AUDIENCE: Consumer, Surgery, Anesthesiology
ISSUE: FDA has approved previously announced label changes regarding the use of general anesthetic and sedation medicines in children younger than 3 years. These changes include:
- A new Warning stating that exposure to these medicines for lengthy periods of time or over multiple surgeries or procedures may negatively affect brain development in children younger than 3 years.
- Addition of information to the sections of the labels about pregnancy and pediatric use to describe studies in young animals and pregnant animals that showed exposure to general anesthetic and sedation drugs for more than 3 hours can cause widespread loss of nerve cells in the developing brain; and studies in young animals suggested these changes resulted in long-term negative effects on the animals' behavior or learning.
General anesthetic and sedation drugs are necessary for patients, including young children and pregnant women, who require surgery or other painful and stressful procedures. In the U.S., surgeries during the third trimester of pregnancy requiring general anesthesia are performed only when medically necessary and rarely last longer than 3 hours. FDA is advising that in these situations, pregnant women should not delay or avoid surgeries or procedures during pregnancy, as doing so can negatively affect themselves and their infants.
Similarly, surgeries or procedures in children younger than 3 years should not be delayed or avoided when medically necessary. Consideration should be given to delaying potentially elective surgery in young children where medically appropriate.
BACKGROUND: This is an update to the MedWatch alert "General Anesthetic and Sedation Drugs: Drug Safety Communication - New Warnings for Young Children and Pregnant Women", available at: http://bit.ly/2pmujDk, issued on December 14, 2016.
RECOMMENDATION: Health care professionals should continue to follow their usual practices of patient counseling including discussing the benefits and risks of surgeries or procedures that require general anesthesia and sedation drugs. FDA will continue to monitor the use of these drugs in children and will update the public if additional information becomes available.
Parents, caregivers, and pregnant women should talk to their health care professionals if they have any questions or concerns about general anesthesia and sedation drugs.
For more information visit the FDA website at: http://www.fda.gov/Safety/MedWatch/SafetyInformation and http://www.fda.gov/Drugs/DrugSafety.
Midazolam may cause serious or life-threatening breathing problems such as shallow, slowed, or temporarily stopped breathing. Your child should only receive this medication in a hospital or doctor's office that has the equipment that is needed to monitor his or her heart and lungs and to provide life-saving medical treatment quickly if his or her breathing slows or stops. Your child's doctor or nurse will watch your child closely after he or she receives this medication to make sure that he or she is breathing properly. Tell your child's doctor if your child has a severe infection or if he or she has or has ever had any airway or breathing problems or heart or lung disease. Tell your child's doctor and pharmacist if your child is 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), morphine (Avinza, Kadian, MS Contin, others), and meperidine (Demerol); sedatives; sleeping pills; or tranquilizers.
Why is this medication prescribed?
Midazolam is given to children before medical procedures or before anesthesia for surgery to cause drowsiness, relieve anxiety, and prevent any memory of the event. Midazolam is in a class of medications called benzodiazepines. It works by slowing activity in the brain to allow relaxation and sleep.
How should this medicine be used?
Midazolam comes as a syrup to take by mouth. It is usually given as a single dose by a doctor or nurse before a medical procedure or surgery.
Other uses for this medicine
This medication may be prescribed for other uses; ask your child's doctor or pharmacist for more information.
What special precautions should I follow?
Before your child receives midazolam,
- tell your child's doctor and pharmacist if he or she is allergic to midazolam, any other medications, or cherries.
- tell your child's doctor if your child is 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 child's doctor may decide not to give midazolam to your child if he or she is taking one or more of these medications.
- tell your child's doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements your child is taking or plans to take. Be sure to mention the medications listed in the IMPORTANT WARNING section and any of the following: amiodarone (Cordarone, Pacerone); aminophylline (Truphylline); antifungals such as fluconazole (Diflucan), itraconazole (Sporanox), and ketoconazole (Nizoral); certain calcium channel blockers such as diltiazem (Cartia, Cardizem, Tiazac, others) and verapamil (Calan, Isoptin, Verelan, others); cimetidine (Tagamet); clarithromycin (Biaxin); dalfopristin-quinupristin (Synercid); erythromycin (E-mycin, E.E.S.); fluvoxamine (Luvox); certain medications for seizures such as carbamazepine (Tegretol), phenobarbital, and phenytoin (Dilantin); methylphenidate (Concerta, Metadate, Ritalin, others); nefazodone; ranitidine (Zantac); rifabutin (Mycobutin); and rifampin (Rifadin, Rimactane). Your child's doctor may need to change the doses of your child's medications or monitor your child carefully for side effects. Many other medications may also interact with midazolam, so be sure to tell your child's doctor about all the medications your child is taking, even those that do not appear on this list.
- tell your child's doctor what herbal products your child is taking, especially St. John's wort.
- tell your child's doctor if your child has glaucoma. Your child's doctor may decide not to give your child midazolam.
- tell your child's doctor if your child has or has ever had kidney or liver disease.
- tell your child's doctor if your child is or may be pregnant, or is breast-feeding.
- you should know that midazolam may make your child very drowsy and may affect his or her memory, thinking, and movements. Do not allow your child to ride a bicycle, drive a car, or do other activities that require him or her to be fully alert for at least 24 hours after receiving midazolam and until the effects of the medication have worn off. Watch your child 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 of midazolam worse.
What special dietary instructions should I follow?
Do not let your child eat grapefruit or drink grapefruit juice while taking this medication.
What side effects can this medication cause?
Midazolam may cause side effects. Tell your child's doctor if any of these symptoms are severe or do not go away:
Some side effects can be serious. If your child experiences any of these symptoms, call his or her doctor immediately:
- uncontrollable shaking of a part of the body
- stiffening and jerking of the arms and legs
- slow or irregular heartbeat
Midazolam may cause other side effects. Call your child's doctor if your child has any unusual problems while taking 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 the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at 911.
Symptoms of overdose may include:
- problems with balance and movement
- slowed breathing and heartbeat
- loss of consciousness
What other information should I know?
Keep all appointments with your child's doctor.
Ask your child's pharmacist or doctor if you have any questions about midazolam.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines your child is taking, as well as many products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time your child visits a doctor or if he or she is admitted to a hospital. It is also important information to carry with you in case of emergencies.