Nayzilam Side Effects Center

Last updated on RxList: 1/29/2023
Nayzilam Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Nayzilam?

Nayzilam (midazolam) 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.

What Are Side Effects of Nayzilam?

Nayzilam may cause serious side effects including:

  • hives,
  • difficulty breathing,
  • swelling of your face, lips, tongue, or throat,
  • seizure,
  • bipolar disorder,
  • pain,
  • depression,
  • suicidal thoughts,
  • mood changes,
  • suicidal thoughts, and
  • severe dizziness

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Nayzilam include:

  • drowsiness,
  • headache,
  • nasal discomfort,
  • throat irritation, and
  • runny nose

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheadedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Nayzilam

The initial dose of Nayzilam is one spray (5 mg dose) administered into one nostril. A second dose of one additional spray (5 mg dose) Nayzilam may be administered into the opposite nostril after 10 minutes if the patient has not responded to the initial dose.

What Drugs, Substances, or Supplements Interact with Nayzilam?

Nayzilam may interact with other drugs that can make you sleepy (other benzodiazepines and sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, opioids, alcohol), ketoconazole, itraconazole, and clarithromycin. Tell your doctor all medications and supplements you use.

Nayzilam During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Nayzilaml it may harm a fetus. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as Nayzilam, during pregnancy. Nayzilam passes into breast milk. Consult your doctor before breastfeeding. Withdrawal symptoms may occur if you suddenly stop taking Nayzilam.

Additional Information

Our Nayzilam (midazolam) Nasal Spray Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

IMAGES

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Nayzilam Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Midazolam nasal can slow or stop your breathing, especially if you have recently used an opioid medication or alcohol. A person caring for you should seek emergency medical attention if you have slow breathing with long pauses, blue colored lips, or if you are hard to wake up.

Tell your doctor right away if you have new or sudden changes in mood or behavior, including new or worse depression or anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, more active or talkative, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • weak or shallow breathing;
  • confusion, paranoia, thoughts about suicide or hurting yourself;
  • a seizure; or
  • blurred vision, eye pain or redness, seeing halos around lights.

Common side effects may include:

  • drowsiness;
  • headache;
  • runny nose, discomfort in your nose; or
  • throat irritation.

After you stop using midazolam nasal, get medical help right away if you have symptoms such as: unusual muscle movements, being more active or talkative, sudden and severe changes in mood or behavior, confusion, hallucinations, seizures, suicidal thoughts or actions.

Some withdrawal symptoms may last up to 12 months or longer after stopping this medicine suddenly. Tell your doctor if you have ongoing anxiety, depression, problems with memory or thinking, trouble sleeping, ringing in your ears, a burning or prickly feeling, or a crawling sensation under your skin.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

What Is Epilepsy? Symptoms, Causes, and Treatments See Slideshow
Nayzilam Professional Information

SIDE EFFECTS

The following serious adverse reactions are discussed in more detail in other sections of the labeling:

  • Risks from Concomitant Use with Opioids [see WARNINGS AND PRECAUTIONS]
  • Abuse, Misuse, and Addiction [see WARNINGS AND PRECAUTIONS]
  • Dependence and Withdrawal Reactions After Use of NAYZILAM More Frequently Than Recommended [see WARNINGS AND PRECAUTIONS]
  • Risks of Cardiorespiratory Adverse Reactions [see WARNINGS AND PRECAUTIONS]
  • CNS Depression from Concomitant Use with Other CNS Depressants or Moderate or Strong CYP3A4 Inhibitors [see WARNINGS AND PRECAUTIONS]
  • Suicidal Behavior and Ideation [see WARNINGS AND PRECAUTIONS]
  • Impaired Cognitive Function [see WARNINGS AND PRECAUTIONS]
  • Glaucoma [see WARNINGS AND PRECAUTIONS]
  • Other Adverse Reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

NAYZILAM was studied for the outpatient treatment of a single seizure cluster in 292 adult and adolescent patients with epilepsy (Study 1) [see Clinical Studies]. The study was conducted in two phases; an open-label Test Dose Phase followed by a double-blind, placebo-controlled, Comparative Phase. The mean age of patients enrolled in the Comparative Phase (N=201) was 33 years, 51% were female, and 95% were White.

