Nayzilam

Nayzilam is a prescription medicine used for the short-term treatment of seizure clusters (also known as “acute repetitive seizures”) in patients 12 years of age and older.

Nayzilam is a federal controlled substance (C-IV) because it can be abused or lead to dependence. Keep Nayzilam in a safe place to prevent misuse and abuse. Selling or giving away Nayzilam may harm others and is against the law. Tell your healthcare provider if you have abused or been dependent on alcohol, prescription drugs, or street drugs.

It is not known if Nayzilam is safe and effective in children under 12 years of age.

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.

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.

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, 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. 

Nayzilam may cause serious side effects, including:

• Impaired mental alertness including memory problems.
• Increase in eye pressure in people with acute narrow-angle glaucoma.
• See prescribing information for more on serious side effects of:
  • interaction with other central nervous system depressants
  • serious breathing problems and excessive sleepiness
  • suicidal thoughts or actions

The most common side effects of Nayzilam include:

• sleepiness
• headache
• runny nose
• nasal discomfort
• throat irritation

These are not all the possible side effects of Nayzilam. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088.

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.
• 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” information in the prescribing information 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.

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.

Table 3: Clinically Significant Drug Interactions with Nayzilam

Drug Abuse And Dependence

Controlled Substance

• Nayzilam contains the benzodiazepine midazolam, a Schedule IV controlled substance under the Controlled Substances Act.

Abuse

• Benzodiazepines, such as midazolam, may be subject to abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. Available data concerning the drug abuse and dependence potential of midazolam suggest that its abuse potential is at least equivalent to that of diazepam.
• The pharmacological profile of Nayzilam is similar to that of other benzodiazepines listed in Schedule IV of the Controlled Substance Act, particularly in its potentiation of GABAergic transmission through its action on GABA_A receptors, which leads to sedation and somnolence.
• Midazolam was actively self-administered in primate models used to assess the positive reinforcing effects of psychoactive drugs. Midazolam produced physical dependence of a mild to moderate intensity in cynomolgus monkeys after 5 to 10 weeks of administration.
• Assessment of the abuse-related subjective effects comparing Nayzilam to oral midazolam syrup was conducted in adult subjects with a history of benzodiazepine recreational drug use. No statistically significant or clinically-relevant differences in subjective positive effects (i.e., Drug Liking, Overall Drug Liking, Take Drug Again, and High) were observed between Nayzilam and oral midazolam syrup.
• However, subjective positive effects on all these measures were significantly greater for Nayzilam than for placebo confirming that Nayzilam has abuse potential. Somnolence occurred at a similar rate in both midazolam groups, but euphoric mood occurred at a greater rate in Nayzilam (4 to 16%) compared to the oral midazolam syrup (4 to 8.5%).

Dependence

• Physical dependence is a state of adaptation that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels of the drug, and/or administration of an antagonist.
• Benzodiazepines can cause physical dependence. Physical dependence results in withdrawal symptoms in patients who abruptly discontinue the drug. Withdrawal symptoms (i.e., convulsions, hallucinations, tremors, abdominal and muscle cramps, vomiting, and sweating), similar in characteristics to those noted with barbiturates and alcohol, have occurred following abrupt discontinuation of midazolam following chronic administration.

Chronic Use

• Nayzilam is not recommended for chronic, daily use as an anticonvulsant because of the potential for development of tolerance to midazolam. In clinical trials, patients were treated with Nayzilam no more frequently than every 3 days.
• Chronic daily use of benzodiazepines may increase the frequency and/or severity of tonic-clonic seizures, requiring an increase in the dosage of standard anticonvulsant medication.
• In such cases, abrupt withdrawal of chronic benzodiazepines may also be associated with a temporary increase in the frequency and/or severity of seizures.

• Use of Nayzilam late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate.
• Monitor neonates exposed to Nayzilam during pregnancy or labor for signs of sedation and monitor neonates exposed to Nayzilam during pregnancy for signs of withdrawal; manage these neonates accordingly.