Midazolam (my DAZ oh lam) has been approved by the FDA 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 (nasal spray only).

Midazolam is a member of a group of drugs known as benzodiazepines. Benzodiazepines are commonly used in epilepsy on an “as needed” basis as a rescue medicine. These treatments are meant to rapidly stop seizures, whether to prevent an emergency or during one while under the care of healthcare providers.

Your epilepsy treatment should always be discussed with your healthcare provider before use. Based on their judgment and knowledge, a drug may be prescribed for situations not included in the indications. For more information, please see the prescribing information.

How can you take midazolam? (Available formulations)

Midazolam is available as a solution for a nasal route only and is administered by a healthcare provider for no more than 2 doses in an emergency setting. It is also available as an oral solution that is not indicated for epilepsy treatment.

Who should not take midazolam?

If you are allergic to midazolam or any other benzodiazepines (alprazolam, diazepam, clonazepam, clobazam), or if you have a known sensitivity to polyethylene glycol, propylene glycol, or benzyl alcohol, then you should not take it.

Patients with acute narrow-angle glaucoma should not take midazolam.

Other considerations may influence whether you should take midazolam. If possible, tell your healthcare provider if you:

  • have a history of depression, mood problems, or suicidal thoughts or behavior.
  • have asthma or other breathing disorders.
  • have kidney or liver problems.
  • have congestive heart failure.
  • have a history of drug or alcohol abuse.
  • are pregnant or plan to become pregnant.
  • are breastfeeding or plan to breastfeed.

What is important to know about taking midazolam?

Do not stop taking midazolam suddenly unless directed to do so by your healthcare provider.

As with all antiseizure medications, midazolam should be withdrawn gradually to minimize the risk of causing or worsening seizures or status epilepticus. You should not stop using midazolam suddenly unless your healthcare provider tells you to stop the medicine because of a serious side effect.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking midazolam with certain other medicines may cause side effects or affect how well they work. Do not start or stop other medicines without talking to your healthcare provider. Especially tell your healthcare provider if you take: opioids, drugs that cause sleepiness or dizziness, or alcohol.

As status epilepticus is a potentially life-threatening condition associated with a high risk of permanent neurological impairment, there may be occasions where the use of midazolam is required despite the risks of serious adverse events. The treatment of status epilepticus requires observation and management of vital functions by healthcare providers within the emergency setting. While it may not be possible in an emergency setting to communicate with your healthcare providers, preparation can overcome this barrier.

Boxed warnings

Midazolam nasal spray is approved by the FDA because the benefits of arresting status epilepticus outweigh the risks. Further, as midazolam nasal spray is administered while directly under the care of a healthcare provider, adverse effects may more easily be managed.

Use with opioids or other central nervous system depressants

Midazolam can slow or stop your breathing, especially if you have recently used an opioid medication, alcohol, or other central nervous system depressants as they also may slow your breathing. If you are administered midazolam nasal spray, your healthcare providers will watch you for symptoms such as weak or shallow breathing.

Tell your healthcare provider right away if you have:

  • weak or shallow breathing
  • severe drowsiness
  • restlessness or you feel agitated or irritable
  • unusual thoughts, hallucinations
  • a light-headed feeling, like you might pass out

Get emergency help right away if you experience shallow or slowed breathing, breathing stops (which may lead to the heart stopping), or excessive sleepiness (sedation).

Abuse, misuse, and addiction

Midazolam is a federally controlled substance (Schedule IV) as it has a risk of abuse, misuse, and addiction, which can lead to overdose or death. Using midazolam more frequently than recommended, even at recommended dosages, may increase these risks, especially when used in combination with other medications (e.g., opioids), alcohol, and/or illicit substances. Talk to your healthcare provider about the signs and symptoms of midazolam addiction.

Dependence and withdrawal reactions

The use of midazolam more frequently than recommended may cause physical dependence. This means that stopping midazolam suddenly can worsen your condition and cause withdrawal symptoms including irritability, sleeplessness, nervousness, and seizures. Physical dependence is not the same as drug addiction. Your healthcare provider can tell you more about the differences between physical dependence and drug addiction.

Women or those who are/plan to become pregnant

Midazolam may hurt your baby if taken while pregnant.

Use in pregnancy

Ordinarily, midazolam should not be used during pregnancy except in serious or life-threatening conditions where safer drugs cannot be used or are ineffective. Status epilepticus may represent such a serious and life-threatening condition. During the first trimester of pregnancy, several studies suggest the use of minor tranquilizers (chlordiazepoxide, diazepam, and meprobamate), which are similar to midazolam, can increase the risk of birth defects. Studies have also shown in humans that midazolam and some metabolites are transferred to the placenta.

If you become pregnant while taking midazolam, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiseizure medicine during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

Use during breastfeeding

Midazolam has been detected in human breast milk. Therefore, nursing people should not take midazolam because, like other benzodiazepines, the possibility exists that midazolam may sedate or otherwise adversely affect the infant.

What are the side effects of midazolam?

Common side effects

The most common side effects associated with midazolam are somnolence, headache, nasal discomfort, throat irritation, and rhinorrhea.

Rare, but serious side effects
Suicidal thoughts or behaviors

Studies have found that people who take antiseizure medications including midazolam may have suicidal thoughts or behaviors, which occur in approximately 1 in 500 patients. If you experience any thoughts or impulses to hurt yourself, you should contact your healthcare provider immediately.

Central nervous system (CNS) depression with other CNS depressants or CYP3A4 inhibitors

Midazolam can make you sleepy or dizzy and can slow your thinking and motor skills. These effects are enhanced when midazolam is taken with CYP3A4 (a protein that breaks down drugs) inhibitors, alcohol, or drugs that cause sleepiness or dizziness. Do not drive, operate heavy machinery, or do other dangerous activities until you know how midazolam affects you. Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking midazolam without first talking to your healthcare provider.

Pre-existing depression may emerge or worsen during the use of benzodiazepines, including midazolam.

Impaired cognitive function

Midazolam is associated with a high incidence of partial or complete impairment of recall for the next several hours. Do not drive or operate heavy machinery until the effects have stopped.