AUDIENCE: Consumer, Surgery, Anesthesiology
ISSUE: FDA is warning that repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than 3 years or in pregnant women during their third trimester may affect the development of children's brains.
Consistent with animal studies, recent human studies suggest that a single, relatively short exposure to general anesthetic and sedation drugs in infants or toddlers is unlikely to have negative effects on behavior or learning. However, further research is needed to fully characterize how early life anesthetic exposure affects children's brain development.
To better inform the public about this potential risk, FDA is requiring warnings to be added to the labels of general anesthetic and sedation drugs (see List of General Anesthetic and Sedation Drugs Affected by this Label Change). FDA will continue to monitor the use of these drugs in children and pregnant women and will update the public if additional information becomes available.
See the FDA Drug Safety Communication, available at: http://bit.ly/2hwlqCL, for a data summary and listing of general anesthetic and sedation drugs affected by this label change.
BACKGROUND: Anesthetic and sedation drugs are necessary for infants, children, and pregnant women who require surgery or other painful and stressful procedures, especially when they face life-threatening conditions requiring surgery that should not be delayed. In addition, untreated pain can be harmful to children and their developing nervous systems.
FDA has been investigating the potential adverse effects of general anesthetic and sedation drugs on children's brain development since the first animal study on this topic was published in 1999. FDA held advisory committee meetings in 2007, 2011, and 2014. To coordinate and fund research in this area, FDA also formed a partnership with the International Anesthesia Research Society (IARS) called SmartTots (Strategies for Mitigating Anesthesia-Related neuroToxicity in Tots). More research is still needed to provide additional information about the safe use of these drugs in young children and pregnant women.
RECOMMENDATION: Health care professionals should balance the benefits of appropriate anesthesia in young children and pregnant women against the potential risks, especially for procedures that may last longer than 3 hours or if multiple procedures are required in children under 3 years. Discuss with parents, caregivers, and pregnant women the benefits, risks, and appropriate timing of surgery or procedures requiring anesthetic and sedation drugs.
Parents and caregivers should discuss with their child's health care professional the potential adverse effects of anesthesia on brain development, as well as the appropriate timing of procedures that can be delayed without jeopardizing their child's health. Pregnant women should have similar conversations with their health care professionals. Also talk with them about any questions or concerns.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Midazolam injection may cause serious or life-threatening breathing problems such as shallow, slowed, or temporarily stopped breathing that may lead to permanent brain injury or death. You should only receive this medication in a hospital or doctor's office that has the equipment that is needed to monitor your heart and lungs and to provide life-saving medical treatment quickly if your breathing slows or stops. Your doctor or nurse will watch you closely after you receive this medication to make sure that you are breathing properly. Tell your doctor if you have a severe infection or if you have or have ever had any lung, airway, or breathing problems or heart disease. Tell your doctor and pharmacist if you are taking any of the following medications: antidepressants; barbiturates such as secobarbital (Seconal); droperidol (Inapsine); medications for anxiety, mental illness, or seizures; narcotic medications for pain such as fentanyl (Actiq, Duragesic, Sublimaze, others), meperidine (Demerol),and morphine (Avinza, Kadian, MS Contin, others); sedatives; sleeping pills; or tranquilizers.
Why is this medication prescribed?
Midazolam injection is used before medical procedures and surgery to cause drowsiness, relieve anxiety, and prevent any memory of the event. It is also sometimes given as part of the anesthesia during surgery to produce a loss of consciousness. Midazolam injection is also used to cause a state of decreased consciousness in seriously ill people in intensive care units (ICU) who are breathing with the help of a machine. Midazolam injection is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow relaxation and decreased consciousness.
How should this medicine be used?
Midazolam injection comes as a solution (liquid) to be injected into a muscle or vein by a doctor or nurse in a hospital or clinic.
If you receive midazolam injection in the ICU over a long period of time, your body may become dependent on it. Your doctor will probably decrease your dose gradually to prevent withdrawal symptoms such as seizures, uncontrollable shaking of a part of the body, hallucinations (seeing things or hearing voices that do not exist), stomach and muscle cramps, nausea, vomiting, sweating, fast heartbeat, difficulty falling asleep or staying asleep, and depression.
Other uses for this medicine
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
What special precautions should I follow?
Before receiving midazolam injection,
- tell your doctor and pharmacist if you are allergic to midazolam or any other medications.
- tell your doctor if you are taking certain medications for human immunodeficiency virus (HIV) including amprenavir (Agenerase), atazanavir (Reyataz), darunavir (Prezista), delavirdine (Rescriptor), efavirenz (Sustiva, in Atripla), fosamprenavir (Lexiva), indinavir (Crixivan),lopinavir (in Kaletra), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), saquinavir (Invirase), and tipranavir (Aptivus). Your doctor may decide not to give you midazolam injection if you are taking one or more of these medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: aminophylline (Truphylline); certain antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral); certain calcium channel blockers such as diltiazem (Cartia, Cardizem, Tiazac, others) and verapamil (Calan, Isoptin, Verelan, others); cimetidine (Tagamet); dalfopristin-quinupristin (Synercid); and erythromycin (E-mycin, E.E.S.). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with midazolam, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
- tell your doctor if you have glaucoma (increased pressure in the eyes that may cause gradual loss of vision). Your doctor may decide not to give you midazolam injection.
- tell your doctor if you have recently stopped drinking large amounts of alcohol or if you have or have ever had kidney or liver disease.
- tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding.
- talk to your doctor about the risks and benefits of receiving midazolam injection if you are 65 years of age or older. Older adults should usually receive lower doses of midazolam injection because higher doses are more likely to cause serious side effects.
- you should know that midazolam may make you very drowsy and may affect your memory, thinking, and movements. Do not drive a car or do other activities that require you to be fully alert for at least 24 hours after receiving midazolam and until the effects of the medication have worn off. If your child is receiving midazolam injection, watch him or her carefully to be sure that he or she does not fall while walking during this time.
- you should know that alcohol can make the side effects from midazolam injection worse.
What special dietary instructions should I follow?
Unless your doctor tells you otherwise, continue your normal diet.
What side effects can this medication cause?
Midazolam injection may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- pain, redness, or hardening of the skin at the injection site
Some side effects can be serious. If you experience any of these symptoms or those listed in the IMPORTANT WARNING section, call your doctor immediately:
- uncontrollable shaking of a part of the body
- stiffening and jerking of the arms and legs
- uncontrollable rapid eye movements
- difficulty breathing or swallowing
Midazolam injection may cause other side effects. Call your doctor if you have any unusual problems while receiving this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Symptoms of overdose may include:
- problems with balance and movement
- slowed reflexes
- slowed breathing and heartbeat
- coma (loss of consciousness for a period of time)
What other information should I know?
Keep all appointments with your doctor.
Ask your doctor or pharmacist if you have any questions about midazolam injection.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
- Versed® Injection