Nayzilam

• 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

  5.1 Risks from Concomitant Use with Opioids

  Concomitant use of benzodiazepines, including NAYZILAM, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for patients for whom alternative treatment options are inadequate.

  Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe NAYZILAM concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when NAYZILAM is used with opioids

  [see Drug Interactions (7.2)]

  .

  and

  7.2 Opioids

  ]

  .
• 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

  5.2 Abuse, Misuse, and Addiction

  The use of benzodiazepines, including NAYZILAM, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death

  [see Drug Abuse and Dependence (9.2)]

  .

  Before prescribing NAYZILAM and throughout treatment, assess each patient's risk for abuse, misuse, and addiction. Use of NAYZILAM, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of NAYZILAM along with monitoring for signs and symptoms of abuse, misuse, and addiction. Do not exceed the recommended dosing frequency; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. If a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate.

  ].
• 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

  1 INDICATIONS AND USAGE

  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.

  and

  2 DOSAGE AND 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.

  2.1 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.

  2.2 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)]

  .

  ]

  , 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

  5.3 Dependence and Withdrawal Reactions After Use of NAYZILAM More Frequently Than Recommended

  For patients using NAYZILAM more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue NAYZILAM (a patient-specific plan should be used to taper the dose). Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use.

  Acute Withdrawal Reactions

  The continued use of benzodiazepines may lead to clinically significant physical dependence. 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, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures)

  [see Drug Abuse and Dependence (9.3)].

  Protracted Withdrawal Syndrome

  In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months

  [see Drug Abuse and Dependence (9.3)]

  .

  ].

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.

Administer NAYZILAM by the nasal route only. (

NAYZILAM is supplied as a single-dose nasal spray unit containing 5 mg of midazolam in 0.1 mL solution.