underlying maternal condition.
Clinical Considerations
Infants exposed to NAYZILAM through breast milk should be monitored for sedation, poor feeding and poor weight gain.
Pediatric Use
Safety and effectiveness of NAYZILAM have been evaluated in the age group 12 to 17 years. Use of NAYZILAM in this age group is supported by evidence from an adequate and well-controlled study of NAYZILAM in adults and adolescents with seizure clusters [see Clinical Studies (14)] and pharmacokinetic and safety data from adult and pediatric patients [see Clinical Pharmacology (12.3)].
Safety and effectiveness in pediatric patients below the age of 12 years have not been established.
Geriatric Use
Safety and efficacy studies of NAYZILAM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Geriatric patients have longer elimination half-lives for midazolam and its metabolites, which may result in prolonged drug exposure. Geriatric patients may have altered drug distribution; diminished hepatic and/or renal function; and subjects over 70 years of age may be particularly sensitive [see Clinical Pharmacology (12.3)]. Administration of intramuscular (IM) midazolam to elderly patients has been associated with rare reports of death under circumstances compatible with cardiorespiratory depression [see Warnings and Precautions (5.4)]. In most of these cases, the patients also received other CNS depressants capable of depressing respiration, especially narcotics [see Warnings and Precautions (5.1, 5.5)]. Close monitoring of geriatric patients is recommended.
Renal Impairment
Based on a population pharmacokinetic analysis of patients administered NAYZILAM, midazolam and 1-OH midazolam pharmacokinetics are expected to be similar in subjects with mild renal impairment when compared to normal subjects. Safety and efficacy studies of NAYZILAM did not include patients with severe renal impairment and there were not enough subjects with moderate renal impairment in clinical studies for population pharmacokinetic analysis. Patients with moderate and severe renal impairment may have slower elimination of midazolam and its metabolites, which may result in prolonged drug exposure [see Clinical Pharmacology (12.3)].
Congestive Heart Failure
Patients with congestive heart failure eliminate midazolam more slowly, which may result in prolonged drug exposure [see Clinical Pharmacology (12.3)].
NAYZILAM is contraindicated in patients with:
- Known hypersensitivity to midazolam.
- Acute narrow-angle glaucoma [see Warnings and Precautions (5.8)].