Table 2 lists the adverse reactions occurring in 2% or more of the NAYZILAM-treated patients and at a rate greater than the placebo-treated patients in the Comparative Phase of Study 1.

Table 2: Adverse Reactionsa that Occurred in ≥2% of Patients (Any NAYZILAM) and Greater than Placebo in the Comparative Phase of Study 1

Body System/Adverse Reaction Placebo
N = 26 %
NAYZILAMb
NAYZILAM 5 mg
N = 91 %
Placebo + NAYZILAM 5 mg
N = 41 %
NAYZILAM 5 mg + 5 mg
N = 43 %
Any NAYZILAM Treatment Group
N = 175 %
Nervous System
Somnolence 4 10 10 9 10
Headache 0 7 0 2 4
Dysarthria 0 2 2 2 2
Application Site
Nasal Discomfort 8 5 7 16 9
Throat Irritation 0 2 2 7 3
Rhinorrhea 0 3 0 5 3
Product Taste Abnormal 0 4 0 0 2
Eye Disorders
Lacrimation Increased 0 1 2 2 2
a Adverse reactions that occurred within 2 days after NAYZILAM administration are included
b Patients in Study 1 were permitted to take a second, open-label dose of NAYZILAM 5 mg between 10 minutes and 6 hours following the initial blinded dose of NAYZILAM 5 mg or placebo if they experience seizure recurrence or an incomplete resolution of the episode. The Placebo + NAYZILAM 5 mg and NAYZILAM 5 mg + 5 mg columns represent patients who received a second dose of NAYZILAM 5 mg and received a blinded initial dose of placebo or NAYZILAM 5 mg, respectively.

For patients who experienced a decrease in peripheral oxygen saturation in the Test Dose Phase of Study 1, the decreases were generally transitory. Two patients (one with a history of sleep apnea and one with intercurrent seizure) with decreases in peripheral oxygen saturation in the Test Dose Phase required therapeutic supplemental oxygen.

DRUG INTERACTIONS

CYP3A4 Inhibitors

Table 3: Clinically Significant Drug Interactions With NAYZILAM

Clinical Impact: Concomitant use of CYP3A4 inhibitors may result in prolonged sedation because of a decrease in plasma clearance of midazolam.
Intervention: Avoid co-administration of NAYZILAM with moderate or strong CYP3A4 inhibitors. NAYZILAM should be used with caution when co-administered with mild CYP3A4 inhibitors.
Examples: Moderate CYP3A4 inhibitors: erythromycin, diltiazem, verapamil Strong CYP3A4 inhibitors: ketoconazole, itraconazole, clarithromycin

Opioids

Clinical Impact: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAa sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists.
Intervention: 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 [see WARNINGS AND PRECAUTIONS].
Examples: Morphine, hydrocodone, oxymorphone, codeine, fentanyl

Other Central Nervous System (CNS) Depressants

Clinical Impact: Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
Intervention: 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 [see WARNINGS AND PRECAUTIONS].
Examples: Other benzodiazepines and sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, opioids, alcohol.

Drug Abuse And Dependence

Controlled Substance

NAYZILAM contains midazolam, a Schedule IV controlled substance.

Abuse

NAYZILAM is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction.

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. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see WARNINGS AND PRECAUTIONS].

The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.

The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).

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 After Use Of NAYZILAM More Frequently Than Recommended

NAYZILAM may produce physical dependence if used more frequently than recommended. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Although NAYZILAM is indicated only for intermittent use [see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION], if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening. Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see WARNINGS AND PRECAUTIONS]. 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].

Acute Withdrawal Signs And Symptoms

Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis, hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.

Protracted Withdrawal Syndrome

Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.

Tolerance

Tolerance to NAYZILAM may develop after use more frequently than recommended. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Tolerance to the therapeutic effect of benzodiazepines may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

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 tonicclonic 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.

Read the entire FDA prescribing information for Nayzilam (Midazolam Nasal Spray)

QUESTION

If you have had a seizure, it means you have epilepsy. See Answer

© Nayzilam Patient Information is supplied by Cerner Multum, Inc. and Nayzilam Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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